Streptomycin

Eur J Cardiothorac Surg, 2001 Jun, 19(6), 806 - 10
Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach; Hadjinikolaou L et al.; OBJECTIVES: Brucella endocarditis is an underdiagnosed complication of human brucellosis, associated with high morbidity and mortality . We report the successful management of a number of cases of Brucella mellitensis endocarditis . PATIENTS AND METHODS: Seven consecutive cases of Brucella mellitensis endocarditis were treated over the last 20 years, based on high suspicion of the disease at first place . The early suspicion of Brucella endocarditis relied on medical history and a standard tube agglutination titer > or =20 . Blood and/or cardiac tissue cultures were positive in all patients, but available late following surgery . All patients were successfully treated with a combination of aggressive medical and early surgical therapy . All affected valves were replaced within 1 week from admission (five aortic and three mitrals) . Medical treatment included co-trimoxazole, tetracyclines and streptomycin, before surgery, followed by co-trimoxazole and tetracyclines for a median of 12 months (range: 3-15 months) after surgery until the titers returned to a level < or =1:160 . RESULTS: There were neither operative deaths nor recurrence of infection . One patient died two years after the operation due to massive cerebrovascular accident . Ten-year survival was 85.7+/-13.2% . CONCLUSION: Although Brucella mellitensis endocarditis is a rare entity, its optimum management should be a combination of aggressive medical treatment and early surgical intervention, based on high degree of suspicion in areas with high incidence of the disease.

Diagn Microbiol Infect Dis, 2001 Apr, 39(4), 229 - 32
Comparison of MB/BacT system and agar proportion method in drug susceptibility testing of Mycobacterium tuberculosis; Yew WW et al.; The drug susceptibilities of 105 isolates/strains of Mycobacterium tuberculosis (101 clinical isolates and four control strains from the American Type Culture Collection) were assessed by the MB/BacT system and conventional agar proportion method . The agreement rates between the two methods were 99.0% for streptomycin, 95.2% for isoniazid and 100% for rifampin . The mean times to detection for drug-resistant isolates were 4.7 days (range: 2.5-13.7 days) using the MB/BacT system and 14.8 days (range: 14-21 days) using the agar proportion method . For drug-susceptible isolates, the times to detection were 10.8 days (mean) and 21 days respectively . Thus, these data have demonstrated that the automated, non-radiometric MB/BacT system is an efficient, accurate and reliable method for assessing drug susceptibilities of M . tuberculosis compared with the conventional agar proportion method.

Med Clin (Barc), 2000 Oct 21, 115(13), 493 - 8
{Drug resistance in Mycobacterium tuberculosis . A multicenter study of the Barcelona area . Grupo de Trabajo sobre Resistencias en Tuberculosis}; Martin-Casabona N et al.; BACKGROUND: The aims of this multicenter study was to establish the level of primary and acquired drug resistance of M . Tuberculosis strains isolated in Barcelona and to identify possible risk groups using clinical data . PATIENTS AND METHODS: All tuberculosis patients with isolation and identification of M . tuberculosis strains from October 1995 to September 1997 were included . Susceptibility tests isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide were performed using the Bactec 460 system and the proportions method on solid medium . Logistic progression was used for statistical analysis . RESULTS: The total number of patients included was 1,749 (1,535 non-treated and 214 previously treated) . Primary drug resistance was 5.7% (isoniazid 3.8%; rifampin 1.0%, streptomycin 2.1%, ethambutol 0.3% and pyrazinamide 1.0%) . Acquired drug resistance was 20.5% (isoniazid 17.3%, rifampin 9.8%, ethambutol 1.9%, streptomycin 4.7% and pyrazinamide 6.5%) . Primary drug resistance was associated with people over 60 years old and women . CONCLUSIONS: The low level of drug resistance enables antituberculosis treatment of non-treated patients to start with the standardised three-drug regimes except in the case of foreign people from countries with a high level of drug resistance . Susceptibility tests are recommended on all M . tuberculosis strains isolated, together with controlled studies of drug resistance surveillance.

Am J Trop Med Hyg, 2000 Jul-Aug, 63(1-2), 56 - 60
Rapid, simple, and culture-independent detection of rpsL codon 43 mutations that are highly predictive of streptomycin resistance in Mycobacterium tuberculosis; Mieskes KT et al.; The substitution of codon 43 in the gene rpsL is the single most common mutation found in streptomycin-resistant Mycobacterium tuberculosis . The characterization of this mutation has been hampered by the need for prior cultivation of the mycobacteria, the need for DNA sequencing, or both . In this report we describe a simple and culture-independent technique to detect this mutation directly from sputum samples, requiring little more than a polymerase chain reaction (PCR) machine and a simple agarose minigel . There is no need for labeled probes or DNA sequencing . In a preliminary test of feasibility, interpretable results were obtained from all of 16 smear-positive and 1 of 4 smear-negative, culture-positive samples . Two of two samples containing M . tuberculosis with rpsL codon 43 mutations were correctly identified.

Int J Antimicrob Agents, 2001 May, 17(5), 415 - 8
Increasing resistance of M . tuberculosis to anti-TB drugs in Saudi Arabia; Khan MY et al.; The incidence of drug resistance in Mycobacterium tuberculosis (MTB) isolated from our hospital between April 1996 and March 1998 was compared with an earlier study (1993-1995) . Thirty (29.7%) of 101 MTB isolates were resistant to one or more anti-TB drugs and 21 (20%) of 101 were multi-drug resistant M . tuberculosis (MDR-TB) . Resistance was most common to isoniazid (28.7%), followed by streptomycin (22.8%) and rifampicin (20.8%) . Resistance to pyrazinamide and ethambutol was 7.9 and 6.9%, respectively . There was a three-fold increase in resistance compared with the earlier study.

Int J Tuberc Lung Dis, 2001 Apr, 5(4), 339 - 45
Heteroresistance in Mycobacterium tuberculosis; Rinder H et al.; SETTING: Drug resistance in Mycobacterium tuberculosis is often linked to specific mutations in a limited number of resistance genes . Detection of these mutations in a cultured isolate can predict the resistant phenotype . Genotypic analysis of the mycobacteria directly in a clinical specimen would result in considerable time saving for resistance prediction . OBJECTIVE: To find out whether resistance-predicting genotypes of mycobacteria found after cultivation always give a good reflection of those in the original clinical sample . DESIGN: Restriction fragment length polymorphisms of repetitive polymerase chain reaction (PCR) amplification and cloning of PCR products were used as nonintegrative methods to describe the composition of katG, rpsL and embB genotypes involved in resistance to isoniazid, streptomycin and ethambutol, respectively, in the original sample . This result was then compared to the phenotypic resistance profile after cultivation . RESULTS: Using both methods, mixed, heteroresistant populations could be detected in almost every fifth analyzed sample (katG: 5 of 16; rpsL: 3 of 17; embB: 1 of 21) . Direct sequencing, a widely used integrative method, repeatedly failed to detect heteroresistance . CONCLUSION: Heteroresistance is a valid phenomenon in clinical tuberculosis . It is not rare and not restricted to a particular resistance gene, and is obscured by cultivation as well as by some, not all, culture-independent resistance prediction tests.

Bioorg Med Chem Lett, 2001 Apr 23, 11(8), 1015 - 8
Study of aminoglycoside-nucleic acid interactions by an HPLC method; Constantinou-Kokotou T et al.; The interactions of a number of aminoglycoside antibiotics with tRNA and DNA were studied by an HPLC method . based on tRNA and DNA peak size exclusion . Among the compounds studied (deoxystreptamine, neamine, neomycin B, kanamycin A, gentamicin A, netilmicin, streptomycin, and the synthetic neamine analogue BKN3), neomycin B and the synthetic analogue of neamine were proved to be the most potent binders.

Br J Pharmacol, 2001 May, 133(1), 5 - 12
The polycationic aminoglycosides modulate the vasoconstrictive effects of endothelin: relevance to cerebral vasospasm; Wickman G et al.; 1 . The vasoactive peptide endothelin (ET) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid haemorrhage . In these studies we investigated the involvement of protein kinase C (PKC) in sustained vasoconstriction induced by ET-1 in canine cerebral arteries . We also examined the ability of the aminoglycoside antibiotics to reverse the effects mediated by ET-1 in canine cerebrovascular smooth muscle cells (CVSMC) . 2 . The ET(A) receptor antagonist, BQ-123, showed a competitive inhibition of the ET-1 responses . 3 . The vasoconstrictor action of both ET-1 (0.5 nM) and phorbol myristate acetate (PMA) (160 nM) was reversed by a selective PKC inhibitor, Ro-32-0432 . 4 . In cerebral arteries precontracted with ET-1 the aminoglycosides caused a concentration-dependent relaxation . The EC(50s) for the relaxation were as follows: 0.54+/-0.05, 0.63+/-0.01, 1.88+/-0.46 and 2.3+/-0.92 mM for gentamicin, neomycin, streptomycin and kanamycin, respectively . 5 . Gentamicin caused a concentration-dependent decrease of the PMA-induced responses in calcium free medium . 6 . PKC activity was elevated in CVSMC exposed to ET-1 (170%) and PMA (167%) for a period of time (60 min) corresponding to maximum tonic contraction induced by these agents in arterial rings . 7 . The administration of the aminoglycosides to CVSMC, in concentrations corresponding to the EC(50s) from contractility studies, reduced the effects of both ET-1 and PMA on PKC activity to the levels not different from controls . 8 . These results show that the aminoglycosides are able to inhibit sustained vasoconstriction induced by ET-1, an effect which is due, at least in part, to the inhibition of PKC.

Curr Genet, 2001 Feb, 39(1), 49 - 60
Chloroplast transformation in Euglena gracilis: splicing of a group III twintron transcribed from a transgenic psbK operon; Doetsch NA et al.; The Escherichia coli aadA gene product, which confers resistance to spectinomycin and streptomycin, has been widely used as a dominant selectable marker for chloroplast transformation of Chlamydomonas and tobacco . An aadA transformation cassette was adapted for expression in Euglena gracilis chloroplasts by replacing the Chlamydomonas promoter and 3' untranslated region (UTR) with the E . gracilis psbA promoter and 3' UTR . Transgenic DNA was introduced into E . gracilis chloroplasts by biolistic transformation . Streptomycin- and spectinomycin-resistant colonies were obtained, which screened positively for the presence of the transforming vector by PCR amplification . Although integration of the transforming DNA into the chloroplast genome was not detected, transforming DNA was stably maintained in the chloroplast as an episomal element during continuous selection on antibiotics . The aadA cassette was also inserted into a transformation vector which contained the independently expressed psbK operon from either E . gracilis or a closely related species, E . stellata . The psbK operon contained at least two group III introns and a group III twintron, was highly expressed, and was only 1.5 kb in length . In transgenic E . gracilis chloroplasts, a truncated E . stellata psbK operon was transcribed, and the resultant pre-mRNA was accurately spliced . This system should allow the first direct analysis of group II and group III intron-splicing mechanisms . In addition, it could prove useful in the study of many other Euglena transcription and processing events.

J Agric Food Chem, 2001 Apr, 49(4), 1669 - 74
Determination of tetracycline and streptomycin in mixed fungicide products by capillary zone electrophoresis; Hsiao YM et al.; A method of capillary zone electrophoresis (CZE) was used to determine tetracycline and streptomycin content in commercial agriculture products . The results indicated that this method was capable of analyzing the mixed fungicide in formulated products with instrument detection limit (IDL) of 0.50 microg/mL and a method detection limit (MDL) of 0.52 microg/mL for tetracycline, and IDL of 1.00 microg/mL and MDL of 1.22 microg/mL for streptomycin . Precision expressed by relative standard deviation (RSD) ranged from 1.44 to 4.37% of tetracycline and 1.00 to 4.20% of streptomycin . Recoveries were in the region of 98.2-102.5% for tetracycline and 95.3--103.0% for streptomycin . The low detection limit, the low RSD values, and the high percentage of recovery confirmed that the CZE technique is a sensitive and selective method . And the CZE method can analyze both tetracycline and streptomycin at the same time without complicated extraction and further derivative reaction.

Mol Microbiol, 2001 Apr, 40(1), 189 - 99
First evidence for gene replacement in Leptospira spp . Inactivation of L . biflexa flaB results in non-motile mutants deficient in endoflagella; Picardeau M et al.; Leptospira spp . offer many advantages as model bacteria for the study of spirochaetes . However, homologous recombination between introduced DNA and the corresponding chromosomal loci has never been demonstrated . A unique feature of spirochaetes is the presence of endoflagella between the outer membrane sheath and the cell cylinder . We chose the flaB flagellin gene, constituting the flagellar core, as a target for gene inactivation in the saprophyte Leptospira biflexa . The amino acid sequence of the FlaB protein of L . biflexa was most similar to those of spirochaetes Brachyspira hyodysenteriae (agent of swine dysentery), Leptospira interrogans (agent of leptospirosis) and Treponema pallidum (agent of syphilis) . A suicide vector containing the L . biflexa flaB gene disrupted by a kanamycin marker was UV irradiated or alkali denatured before electroporation . This methodology allowed the selection of many kanamycin-resistant colonies resulting from single and double cross-over events at the flaB locus . The double recombinant mutants are non-motile, as visualized in both liquid and semi-solid media . In addition, a flaB mutant selected for further analysis was shown to be deficient in endoflagella by electron microscopy . However, most of the transformants had resulted from a single homologous recombination event, giving rise to the integration of the suicide vector . We evaluated the effect of the sacB and rpsL genes in L . biflexa as potential counterselectable markers for allelic exchange, and then used the rpsL system for the positive selection of flaB double recombinants in a streptomycin-resistant strain . Like the flaB mutant studied above, the Strr double cross-over mutant was non-motile and deficient in endoflagella . Our results demonstrate that FlaB is involved in flagella assembly and motility . They also show the feasibility of performing allelic replacement in Leptospira spp . by homologous recombination.

J Cardiovasc Electrophysiol, 2001 Mar, 12(3), 323 - 9
Heterogeneous changes of monophasic action potential induced by sustained stretch in atrium; Babuty D et al.; INTRODUCTION: Chronic enlargement of atrium is common in atrial fibrillation, and the effects of stretch on atrial action potentials seem inconsistent . As atrial muscle is heterogeneous, we suggest that atrial stretch induces a variable electrophysiologic response and that the effects of stretch are only partially mediated by stretch-activated channels . METHODS AND RESULTS: Sixteen guinea pig hearts were perfused by the Langendorff method using Kreb's solution with and without 80 microM streptomycin, which is a stretch-activated channel blocker . Suction electrodes were used to record monophasic action potentials (MAPs) of the left atrium . Left auricular pressure was monitored by a balloon . We determined the MAP duration at 50% and 90% repolarization (MAPD50 and MAPD90) in basal conditions and after a slow onset but sustained stretch of the atrium in the absence and presence of streptomycin . Stretch induced no overall consistent or significant change in mean MAPD50 and MAPD90 . The individual responses were markedly variable . The most frequent response (about 50%) was a decrease in MAPD50 and MAPD90 . In 25% of cases, there was no change, and in 25% we observed increases in MAPD50 and MAPD90 . Streptomycin did not affect MAPD50 and MAPD90, but it dramatically modified the distribution of MAPD changes induced by stretch . In particular, streptomycin removed stretch-induced shortening of MAPD50 and MAPD90, whereas it did not affect stretch-induced lengthening . CONCLUSION: Sustained stretch of atrium induces variable modifications of MAPD that are only partially inhibited by streptomycin . This suggests the participation of ionic channels other than specific stretch-activated channels in the response of atrial myocardium to sustained stretch.

J Assoc Physicians India, 2000 Apr, 48(4), 376 - 80
Clinical profile of neurobrucellosis--a report on 12 cases from Bikaner (north-west India); Kochar DK et al.; OBJECTIVE: To study the spectrum of neurobrucellosis in a prospective study at Bikaner which is supposed to be uncommon in India . METHOD: This study was done on admitted patients of brucellosis from June 1996 to June 1999 in whom the diagnosis was done by history of exposure to animals, fever and arthralgia and demonstration of brucella antibody titres in serum 1:160 . CSF examination was done in all the patients . All cases were treated by combination of doxycycline 100 mg twice daily, rifampicin 900 mg daily for 6-8 weeks and injection streptomycin 0.75 to 1 gm i.m . per day for initial 14 days . Detailed neurological examination and antibody titres of serum and CSF again measured at the end of treatment . RESULTS: Twelve out of 92 patients revealed evidence of neurobrucellosis in which four cases were of meningoencephalitis, two cases of myelitis leading to spastic paraparesis, five cases of polyradiculoneuropathy and one case of polyneuroradiculomyeloencephalopathy . The treatment regimen used was associated with a high cure rate and significant reduction in antibody titres in serum and CSF . CONCLUSION: Neurobrucellosis is an uncommon but serious manifestation affecting central and peripheral nervous system . The clinical profile of the disease mimicks closely to commonly seen neurological infective diseases like tubercular meningitis, viral encephalitis, aseptic meningitis, cerebral malaria and viral encephalopathy . Serum and CSF testing for brucella antibody titre is an important test for the diagnosis . Blood culture is not an ideal test for neurobrucellosis because of low yield and longer time required for the diagnosis . High degree of suspicion is prudent for the diagnosis . High degree of cure rate can be achieved by treatment with present regimen in a disease which is otherwise having high mortality and morbidity.

Indian J Med Sci, 2000 Feb, 54(2), 55 - 8
Drug resistance in tuberculosis patients in Jodhpur district; Mathur ML et al.; Drug resistant tuberculosis is a serious problem in control of tuberculosis . To assess this problem in Jodhpur district, Sputum samples of symptomatic quarry workers and cases of pulmonary tuberculosis attending District Tuberculosis Clinic (DTC) Jodhpur were tested for culture of Mycobacterium tuberculosis complex (MTB) and their sensitivity to antituberculous drugs, using proportion method . Primary drug resistance to isoniazid was observed in 16.67%, to streptomycin in 16.67%, to ethambutol in 6.67% and to rifampicin in 6.67% . Acquired resistance to isoniazid was 61.76%, to streptomycin was 51.52%, to rifampicin was also 70.59%, and to ethambutol was 39.39% . Proportion of Multi-drug resistant (MDR) TB defined as resistant to at least isoniazid and and rifampicin, was 3.3% in new cases (primary drug resistance) and 38.2% in old cases (acquired drug resistance), the later may be due to inadequate treatment, the the history of which was present in most cases . Adequate treatment of such cases with effective regimens is of vital importance to prevent the spread of MDR TB.

Int J Tuberc Lung Dis, 2001 Jan, 5(1), 65 - 9
The management of anti-tuberculosis drug-induced hepatotoxicity; Tahaoglu K et al.; SETTING: A tuberculosis ward in a chest disease teaching hospital . OBJECTIVE: To compare the efficacy of two different retreatment protocols on hepatotoxicity recurrence in tuberculosis treatment . DESIGN: In a prospective, randomised study, 45 patients with new tuberculosis developed hepatotoxicity after anti-tuberculosis treatment . Patients in Group I (n = 20) were retreated with a drug regimen consisting of isoniazid, rifampicin, ethambutol and streptomycin administered by gradually increasing the number and dosage of the drugs . Patients in Group II (n = 25) were retreated with the same regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) in the same dosages throughout . RESULTS: Hepatotoxicity recurred in respectively zero and six (24%) patients in Groups I and II (P = 0.021) . Of the six patients with recurrence of hepatitis, one could not be followed up . The other five received the same retreatment protocol as Group I . By the end of retreatment, all patients were cured . CONCLUSION: The recurrence rate of hepatotoxicity in the retreatment of tuberculosis is higher in the reintroduction of a full-dose regimen including pyrazinamide, which causes more hepatotoxicity than gradual reintroduction of a regimen without pyrazinamide.

Zhonghua Jie He He Hu Xi Za Zhi, 1998 Feb, 21(2), 76 - 8
{Comparative study on efficacy of regimens including streptomycin or ethambutol}; Li Q et al.; OBJECTIVE: To evaluate the advantages and disadvantages of regimens of 2E3H3R3Z3/4H3R3(EMB regimen) and 2S3H3R3Z3/4H3R3(SM regimen) in tuberculosis control program . METHOD: Retrospective, cross-sectional and prospective studies were carried out in Shijiazhuang city, Hebei province from January 1994 to June 1996 . RESULT: There was no significant difference between the two regimens in efficacy, relapse rate and full course supervision . The EMB regimen was found more applicable than the SM regimen, and the SM regimen caused more side effects than the EMB regimen . Streptomycin skin test had a 4.5% positive rate, and using SM costs 84% more than using EMB . One of the drawbacks found in the SM regimen was that only in 42.9% of the rural sanitation units the disinfection standard could be fulfilled, and the patients preferred the EMB regimen to the SM regimen . CONCLUSION: The EMB regimen is more applicable than the SM regimen in the tuberculosis control program.

J Antimicrob Chemother, 1999 Feb, 43(2), 281 - 4
Relationship between genetic alteration of the rpsL gene and streptomycin susceptibility of Mycobacterium tuberculosis in Japan; Fukuda M et al.; We have investigated the effect of genetic alterations in the rpsL gene on the MICs of streptomycin for Mycobacterium tuberculosis strains . Direct DNA sequencing showed a point mutation in 23/121 strains; in 18 strains the mutation was associated with an amino acid change . The MICs of streptomycin in 22 out of 23 point-mutated strains were > or = 256 mg/L . Restriction fragment length polymorphism (RFLP) analysis showed mutations at codon 43 in all 18 strains with point mutations in the same codon . Our results suggest that both RFLP and base sequencing analysis of the rpsL gene are useful for the rapid prediction of highly streptomycin-resistant strains of M . tuberculosis.

J Neurophysiol, 2001 Mar, 85(3), 1119 - 28
Visual influences on the development and recovery of the vestibuloocular reflex in the chicken; Goode CT et al.; Whenever the head turns, the vestibuloocular reflex (VOR) produces compensatory eye movements to help stabilize the image of the visual world on the retina . Uncompensated slip of the visual world across the retina results in a gradual change in VOR gain to minimize the image motion . VOR gain changes naturally during normal development and during recovery from neuronal damage . We ask here whether visual slip is necessary for the development of the chicken VOR (as in other species) and whether it is required for the recovery of the VOR after hair cell loss and regeneration . In the first experiment, chickens were reared under stroboscopic illumination, which eliminated visual slip . The horizontal and vertical VORs (h- and vVORs) were measured at different ages and compared with those of chickens reared in normal light . Strobe-rearing prevented the normal development of both h- and vVORs . After 8 wk of strobe-rearing, 3 days of exposure to normal light caused the VORs to recover partially but not to normal values . In the second experiment, 1-wk-old chicks were treated with streptomycin, which destroys most vestibular hair cells and reduces hVOR gain to zero . In birds, vestibular hair cells regenerate so that after 8 wk in normal illumination they appear normal and hVOR gain returns to values that are normal for birds of that age . The treated birds in this study recovered in either normal or stroboscopic illumination . Their hVOR and vVOR and vestibulocollic reflexes (VCR) were measured and compared with those of untreated, age-matched controls at 8 wk posthatch, when hair cell regeneration is known to be complete . As in previous studies, the gain of the VOR decreased immediately to zero after streptomycin treatment . After 8 wk of recovery under normal light, the hVOR was normal, but vVOR gain was less than normal . After 8 wk of recovery under stroboscopic illumination, hVOR gain was less than normal at all frequencies . VCR recovery was not affected by the strobe environment . When streptomycin-treated, strobe-recovered birds were then placed in normal light for 2 days, hVOR gain returned to normal . Taken together, the results of these experiments suggest that continuous visual feedback can adjust VOR gain . In the absence of appropriate visual stimuli, however, there is a default VOR gain and phase to which birds recover or revert, regardless of age . Thus an 8-wk-old chicken raised in a strobe environment from hatch would have the same gain as a streptomycin-treated chicken that recovers in a strobe environment.

Eur J Clin Microbiol Infect Dis, 2001 Jan, 20(1), 33 - 9
Comparison of two rapid colorimetric methods for determining resistance of mycobacterium tuberculosis to rifampin, isoniazid, and streptomycin in liquid medium; De Logu A et al.; The usefulness of two colorimetric methods for the determination of the susceptibility or resistance of Mycobacterium tuberculosis to rifampin, streptomycin, and isoniazid in liquid medium based on the reduction of 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide (XTT) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was investigated . The agar proportion method was used as the reference method . Results obtained indicate that the sensitivity of the XTT reduction assay for the detection of rifampin resistance was comparable to that observed, and previously described, for the MTT assay . However, the reduction of XTT yields a water-soluble formazan that can be easily quantified without performing additional steps such as addition of lysing buffer and solubilization . Furthermore, the colorimetric assays, based on the reduction of XTT and MTT for the detection of isoniazid and streptomycin resistance in Mycobacterium tuberculosis, were standardized . The inhibition of MTT and

Ear Nose Throat J, 2001 Feb, 80(2), 76 - 8, 81-2, 84 passim
Delayed endolymphatic hydrops: study and review of clinical implications and surgical treatment; Huang TS et al.; Delayed endolymphatic hydrops (DEH) differs from Meniere's disease in that it occurs in pre-existing ear pathology in patients who have a profound unilateral or total deafness that was caused by infection, trauma, or unknown causes during childhood or adulthood . We performed a retrospective review of 160 patients with ipsilateral, contralateral, or bilateral DEH . Eighty-seven patients who did not respond to medical therapy underwent surgical treatment . Our findings indicate that the more conservative surgical procedures--endolymphatic sac surgery, cochleosacculotomy, and streptomycin perfusion--are all as effective as and less destructive than labyrinthectomy for controlling vertigo . The clinical results of this study would seem to support the observations of others that DEH and Meniere's disease are related disorders caused predominantly by cases of viral labyrinthitis with unknown etiology.

Am J Ophthalmol, 2001 Feb, 131(2), 283 - 4
Parinaud's oculoglandular syndrome attributable to an encounter with a wild rabbit; Thompson S et al.; PURPOSE: To describe the clinical and histopathologic findings in a patient with Parinaud's oculoglandular syndrome attributable to Francisella tularensis obtained from an encounter with a wild baby rabbit . METHODS: In an 18-year-old man, the clinical course, laboratory findings, and histopathologic findings are described . RESULTS: Parinaud's oculoglandular syndrome should be considered in the differential diagnosis of a patient presenting with unilateral granulomatous conjunctivitis, painful preauricular, and submandibular lymphadenopathy combined with systemic symptoms of general malaise and fever . CONCLUSION: Tularemia is one etiology of Parinaud's oculoglandular syndrome . It is caused by Francisella tularensis and is usually transmitted to humans via infected animal blood or through an insect bite, most often a tick . For treatment, intramuscular streptomycin is the drug of choice.

Scott Med J, 2000 Dec, 45(6), 183 - 5
Tuberculosis revisited or how we nearly conquered tuberculosis; Williamson J; This article recounts the author's experience as a chest physician in the years after the Second World War when Scotland experienced a serious epidemic of tuberculosis . With the discovery of streptomycin, PAS and isoniazid this disease became for the first time eminently treatable, and the team in Edinburgh demonstrated how the routine use of these three drugs in all cases ensured that the patient progressed to cure with virtually no cases of drug resistance . This policy, although fully supported by follow-up studies, was only very slowly adopted elsewhere, and since that time there have been numerous errors and difficulties in treatment regimens in many parts of the world . The result is that a great therapeutic opportunity has been lost and the Worldwide situation is worse than ever, mainly due to increased incidence of TB in the countries of the Third World.

J Environ Pathol Toxicol Oncol, 2001, 20(1), 23 - 6
A common regulator of cold and radiation response in Escherichia coli; Mangoli S et al.; High levels of the protein product of gicA/cspE, a member of cspA family of cold stress genes, are known to be associated with several pleiotropic phenotypes in Escherichia coli . These include growth retardation in cold, suppression of rpsL31-mediated streptomycin resistance in cold, suppression of the chromosome partitioning mutation mukB, and cellular resistance to camphor . In this article, we demonstrate that the product of this gene is also involved in regulating UV and gamma radiation sensitivity . When present on a multicopy plasmid, gicA conferred UV sensitivity on those strains of E . coli K-12, in which it produces the cold-dependent growth retardation and streptomycin sensitivity but did not confer any gamma radiation sensitivity . A gicA::cat mutation, that inactivates the chromosomal gicA, made the cells highly sensitive to both UV and gamma radiation . These results indicate that the cellular level of GicA is quite critical in some aspects of DNA metabolism and suggest that this protein is a global regulator of multiple pathways affecting growth and translational fidelity in cold, DNA condensation, and chromosome partitioning during cell division.

J Med Liban, 2000 Jul-Aug, 48(4), 248 - 54
Mycobacteria: treatment approaches and mechanisms of resistance; Frothingham R; First-line drugs for tuberculosis treatment include isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide . Molecular mechanisms for resistance to each of these drugs have been elucidated . In every case, resistance is conferred by mutations in existing genes, not by the acquisition of new genetic material . Drug resistance is a major problem worldwide, but the rates vary widely among countries and within countries . Acquired resistance in previously-treated patients is much more common than primary resistance in patients with no previous treatment . High rates of acquired resistance have been reported from referral centers in Saudi Arabia and Lebanon . Successful TB treatment requires prolonged therapy with at least two active drugs . Directly-observed therapy (DOT) improves success rates and reduces the risk of acquired resistance . TB due to susceptible strains can be cured in over 95% of cases.

Mikrobiologiia, 2000 Nov-Dec, 69(6), 805 - 9
{Growth of Escherichia coli cell culture and frequency of mutation, induced by N-methyl-N'-nitro-N-nitrosoguanidine}; Goliasnaia NV et al.; The rate of Escherichia coli mutation with N-methyl-N'-nitro-N-nitrosoguanidine was found to depend on the age of the culture and the pH value of the incubation medium . The mutability of late-logarithmic cells was higher than that of mid-logarithmic cells . Rifampicin, a transcription inhibitor, enhanced the mutagenic action of MNNG on cells from the late logarithmic and early stationary phases suspended in a medium with a pH of 7.4, and on cells from the mid-logarithmic phase suspended in a medium with a pH of 6.5 . Conversely, streptomycin decreased the frequency of induced mutations in cells from the late logarithmic and early stationary phases suspended in the medium with a pH of 7.4, and in cells from the mid-logarithmic and early stationary phases suspended in the medium with a pH of 6.5 . These data were interpreted as showing that the repair of premutational DNA lesions induced by MNNG depends on the level of DNA transcription and translation.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 800 - 4
Characterization of P55, a multidrug efflux pump in Mycobacterium bovis and Mycobacterium tuberculosis; Silva PE et al.; The Mycobacterium bovis P55 gene, located downstream from the gene that encodes the immunogenic lipoprotein P27, has been characterized . The gene was identical to the open reading frame of the Rv1410c gene in the genome of Mycobacterium tuberculosis H37Rv, annotated as a probable drug efflux protein . Genes similar to P55 were present in all species of the M . tuberculosis complex and other mycobacteria such as Mycobacterium leprae and Mycobacterium avium . By Western blotting, P55 was located in the membrane fraction of M . bovis . When transformed into Mycobacterium smegmatis after cloning, P55 conferred aminoglycoside and tetracycline resistance . The levels of resistance to streptomycin and tetracycline conferred by P55 were decreased in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone and the pump inhibitors verapamil and reserpine . M . smegmatis cells expressing the plasmid-encoded P55 accumulated less tetracycline than the control cells . We conclude that P55 is a membrane protein implicated in aminoglycoside and tetracycline efflux in mycobacteria.

Clin Microbiol Infect, 2000 Jul, 6(7), 363 - 7
Rapid susceptibility testing of Mycobacterium tuberculosis by the Mycobacteria Growth Indicator Tube (MGIT AST SIRE); Macondo EA et al.; OBJECTIVE: To evaluate the reliability of the Mycobacteria Growth Indicator Tube (MGIT AST) for susceptibility testing of Mycobacterium tuberculosis . METHODS: Seventy strains of M . tuberculosis were tested for susceptibility to streptomycin, isoniazid, rifampicin and ethambutol by comparing MGIT AST results to those obtained by the method of proportion (MOP) on Lowenstein-Jensen (LJ) and Middlebrook 7H10 media . The 7H10 MOP was considered the method of reference . RESULTS: The turnaround time for MGIT AST was 6.2 days (5-10 days) and for MOP it was 18-21 days . With rifampicin, MGIT AST agreed for all isolates with both MOP . For streptomycin, MGIT AST and 7H10 MOP agreed for 64 isolates (91.4%); 61 were susceptible and three resistant . LJ MOP and 7H10 MOP agreed for 64 isolates (92.2%); 62 were susceptible and three resistant . With isoniazid, both MOP agreed for all isolates, while MGIT AST and 7H10 MOP had two discrepancies . For ethambutol, MGIT AST and 7H10 MOP were concordant for 66 isolates; 65 were susceptible and one resistant . Both MOP were concordant for 67 isolates; 66 were susceptible and one resistant . CONCLUSIONS: Based on these results, MGIT AST is a time-saving method and can be used as an alternative to the BACTEC System . MGIT AST is reliable as far as rifampicin and isoniazid are concerned; however, additional studies are needed for streptomycin and ethambutol.

Int J Dev Neurosci, 2000 Dec, 18(8), 855 - 67
Hair cell and supporting cell density and distribution in the normal and regenerating posterior crista ampullaris of the pigeon; Kevetter GA et al.; The numbers of supporting cells and the numbers and types of hair cells in three distinct longitudinal regions through the posterior canal cristae of control and streptomycin-treated pigeons were determined using stereological techniques . For control cristae, type I (3758) and type II (3517) hair cells occurred in approximately equal numbers . However, the proportions varied in different longitudinal zones: Zone I (peripheral region) had four times more type II hair cells (2083) than type I (483), while Zone II (intermediate region) had almost seven times more type I (2517) than type II (367) hair cells and Zone III (central region) had relatively equal numbers of type I (758) and type II (1067) hair cells . Novel findings included the following: (1) immediately after the post-injection sequence (PIS) of streptomycin, there was a significant reduction in both hair cells (-93%) and supporting cells (-45%); (2) by 70 days after the PIS, the population of type I hair cells returned to control values (however, the normal complement of complex calyces took 1 year to recover); (3) during the first 143 days after the PIS, the number of type I and type II hair cells across all zones returned linearly with about the same slope (46 and 43 cells per day, respectively), although the rate of return differed significantly in different zones; (4) there was a massive overproduction of hair cells (+150%) and supporting cells (+120%) during the first 5 months of recovery; and (5) during the first year after the PIS, both hair cells and supporting cells increased and their increases in numbers were correlated (r = 0.88, P < 0.01) . Knowledge of the sequence and numbers of regenerating hair cells may help elucidate common modes of cell survival, recovery, and compensation from neural insult.

Arch Bronconeumol, 2000 Nov, 36(10), 551 - 6
{Evolution of drug-resistant Mycobacterium tuberculosis in the province of Castellón . 1992-1998}; Marin Royo M et al.; OBJECTIVES: To determine the frequency of resistant Mycobacterium tuberculosis and the risk factors associated with resistance in the province of Castellon (Spain) . MATERIAL AND METHODS: This prospective study of M . tuberculosis sensitivity applied Canetti's method of proportions to all strains isolated in Castellon (n = 532) from January 1992 through December 1998 (7 years); 461 cases were new . RESULTS: The overall frequency of resistant strains was 4.7% (25/532), of which 3.9% (18/461) were instances of primary resistance and 11.1% (7/63) were of secondary resistance . Three percent were resistant to isoniazid, 1.87% to rifampicin, 1.87% to streptomycin and 0.56% to ethambutol . Multiple drug resistance was found in 0.2% (1/461) of the new cases and 1.1% (6/532) overall . The presence of resistant M . tuberculosis was associated with a history of antituberculous treatment (OR = 3.14; p = 0.017) and the presence of one or more risk factors for tuberculosis (OR = 3.32; p = 0.066) . CONCLUSIONS: The overall rates of resistant M . tuberculosis and multiple drug resistance are low in the province of Castellon; however resistance is associated with higher mortality such that controlling some preventable risk factors might reduce the frequency of resistance.

Ethiop Med J, 2000 Jan, 38(1), 43 - 7
Multiforme skin lesions in Yekatit 12 Hospital, 1976-1994; Gessesse B et al.; Because the number of cases of multiforme skin lesions encountered in the medical department of Yekatit 12 Hospital has increased in recent years, we conducted a retrospective study to identify the likely precipitating factors and the possible relationship of these with HIV infection . Forty-seven patients with Multiforme Skin Lesions (29 males, 18 females) were admitted between 1976 and January 1994, of whom 43 (92%) were admitted in the past 5 years . Most patients were aged 15-49 years . Thirty patients (64%) were discharged improved and 14 (30%) expired in hospital . The outcome of 3 patients are not known . The charts of only 16 patients could be retrieved for review . Fifteen of these (94%) gave a history of intake of streptomycin, isoniazed and thiacetazone prior to developing the skin manifestation . The anti-TB medications were discontinued initially; 14 patients were restarted on STM, INH and ethambutol without recurrence of the rash . All but 1 were discharged improved . HIV screening tests were done on 24 patients with multiforme skin lesion of whom 21 (88%) were seropositive . Our study suggested that the adverse effects of thiacetazone are increased in HIV associated tuberculous patients . We recommend that further studies be conducted in HIV seropositive and seronegative patients.

Kekkaku, 2000 Nov, 75(11), 661 - 4
{A case report of pulmonary Mycobacterium kansasii infection found regular medical examination in our medical college of nursing}; Inatomi K; A 20-year-old female was checked by chest X-ray film just before starting practical nurse training in the hospital . She was diagnosed as tuberculosis in the initial phase of treatment . In Japan, the number of newly registered tuberculosis has been increasing since 1997, and the stop-tuberculosis campaign is organized by the Ministry of Health and Welfare . The incidence rate of tuberculosis announced officially by the Ministry of Public Welfare was 33.9 per 100,000 in 1997, while that of nontuberculous mycobacteriosis has been increasing year by year, and it was 2.45 in 1997 . The one out of 4 nontuberculous mycobacteriosis is caused by M . kansasii . Six colonies of Mycobacterium kansasii were detected by gastric juice culture from this patient . Untreated strains of M . kansasii are susceptible to rifampicin, isoniazid, ethambutol, ethionamide, streptomycin and cycloserine at concentrations readily available in the serum with usual therapeutic doses . Isolates are usually resistant to available serum level of pyrazinamide . The patient was treated with rifampicin, isoniazid and ethambutol for 6 months . Pyrazinamide was stopped at 1 month and 10 days treatment due to liver dysfunction and resistance to the organism . Pulmonary infiltration with cavity disappeared during follow-up examination . Nowadays we must take into account not only tuberculosis but also primary nontuberculous mycobacteriosis at regular medical check of young female.

J Pharm Biomed Anal, 2000 Dec 15, 24(2), 219 - 26
Liquid chromatographic analysis of streptomycin sulfate; Adams E et al.; The analysis of streptomycin sulfate using a column packed with base deactivated reversed phase silica gel and ultraviolet (UV) detection at 205 nm is described . The mobile phase consists of an aqueous solution containing 14 g/l of sodium sulfate, 1.5 g/l of sodium octanesulfonate, 50 ml/l of acetonitrile and 50 ml/l of a 0.2 M phosphate buffer at pH 3.0 . The method allows separating streptidine, streptomycin B, streptomycin and dihydrostreptomycin, as well as several other components, which were not yet identified . The total time of analysis is 50 min . The effects of the different chromatographic parameters on the separation were investigated . A number of commercial samples were analyzed using this method.

Vet Microbiol, 2001 Jan 5, 78(1), 13 - 28
Genetic diversity and evolution of Mycoplasma capricolum subsp . capripneumoniae strains from eastern Africa assessed by 16S rDNA sequence analysis; Heldtander M et al.; Mycoplasma capricolum subsp . capripneumoniae (M . capripneumoniae), the causal agent of contagious caprine pleuropneumonia (CCPP), is a member of the so-called Mycoplasma mycoides cluster . These mycoplasmas have two rRNA operons in which intraspecific variations have been demonstrated . The sequences of the 16S rRNA genes of both operons from 13 field strains of M . capripneumoniae from three neighbouring African countries (Kenya, Ethiopia, and Tanzania) were determined . Four new and unique polymorphism patterns reflecting the intraspecific variations were found . Two of these patterns included length differences between the rrnA and rrnB operons . The length difference in one of the patterns was caused by a two-nucleotide insert (TG) in the rrnB operon and the length difference in the other pattern was due to a three-nucleotide deletion, also in the rrnB operon . Another pattern was characterised by a polymorphic position caused by a mutation that is known to cause streptomycin resistance in other bacterial species . The strain with this pattern was also found to be resistant to streptomycin . Streptomycin resistant clones were selected from four M . capripneumoniae strains to further investigate the correlation of this mutation to streptomycin resistance . Mutations in the 16S rRNA genes had occurred in two of these strains . The fourth pattern included a new polymorphism in position 1059 . The results show that polymorphisms in M . capripneumoniae strains can be used as epidemiological markers for CCPP in smaller geographical areas and to study the molecular evolution of this species.

Biochem Biophys Res Commun, 2000 Dec 20, 279(2), 457 - 61
Bioluminescent Mycobacterium aurum expressing firefly luciferase for rapid and high throughput screening of antimycobacterial drugs in vitro and in infected macrophages; Deb DK et al.; The slow growth and highly infectious nature of Mycobacterium tuberculosis is a limiting factor in its use as test organism in high throughput screening for inhibitory compounds . To overcome these problems, use of surrogate strains and reporter genes have been considered . In this study, we have investigated the application of a fast growing nonpathogenic M . aurum expressing firefly luciferase in rapid screening of antituberculosis compounds in vitro and in infected macrophages using bioluminescence assay . The assay is based on luminescence determination using luciferin as substrate . Inhibition of bioluminescence was obtained with frontline antimycobacterial drugs like streptomycin, rifampicin, isoniazid, ethambutol, ofloxacin, and sparfloxacin at their reported MICs . Inhibition could be observed as early as 2 h in vitro and within 24 h in infected macrophages . The system can reliably be used in high throughput screening .

J Cardiovasc Pharmacol, 2000 Dec, 36(6), 711 - 21
Modification of stretch-induced shortening of repolarization by streptomycin in the isolated rabbit heart; Eckardt L et al.; The exact mechanism of mechano-electrical feedback and stretch-induced arrhythmias is unknown, but the role of stretch-activated ion channels and specific calcium channels has been proposed . The aim of the present study was to test the hypothesis that stretch-activated ion channels and not calcium channels contribute to stretch-related alterations of repolarization and that these effects can be neutralized by stretch-activated channel block . We studied the interaction of acute ventricular dilatation and the stretch-activated channel blocker streptomycin and the specific calcium channel blocker verapamil in an isolated retrogradely perfused rabbit heart model in which the left ventricular size is modified by abruptly changing the volume of a fluid-filled balloon placed in the left ventricle . Acute ventricular dilatation led to a rate-dependent decrease in repolarization . The mean effective refractory period (ERP) and monophasic action potential duration (MAP90) for cycle lengths between 300 and 1,000 ms decreased from 174.2+/-9 ms and 178.9+/-7 ms to 161.6+/-11 ms and 169.7+/-5 ms, respectively . Streptomycin (80 microM) inhibited this stretch-related shortening of repolarization (ERP: 175.4+/-8 ms; MAP90: 179.7+/-8 ms, p < 0.05) but had almost no effect on already dilated ventricles . Counteraction of the observed electrophysiologic changes could only be achieved by increasing the streptomycin concentration to 200 microM . Streptomycin nearly completely suppressed stretch-related ectopic ventricular complexes . In contrast, verapamil (1 microM) had no effect on stretch-related changes in repolarization and stretch-induced arrhythmias . The present study indirectly implicates stretch-activated ion channels in the genesis of stretch-related changes in repolarization and arrhythmias . The electrophysiologic changes after ventricular dilatation to a degree that increases left ventricular pressure in a clinically relevant range can be influenced by the stretch-activated channel blocker streptomycin but not by specific calcium channel block . This may have clinically important implications for the development of new antiarrhythmic drugs.

Biochim Biophys Acta, 2001 Jan 19, 1503(3), 357 - 68
Polycations induce the release of soluble intermembrane mitochondrial proteins; Mather M et al.; The release of proapoptotic proteins from the intermembrane space of mitochondria is an early critical step in many pathways to apoptosis . Induction of the mitochondrial permeability transition pore (PTP) was suggested to be the mechanism of the release of soluble mitochondrial intermembrane proteins (SIMP) in apoptosis . However, several studies suggested that proapoptotic proteins (e.g . Bax and Bid) can induce the release of SIMP (e.g . cytochrome c (cyt c) and adenylate kinase 2 (AK2)) in vivo and in vitro independent of PTP . We have found that a number of structurally diverse polycations, such as aliphatic polyamines (e.g . spermine and to a lesser extent spermidine), aminoglycosides (e.g . streptomycin, gentamicin and neomycin), and cytotoxic peptides (e.g . melittin), induce the release of SIMP from liver mitochondria, in vitro . All the polycations released AK2 together with cyt c, suggesting that rupture of the outer membrane is a common mechanism of cyt c release by these polycations . Several polycations (e.g . spermine, spermidine and neomycin) induced SIMP release without inducing significant swelling, and this release was not inhibited significantly by the PTP inhibitor cyclosporin . In contrast, under the same conditions, streptomycin and melittin induced swelling and SIMP release that was inhibited strongly by cyclosporin . Gentamicin-induced swelling and release of SIMP were partially inhibited by cyclosporin . The affinity of polyamines to the anionic phospholipids of the mitochondrial membranes (spermine=neomycin>gentamicin>streptomycin=spermidine) correlated roughly with their ability to induce PTP-independent release of SIMP, which suggests that the binding of polycations to the anionic phospholipids of the outer mitochondrial membrane facilitates the rupture of this membrane . However, some polycations facilitated the induction of PTP, possibly by binding to cardiolipin on the inner membrane . This dual mechanism may be relevant to the induction of SIMP release in apoptosis.

Hinyokika Kiyo, 2000 Sep, 46(9), 619 - 22
{A case of psoas cold abscess in a young tuberculosis patient}; Ikeda T et al.; A 28-year-old man was referred to our hospital with a complaint of painful induration of right epididymis accompanied with right back pain and persistent low-grade fever . He was finally diagnosed with tuberculosis by sputum culture . Abdominal computed tomography (CT) revealed right psoas abscess and vertebral caries . He underwent a percutaneous drainage of the abscess followed by multidrug (streptomycin, pyrazinamide, refanpicin, isoniazide) combination therapy . Immediately after the drainage, symptoms began to improve with these therapies . However, four months later, abdominal CT showed a worsening of the abscess . Recently there is a stagnation in the decline of incidence of tuberculosis . It is still necessary to examine young people carefully bearing urogenital tuberculosis in mind . The pathogenesis and management of this rare condition are discussed.

J Clin Microbiol, 2000 Dec, 38(12), 4663 - 4
Comparison of susceptibility testing of Mycobacterium tuberculosis using the ESP culture system II with that using the BACTEC method; Ruiz P et al.; The ESP Culture System II was evaluated for its capacity to test the susceptibility of 389 cultures of Mycobacterium tuberculosis to streptomycin, rifampin, ethambutol, and isoniazid . Good agreement with results with the BACTEC TB 460 was found . ESP II is a reliable, rapid, and automated method for performing susceptibility testing.

Mutagenesis, 2000 Nov, 15(6), 489 - 94
Chromosomal aberrations and micronuclei in lymphocytes of patients before and after exposure to anti-tuberculosis drugs; Masjedi MR et al.; To evaluate the genetic damage induced by tuberculosis infection and also by a combination of therapeutic exposure to anti-tuberculosis (anti-TB) drugs (isoniazid + rifampicin + pyrazinamide + ethambutol or streptomycin) we have considered chromosome aberrations (CA) and micronuclei (MN) in binucleate peripheral blood lymphocytes from 36 patients diagnosed with pulmonary tuberculosis prior to receiving anti-TB drugs in the first phase and in the second phase after 6 months of therapy with anti-TB drugs . The same cytogenetic study has also been performed on 36 healthy individual controls . It was shown that the frequencies of both CA and micronucleated binucleate cells increased significantly after therapy with anti-TB drugs as compared with TB patients and controls . In addition, we observed that both cytogenetic markers (CA and MN) in patients before treatment with anti-TB drugs were significantly (P: < 0.05) higher than controls . No relationship was found between the frequency of MN and donor age . Thus, apart from drug effects, infection with tuberculosis is associated with increased CA and MN.

Mol Plant Microbe Interact, 2000 Nov, 13(11), 1243 - 50
Improved gfp and inaZ broad-host-range promoter-probe vectors; Miller WG et al.; A new set of broad-host-range promoter-probe vectors has been constructed . One subset contains the pVS1 and p15a replicons and confers resistance to either gentamicin or kanamycin . The other set contains the broad-host-range replicon from pBBR1 and confers resistance to kanamycin, tetracycline, ampicillin, or spectinomycin/streptomycin . Both plasmid sets are highly stable and are maintained without selection for more than 30 generations in several bacterial taxa . Each plasmid contains a promoter-probe cassette that consists of a multicloning site, containing several unique restriction sites, and gfp or inaZ as a reporter gene . The cassette is bound by transcriptional terminators to permit the insertion of strong promoters and to insulate the cassette from external transcription enabling the detection of weak or moderate promoters . The vector suite was augmented with derivatives of the kanamycin-resistant gfp promoter-probe plasmids that encode Gfp variants with different half-life times.

Int J Tuberc Lung Dis, 2000 Oct, 4(10), 940 - 6
Surveillance of anti-tuberculosis drug resistance: results of the 1998/1999 proficiency testing in Italy . SMIRA (Italian Multicentre Study on Antituberculosis Drug Resistance) Study Group; Migliori GB et al.; OBJECTIVE: To determine the accuracy of drug-susceptibility testing (DST) for isoniazid, rifampicin, ethambutol and streptomycin in a provisional network of 22 regional laboratories in Italy . METHODS: Methods, definitions and reference Mycobacterium tuberculosis strains were derived from the WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance . The laboratories were selected based on technical skills required by the project, the number of DST performed annually and geographic localisation . The results (sensitive/resistant strain) were compared with the gold standard (global project results) . Sensitivity (ability to detect true resistance), specificity (ability to detect true susceptibility), positive predictive values for resistance and susceptibility, efficiency and reproducibility were calculated in two rounds . RESULTS: Eighteen of 22 laboratories completed the first round of proficiency testing for the four drugs . Sensitivity was 76.6%, specificity 97.2%, predictive value of a resistant test 89.8% and of a susceptible test 86.8%, efficiency 87.8% and reproducibility 92.8% . A second round was performed by all those laboratories that did not achieve > or = 90% agreement with the results of the Global Project . Overall, after the second round, all the parameters except specificity improved, exceeding 90% . CONCLUSIONS: A network of 15 regional laboratories that fulfil the quality criteria for determining the susceptibility of M . tuberculosis to the four primary antituberculosis drugs was established in Italy.

J Clin Microbiol, 2000 Oct, 38(10), 3834 - 6
Evaluation of Etest for susceptibility testing of Mycobacterium tuberculosis; Joloba ML et al.; The Etest method for susceptibility testing of Mycobacterium tuberculosis was compared to the agar proportion method using four first-line agents and two fluoroquinolones . Catergorical agreement between the methods was 100% for rifampin, ethambutol, streptomycin, and ofloxacin and 98% for isoniazid . Results were obtained in 6 to 10 days by Etest . The Etest method is suitable for testing the agents evaluated against M . tuberculosis.

Clin Infect Dis, 2000 Aug, 31(2), 427 - 32 Epub 2000 Aug 16.
Increasing drug resistance of Mycobacterium tuberculosis isolates in Ontario, Canada, 1987-1998; Remis RS et al.; We examined trends in resistance to first-line antituberculous agents for Mycobacterium tuberculosis strains isolated in Ontario, Canada from 1987 through 1998 (n=8069) . The proportions resistant were as follows: isoniazid, 9.6%; rifampin, 1.9%; streptomycin, 4 . 9%; ethambutol, 1.3%; and pyrazinamide, 1.7% . Resistance to isoniazid has increased markedly since 1990, whereas resistance to streptomycin, ethambutol, and pyrazinamide increased from 1997 through 1998 . Resistance to both isoniazid and rifampin did not increase . The incidence of persistence and reactivation (early or late treatment failure) was 1-2 per 100 person-years (PY) in the first 7-12 months and 0.3-0.9 per 100 PY from 13 months to 5 years thereafter . For initially susceptible strains, the incidence of resistance to isoniazid was 0.11 per 100 PY and for and rifampin was 0.06 per 100 PY in the first year and negligible thereafter, with an overall risk of 0.14% for isoniazid and 0.10% for rifampin . Resistance of M . tuberculosis to antituberculous agents, and in particular to isoniazid, is a growing problem in Ontario and is higher than elsewhere in Canada.

East Mediterr Health J, 1999 Sep, 5(5), 895 - 902
Brucellosis in children in south Jordan; Issa H et al.; Retrospectively we evaluated the records of 68 children with brucellosis . We found 58.2% had consumed unpasteurized milk and dairy products . Nonspecific manifestations included: arthralgia (78%), fever (75%) and sweating (60%) . Localized manifestations included limping (75%) and arthritis (54%) . Leukopenia was found in 51% of children and anaemia in 24% . Brucella species was cultured for blood of 16 (23.5%) patients . Combination therapy containing streptomycin was more effective than gentamicin combinations.

Bull Exp Biol Med, 2000 May, 129(5), 499 - 501
Use of cultured human fibroblasts for rapid evaluation of cytotoxic effects of bioactive substances; Chernikov VG et al.; A test system for detecting cytotoxic effects of bioactive substances based on human fibroblast culture is proposed . The effects of acrylamide, streptomycin, cycloheximide, sodium dodecyl sulfate, sanguiritrine, and ethanol were evaluated by organic stain binding . Typical dose-effect relationships were detected for all substances except cycloheximide . The proposed test system can be used for screening of bioactive substances in preclinical trials.

J Bacteriol, 2000 Aug, 182(16), 4596 - 605
An A-factor-dependent extracytoplasmic function sigma factor (sigma(AdsA)) that is essential for morphological development in Streptomyces griseus; Yamazaki H et al.; A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) at an extremely low concentration triggers streptomycin production and aerial mycelium formation in Streptomyces griseus . A-factor induces the expression of an A-factor-dependent transcriptional activator, AdpA, essential for both morphological and physiological differentiation by binding to the A-factor receptor protein ArpA, which has bound and repressed the adpA promoter, and dissociating it from the promoter . Nine DNA fragments that were specifically recognized and bound by histidine-tagged AdpA were isolated by cycles of a gel mobility shift-PCR method . One of them was located in front of a gene encoding an extracytoplasmic function sigma factor belonging to a subgroup of the primary sigma(70) family . The cloned gene was named AdpA-dependent sigma factor gene (adsA), and the gene product was named sigma(AdsA) . Transcription of adsA depended on A-factor and AdpA, since adsA was transcribed at a very low and constant level in an A-factor-deficient mutant strain or in an adpA-disrupted strain . Consistent with this, transcription of adsA was greatly enhanced at or near the timing of aerial hyphae formation, as determined by low-resolution S1 nuclease mapping . High-resolution S1 mapping determined the transcriptional start point 82 nucleotides upstream of the translational start codon . DNase I footprinting showed that AdpA bound both strands symmetrically between the transcriptional start point and the translational start codon; AdpA protected the antisense strand from positions +7 to +41 with respect to the transcriptional start point and the sense strand from positions +12 to +46 . A weak palindrome was found in the AdpA-binding site . The unusual position bound by AdpA as a transcriptional activator, in relation to the promoter, suggested the presence of a mechanism by which AdpA activates transcription of adsA in some unknown way . Disruption of the chromosomal adsA gene resulted in loss of aerial hyphae formation but not streptomycin or yellow pigment production, indicating that sigma(AdsA) is involved only in morphological development and not in secondary metabolic function . The presence of a single copy in each of the Streptomyces species examined by Southern hybridization suggests a common role in morphogenesis in this genus.

Mech Ageing Dev, 2000 Jun 20, 115(3), 127 - 38
Increased depolarization, prolonged recovery and reduced adaptation of the resting membrane potential in aged rat skeletal muscles following eccentric contractions; McBride T; Previously it was shown in young-adult muscles that eccentric contractions (EC) produce a significant (24 h) depolarization of the resting membrane potential (RMP), and that in-vitro (Gd(3+)) and in-vivo (streptomycin) blockade of stretch activated ion channels (SAC) result in a partial repolarization of the RMP . The portion of the depolarization not restored by SAC blockade is believed to be from sarcolemmal injury . A second exposure to EC results in less depolarization and a more rapid recovery of the RMP . Aged muscles were subjected to the same EC protocol to test the hypotheses that: (1) Aged muscles will experience a more significant and prolonged depolarization of the RMP following EC . (2) The depolarization in aged muscles will occur by a greater contribution from membrane damage, rather than the opening of SAC . (3) The aged muscles will demonstrate a reduced capacity to adapt to EC, and will experience a similar degree of depolarization following repeated exposures to EC . The results indicate a significantly greater and longer lasting depolarization in aged compared to young-adult muscles . Blocking SAC did not produce a repolarization of the RMP in aged muscles . Aged muscles had a significantly reduced adaptive response to EC compared to young-adult . It is speculated that the different response in aged muscles results from a reduced number of functional SAC.

Probl Tuberk, 2000, (3), 20 - 3
{Efficiency of shorter chemotherapy courses for intrathoracic tuberculosis in children}; Iukhimenko NV; To develop differential chemotherapy regimes for intrathoracic tuberculosis in children aged 3-12 years, 255 children with active tuberculosis underwent clinical and X-ray examination . Of them, 120 children received shorter chemotherapy in an early intensive phase by using three drugs (isoniazid, rifampicin, and pyrazinamide supplemented by streptomycin) in complicated tuberculosis . A control group (n = 135) had therapy without pyrazinamide . Shorter courses of therapy were shown not only to reduce total treatment duration on an average to 6.4 and 9.2 months in uncomplicated and complicated tuberculosis, respectively, but to contribute to more perfect healing processes and resolution of abnormal changes in 85.3 and 60.0% of children with uncomplicated and complicated forms, respectively . At the same time shorter treatment is well tolerated . It shows much fewer side effects than does longer treatment (20 and 36%) . There are no increases in the incidence of recurrent tuberculosis late at follow-up (2.7 and 2.7%, respectively).

J Antimicrob Chemother, 2000 Jul, 46(1), 87 - 9
Two new gene cassettes, dfr17 (for trimethoprim resistance) and aadA4 (for spectinomycin/streptomycin resistance), inserted in an Escherichia coli class 1 integron; Chang CY et al.; Two new gene cassettes, dfr17 and aadA4, inserted in a class 1 integron of Escherichia coli EC107, are described here . The dfr17 cassette encodes trimethoprim resistance and has 91% identity with the dfrVII dihydrofolate reductase gene . The aadA4 cassette confers resistance to spectinomycin and streptomycin and shows 94% identity with the aadA3 gene . The integron carrying the dfr17 and aadA4 cassettes was located on a conjugative plasmid, pEC1072.

EMBO J, 1983, 2(8), 1351 - 6
Codon-specific missense errors in vivo; Bouadloun F et al.; We have developed a simple method for measuring the missense substitution of amino acids at specified positions in proteins synthesized in vivo . We find that the frequency of cysteine substitution for the single arginine in Escherichia coli ribosomal protein L7/L12 is close to 10(-3) for wild-type bacteria, decreases to 4 x 10(-4) in streptomycin-resistant bacteria containing mutant S12 (rpsL), and is virtually unchanged in Ram bacteria containing mutant S4 (rpsD) . We have also found that the frequency of the cysteine substitution for the single tryptophan in E . coli ribosomal protein S6 is 3-4 x 10(-3) for wild-type bacteria, decreases to 6 x 10(-4) in streptomycin-resistant bacteria and is elevated to nearly 10(-2) in Ram bacteria.

Microb Drug Resist, 2000 Spring, 6(1), 19 - 27
Characterization of aminoglycoside resistance genes and class 1 integrons in porcine and bovine gentamicin-resistant Escherichia coli; Sandvang D et al.; A total of 78 gentamicin-resistant Escherichia coli strains from swine (27) and cattle (51) were characterized by phenotypic resistance, presence of selected aminoglycoside resistance genes, class 1 integrons and gene cassettes, and pulsed-field gel electrophoresis . Gentamicin resistance was mainly encoded by the ant(2'')-I gene that was found in 76% of all the strains investigated, whereas the aac(3)-IIa gene was found in 14% . The ant(2'')-I gene was predominant in strains from cattle, whereas the porcine strains contained both ant(2'')-I, aac(3)-IIa, and the aac(3)-IVa genes . The pulsed-field gel electrophoresis (PFGE) investigation indicated a close clonal relationship in half of the bovine strains whereas the remaining E . coli were unrelated . Among the E . coli investigated, 20% contained class 1 integrons . Genes encoding resistance to trimethoprim (dhfrI, dhfrIb, and dhfrVII), gentamicin, tobramycin, and kanamycin (ant(2'')-Ia streptomycin and spectinomycin (ant(3'')-Ia) and streptothricin (sat1) were identified as gene cassettes . The most prevalent gene cassettes were ant(3'')-Ia (11 isolates) and the dhfrI (nine isolates).

Rev Mal Respir, 2000 Apr, 17(2), 477 - 80
{Simultaneous resistance to rifampicin and isoniazid in patients with pulmonary tuberculosis}; Ouedraogo M et al.; Percentages of primary and acquired resistance to anti-tuberculosis drugs provide an epidemiological indicator useful for assessing national anti-tuberculosis programs . Rifampicin and isoniazide are widely used in countries with a high prevalence of tuberculosis . In tropical Africa, these drugs are the mainstay treatment for tuberculosis, used both in the initial and long-term regimens . Simultaneous resistance to these two antibiotics would seriously jeopardize therapeutic efficacy . We studied simultaneous rifampicin and isoniazide resistance in patients hospitalized for tuberculosis in the respiratory disease unit of the Treichville University hospital in Abidjan, Ivory Coast . Mycobacterium tuberculosis was isolated in 8 patients . All the strains isolated were resistant to streptomycin . History taking revealed that resistance was observed at the initial prescription in 6 cases . A notion of contagion was present in 4 cases . Six patients were HIV-positive . Surveillance of resistance to anti-tuberculosis drugs is helpful in detecting early changes which could compromise the efficacy of the therapeutic scheme.

Jpn J Cancer Res, 2000 May, 91(5), 482 - 91
Different mutation frequencies and spectra among organs by N-methyl-N-nitrosourea in rpsL (strA) transgenic mice; Shioyama Y et al.; The frequencies and spectra of N-methyl-N-nitrosourea (MNU)-induced in vivo somatic mutations were determined in rpsL (strA) transgenic mice . The wild-type rpsL gene, which exhibits a streptomycin-sensitive (Sm(S)) phenotype, was used as the rescue marker gene . Studies of mutation spectra among different organs and tissues were simplified using this system because of the short coding sequence (375 bp) of the rpsL gene . MNU administration to transgenic mice significantly elevated the mutation frequencies in various adult organs . Two distinctive patterns of mutation spectrum were observed, depending on the organs tested . Mutations derived from labile organs (spleen and thymus) were predominantly G:C to A:T transitions, as expected for MNU mutagenesis . Stable organs like the liver and brain, however, carried many fewer G:C to A:T transitions but significantly more single base deletions, of which the spectrum was very similar to that of background mutations in the rpsL transgenic mice . This spectrum difference among more and less proliferating organs was confirmed by the predominant occurrence of G:C to A:T transitions in fetal liver cells exposed to transplacental MNU treatment . In addition, most (approximately 90%) of the G:C to A:T transitions induced by MNU were detected in the first nucleotide of some 5'-G-(C or G)-3' sequences, many of which corresponded to the middle guanine residue of 5'-purine-G-(C or G)-3' sequences . It is thus suggested that at particular sites, the neighboring bases in both the 5' side and 3' side seem to influence either the susceptibility to DNA damage or the ability to repair MNU-induced lesions.

Hear Res, 2000 Jun, 144(1-2), 109 - 23
Gap junctional communication in the vibration-sensitive response of sea anemones; Mire P et al.; Although gap junctions occur in auditory and vestibular systems, their function is unclear . Here we present evidence for gap junctional communication in transmitting mechanosensory signals in a sea anemone model system . Hair bundles on anemone tentacles are vibration-sensitive mechanoreceptors that regulate discharge of nematocyst from effector cells . We find that vibration-dependent nematocyst discharge is selectively and reversibly blocked by the gap junction uncouplers, heptanol and arachidonic acid . Epidermal cells within excised tentacles exhibit a low level of dye coupling which is significantly enhanced upon deflection of overlying hair bundles . Dye coupling is inhibited both by gap junction uncouplers and by agents that interfere with mechanotransduction, including streptomycin and elastase . Electrophysiological data suggest gap junctional communication between cells giving rise to different hair bundles . When hair bundles are stimulated with a sweep of vibrations, individual cells show responses to five to eight frequencies . The number of responsive frequencies is reduced to one or two by heptanol and essentially abolished with streptomycin treatment . Immunoreactivity to the gap junction protein, connexin 43, is abundant in the tentacle epidermis and localized to membranes at junctions between several cell types . Small areas of close membrane apposition are observed between these cell types with intermembrane clefts of 4-7 nm . Of the several membrane proteins isolated from tentacles, immunoreactivity to connexin 43 is observed in a single band with an apparent molecular weight of approximately 46 kDa.

Emerg Infect Dis, 2000 May-Jun, 6(3), 302 - 5
Mycobacterium tuberculosis Beijing genotype emerging in Vietnam; Anh DD et al.; To assess whether the Mycobacterium tuberculosis Beijing genotype is emerging in Vietnam, we analyzed 563 isolates from new cases by spoligotyping and examined the association between the genotype and age, resistance, and BCG vaccination status . Three hundred one (54%) patients were infected with Beijing genotype strains . The genotype was associated with younger age (and hence with active transmission) and with isoniazid and streptomycin resistance, but not with BCG vaccination.

Ann Otol Rhinol Laryngol Suppl, 2000 May, 181, 20 - 5
Temporal bone studies of the human peripheral vestibular system . Aminoglycoside ototoxicity; Tsuji K et al.; Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on 17 temporal bones from 10 individuals who had well-documented clinical evidence of aminoglycoside ototoxicity (streptomycin, kanamycin, and neomycin) . Assessment of vestibular hair cells was performed by Nomarski (differential interference contrast) microscopy . Hair cell counts were expressed as densities (number of cells per 0.01 mm2 surface area of the sensory epithelium) . The results were compared with age-matched normal data . Streptomycin caused a significant loss of both type I and type II hair cells in all 5 vestibular sense organs . In comparing the ototoxic effect on type I versus type II hair cells, there was greater type I hair cell loss for all 3 cristae, but not for the maculae . The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, but the small sample size precluded definitive conclusions from being made . Neomycin did not cause loss of vestibular hair cells . Within the limits of this study (maximum postototoxicity survival time of 12 months), there was no significant loss of Scarpa's ganglion cells for any of the 3 drugs . The findings have implications in several clinical areas, including the correlation of vestibular test results to pathological findings, the rehabilitation of patients with vestibular ototoxicity, the use of aminoglycosides to treat Meniere's disease, and the development of a vestibular prosthesis.

J Clin Microbiol, 2000 May, 38(5), 1988 - 9
Evaluation of the MB/BacT mycobacterium detection system for susceptibility testing of Mycobacterium tuberculosis; Diaz-Infantes MS et al.; The MB/BacT mycobacterium detection system was evaluated for its performance in the susceptibility testing of Mycobacterium tuberculosis . Eighty-three M . tuberculosis isolates were processed . Results for all isoniazid-, rifampin- and streptomycin-susceptible, isoniazid-resistant, and rifampin-resistant M . tuberculosis isolates with the MB/BacT system agreed 100% with those obtained by the agar proportion method . The agreements between the two methods for streptomycin- and ethambutol-resistant isolates were 96.4 and 90.4%, respectively . The susceptibility test results were obtained in 7 days, on average . These data demonstrate that the MB/BacT system is an accurate, nonradiometric method for rapid susceptibility testing of M . tuberculosis.

Int J Tuberc Lung Dis, 2000 Apr, 4(4), 356 - 60
Anti-tuberculosis drug resistance in the West Province of Cameroon; Kuaban C et al.; SETTING: All 15 district hospitals of the West Province of Cameroon, between July 1997 and June 1998 . OBJECTIVE: To determine the prevalences of initial and acquired resistance to the main anti-tuberculosis drugs 2 years after the implantation of a tuberculosis control programme in the province . METHODS: A total of 615 adults consecutively admitted to the 15 district hospitals with sputum smear-positive pulmonary tuberculosis were systematically studied . Sputum specimens collected from each patient were cultured on Lowenstein-Jensen medium . Testing of susceptibility to the major anti-tuberculosis drugs was performed by the indirect proportion method . RESULTS: Growth of Mycobacterium tuberculosis complex strains was obtained from specimens of 566 (92%) of the 615 patients . The overall resistance rate (one or more drugs) was 26.9%, with initial resistance being 19.7% (86/437) and acquired resistance 51.1% (66/129) . Initial resistance to isoniazid was the most common (12.1%), followed by streptomycin (11.7%), ethambutol (2.5%) and rifampicin (2.1%) . Initial resistance was noted as 13.5% to one drug, 4.3% to two, 1.1% to three and 0.7% to four . Acquired resistance to isoniazid was the most frequent (41.1%), followed by streptomycin (26.4%), rifampicin (14.7%) and ethambutol (9.3%) . Acquired resistance was 25.6% to one drug, 14.7% to two, 7% to three and 3.9% to four . CONCLUSION: The proportion of resistant tuberculosis in the West Province is quite high . This underscores the need for the improvement of the control programme by introducing the DOTS strategy.

East Afr Med J, 2000 Feb, 77(2), 111 - 5
Determination of drug susceptibility and DNA fingerprint patterns of clinical isolates of Mycobacterium tuberculosis from Kampala, Uganda; Joloba ML et al.; OBJECTIVE: To ascertain the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis in Kampala, Uganda . SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital, Kampala, Uganda and Case Western Reserve University, Cleveland, Ohio, USA and McClellan Memorial Veterans Hospital, Little Rock, Arkansas, USA . METHODS: Using a radiometric BACTEC 460 TB system, susceptibility of 215 M . tuberculosis isolates from previously untreated patients from Kampala, Uganda (age range, 17-48 years, mean, 28 years; 56% males and 69% human immunodeficiency virus (HIV)-seropositive) was determined for isoniazid, rifampin, streptomycin and ethambutol . Isolates from 73 patients, selected on the basis of geographical location, were tested for strain diversity or relatedness using the IS6110 DNA fingerprinting technique . RESULTS: Resistance rates were as follows: isoniazid, 7.9% streptomycin, 6.1% rifampin, 1.4% and ethambutol 0.9% . Twelve per cent of the strains were resistant to at least one of the first line drugs tested and 4.7% were multiply resistant . There were no significant differences in resistance rates between patients with and without HIV infection . Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical RFLP patterns were found out of the 73 isolates tested (8.2%) . Each cluster contained two isolates . Three (4.1%) isolates had less than seven copies of IS6110 . CONCLUSION: This study shows that in Uganda initial drug resistance rates to anti-tuberculosis agents are low and similar to other sub-Saharan African countries and that multiple strains of M . tuberculosis have been transmitted within the communityPIP: This study was undertaken to determine the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis (TB) in Kampala, Uganda . Using a radiometric BACTEC 460 TB system, 215 M . tuberculosis isolates from previously untreated patients (aged 17-48 years, mean age = 28 years; 56% males and 69% HIV-seropositive) were analyzed for susceptibility to isoniazid, rifampin, streptomycin, and ethambutol . Isolates from 73 patients were examined for strain diversity or relatedness using the insertional sequence 6110 (IS6110) DNA fingerprinting technique . The study revealed the following drug resistance rates: isoniazid, 7.9%; streptomycin, 6.1%; rifampin, 1.4%; and ethambutol, 0.9% . Resistance to at least one of the first line drugs tested were developed by 12% of the strains, while 4.7% showed multiple resistance . However, no significant differences in resistance rates were found between patients with and without HIV infection . Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical patterns were found out of the 73 isolates tested (8.2%) . Each cluster contained two isolates, and three isolates had less than 7 copies of IS6110 . These findings suggest that initial drug resistance to anti-tuberculosis agents in this region is low and similar to other countries in sub-Saharan Africa and that multiple strains of M . tuberculosis have been transmitted within the community .

Infect Immun, 2000 May, 68(5), 2518 - 24
rpoS gene function is a disadvantage for Escherichia coli BJ4 during competitive colonization of the mouse large intestine; Krogfelt KA et al.; The ability of Escherichia coli to survive stress during growth in different environments is, in large part, dependent on rpoS and the genes that comprise the rpoS regulon . E . coli BJ4 and an isogenic BJ4 rpoS mutant were used to examine the influence of the rpoS gene on E . coli colonization of the streptomycin-treated mouse large intestine . Colonization experiments in which the wild-type E . coli BJ4 and its rpoS mutant were fed individually as well as simultaneously to mice suggested that E . coli BJ4 does not face prolonged periods of nutrient starvation in the mouse large intestine and that the rpoS regulon is not expressed during long-term colonization after adaptation of the bacteria to the gut environment.

Int J Tuberc Lung Dis, 2000 Mar, 4(3), 262 - 7
Rifapentine and isoniazid in the continuation phase of a 6-month regimen . Interim report: no activity of isoniazid in the continuation phase; Tam CM et al.; SETTING: Clinical trial amongst 762 patients with newly diagnosed pulmonary tuberculosis in Hong Kong . After an initial 2 months of a four-drug intensive phase consisting of streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ), a random allocation in continuation to once-weekly rifapentine + isoniazid (HRp1), HRp1 given in 2 of every 3 weeks (HRp1.2/3), or to three times weekly isoniazid + rifampicin (HR3) . OBJECTIVE: Interim report evaluating progress of study and the role of isoniazid in the continuation phase . METHODS: Kaplan-Meier analysis and response of patients related to susceptibility of pretreatment organisms to isoniazid and to rate of isoniazid acetylation determined by NAT2 genotyping . RESULTS: In the 30-month follow-up, rates for adverse treatment events (failure and relapse) were 4.2% in the HR3, 10.2% in the HRp1 and 11.2% in the HRp1.2/3 series (P = 0.02 for HR3 vs HRp1 and P = 0.01 for HR3 vs HRp1.2/3) . Occurrence of adverse events was not related to initial susceptibility to isoniazid nor to the rate of acetylation of isoniazid . CONCLUSIONS: The two rifapentine regimens had similar final rates of adverse events which were unsatisfactory . Isoniazid had little or no activity in the continuation phase, indicating that no improvement of the continuation regimen is likely to be obtained by alteration of the isoniazid dosage.

East Afr Med J, 1999 Jun, 76(6), 307 - 13
Tuberculosis chemotherapy and sputum conversion among HIV-seropositive and HIV-seronegative patients in south-eastern Uganda; Bwire R et al.; OBJECTIVE: To investigate if there is a difference in response to tuberculosis treatment between HIV seronegative and HIV seropositive patients following two months of intensive phase tuberculosis treatment . DESIGN: Prospective cohort study . SETTING: St . Francis Leprosy Centre, south-east Uganda . SUBJECTS: Four hundred fifty seven patients with never previously treated sputum smear-positive tuberculosis admitted during a two-year period in 1991/1993 . INTERVENTION: Intensive phase treatment with streptomycin, isoniazid, rifampicin and pyrazinamide . MAIN OUTCOME MEASURES: Sputum conversion from a positive to a negative smear at eight weeks of treatment . RESULTS: HIV seropositivity prevalence was 28% . Among HIV seronegative patients, conversion to a negative smear status occurred in 76% persons compared to 78% in HIV seropositive patients . This difference was not statistically significant (OR = 0.9; 95% CI, 0.6-1.5) . HIV seropositive patients, however, were more likely to die (p = 0.017) . A high prevalence of resistance to isoniazid and streptomycin was found . Isoniazid resistance was more likely in HIV seronegative patients with M . tuberculosis strains compared to HIV seropositive persons (p < 0.005) . Initial resistance to antituberculosis drugs did not have a significant effect on smear conversion . CONCLUSION: This study demonstrates that HIV-seropositive status is not a principal factor in delaying sputum conversion among patients receiving intensive phase tuberculosis treatmentPIP: A prospective cohort study was undertaken to investigate the response of HIV-seropositive and -seronegative patients at St . Francis Leprosy Center, southeastern Uganda, to tuberculosis chemotherapy . The study population included 457 patients without a history of prior tuberculosis therapy between 1991 and 1993 . The subjects were exposed to an intensive phase therapy of rifampicin, streptomycin, isoniazid, and pyrazinamide . After the treatment, sputum culture and sensitivity tests were conducted . Findings showed that 77% of the patients who never received tuberculosis treatment in the past converted to a negative smear status after the 8-week treatment . There was no significant difference in sputum conversion rates between HIV-seropositive and -seronegative patients . The study also revealed that HIV seropositivity prevalence was 28% . Among HIV-seronegative patients, conversion to a negative smear status occurred in 76% compared to 78% HIV-seropositive patients . Moreover, a significant number of HIV-seronegative patients died during the initial course of the therapy . Also, a high prevalence of isoniazid and streptomycin resistance was noted; however, this result never affected the conversions of smears . In conclusion, the study clearly demonstrates that other factors outside the seropositive status may be the principal causes of the delay in sputum conversion among patients receiving intensive tuberculosis chemotherapy .

J Antimicrob Chemother, 2000 Apr, 45(4), 541 - 5
Failure of oily chloramphenicol depot injection to treat plague in a murine model; Rahalison L et al.; Effective low-cost single-dose therapy would be invaluable in treating human plague . The efficacy of single- or two-dose injections of oily chloramphenicol (OCm) was compared with that of standard multiple injections of reference drugs (streptomycin or chloramphenicol) in a murine plague model . A single injection of OCm was ineffective . Two doses cleared bacteraemia and limited bacterial growth in the mouse spleen but were less effective in reducing mortality than standard therapy . However, because of the marked pharmacokinetic differences between mice and humans, the failure of depot injection of OCm in murine plague treatment is not indicative of its ineffectiveness in human plague.

ORL J Otorhinolaryngol Relat Spec, 2000 Mar-Apr, 62(2), 60 - 2
Effectiveness and utility of chemical labyrinthectomy with streptomycin using osmotic pump; Shimogori H et al.; To investigate the utility of osmotic pumps, labyrinthectomy was performed surgically (surgical group) or chemically with 30% streptomycin sulfate (SM) using osmotic pumps (SM group) in guinea pigs . After treatment, no statistical difference was observed in the frequency of spontaneous nystagmus and the degree of yaw head tilt between the groups . These data indicate the reliability and efficacy of osmotic pumps, and it might be possible to make guinea pig models using osmotic pumps to predict various grades of damage in the vestibular periphery of humans .

Kekkaku, 2000 Feb, 75(2), 103 - 24
{Current status of tuberculosis education in universities and future tasks}; Replacement vectors for localized gene cloning in the specified region of Streptomyces lividans 66 and model method for the screening of desired recombinants via counter-selection; Huazhong Agricultural University, Wuhan, ChinaTwo DNA fragments (3.5 kb and 3.8 kb in size) flanking both ends of the phi HAU3R gene in the genome of Streptomyces lividans 66 were determined and cloned in their natural relative orientations in pIJ653, a cosmid vector derived from the multi-copy Streptomyces plasmid pIJ101, resulting in pHZ806 . After insertion of spectinomycin/streptomycin (spc/str) resistance gene into the pIJ101 replication region in pHZ806 and insertion of a hygromycin (hyg) resistance gene between 3.5 kb and 3.8 kb DNA fragments, a new vector with a non-functional Streptomyces replicon, pHZ808, was obtained . In principle, any DNA fragment cloned between 3.5 kb and 3.8 kb fragments of this vector can be stably integrated between the two corresponding regions after introduction into the wild-type S.lividans strains, with synchronous replacement of the DNA between the two regions of the chromosome within which phi HAU3R gene is located . The resultant recombinant strains will thus become phi HAU3-sensitive (phi HAU3S) . This phenotype could serve as a good indication that the desired gene replacement has occurred . This principle was demonstrated to be successful using pHZ808 as vector . phi HAU3-resistance gene (phi HAU3R) from the genome of S.lividans 66 was substituted by the hygromycin resistance gene (hyg) from pHZ808 . An additional advantage of using pHZ808 as the vector to clone foreign genes is that hyg could be served as a reportor gene to imply that foreign DNA fragment has been co-integrated with hyg . The recombinants will have both hygR and phi HAU3S.

J Pharm Biomed Anal, 1999 Dec, 21(4), 715 - 22
Liquid chromatographic analysis of dihydrostreptomycin sulfate; Adams E et al.; The analysis of dihydrostreptomycin sulfate using a column packed with base deactivated reversed phase silica gel and ultraviolet detection at 205 nm is described . The mobile phase consists of an aqueous solution containing 4 g/l of sodium sulfate, 1.5 g/l of sodium octanesulfonate, 100 ml/l of acetonitrile and 50 ml/l of a 0.2-M phosphate buffer at pH 3.0 . The method allows separation of streptidine, dihydrostreptomycin B, streptomycin, dihydrostreptomycin and deoxydihydrostreptomycin, as well as some other components which were not identified . The total time of analysis is 55 min . The effects of the different chromatographic parameters on the separation were also investigated . A number of commercial samples were analyzed using this method.

Tuber Lung Dis, 1999, 79(6), 343 - 8
Detection of mutations in drug resistance genes of Mycobacterium tuberculosis by a dot-blot hybridization strategy; Victor TC et al.; SETTING: Mycobacterium tuberculosis isolates from patients in communities endemic for tuberculosis in South Africa . OBJECTIVE: To develop a reliable PCR-based dot-blot hybridization strategy to detect mutations conferring drug resistance . DESIGN: Different loci in six genes associated with drug resistance to isoniazid, rifampacin, streptomycin and ethambutol were selected to develop the PCR-based dot-blot hybridization strategy . RESULTS: Primers and probes to detect mutations at codons 315, 463 (katG) 269 (kasA), 531, 526 (rpoB) 43 (rpsL), 513 (rrs) and 306 (embB) were designed and used to develop a PCR-based dot-blot hybridization strategy . The dot-blot hybridization strategy with wild-type probes can efficiently be used to detect drug resistant mutations since these do not hybridize to mutant loci . Stripped blots and mutant probes can be used to identify the precise mutation . The embB gene (ethambutol resistance) was used to show how the dot-blot strategy can assist with the prediction of drug resistance more accurately . The method is rapid, reproducible, not technically demanding and samples can be done in batches . Additional loci can easily be incorporated . CONCLUSIONS: A PCR-based dot-blot hybridization strategy is described which can accurately identify drug resistant strains and the method is useful for patients at risk and in areas endemic for tuberculosis.

Hunan Yi Ke Da Xue Xue Bao, 1998, 23(2), 133 - 6
{Study on the effects of hyaluronic acid-streptomycin perfusion through the round window on the function and morphology in guinea pig inner ears.}; Yin T et al.; To investigate the effects of the hyaluronic acid-streptomycin (HA-SM) perfusion through round window on the function and morphology of the inner ear in guinea pig, membrous labyrinth mapping, temporal bone section after celloidin embedding, transmission electron microscopy, electrocochlegraphy (ECochG) and electronystagmography (ENG) were examined . The nystagmus duration induced by caloric test was obviously reduced in comparison with that of the preoperation (P< 0.01), while the action potential(AP) by ECochG was not obviously changed . The sensory cells of estibular organs were severely damaged, while the morphology of corti's organs were significantly damaged after HA-SM perfusion . The results suggest that the HA-SM perfusion through the round window may selectively destroy the vestibular function, whereas the auditory function is not obviously damaged.

Farmaco, 1999 Nov-Dec, 54(11-12), 721 - 7
Antimycobacterial activity of new ortho-, meta- and para-toluidine derivatives; Biava M et al.; Novel toluidine derivatives are described . Some of them showed an interesting in vitro activity against Mycobacterium tuberculosis, M . smegmatis, M . marinum, M . gordonae, and M . avium . Some of them were more active than Streptomycin and Isoniazid, which were used as controls, against M . avium and M . gordonae . In particular, we confirm the good activity of biphenyl derivatives.

Therapie, 1999 Sep-Oct, 54(5), 623 - 5
Mycobacterium resistance to antimycobacterial reagent; Aghandous R et al.; This study was carried out in the tuberculosis laboratory of the Institut National d'Hygiene in Rabat, Morocco, in 1997 . The aim was to determine the percentages of drug-resistant strains by using 150 antibiograms . Six antimycobacterial medications were used as tuberculosis treatment: isoniazid (INH), streptomycin (STM), rifampicin (RIF), ethambutol (EMB), kanamycin (KAN) and p-amino-salicylic acid (PAS) . The cultures were plated onto a simple agar (Lowenstein-Jensen) plate containing different concentrations of drugs . This test demonstrated the presence of major antimycobacterial (INH, RIF, STM)-resistant strains of Mycobacterium tuberculosis in the following percentages respectively: 34.6 per cent, 33.1 per cent and 26.1 per cent and 80 per cent, 70 per cent and 40 per cent in the case of atypical mycobacteria . The association of INH/RIF showed the highest percentage (27.6 per cent) for Mycobacterium tuberculosis and 70 per cent for atypical strains, whereas, when we associate INH/RIF/STM, the resistance rate becomes 17.69 per cent for Mycobacterium tuberculosis and 25 per cent for atypical mycobacteria . The resistance in question was a secondary or acquired resistance because the tested strains were isolated from patients who had not responded to standard tuberculosis treatment.

Mem Inst Oswaldo Cruz, 2000 Jan-Feb, 95(1), 127 - 9
Standardization of broth microdilution method for Mycobacterium tuberculosis; Leite CQ et al.; Indirect drug susceptibility tests of Mycobacterium tuberculosis was done to investigate the accuracy and feasibility of a broth microdilution method (BMM) for determining minimal inhibitory concentrations of conventional drugs against M . tuberculosis . Test drugs included isoniazid (H), rifampicin (R), ethambutol (E), streptomycin (S) and pyrazinamide (Z) . Fifty isolates of M . tuberculosis from patients who had never received drug therapy, and H37Rv strain for control, were evaluated in the system . When comparing this method with the gold standard proportional method in Lowenstein-Jensen medium, sensitivity of 100% for all drugs and specifities of 91, 100, 96, 98 and 85% were observed respectively for H, R, E, S and Z . The BMM was read faster (14-20 days) than the proportional method (20-28 days) . The microdilution method evaluated allows the testing of multiple drugs in multiple concentrations . It is easy to perform and does not require special equipment or expensive supplies . In contrast to radiometric method it does not use radioactive material.

Kekkaku, 1999 Dec, 74(12), 879 - 83
{Aerosolized therapy with streptomycin and steroids in treatment of bronchial stenosis due to endobronchial tuberculosis}; Rikimaru T et al.; We had reported that aerosolized therapy with streptomycin and steroids is useful for ulcerative EBTB . However, the effectiveness of this therapy for bronchial stenosis has yet to be clarified . This study was undertaken to determine the effectiveness of aerosolized streptomycin and steroids in the treatment of bronchial stenosis due to EBTB . We performed flexible bronchoscopy in 64 patients with active erosive or ulcerative EBTB . Flexible bronchoscopy was performed at least twice in 54 patients, 27 patients treated with conventional therapy and 27 patients treated with aerosol therapy . In those, we estimated the degree of bronchial stenosis between the first and last bronchoscopic examinations . We compared conventional therapy with aerosol therapy to clarify the usefulness of aerosol therapy for bronchial stenosis . We graded bronchial stenosis as minimal, mild, moderate, severe, or obstructive . We assessed the follow-up of bronchial stenosis as aggravation, no change, or improvement, using the first and last endoscopic findings . "Improvement" was defined as the last endoscopic findings improving by at least two grades . "Aggravation" was defined as the last endoscopic findings worsening by at least two grades . Other cases were defined as "no change" . Conventional therapies led to aggravation in 13 patients, no change in 13 patients, and improvement in 1 patient . Aerosol therapy led to no change in 24 patients, improvement in 3 patients . No patients developed aggravation . The differences between the therapeutic groups were significant . We concluded that aerosol therapy with streptomycin and steroids helps to treat bronchial stenosis due to ulcerative EBTB.

J Pak Med Assoc, 1999 Nov, 49(11), 262 - 5
Drug resistance in Mycobacterium tuberculosis: a four years experience; Karamat KA et al.; OBJECTIVE: To assess the prevalence of drug resistance amongst the clinical isolates of M . tuberculosis . SETTING: Armed Forces Institute of Pathology, Rawalpindi . METHOD: Four first line anti-tuberculosis drugs, isoniazid (INH), rifampicin (RIF), ethambutol (ETH) and streptomycin (STR) were tested on 300 isolates from clinical samples, by agar dilution method on Lowenstein Jensen medium . The sensitivities were interpreted by the resistance ratio method . RESULTS: One hundred and fifty eight (52.66%) isolates were found resistant to one drug at least . Among the resistant isolates, 79 (26.33%) were resistant to INH, 72 (24.0%) to RIF, 84 (28.0%) to STR and 70 (23.33%) to ETH with or without resistance to other drugs . Multi-drug resistance (MDR) was found in 41 isolates (13.66%) . CONCLUSION: To overcome this problem there is a need to establish centres at a number of places all over the country with professionals trained to handle the emerging problem of MDR . Each centre must be equipped with adequate facilities for susceptibility testing so that the resistance pattern can be ascertained and treatment regimens tailored accordingly.

J Appl Physiol, 2000 Jan, 88(1), 91 - 101
Stretch-activated ion channels contribute to membrane depolarization after eccentric contractions; McBride TA et al.; We tested the hypothesis that eccentric contractions activate mechanosensitive or stretch-activated ion channels (SAC) in skeletal muscles, producing increased cation conductance . Resting membrane potentials and contractile function were measured in rat tibialis anterior muscles after single or multiple exposures to a series of eccentric contractions . Each exposure produced a significant and prolonged (>24 h) membrane depolarization in exercised muscle fibers . The magnitude and duration of the depolarization were related to the number of contractions . Membrane depolarization was due primarily to an increase in Na(+) influx, because the estimated Na(+)-to-K(+) permeability ratio was increased in exercised muscles and resting membrane potentials could be partially repolarized by substituting an impermeant cation for extracellular Na(+) concentration . Neither the Na(+)/H(+) antiport inhibitor amiloride nor the fast Na(+) channel blocker TTX had a significant effect on the depolarization . In contrast, addition of either of two nonselective SAC inhibitors, streptomycin or Gd(3+), produced significant membrane repolarization . The results suggest that muscle fibers experience prolonged depolarization after eccentric contractions due, principally, to the activation of Na(+)-selective SAC.

Infect Immun, 2000 Feb, 68(2), 429 - 36
A peptide permease mutant of Mycobacterium bovis BCG resistant to the toxic peptides glutathione and S-nitrosoglutathione; Green RM et al.; Oligopeptides play important roles in bacterial nutrition and signaling . Using sequences from the available genome database for Mycobacterium tuberculosis H37Rv, the oligopeptide permease operon (oppBCDA) of Mycobacterium bovis BCG was cloned from a cosmid library . An opp mutant strain was constructed by homologous recombination with an allele of oppD interrupted by kanamycin and streptomycin resistance markers . The deletion was complemented with a wild-type copy of the opp operon . Two approaches were taken to characterize the peptide transporter defect in this mutant strain . First, growth of wild-type and mutant strains was monitored in media containing a wide variety of peptides as sole source of carbon and/or nitrogen . Among 25 peptides ranging from two to six amino acids in length, none was capable of supporting measurable growth as the sole carbon source in either wild-type or mutant strains . The second approach exploited the resistance of permease mutants to toxic substrates . The tripeptide glutathione (gamma-glutamyl-L-cyteinylglycine {GSH}) is toxic to wild-type BCG and was used successfully to characterize peptide uptake in the opp mutant . In 2 mM GSH, growth of the wild-type strain is inhibited, whereas the opp mutant is resistant to concentrations as high as 10 mM . Similar results were found with the tripeptide S-nitrosoglutathione (GSNO), thought to be a donor of NO in mammalian cells . Using incorporation of {(3)H}uracil to monitor the effects of GSH and GSNO on macromolecular synthesis in growing cells, it was demonstrated that the opp mutant is resistant, whereas the wild type and the mutant complemented with a wild-type copy of the operon are sensitive to both tripeptides . In uptake measurements, incorporation of {(3)H}GSH is reduced in the mutant compared with wild type and the complemented mutant . Finally, growth of the three strains in the tripeptides suggests that GSH is bacteriostatic, whereas GSNO is bacteriocidal.

Rev Clin Esp, 1999 Nov, 199(11), 711 - 5
{Epidemic outbreak of tularemia in Palencia}; Andres Puertas C et al.; BACKGROUND: Tularemia can become a health problem after its recent emergence in Spain . OBJECTIVE: To describe the clinico-epidemiologic characteristics of a tularemia outbreak occurred in Palencia (October 1997 to March 1998) . DESIGN: Case-control study . MATERIAL AND METHODS: A clinico-epidemiologic survey was conducted . The Chi square test and the Student "t" test were used and a logistic regression analysis was made . The diagnosis was made by serology (microagglutination or macroagglutination) or culture . RESULTS: There were 151 cases; 74.5% of cases were confirmed or likely . The ulceroglandular was the most common clinical form of the disease (49%) and 23.2% of patients required hospital admission; 93.4% of patients had exposure to hares, and 86.7% of them handled them . Higher risk practices included skinning (adjusted OR: 3.9; 95% CI {1.03-14.7}; p = 0.04) and cutting/cooking (adjusted OR: 2.7; 95% CI {1.01-6.7}; p = 0.03) . Streptomycin therapy was used for 51.6% of cases . CONCLUSIONS: The clinico-epidemiologic surveillance of this disease in Spain is necessary.

Arch Pathol Lab Med, 2000 Jan, 124(1), 82 - 6
Evaluation of the BBL MGIT (Mycobacterial growth indicator tube) AST SIRE system for antimycobacterial susceptibility testing of Mycobacterium tuberculosis to 4 primary antituberculous drugs; Bergmann JS et al.; OBJECTIVE: To evaluate the performance of the BBL MGIT (Mycobacterial Growth Indicator Tube) AST SIRE system for the antimycobacterial susceptibility testing of Mycobacterium tuberculosis to isoniazid (at a concentration equivalent to the lower concentration used for testing by the method of proportion), rifampin, ethambutol, and streptomycin . DESIGN: Thirty-one clinical isolates and 30 challenge strains provided by the Centers for Disease Control and Prevention (CDC) were tested by MGIT AST SIRE using 2 methods of inoculum preparation, and results were compared with those of the method of proportion, which was considered the reference method . Clinical isolates for which the results of the 2 methods were discordant also were tested at 2 reference laboratories . RESULTS: Based on data from our site and the reference laboratories, agreement rates between initial MGIT AST SIRE results and the method of proportion for the clinical isolates with the inoculum prepared from a McFarland equivalent and from a positive MGIT tube, respectively, were 100% and 96.8% for isoniazid, 100% and 100% for rifampin, 96.8% and 100% for ethambutol, and 100% and 100% for streptomycin, excluding the isolate for which the discordant streptomycin result could not be resolved . For the 30 challenge isolates, agreement rates between MGIT AST SIRE and expected results and between method of proportion and expected results, respectively, were 96.7% and 93.3% for isoniazid, 93.3% and 100% for rifampin, 83 . 3% and 100% for ethambutol, and 93.3% and 100% for streptomycin . For the clinical isolates, the mean time to an MGIT AST SIRE result of susceptible was 6.15 +/- 0.13 days (range, 5-8 days) . For a result of resistant, the mean time overall was 5.00 +/- 0.24 days (range, 3-8 days) . CONCLUSION: These data suggest that the MGIT AST SIRE system, using either method of inoculum preparation, is an acceptable alternative to the BACTEC 460 TB method of susceptibility testing of clinical isolates of M tuberculosis to isoniazid, rifampin, ethambutol, and streptomycin . Reasons for the lower agreement with the CDC challenge isolates should be investigated . Further evaluation of the MGIT AST SIRE system using a concentration of isoniazid equivalent to the higher concentration tested by the method of proportion would be useful, because the decision concerning use of this agent generally is based on the susceptibility test result at the higher concentration.

Sante, 1999 Jul-Aug, 9(4), 225 - 9
{Profile of the patients lost to treatment in the National Anti-Tuberculosis Program in Madagascar}; Rakotomanana F et al.; A national anti-tuberculosis program has been in operation in Madagascar since 1991 . Despite the significant efforts made in the management, education and surveillance of patients, the number of patients lost to treatment remains high (18.8%) . Noncompliance with treatment is the principal cause of treatment failure and of the development of resistance to tuberculosis drugs . This study investigated the profile of the patients who discontinue treatment . The study population consisted of the patients withdrawing from a clinical trial carried out between August 1994 and September 1996 . The aim of the trial was to compare several treatments in routine practice conditions in Madagascar . The treatments tested were streptomycin (S) or ethambutol (E) associated with isoniazid (H), rifampicin (R) or pyrazinamide (Z) for the first two months, followed by 6 months of treatment H and thiacetazone (T) . The trial involved four public and three private diagnosis and treatment centers in Antananarivo, Fianarantsoa and Mahajanga . A total of 1, 023 patients were included in the trial and 192 (18.8%) withdrew during the eight-month treatment period . We tracked down 109 of these patients (56.8%) and 19 patients came back to the treatment center on their own initiative for a checkup . The rate of response to a recall letter sent by mail was low . The 106 patients interviewed mostly gave professional, financial or family reasons for discontinuing treatment . Many patients stopped the treatment as soon as they began to feel better . To reduce the number of patients discontinuing treatment, the National Anti-Tuberculosis Program should improve the education of patients and their families.

Analyst, 1999 Mar, 124(3), 301 - 5
Immunochemical detection of aminoglycosides in milk and kidney; Haasnoot W et al.; In 1996, the European Union established provisional maximum residue limits (MRL) for gentamicin, neomycin, streptomycin and dihydrostreptomycin in milk and tissue (0.1-5 mg kg-1) . For the detection of these four aminoglycosides, three enzyme linked immunosorbent assays (ELISA) for applications in milk and kidney were developed . The screening of defatted and diluted milk resulted in limits of determination (LDM) of < 0.01 mg l-1 . Kidney samples were deproteinized with a trichloroacetic acid solution (3%) and after filtration and the addition of buffer, aliquots were used in the ELISA . The LDM of the four aminoglycosides in kidney were < 0.05 mg kg-1 . The ELISA were found suitable for the semi-quantitative screening of milk and kidney for the presence of the four aminoglycosides far below the MRL levels . In randomly taken milk samples (n = 776) and in kidneys derived from healthy pigs (n = 124), the aminoglycoside residues found were far below their established MRL . In eight out of the 94 kidney samples obtained from diseased animals after emergency slaughter, aminoglycoside residues were above the MRL.

Mol Microbiol, 1999 Oct, 34(1), 102 - 11
The A-factor regulatory cascade leading to streptomycin biosynthesis in Streptomyces griseus : identification of a target gene of the A-factor receptor; Ohnishi Y et al.; In Streptomyces griseus, A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) at an extremely low concentration triggers streptomycin biosynthesis and cell differentiation by binding a repressor-type receptor protein (ArpA) and dissociating it from DNA . An A-factor-responsive transcriptional activator (AdpA) able to bind the promoter of strR, a pathway-specific regulatory gene responsible for transcription of other streptomycin biosynthetic genes, was purified to homogeneity and adpA was cloned by PCR on the basis of amino acid sequences of purified AdpA . adpA encoding a 405-amino-acid protein containing a helix-turn-helix DNA-binding motif at the central region showed sequence similarity to transcriptional regulators in the AraC/XylS family . The -35 and -10 regions of the adpA promoter were found to be a target of ArpA; ArpA bound the promoter region in the absence of A-factor and exogenous addition of A-factor to the DNA-ArpA complex immediately released ArpA from the DNA . Consistent with this, S1 nuclease mapping showed that adpA was transcribed only in the presence of A-factor and strR was transcribed only in the presence of intact adpA . Furthermore, adpA disruptants produced no streptomycin and overexpression of adpA caused the wild-type S . griseus strain to produce streptomycin at an earlier growth stage in a larger amount . On the basis of these findings, we propose here a model to demonstrate how A-factor triggers streptomycin biosynthesis at a late exponential growth stage.

Brain Res, 1999 Nov 20, 847(2), 357 - 9
Cytochrome c redistribution in apoptosis of guinea pig vestibular hair cells; Nakagawa T et al.; We examined the cellular location of cytochrome c in healthy and in streptomycin-damaged vestibular hair cells by immunohistochemistry . Staining for cytochrome c revealed an immunostain pattern that was consistent with a mitochondrial distribution of this enzyme in healthy hair cells, while in hair cells affected by aminoglycosides, a diffuse distribution in the cytoplasm was found together with apoptotic nuclear morphology . These findings suggest that redistribution of cytochrome c is involved in the pathway of apoptosis in vestibular hair cells induced by aminoglycosides.

Nucleic Acids Res, 1999 Dec 15, 27(24), 4783 - 91
Expression of the human immunodeficiency virus frameshift signal in a bacterial cell-free system: influence of an interaction between the ribosome and a stem-loop structure downstream from the slippery site; Brunelle MN et al.; A-1 frameshift event is required for expression of the pol gene when ribosomes translate the mRNA of human immunodeficiency virus type-1 (HIV-1) . In this study, we inserted the frameshift region of HIV-1 (a slippery heptanucleotide motif followed by a stem-loop) in a reporter gene coding for firefly luciferase . The ability of the corresponding mRNA, generated by in vitro transcription, to be translated in an Escherichia coli cell-free extract is the first demonstration that the HIV-1 frameshift can be reproduced in a bacterial cell-free extract, providing a powerful approach for analysis of the frameshift mechanism . The responses of the frameshift signal to chloramphenicol, an inhibitor of peptide bond formation, and spectinomycin, an inhibitor of translocation, suggest that the frameshift complies with the same rules found in eukaryotic translation systems . Furthermore, when translation was performed in the presence of streptomycin and neamine, two error-inducing antibiotics, or with hyperaccurate ribosomes mutated in S12, the frameshift efficiency was increased or decreased, respectively, but only in the presence of the stem-loop, suggesting that the stem-loop can influence the frameshift through a functional interaction with the ribosomes.

Rev Clin Esp, 1999 Sep, 199(9), 564 - 8
{Infection by resistant Mycobacterium tuberculosis in a hospital population . A longitudinal study of incidental cases at the Fundación Jiménez Díaz}; Garcia Vazquez E et al.; OBJECTIVE: Evaluation of epidemiologic, clinical and prognostic characteristics in cases of resistant tuberculosis (MRTB) . METHODS: Retrospective longitudinal and observational study of resistant cases of tuberculosis at Fundacion Jimenez Diaz (1991-1997) . Statistical analysis of conventional tests and significance level at p < 0.05 . RESULTS: Twenty patients out of 558 with recovery of Mycobacterium tuberculosis showed resistance to some drugs (isoniazid, rifampicin, ethambutol, streptomycin or pyrazinamide) . Information was gathered from 19 patients: eight (42%) HIV-positive patients; eight (42%) with the antecedent of tuberculosis (2 abandoned treatment) . There were eleven cases (58%) of secondary resistance and eight of primary resistance but only five (25%) with multi-resistance criteria (1 primary and 4 secondary); five cases showed primary resistance to isoniazid . The number of resistances and HIV seropositivity or antecedent of prophylaxis was not statistically significant . In contrast, the higher number of resistances and tuberculosis antecedent were indeed statistically significant . CONCLUSIONS: There was a low resistance rate at our institution . All multi-resistant cases had antecedents of therapy or prophylaxis abandon or previous tuberculosis . Only one case was MRTB . The relevance of complying with a proper therapy is emphasized (consider therapies directly monitored if there is risk of abandon) . In patients with epidemiologic risk factors susceptibility studies should be performed and also start therapy with four drugs . The objective is to decrease the percentages of resistance and morbi-mortality.

Clin Exp Pharmacol Physiol, 1999 Oct, 26(10), 842 - 4
Pro- and anti-arrhythmic effects of a kappa opioid receptor agonist: a model for the biphasic action of a local hormone in the heart; Yu X et al.; 1 . The effects of kappa opioid receptor stimulation on cardiac rhythm and the underlying signal pathways were investigated in the rat . 2 . Stimulation of kappa opioid receptors with 40-50 mumol/L U50 488H, a selective kappa opioid receptor agonist, induced dysrhythmias and increased inositol 1,4,5-trisphosphate (IP3) production in rat isolated, perfused heart . The pro-arrhythmic effects of U50 488H were abolished by 5 mumol/L norbinaltorphimine (nor-BNI), a specific kappa opioid receptor antagonist . 3 . The effect of U50 488H on cardiac dysrhythmia and IP3 production were abolished by 1 mmol/L neomycin and streptomycin, phospholipase C (PLC) inhibitors . 4 . At 1 mumol/L, U50 488H, which itself has no effect on cardiac rhythm and IP3 production, significantly attenuated the potentiating effect of 1 mumol/L noradrenaline (NA) on dysrhythmias, which were induced by low flow in the isolated heart . The effects of U50 488H were abolished by 1 mumol/L nor-BNI . Cytosolic cAMP production was augmented by 1 mumol/L NA and this was significantly attenuated by 1 mumol/L U50 488H . 5 . At 1 mumol/L, U50 488H also reduced {Ca2+}i oscillations induced by 0.5 mumol/L NA and 0.5 mumol/L forskolin, an activator of adenylate cyclase (AC) . 6 . In conclusion, U50 488H exerted pro- and anti-arrhythmic actions at high and lower concentrations, respectively . The former effect was mediated via the PLC/IP3 pathway, while the latter was mediated via the AC/cAMP pathway.

Hear Res, 1999 Nov, 137(1-2), 1 - 7
Capability of serum to convert streptomycin to cytotoxin in patients with aminoglycoside-induced hearing loss; Wang S et al.; Individual variations in sensitivity to the ototoxic effects of aminoglycoside antibiotics are well documented . Our research demonstrates that there is an apparent difference in serum from patients who are resistant or susceptible to aminoglycoside ototoxicity . In the first study, the cytotoxicity of sera from patients with and without hearing loss after various time periods following the discontinuation of aminoglycoside treatment was assayed using the isolated outer hair cell toxicity assay . The results indicate that sera from patients with hearing loss were significantly more toxic than sera from patients with normal hearing or minimal hearing loss . This toxicity may persist for up to 1 year after discontinuation of aminoglycoside therapy . In a second study, sera were obtained from patients who had received aminoglycoside therapy several years previously . None of these sera was toxic to isolated outer hair cells in vitro . Streptomycin was then incubated with the sera or a protein fraction isolated from sera, and the incubation mixtures were tested for toxicity . The percentage of damaged outer hair cells was significantly higher when streptomycin had been treated with sera or a serum protein fraction from patients with hearing loss (58+/-10% and 68+/-9%, respectively) than with sera or a serum protein fraction from a control group (10+/-5% and 17+/-4%, respectively) . In addition, several incubation mixtures were analyzed using high performance liquid chromatography . A new chromatographic peak was only found in the incubations of streptomycin with serum protein from patients with hearing loss . The results suggest that sera from individuals sensitive to aminoglycoside antibiotics may metabolize these drugs to cytotoxins.

J Neurobiol, 1999 Nov 15, 41(3), 424 - 34
Defective calmodulin-dependent rapid apical endocytosis in zebrafish sensory hair cell mutants; Seiler C et al.; Vertebrate mechanosensory hair cells contain a narrow "pericuticular" zone which is densely populated with small vesicles between the cuticular plate and cellular junctions near the apical surface . The presence of many cytoplasmic vesicles suggests that the apical surface of hair cells has a high turnover rate . The significance of intense membrane trafficking at the apical surface is not known . Using a marker of endocytosis, the styryl dye FM1-43, this report shows that rapid apical endocytosis in zebrafish lateral line sensory hair cells is calcium and calmodulin dependent and is partially blocked by the presence of amiloride and dihydrostreptomycin, known inhibitors of mechanotransduction channels . As seen in lateral line hair cells, sensory hair cells within the larval otic capsule also exhibit rapid apical endocytosis . Defects in internalization of the dye in both lateral line and inner ear hair cells were found in five zebrafish auditory/vestibular mutants: sputnik, mariner, orbiter, mercury, and skylab . In addition, lateral line hair cells in these mutants were not sensitive to prolonged exposure to streptomycin, which is toxic to hair cells . The presence of endocytic defects in the majority of zebrafish mechanosensory mutants points to a important role of apical endocytosis in hair cell function .

Microbiology, 1999 Sep, 145 ( Pt 9), 2281 - 92
An AfsK/AfsR system involved in the response of aerial mycelium formation to glucose in Streptomyces griseus; Umeyama T et al.; In Streptomyces coelicolor A3(2), a protein serine/threonine kinase (AfsK) and its target protein (AfsR) control secondary metabolism . AfsK and AfsR homologues (AfsK-g and AfsR-g) from Streptomyces griseus showed high end-to-end similarity in amino acid sequence with the respective S . coelicolor A3(2) proteins, as determined by cloning and nucleotide sequencing . AfsK-g and a fusion protein between AfsK-g and thioredoxin (TRX-AfsK-g) produced in high yield as inclusion bodies in Escherichia coli were solubilized with urea, purified by column chromatography and then refolded to an active form by dialysis to gradually remove the urea . AfsR-g was also fused to glutathione S-transferase (GST-AfsR-g); the fusion product in the soluble fraction in E . coli was purified . Incubation of AfsK-g or TRX-AfsK-g in the presence of {gamma-32P}ATP yielded autophosphorylated products containing phosphoserine and phosphothreonine residues . In addition, TRX-AfsK-g phosphorylated serine and threonine residues of GST-AfsR-g in the presence of {gamma-32P}ATP . Disruption of chromosomal afsK-g had no effect on A-factor or streptomycin production, irrespective of the culture conditions . The afsK-g disruptants did not form aerial mycelium or spores on media containing glucose at concentrations higher than 1%, but did form spores on mannitol- and glycerol-containing media; this suggests that afsK-g is essential for morphogenesis in the presence of glucose . Introduction of afsK-g restored aerial mycelium formation in the disruptants . The phenotype of afsR-g disruptants was similar to that of afsK-g disruptants; introduction of afsR-g restored the defect in aerial mycelium formation on glucose-containing medium . Thus the AfsK/AfsR system in S . griseus is conditionally needed for morphological differentiation, whereas in S . coelicolor A3(2) it is conditionally involved in secondary metabolism.

West Afr J Med, 1999 Apr-Jun, 18(2), 119 - 23
Management of pulmonary tuberculosis PTB: regimen employed in Lagos, Nigeria; Alakpa GE et al.; The regimen(s) employed for the management of pulmonary tuberculosis (PTB) by health institutions in Lagos State, Nigeria was determined . Results from the 134 health institutions, showed that only 71.7% of the 120 (89.6%) health institutions with records of PTB, manage these cases . 28.3% refer diagnosed cases to referral (chest) centres . 4.7% administered multiple regimen and 93.0%, single regimen of different drug combinations for different treatment periods/durations . The study showed that 36.9% of the health institutions in Lagos employed a short course chemotherapy (SCC) treatment of between 6 to 9 months duration, while 32.2% employ the longer course of chemotherapy with duration of treatment not less than 10 months . Majority, employed the SCC regimen of 6 months duration using 2SRHZ/4RH combination . Most of the institutions employed a regimen outside the national adopted 8 months regimen that consist of four drugs: streptomycin (S), or ethambutol (E), rifampicin (R), isoniazid (H), and pyrazinamide (Z) for the first two months of intensive treatment and two drugs of isoniazid (H) and thiacetazone (T), for the final continuation phase of six months . (i.e . a regimen of 2S or ERHZ/6TH) . The overall results, showed there is no commonly accepted PTB treatment regimen in Lagos and the national adopted regimen is not favoured by many health institutions . There is the need for the development of a standard, generally accepted, affordable and cost effective treatment regimen for the state and country, for effective monitoring and coordination.

World J Surg, 1999 Nov, 23(11), 1114 - 7
Thoracoscopic surgery for pulmonary tuberculosis; Yim AP et al.; Tuberculosis historically was a major impetus for the development of thoracic surgery, and it remains a serious health problem of global proportion . Thoracoscopy was first introduced at the turn of this century for closed chest adhesiolysis as an adjunct to collapse therapy for treatment of tuberculosis . This indication became obsolete with the discovery of streptomycin during the 1940s; and for a long time since then thoracoscopy was used only sporadically for the diagnosis of pleural disease . However, over the last few years, modern video-assisted thoracoscopic surgery (VATS) has provided a new approach to the management of pulmonary tuberculosis . Over the last 5 years we have used VATS for diagnosis or treatment (or both) of 62 patients with pulmonary tuberculosis, including 20 pleural biopsies, 8 decortications, 17 wedge lung resections, 8 drainages of empyema, and 9 lobectomies . There was no surgical mortality, and complications were few . We conclude that VATS provides a safe, effective diagnostic modality (pleural biopsy, wedge resections) and therapeutic modality (decortications, drainage of empyema) for selected patients with pulmonary tuberculosis.

J Pharmacol Exp Ther, 1999 Oct, 291(1), 285 - 91
Polyamine-like actions of aminoglycosides at recombinant N-methyl-D-aspartate receptors; Harvey SC et al.; Recent pharmacological studies have led to the hypothesis that aminoglycoside-induced ototoxicity is an excitotoxic process mediated, at least in part, by a polyamine-like modulation of N-methyl-D-aspartate (NMDA) receptors . To explore this hypothesis, we compared the effects of several aminoglycosides (neomycin B, kanamycin A, streptomycin, and dihydrostreptomycin) with spermine on recombinant NMDA receptors of defined composition expressed in Xenopus oocytes . Like spermine, aminoglycosides potentiate agonist-induced responses in the presence of both saturating glycine ("glycine-independent") and subsaturating glycine ("glycine-dependent") concentrations on NR1A/2B receptors . Likewise, aminoglycosides and spermine potentiated the agonist responses under glycine-dependent conditions on NR1A/2A receptors . Despite these similarities, several prominent differences were observed between spermine and aminoglycosides as well as among individual aminoglycosides . For example, neomycin B, streptomycin, and kanamycin A, but neither spermine nor dihydrostreptomycin, potentiated glycine-dependent responses on NR1A/2C receptors . Differences between spermine and aminoglycosides also were observed with respect to the voltage dependence of polyamine-like actions . For example, under glycine-dependent conditions, potentiation at NR1A/2B receptors by spermine was voltage dependent, decreasing as the holding potential was changed from -35 to -85 mV; in contrast, potentiation induced by aminoglycosides at NR1A/2B receptors was voltage independent . No direct relationships emerged between the effect of an aminoglycoside at a specific NMDA receptor subtype and the ototoxicity of these antibiotics.

Neuroimmunomodulation, 1999 Sep-Oct, 6(5), 344 - 54
Acute stress may facilitate recovery from a subcutaneous bacterial challenge; Deak T et al.; The effects of stress on the immune system vary with both the duration and type of stressor . Many studies suggest that stress may compromise an organism's ability to recover from immune challenge . However, recent findings suggest that stress may actually enhance some aspects of immune function . For example, exposure to a single session ( approximately 2 h) of intermittent inescapable tailshocks (IS) has been shown to activate the acute phase response and increase some aspects of macrophage function . Thus, the following experiments assessed whether IS exposure would alter local inflammation produced by peripheral injection of streptomycin-killed bacteria . Rats (Harlan Sprague Dawley) were exposed to IS (100 1 . 6-mA, 60 s variable intertrial interval) and injected with Escherichia coli ( approximately 2.5 x 10(8) CFU s.c . posterior to the shoulder blades) . The area of inflammation was measured until the inflammation had completely resolved (typically 7-8 days) . When bacteria were administered immediately after IS, rats resolved inflammation significantly faster than did nonstressed rats . Since adrenalectomy did not reduce the effect of IS, it is unlikely that this effect is a result of elevated corticosterone levels . Furthermore, IS does not appear to alter the rat's ability to sequester bacteria in the subcutaneous space since no swelling of lymph nodes or chronic activation of the hypothalamic-pituitary-adrenal axis was observed.

Lancet, 1999 Mar 20, 353(9157), 969 - 73
First-line tuberculosis therapy and drug-resistant Mycobacterium tuberculosis in prisons; Coninx R et al.; BACKGROUND: We assessed a programme of tuberculosis control in a prison setting in Baku, Azerbaijan . The programme used first-line therapy and DOTS (directly observed treatment, short course) . METHODS: 467 patients had sputum-positive tuberculosis . Their treatment regimens followed WHO guidelines, and they had regular clinical examinations and dietary supplements . Isolates were tested by standard methods for resistance to isoniazid, rifampicin, ethambutol, and streptomycin in three laboratories . Treatment success was defined as three consecutive negative sputum smears at end of treatment . Factors independently associated with treatment failure were estimated by logistic regression . FINDINGS: Drug-resistance data on admission were available for 131 patients . 55% of patients had strains of Mycobacterium tuberculosis resistant to two or more antibiotics . Mortality during treatment was 11%, and 13% of patients defaulted . Overall, treatment was successful in 54% of patients, and in 71% of those completing treatment . 104 patients completed a full treatment regimen and remained sputum-positive . Resistance to two or more antibiotics, a positive sputum result at the end of initial treatment, cavitary disease, and poor compliance were independently associated with treatment failure . INTERPRETATION: The effectiveness of a DOTS programme with first-line therapy fell short of the 85% target set by WHO . First-line therapy may not be sufficient in settings with a high degree of resistance to antibiotics.

Analyst, 1998 Dec, 123(12), 2797 - 801
Detection of incurred dihydrostreptomycin residues in milk by liquid chromatography and preliminary confirmation methods; Suhren G et al.; An LC method for the determination of the aminoglycosides streptomycin (STR) and dihydrostreptomycin (DHS) in milk was developed/modified on the basis of published papers . Mean recoveries were 87 and 95% for STR and DHS, respectively . Recoveries are dependent on the concentration level and batch of solid-phase extraction columns used, and independent of fat content and homogenization . The relative standard deviations are 15.6 and 9.6% for STR and DHS, respectively, at a level of 100 micrograms kg-1 . Limits of detection (8 and 12 micrograms kg-1, respectively) and quantification (12 and 18 micrograms kg-1, respectively) are far below the EU maximum residue limit of 200 micrograms kg-1 . Lyophilized DHS samples can be used for internal control of the analysis as the DHS concentration is not influenced by the lyophilization process and subsequent storage at 6 degrees C . In incurred milk samples no false negative results of preliminary confirmation tests (Charm II Aminoglycoside test, Ridascreen Streptomycin ELISA) with respect to DHS concentrations > or = 20 micrograms kg-1 as determined by the LC method are observed . DHS concentrations of incurred samples determined by ELISA are higher than those obtained by the LC method . These differences were more pronounced with incurred than with spiked milk samples, thus leading to the conclusion that in incurred samples substances are present which co-react in the ELISA and which are not detected by the LC method.

Clin Infect Dis, 1999 Jul, 29(1), 85 - 92; discussion 93-5
Spread of strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, across the United States; Agerton TB et al.; Strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, was responsible for large nosocomial outbreaks in New York in the early 1990s . To describe the spread of strain W outside New York, we reviewed data from epidemiologic investigations, national tuberculosis surveillance, regional DNA fingerprint laboratories, and the Centers for Disease Control and Prevention Mycobacteriology Laboratory to identify potential cases of tuberculosis due to strain W . From January 1992 through February 1997, 23 cases were diagnosed in nine states and Puerto Rico; 8 were exposed to strain W in New York before their diagnosis; 4 of the 23 transmitted disease to 10 others . Eighty-six contacts of the 23 cases are presumed to be infected with strain W; 11 completed alternative preventive therapy . Strain W tuberculosis cases will occur throughout the United States as persons infected in New York move elsewhere . To help track and contain this strain, health departments should notify the Centers for Disease Control and Prevention of cases of tuberculosis resistant to isoniazid, rifampin, streptomycin, and kanamycin.

Am J Otol, 1999 Jul, 20(4), 457 - 64
Comparison of vestibular and cochlear ototoxicity from transtympanic streptomycin administration; Wanamaker HH et al.; HYPOTHESIS: The relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected streptomycin (SM) compared to that of gentamicin (GM) was assessed . BACKGROUND: Although SM, the first aminoglycoside used transtympanically, is thought to be selectively vestibulotoxic, it has been replaced by GM in current clinical use . Little experimental data exist that directly demonstrate the relative cochlear and vestibular ototoxicity resulting from transtympanic administration of SM compared to GM . METHODS: Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage . Comparisons were made between animals receiving single (1 x SM) and five daily (5 x SM) injections of SM/Gelfoam-slurry and similarly injected and noninjected controls . These data were compared to results obtained using GM (1 x GM and 5 x GM) reported previously . RESULTS: Two weeks after injection, parallel qualitative and quantitative changes were seen in posterior cristae and cochlear sensory epithelia in the 1 x and 5 x SM injected groups, similar to those resulting from GM injections . Statistically significant decreases in number of hair cells were seen when 5 x SM injected ears were compared to 1 x SM injected ears and control ears . Increased damage was seen with increased dosage of each drug . Whenever damage was observed to the posterior crista sensory cells, damage was also seen in cochlear hair cells . CONCLUSIONS: In this model, SM and GM produced significant cochlear damage when vestibular damage occurred . These results suggest that, in the gerbil, SM and GM are ototoxic but not selectively vestibulotoxic . Increasing the number of transtympanic injections generally increases the damage to sensory hair cells in the posterior crista and the cochlea . A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in cochlear and vestibular hair cells from the same animal . No evidence for selective vestibular ototoxicity from transtympanic SM was found.

Int Orthop, 1999, 23(2), 73 - 81
Five-year assessment of controlled trials of short-course chemotherapy regimens of 6, 9 or 18 months' duration for spinal tuberculosis in patients ambulatory from the start or undergoing radical surgery . Fourteenth report of the Medical Research Council Working Party on Tuberculosis of the Spine; Simple procedure for drug susceptibility testing of Mycobacterium tuberculosis using a commercial colorimetic assay; Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, BelgiumThe aim of this study was to evaluate a simple method using a commercial colorimetric assay (Alamar Blue Oxidation-Reduction Indicator; Accumed, USA) in a microtiter format for testing the susceptibility of 94 strains of Mycobacterium tuberculosis to isoniazid, rifampicin, ethambutol and streptomycin . The method makes use of one critical concentration of each drug, and the results are available within 8-10 days . Overall, 97.1% agreement with the proportion method was obtained . Full agreement was obtained for isoniazid and rifampicin . The method is simple to perform, permits visual reading of results, and is practicable for laboratories with limited resources.

J Microencapsul, 1999 Jul-Aug, 16(4), 523 - 9
A new stabilizer used in microencapsulation; Lu Z et al.; In this communication, a new microencapsulation method is reported to entrap solid drug powder in an aqueous system . A hydrophobically modified, random polyacrylamide derivative was used as a stabilizer: with a hydrophilic back bone and hydrophobic side chain, it showed good dispersing and stabilizing effects in the preparation of microcapsules . The preparation of streptomycin microcapsules, using poly(lactide) and poly(caprolactone), showed the successful entrapment of streptomycin powder which is readily soluble in water (solubility larger than 20 mg/ml) . In addition, a low concentration of stabilizer (0.25%) is used and a short preparation process is also an advantage of the method.

Hear Res, 1999 Jul, 133(1-2), 17 - 26
Distribution and time course of hair cell regeneration in the pigeon utricle; Dye BJ et al.; Vestibular and cochlear regeneration following ototoxic insult from aminoglycoside antibiotics has been well documented, particularly in birds . In the present study, intraotic application of a 2 mg streptomycin paste was used to achieve complete vestibular hair cell destruction in pigeons (Columba livia) while preserving regenerative ability . Scanning electron microscopy was used to quantify hair cell density longitudinally during regeneration in three different utricular macula locations, including the striola, central and peripheral regions . The utricular epithelium was void of stereocilia (indicating hair cell loss) at 4 days after intraotic treatment with streptomycin . At 2 weeks the stereocilia began to appear randomly and mostly in an immature form . However, when present most kinocilia were polarized toward the developing striola . Initially, regeneration occurred more rapidly in the central and peripheral regions of the utricle as compared to the striola . As regeneration proceeded from 2 to 12 weeks, hair cell density in the striola region equaled the density noted in the central and peripheral regions . At 24 weeks, hair cell density of the central and peripheral regions was equal to normal values, however the striola region had a slightly greater hair cell density than that observed for normal animals.

J Otolaryngol, 1999 Jun, 28(3), 121 - 8
Middle ear instillation of gentamicin and streptomycin in chinchillas: morphologic appraisal of selective ototoxicity; Chen JM et al.; OBJECTIVE: To determine selective cochlear and vestibular ototoxicity of two aminoglycoside antibiotics (gentamicin and streptomycin) in the chinchilla model . Middle ear application of these agents mirrors the clinical practice of chemical vestibular ablation used in Meniere's disease . BACKGROUND: Middle ear instillation of gentamicin or streptomycin has become a popular form of vestibular ablative treatment for disabling Meniere's disease . The vestibular selectivity of these two drugs applied in this fashion has clinical support but is not fully established in humans . Our understanding in this regard has largely been limited to animal models exposed to systemic infusion of aminoglycosides . METHOD: Ten chinchillas underwent left middle ear instillation of one of three agents using variable dosing schedules: gentamicin (n = 6), streptomycin (n = 2), and saline (n = 2) as control . Animals were sacrificed for temporal bone studies using scanning electron microscopy . Morphologic changes in the cochlear and vestibular neuroepithelia were identified . RESULTS: Widespread cochlear and vestibular neuroepithelial injuries were observed with both gentamicin and streptomycin . Contralateral ototoxicity was variable and not related to the total dose of drug delivered . The effect of these two aminoglycosides on the dark cells of the vestibular system appeared negligible . CONCLUSION: We were unable to confirm the selective damage of vestibular end-organ in the chinchilla by either gentamicin or streptomycin, a phenomenon that is generally perceived to occur in humans . Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.

Neurosci Lett, 1999 May 21, 267(1), 57 - 60
Involvement of nitric oxide in aminoglycoside vestibulotoxicity in guinea pigs; Nakagawa T et al.; Involvement of nitric oxide (NO) has been reported in physiological and pathological conditions in the inner ear . Recently, the presence of nitric oxide synthase (NOS) was demonstrated in the vestibular epithelium . In this study we used nicotinamide adenine dinucleotide phosphate-diapholase staining to monitor NOS activity during degeneration of guinea pig vestibular epithelia affected by streptomycin . Increased NOS activity was observed in affected epithelia in a dose- and time-dependent manner and a NOS inhibitor could protect hair cells from apoptosis . Additionally, cycloheximide significantly reduced NOS activity and the occurrence of apoptosis . These findings suggest that NO is involved in the degenerative process of vestibular epithelia caused by aminoglycosides.

Indian J Public Health, 1998 Oct-Dec, 42(4), 126 - 30
Drug resistance to the first line of antitubercular regimen (a preliminary report); Varaiya A et al.; Sputum samples from 100 patients of pulmonary tuberculosis were processed . These patients were admitted in group of Tuberculosis Hospital at Sewri, Mumbai, which is a referral tuberculosis hospital . Isolates were identified as M . Tuberculosis by biochemical tests . Antitubercular sensitivity testing for Isoniazid, Rifampicin, Ethambutol and Streptomycin was performed by resistance ratio method . Total resistance was 36% in our study . Resistance to Isoniazid was 61%: to Rifampicin was 50%, to Ethambutol was 8% and to Streptomycin was 41% . Primary drug resistance to Isoniazid was 45% to Rifampicin was 27%, to Ethambutol was 9%, and to Streptomycin was 54% . Secondary drug resistance to Isoniazid was 68% to Rifampicin was 60%, to Ethambutol was 8% and to Streptomycin was 36% . Secondary drug resistance to Isoniazid and Rifampicin is rising as compared to primary drug resistance to Isoniazid and Rifampicin . This is statistically significant (p < 0.001) . 11 out of 36 cases (30%) showed multi drug resistance to Isoniazid and Rifampicin.

Genetics, 1999 Jul, 152(3), 1111 - 22
Homeologous plastid DNA transformation in tobacco is mediated by multiple recombination events; Kavanagh TA et al.; Efficient plastid transformation has been achieved in Nicotiana tabacum using cloned plastid DNA of Solanum nigrum carrying mutations conferring spectinomycin and streptomycin resistance . The use of the incompletely homologous (homeologous) Solanum plastid DNA as donor resulted in a Nicotiana plastid transformation frequency comparable with that of other experiments where completely homologous plastid DNA was introduced . Physical mapping and nucleotide sequence analysis of the targeted plastid DNA region in the transformants demonstrated efficient site-specific integration of the 7.8-kb Solanum plastid DNA and the exclusion of the vector DNA . The integration of the cloned Solanum plastid DNA into the Nicotiana plastid genome involved multiple recombination events as revealed by the presence of discontinuous tracts of Solanum-specific sequences that were interspersed between Nicotiana-specific markers . Marked position effects resulted in very frequent cointegration of the nonselected peripheral donor markers located adjacent to the vector DNA . Data presented here on the efficiency and features of homeologous plastid DNA recombination are consistent with the existence of an active RecA-mediated, but a diminished mismatch, recombination/repair system in higher-plant plastids.

Minerva Ginecol, 1999 Apr, 51(4), 149 - 52
{A case of peritoneal tuberculosis . Contribution of mini-endoscopy}; Iannello A et al.; BACKGROUND: Tuberculosis in the genital and peritoneal region is increasing in last years . For this reason, the high value and efficacy of laparoscopy using a small caliber endoscope for the diagnosis of this disease, which often presents no specific and heterogeneous clinical features, is underlined . METHODS: A case of peritoneal tuberculosis in a young female presenting fever, asthenia and peritoneal effusion, is reported . Blood tests, X-ray and cytological examination of the peritoneal fluid all failed to point out the right diagnosis . Then multiple biopsies of the peritoneum and the external surface of uterus and ovaries were made using laparoscopy . RESULTS: Laparoscopy clearly showed the miliary nodules . The histology showed multiple granulomas composed by inner caseous necrosis and outer layer of epithelioid histiocytes and Langhans cells, leading thus to the diagnosis of peritoneal tuberculosis . The patient, treated with streptomycin and rifampicin, five months after diagnosis, did not show any feature of tubercular disease . CONCLUSIONS: Because of its safety, laparoscopy is a very useful and powerful diagnostic technique especially in those young women presenting with painful abdominal symptoms without any clear evident cause.

Microbiology, 1999 May, 145 ( Pt 5), 1161 - 72
Possible involvement of cAMP in aerial mycelium formation and secondary metabolism in Streptomyces griseus; Kang DK et al.; In Streptomyces griseus, A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) triggers secondary metabolism and morphogenesis by binding a repressor protein (ArpA) and dissociating it from DNA . UV-mutagenesis of the A-factor-deficient mutant HH1 generated strain HO2, defective in the synthesis of ArpA and therefore able to form aerial mycelium, spores and streptomycin . Shotgun cloning of chromosomal DNA from wild-type S . griseus in strain HO2 yielded a gene that suppressed aerial mycelium formation and streptomycin production . Nucleotide sequencing and subcloning revealed that the gene encoded a eukaryotic-type adenylate cyclase (CyaA) . In mutant HO2 production of cAMP was growth-dependent until the middle of the exponential growth stage; the production profile was the same as in the wild-type strain . However, the amount of cAMP produced was five times larger when mutant HO2 harboured cyaA on the high-copy-number plasmid pIJ486 . Consistent with this, supplying cAMP exogenously at a high concentration to mutant HO2 suppressed formation of both aerial mycelium and streptomycin . On the other hand, some lower concentrations of cAMP stimulated or accelerated aerial mycelium formation . No effects of exogenous cAMP on morphogenesis and secondary metabolism were apparent in the wild-type strain . In addition, disruption of the chromosomal cyaA gene in the wild-type strain had almost no effect . Introducing cyaA cloned in either a low- or a high-copy-number plasmid suppressed morphogenesis and secondary metabolism not only in mutant HO2 but also in other arpA mutants, implying that the effects of cAMP became apparent in the arpA-defective background . When mutant HO2 carried cyaA on a plasmid, synthesis of the stringent response factor ppGpp was greatly reduced; this may account for the observed suppression by cAMP of morphogenesis and secondary metabolism . cAMP also affected protein tyrosine phosphorylation, as determined with antiphosphotyrosine antibody.

Zhonghua Jie He He Hu Xi Za Zhi, 1997 Dec, 20(6), 332 - 5
{Study on the molecular mechanism of multi-drug resistance in clinical isolates of Mycobacterium tuberculosis}; Wu X et al.; OBJECTIVE: To study the molecular mechanism of multi-drug resistance in M . Tuberculosis, and to develop a new method for detecting genes related with multi-drug resistance . METHOD: The ropB, rpsL, katG genes and inhA regulatory sequence in clinical isolates of M . tuberculosis were analyzed with PCR and PCR-SSCP techniques . RESULT: The sensitivity of amplifing the drug-resistant genes with PCR was 1-10 pg DNA . Of the 20 multiple resistant strains with reduced sensitivity to streptomycin, rifampin and isoniazid, 90% showed mutations in more than two genetic markers associated with resistance to each of these three drugs, 10% revealed only mutations in rpoB gene . CONCLUSION: Multi-drug resistance in M . tuberculosis could be caused by an accumulation of mutations in chromosomal genes encoding drug targets or an alteration at a single multiple resistance locus . PCR and PCR-SSCP techniques might become simple, rapid and reliable diagnostic tests for multi-drug resistance.

Neurol India, 1999 Mar, 47(1), 58 - 60
Systemic brucellosis with chronic meningitis: A case report; Ghosh D et al.; A young adult presenting with 11 months history of fever, headache, vomiting was found to have CSF lymphocytic pleocytosis with increased protein . His serum tested strongly positive for Brucella (standard tube agglutination titre 1: 320) whereas CSF was weakly positive . He became asymptomatic on treatment with tetracycline, rifampicin and streptomycin with significant CSF response . This case is reported because of its rarity.

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 1997 Nov, 11(11), 496 - 8
{Treatment of sensorineural hearing loss with delayed onset of vertigo (report of 13 cases)}; Lu Y et al.; Sensorineural hearing loss with delayed onset of vertigo (SHL-DV) is a syndrome consisting of preexisting SHL and subsequent episodes of vertigo . The possible underlying pathophysiology is delayed endolymphatic hydrops . This paper details our clinical experience with 8 patients with SHL-DV caused by otitis media and 6 patients following sudden deafness and hearing loss due to an unknown cause . The average period of onset of vertigo after the occurance of the hearing loss was 22.6 years . The average period of vertigo was 6.2 years . Surgical treatment was performed in 13 patients (14 ears) because of disabling vertigo . Endolymphatic sac decompression was performed in 2 ears, transmastoid labyrinthectomy in 3 ears, gentamycin perfusion of the tympanic cleft in 3 ears, streptomycin perfusion of the labyrinth in 6 ears . Follow-up for 13 patients who had surgery averaged 2.3 years, all patients were cured of their episodic vertigo . Three patients underwent surgical labyrinthectomy suffering with total hearing loss, but aminoglycoside antibiotics induced labyrinthectomy preserving some hearing . We conclude that chemical labyrinthectomy is the therapy of choice for the severe SHL-DV who has serviceable hearing.

Jpn J Pharmacol, 1999 Mar, 79(3), 343 - 50
Alkalinization-induced K+ current of the mouse megakaryocyte; Murakami M et al.; We have recently found that mouse megakaryocytes responded to extracellular alkalinization to pH > 8.0, generating a K+ current under voltage-clamped conditions with the whole cell recording mode of the patch-clamp technique . The purpose of this study was to physiologically and pharmacologically characterize the alkaline-dependent K+ conductance of the megakaryocyte membrane . The alkalinization-induced K+ current (I(ALK)) did not seem to be Ca2+-dependent since I(ALK) was allowed to be generated under intracellularly Ca2+-buffered conditions with 10 mM EGTA, which completely prevented the generation of caffeine-induced Ca2+-activated currents of mouse megakaryocytes; and no {Ca2+}i elevation was evoked by the alkalinization protocol in contrast to a significant increase in {Ca2+}i in response to caffeine when {Ca2+}i was measured with a fura 2 ratiometry . I(ALK) was strongly suppressed with tetraethylammonium (TEA), 4-aminopyridine (4-AP) and streptomycin (SM), but was completely resistant to quinidine (QND) . The values of IC50 for the suppression of I(ALK) with TEA, 4-AP and SM were 5.6, 0.47 and 1.5 mM, respectively . Voltage-gated K+ currents (I(K)) of the same megakaryocyte preparation were weakly suppressed with TEA and 4-AP, while they were significantly suppressed with either SM or QND . These results suggest that mouse megakaryocytes possess K+ conductance that was activated by extracellular alkalinization and that probably differs from conventional K+ conductance in its pharmacological properties.

Int J Tuberc Lung Dis, 1999 Apr, 3(4), 344 - 8
Evaluation of Mycobacteria Growth Indicator Tube (MGIT) for drug susceptibility testing of Mycobacterium tuberculosis; Palomino JC et al.; SETTING: Mycobacteria Supranational Reference Laboratory . OBJECTIVE: To evaluate the Mycobacteria Growth Indicator Tube (MGIT) method for drug susceptibility testing of Mycobacterium tuberculosis . DESIGN: One hundred and one clinical strains of M . tuberculosis were evaluated for their susceptibilities to isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (SM) by MGIT and by the proportion method on Lowenstein-Jensen (L-J) medium . The concentrations of drugs in MGIT were: 0.1, 1.0, 3.5 and 0.8 microg/ml for INH, RIF, EMB and SM, respectively . RESULTS: The results for individual drugs showed a good correlation: the specificity was 100% for INH, RIF and EMB and 92% for SM; the sensitivity was 100%, 94.6%, 96.1% and 89.7% for INH, RIF, EMB and SM, respectively, and the accuracy values 1.0, 0.98, 0.99 and 0.91 . CONCLUSION: The MGIT system appears to be a reliable and simple non-radiometric method for the drug susceptibility testing of M . tuberculosis.

J Hum Lact, 1998 Dec, 14(4), 337 - 40
The safety of antituberculosis medications during breastfeeding; Tran JH et al.; Most antituberculosis drugs appear to be safe for use with breastfeeding . These agents are excreted in breast milk at relatively small concentrations . No adverse effects have been reported to date . The percentages of the therapeutic dose of antituberculosis agents that potentially may be delivered to the nursing infants range from 0.05% to 28% . Currently isoniazid, rifampin, ethambutol, streptomycin (first-line agents), kanamycin and cycloserine (second-line agents) are the only agents considered by the AAP to be compatible with breastfeeding . Unfortunately, there are still no clear data on the safety of pyrazinamide, ethionamide, and capreomycin during breastfeeding . If the mother chooses to breastfeed, it may be prudent to examine the infant for signs and symptoms of toxicity . In infants requiring treatment with antituberculosis agents, it is important to use therapeutic doses since drug concentrations in breast milk are not adequate as effective therapy for treatment or prevention . However, dosing at the lower end of the therapeutic range should be prescribed (i.e., 10 mg/kg/day of isoniazid) to decrease the risk of toxicity.

Clin Otolaryngol, 1999 Feb, 24(1), 55 - 7
Streptomycin perfusion of the labyrinth in the treatment of Menière's disease: a modified technique; Adair RA et al.; The ideal surgical procedure for Meniere's disease would combine the high rate of vertigo control and the good hearing preservation of vestibular nerve section with the low morbidity of labyrinthectomy . Shea's technique of streptomycin perfusion of the labyrinth has been modified by making an additional opening into the posterior semicircular canal in an effort to limit the amount of streptomycin going into the cochlea . Seventeen patients with definite Meniere's with poor hearing have had this procedure . Vertigo was controlled in 94% and the hearing preserved in 55% . Vestibular rehabilitation was not a problem . It is speculated that hearing preservation would be better if the procedure were not restricted to those with poor hearing . This method of destruction of the vestibular system carries the possibility of hearing preservation and maintains the possibility of cochlear implantation should this ever be required.

Int J Tuberc Lung Dis, 1999 Mar, 3(3), 219 - 23
The prevalence of Mycobacterium tuberculosis drug resistance in New Caledonia, 1995-1996; Duval P et al.; SETTING: Study of the susceptibility to anti-tuberculosis drugs of Mycobacterium tuberculosis strains isolated in New Caledonia, a French South Pacific Territory, where tuberculosis continues to be a public health problem . OBJECTIVE: To assess the stability of this susceptibility in order to justify both non-systematic susceptibility testing and the implementation of simplified chemotherapy regimens . METHODS: Over a period of nearly 2 years (1995-1996), every new case of tuberculosis confirmed by the laboratory was included in the study . A total of 105 strains were tested against five anti-tuberculosis drugs: isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin . RESULTS: No primary drug resistance was detected for the main drugs . One strain with acquired resistance to isoniazid and streptomycin was isolated from one of the 12 patients suffering a relapse of the disease . CONCLUSIONS: The results of this exhaustive study justify the non-systematic approach to susceptibility testing for new patients . However, for strains isolated from patients suffering from relapse or therapeutic failure, or who belong to a high risk population, drug susceptibility testing should be performed . This kind of management will aid in the detection of possible isoniazid and streptomycin resistance, thus avoiding the selection and possible emergence of strains resistant to rifampicin . The results of the study argue for the use of a fixed dose regimen using triple combination tablets of isoniazid, rifampicin and pyrazinamide (HRZ) for 2 months, followed by dual drug therapy (HR) for 4 months.

Laryngoscope, 1999 Mar, 109(3), 356 - 61
Streptomycin ototoxicity and hair cell regeneration in the adult pigeon utricle; Frank TC et al.; OBJECTIVE: The purpose of this study was to develop a technique to investigate the regeneration of utricular hair cells in the adult pigeon (Columba livia) following complete hair cell loss through administration of streptomycin . STUDY DESIGN: Experimental animal study . METHODS: Animals were divided into four groups . Group 1 received 10 to 15 days of systemic streptomycin injections . Animals in Groups 2 and 3 received a single direct placement of a 1-, 2-, 4-, or 8-mg streptomycin dose into the perilymphatic space . Animals in Groups 1 and 2 were analyzed within 1 week from injection to investigate hair cell destruction, whereas Group 3 was investigated at later dates to study hair cell recovery . Group 4 animals received a control injection of saline into the perilymphatic space . Damage and recovery were quantified by counting hair cells in isolated utricles using scanning electron microscopy . RESULTS: Although systemic injections failed to reliably achieve complete utricular hair cell destruction, a single direct placement of a 2-, 4-, or 8-mg streptomycin dose caused complete destruction within the first week . Incomplete hair cell loss was observed with the 1-mg dose . Over the long term, regeneration of the hair cells was seen with the 2-mg dose but not the 8-mg dose . Control injections of saline into the perilymphatic space caused no measurable hair cell loss . CONCLUSIONS: Direct placement of streptomycin into the perilymph is an effective, reliable method for complete destruction of utricular hair cells while preserving the regenerative potential of the neuroepithelium.

Ned Tijdschr Geneeskd, 1999 Jan 2, 143(1), 1 - 3
{50 years of clinical trials; a new direction in medicine}; Van Gijn J; In 1998 the medical community commemorated the completion of the first truly randomised trial, the Medical Research Council Streptomycin Study . This invention is at least as important as Harrison's clocks, which in the 18th century solved the problem of measuring longitude at sea . Naturally the idea of randomised controls had evolved from previous notions . Obtaining informed consent remains essentially a matter between patient and physician, but in the meantime four other interested parties have joined in: governing bodies, the pharmaceutical industry, medical journals, and the mass media . In order to keep all these forces in check, lawmakers should protect the weakest parties against the more powerful ones . There is a great deal to be done in the next 50 years.

Protein Sci, 1998 Aug, 7(8), 1829 - 35
A superfamily of metalloenzymes unifies phosphopentomutase and cofactor-independent phosphoglycerate mutase with alkaline phosphatases and sulfatases; Galperin MY et al.; Sequence analysis of the probable archaeal phosphoglycerate mutase resulted in the identification of a superfamily of metalloenzymes with similar metal-binding sites and predicted conserved structural fold . This superfamily unites alkaline phosphatase, N-acetylgalactosamine-4-sulfatase, and cerebroside sulfatase, enzymes with known three-dimensional structures, with phosphopentomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, phosphoglycerol transferase, phosphonate monoesterase, streptomycin-6-phosphate phosphatase, alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1, and several closely related sulfatases . In addition to the metal-binding motifs, all these enzymes contain a set of conserved amino acid residues that are likely to be required for the enzymatic activity . Mutational changes in the vicinity of these residues in several sulfatases cause mucopolysaccharidosis (Hunter, Maroteaux-Lamy, Morquio, and Sanfilippo syndromes) and metachromatic leucodystrophy.

J Infect Dis, 1999 Apr, 179(4), 1025 - 9
Application of molecular methods for detection and transmission analysis of mycobacterium tuberculosis drug resistance in patients attending a reference hospital in Italy; Cingolani A et al.; A molecular analysis of drug-resistant isolates of Mycobacterium tuberculosis was done in a population with a high prevalence of human immunodeficiency virus infection . Seventy-one consecutive isolates were tested for genotypic resistance to isoniazid, rifampicin, streptomycin, and ethambutol by polymerase chain reaction-single strand conformation polymorphism analysis and automated sequencing of target regions . Phenotypic and genotypic resistance to isoniazid, rifampicin, streptomycin, and ethambutol were detected in 23.4%, 11.2%, 7%, and 5.6% of isolates and in 87%, 88%, 40%, and 100% of resistant isolates, respectively . Specificity was 100% for all target regions . When rpoB, katG, and ahpC mutation analysis were combined, 86% of resistant isolates to any drug were identified . No mutations in inhA were found in isoniazid-resistant isolates . Molecular detection of drug resistance, particularly for isoniazid and rifampicin, may represent a sensitive and very specific technique . The strategy of selecting rpoB, katG, and ahpC to quickly identify most resistant isolates, with a relevant saving of resources, is warranted.

Nihon Kokyuki Gakkai Zasshi, 1998 Dec, 36(12), 1066 - 70
{Lung cancer accompanying sarcoidosis with diffuse myocardial involvement}; Itoh T et al.; We describe an interesting case of adenocarcinoma of the lung accompanying sarcoidosis with diffuse myocardial involvement . A 69-year-old man had a tumor shadow on chest X-ray films of the right upper lung field . Bronchofiberscopy was performed in Jan . 1997 . Because transbronchial biopsy specimens disclosed granuloma, the patient was treated with isoniazid, rifampicin, and streptomycin sulfate for tuberculosis, but did not show any improvement . In March 1997, the patient was examined by an ophthalmologist for blurred vision . He was given a diagnosis of uveitis and referred to us for evaluation because his serum ACE and lysozyme levels were elevated . Bronchofiberscopy was performed again, and a diagnosis of lung cancer accompanying sarcoidosis was made based on the findings of transbronchial biopsy and bronchoalveolar lavage . The disease progressed rapidly, and the patient died 47 days after admission . Autopsy disclosed sarcoid granulomas in cardiac muscle tissue and lung tissue . There have been very few reports on the co-existence of sarcoidosis and lung cancer, and the relationship between the two diseases is unclear.

J Chromatogr A, 1999 Jan 15, 830(2), 345 - 51
Determination of streptomycin residues in food by solid-phase extraction and liquid chromatography with post-column derivatization and fluorometric detection; Edder P et al.; A reliable and sensitive procedure is presented for the analysis of streptomycin (STP) in food of animal origin, like meat, milk and honey . The method is based on a separation by ion-pair liquid chromatography with beta-naphthoquinone-4-sulfonate (NQS) postderivatization and fluorescence detection . The clean-up of the extract is done by solid-phase extraction, firstly with a cation-exchange cartridge and secondly with an octadecyl cartridge . The selectivity is very good and not many interfering peaks are observed for various food matrices . The streptomycin recovery of the total procedure is superior to 80% . The procedure is quantitatively characterized and repeatability, linearity, detection and quantification limits are very satisfactory . A special focus is given to STP residues in honeys and a survey on 64 commercial honeys is presented . For honey analysis, the HPLC method is compared with an immunoassay test (ELISA), and the possibility of using this test for screening with and without solid-phase extraction clean-up is also discussed.

Clin Infect Dis, 1999 Jan, 28(1), 130 - 5
Issues in the treatment of active tuberculosis in human immunodeficiency virus-infected patients; Schluger NW; Most HIV-infected patients with tuberculosis can be treated satisfactorily with standard regimens with expectations of good results . Treatment of tuberculosis in these patients has been complicated by the introduction of HAART, which relies on drugs that interfere with the most potent class of antituberculous medications . Rifampin-free regimens or regimens that employ rifabutin may be acceptable strategies for patients who are receiving protease inhibitors, although these regimens have not been rigorously evaluated in patients with AIDS . At present, there is good reason to believe that a 6-month course of a rifabutin-containing regimen or a 9-12-month course of a regimen of streptomycin, isoniazid, and pyrazinamide should be adequate therapy for most patients with drug-susceptible disease . As the treatment of HIV infection with antiretroviral agents evolves, the treatment of tuberculosis in patients with AIDS is likely to evolve as well . This will require careful coordination of antituberculosis and antiretroviral therapies.

Biochim Biophys Acta, 1999 Jan 11, 1429(2), 293 - 8
Protein folding in Escherichia coli: role of 23S ribosomal RNA; Chattopadhyay S et al.; Post-translational control of Escherichia coli ribosome on newly synthesised polypeptide leading to its active conformation (protein folding) has been shown in the case of the enzyme beta-galactosidase . As expected, antibiotics chloramphenicol and lincomycin, which bind to 23S rRNA/50S subunit and kasugamycin and streptomycin which interact with the 30S subunit instantaneously inhibited protein synthesis when they were added to the growing cells . The increase in beta-galactosidase activity, though stopped immediately after the addition of chloramphenicol and lincomycin, went on considerably in the presence of streptomycin and kasugamycin even after the stoppage of protein synthesis.

Gac Med Mex, 1998 Nov-Dec, 134(6), 705 - 11
{Aminoglycosides, their ototoxic effect}; de la Rosa-Galvez A et al.; The aminoglycosides are broad-spectrum antibiotics especially effective against many strains of gramnegative bacteria . Since streptomycin was used for tuberculosis treatment, the toxic side effects of such antibiotics were identified . The kidney and the inner ear are affected . The nephrotoxicity is usually reversible, while the chronic ototoxicity is irreversible . Within the inner ear, it is the cochlear and vestibular sensory epithelium that is damaged . A toxic mechanism in which an interference with mitochondrial protein synthesis is central has been inferred . During the last fifty years, risk factors for aminoglycoside-induced-ototoxicity have been identified, including a genetically transmitted hypersensitivity to the ototoxic effect . Although several strategies to prevent the damage have been proposed, today it is not rare that patients suffer permanent loss of hearing and loss of balance due to aminoglycoside toxicity . This review gives a brief background of aminoglycoside ototoxicity, some strategies to prevent it, and the therapeutic use of the vestibulo-toxic effect.

Biochemistry, 1998 Dec 22, 37(51), 17664 - 72
Crystal structure of L-arginine:inosamine-phosphate amidinotransferase StrB1 from Streptomyces griseus: an enzyme involved in streptomycin biosynthesis; Fritsche E et al.; Inosamine-phosphate amidinotransferases catalyze two nonconsecutive transamidination reactions in the biosynthesis of the streptomycin family of antibiotics . L-Arginine:inosamine-phosphate amidinotransferase StrB1 from Streptomyces griseus (StrB1) was cloned as an N-terminal hexa-histidine fusion protein, purified by affinity chromatography, and crystallized, and its crystal structure was solved by Patterson search methods at 3.1 A resolution . The structure is composed of five betabeta alphabeta-modules which are arranged circularly into a pseudo-5-fold symmetric particle . The three-dimensional structure is closely related to the structure of human L-arginine:glycine amidinotransferase (AT), but five loops (the 40-, 170-, 220-, 250-, and 270-loop) are organized very differently . The major changes are found in loops around the active site which open the narrow active site channel of AT to form an open and solvent-exposed cavity . In particular, module II of StrB1 is AT-like but lacks a 10-residue alpha-helix in the 170-loop . The concomitant reorganization of neighboring surface loops that surround the active site, i.e., the 40-loop and the 270-loop, results in an arrangement of loops which allows an unrestricted access of substrates to the cavity . However, the residues which are involved in substrate binding and catalysis are conserved in AT and StrB1 and are at equivalent topological positions, suggesting a similar reaction mechanism among amidinotransferases . The binding site for L-arginine had been deduced from its complex with AT . Molecular modeling revealed a possible binding mode for the second substrate scyllo-inosamine 4-phosphate.

Curr Top Dev Biol, 1999, 43, 51 - 84
A comparison of hair bundle mechanoreceptors in sea anemones and vertebrate systems; Watson GM et al.; Hair bundle mechanoreceptors of the acousticolateralis system of vertebrates are similar to hair bundles found on tentacles of sea anemones, primitive marine invertebrates . In each case, hair bundles consist of actin-based stereocilia interconnected by extracellular linkages . Recently, considerable attention has been directed to one class of linkages called "tip links." Tip links interconnect the tip of one stereocilium to the adjacent, taller stereocilium . According to the currently favored hypothesis for signal transduction, tip links may be "gating springs" that gate cation channels opened during deflection of the hair bundle . To depolarize the membrane, deflections must be directed so as to induce strain on the tip links . Deflections in the opposite direction lead to hyperpolarization of the membrane . Hair cells adapt to prolonged deflection of hair bundles . Whereas in some vertebrates, adaptation is incomplete (i.e., the current fails to return to baseline), adaptation in anemones appears to be complete . Signal transduction is reversibly blocked by agents thought to interact with the transduction channel including streptomycin . In addition, signal transduction is abolished following exposure to agents thought to attack tip links including calcium-depleted buffers or elastase . Hair cells of lower vertebrates can be replaced by division and differentiation of supporting cells . In chickens, a repair system exists wherein tip links are replaced via a mechanism that does not involve protein synthesis . The repair mechanism of anemones involves synthesis of new proteins that may constitute replacement linkages and accessory proteins that attach the linkages to appropriate integral proteins.

Gene, 1999 Jan 8, 226(1), 103 - 9
Chromosomal organization and nucleotide sequence of the genes coding for the elongation factors G and Tu of the apple proliferation phytoplasma; Berg M et al.; Genes coding for elongation factors G (fus) and Tu (tuf) of the non-culturable apple proliferation (AP) phytoplasma were cloned and sequenced . Arrangement of these genes and identification of the ribosomal protein gene rps7 upstream of the fus gene suggest a transcriptional organization similar to that of the streptomycin operon of Escherichia coli and other bacteria . The fus and tuf genes from other tested phytoplasmas were found to be similarly linked as in the AP agent . Thus, it is likely that they show a similar chromosomal arrangement . This organization would be in contrast to that of the phylogenetically distinctly different culturable mollicutes of the genus Mycoplasma in which the tuf and fus genes are separately transcribed.

Microbiology, 1998 Dec, 144 ( Pt 12), 3309 - 16
A kirromycin-resistant EF-Tu species reverses streptomycin dependence of Escherichia coli strains mutated in ribosomal protein S12; Zuurmond AM et al.; Streptomycin dependence can be caused by mutations in ribosomal protein S12 . Mutations suppressing such streptomycin dependence have been found in ribosomal proteins S4 and S5, and in 16S rRNA . Here a new suppressor mutation localized in elongation factor Tu (EF-Tu) is described, consistent with recent models of ribosome-EF-Tu-tRNA interaction at the decoding centre . The EF-Tu mutation was obtained by genetic selection for streptomycin independence; it was identified as Ala375 --> Thr, previously described as EF-TuA(R) and known to confer a kirromycin-resistant, error-prone phenotype . Also, other streptomycin-dependent (SmD) S12 mutations could be complemented by this mutation . The streptomycin-independent (Sm1) strain grows more slowly than the wild-type (wt), suggesting that not all the defects of the S12 mutation can be complemented by EF-Tu{A375T} . Moreover, this strain is more susceptible than wt to reduction in the cellular EF-Tu concentration, and disruption of tufB led to considerable growth-rate impairment . Expression of EF-Tu from tufB, not only of wt EF-Tu and EF-Tu{A375T} but, remarkably, also of EF-Tu{G222D}, known as EF-TuB0 and defective in protein synthesis, equally contributed to cell growth . In vitro analysis revealed a decreased translational activity of wt EF-Tu with SmD ribosomes as compared to EF-Tu{A375T}, while EF-Tu{G222D} showed no activity at all, just as with wt ribosomes . Possible mechanisms are discussed for the improved growth rate observed in such Sm1 strains when they include wt EF-Tu or EF-Tu{G222D}.

Nippon Rinsho, 1998 Dec, 56(12), 3100 - 3
{Central nervous system tuberculosis: diagnosis and therapy}; Nozaki H et al.; Tuberculous meningitis is the most serious form of tuberculosis, but often the only manifestation of tuberculosis with non-specific initial signs and symptoms . Therefore, delayed diagnosis occasionally results into rapid progression of neurologic deficits and a poor prognosis . So, it is needless to mention that appropriate chemotherapy should be started as fast as possible under swift diagnosis . According to recent progression of molecular biological technique, PCR and other nucleic acid amplification methods are becoming to be quite useful for rapid detection of Mycobacterium tuberculosis in the cerebrospinal fluid . If diagnostic tests are not definitely positive but there is a strong clinical suspicion for tuberculous meningitis, it is advisable to start the antituberculous chemotherapy as soon as possible . The combination chemotherapy with isoniazid, rifampicin, pyrazinamide, and streptomycin (or ethambutol) is a standard treatment for tuberculous meningitis . The administration of corticosteroids with adequate antituberculous chemotherapy should be considered in severe cases for reduction in mortality and neurologic sequelae, especially when there is the indication of subarachnoid block or impending brain herniation.

Nippon Rinsho, 1998 Dec, 56(12), 3087 - 90
{Short-course chemotherapy of tuberculosis with pyrazinamide}; Asai S et al.; A 6-month regimen consisting of isoniazid (INH . 0.3-0.5 g).rifampicin (RFP . 0.3-0.45 g).pyrazinamide (PZA . 1.2-2.0 g) and streptomycin (SM . 0.75 g) or ethambutol (EB . 0.75-1.0 g) given for 2 month followed by isoniazid and rifampicin for 4 month is the preferred treatment for patients with fully susceptible organism, who adhere to treatment . Consideration should be given to treating all patients with directly observed treatment.

Nippon Rinsho, 1998 Dec, 56(12), 3023 - 9
{Mechanisms of drug-resistance in mycobacteria}; Ohno H et al.; According to the recent advances of molecular biological technics, some of the genetic mechanisms of drug-resistance of Mycobacteria has been uncovered . Generally, drug-resistance of Mycobacterium tuberculosis was caused by point mutations in chromosomal gene . In isoniazid (INH) resistant M . tuberculosis, mutations and genetic deletions in catalase-peroxidase gene (katG), inhA gene, or alkyl hydroperoxide reductase gene were reported . On the other hand, mutations and other genetic alterations in RNA polymerase beta subunit gene (rpoB) were the major mechanisms of resistance to rifampicin (RFP) with high frequencies of 90% or more . Moreover, these genetic alterations in rpoB gene were suspected as the resistant mechanism to other rifamycin antituberculosis drugs, such as rifabutin . In addition, it was reported that point mutations in 16S rRNA gene (rrs) and ribosomal protein S12 gene (rpsL) induced M . tuberculosis as streptomycin (SM) resistant phenotype . Furthermore, nicotinamidase (pncA) gene, DNA gyrase A subunit (gyrA) gene, and embB gene were reported as the responsible gene to pyrazinamide-, quinolone- and ethambutol-resistance, respectively . Although all mechanisms of drug-resistance were still unclear, these information are very useful and helpful for development of rapid diagnosis system of drug-resistant M . tuberculosis.

Acta Otolaryngol Suppl, 1998, 538, 36 - 9
Cycloheximide blocks the toxic effect of streptomycin in guinea pig vestibular hair cells; Nakagawa T et al.; Apoptosis has been suggested to be a predominant cell death process for streptomycin-induced degeneration of vestibular hair cells . However, the biochemical aspects of this have not been studied . The purpose of this study was to examine the biochemical aspects of apoptosis of vestibular hair cells caused by streptomycin . Cycloheximide is a widely used protein synthesis inhibitor in studies of apoptosis . We therefore investigated cycloheximide effects on degeneration of vestibular hair cells following streptomycin applications . Supplements of cycloheximide significantly prevented DNA fragmentation in hair cell nuclei and reduced the loss of hair cells . This suggests that cycloheximide possibly inhibits apoptosis of hair cells and attenuates streptomycin-induced degeneration of the vestibular epithelium.

Acta Otolaryngol Suppl, 1998, 538, 32 - 5
Time-dependent response of vestibular hair cells of guinea pigs following high-dose applications of streptomycin; Nakagawa T et al.; Apoptosis has been reported to occur in vestibular hair cells following aminoglycoside treatment and is suggested to play a predominant role in deletion of affected hair cells . However, the type of cell death occurring during an acute phase of vestibular damage following high-dose application of streptomycin has not yet been determined . Hence, in this study we examined the cell death mode of vestibular hair cells during the acute phase . The numbers of hair cell nuclei stained by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method and residual hair cells were quantitatively analysed . Hoechst nuclear staining was used for analysis of the nuclear morphology of affected hair cells . TUNEL staining of hair cell nuclei and lost hair cells began to appear 6 h after streptomycin treatment and increased with more exposure time . Apoptotic nuclear features could also be found from 6 h after streptomycin treatment . These findings support the thesis that apoptosis is a predominant cell death mode in degeneration of vestibular hair cells due to streptomycin ototoxicity.

J Neurophysiol, 1998 Dec, 80(6), 3297 - 311
Recovery of semicircular canal primary afferent activity in the pigeon after streptomycin ototoxicity; Li W et al.; Recovery of semicircular canal primary afferent activity in the pigeon after streptomycin ototoxicity . J . Neurophysiol . 80: 3297-3311, 1998 . The electrophysiological activity of horizontal semicircular canal primary afferents (HSCPA) was investigated in vivo in the barbiturate-anesthetized pigeon by means of extracellular single-fiber vestibular nerve action potential recordings . The spontaneous and driven discharges to pulse (step/trapezoid waveform, peak velocity = 120 degrees/s) and sum-of-sines (0.03, 0.09, 0.21, 0.39, 0.93, 1.83 Hz, peak velocity = 30 degrees/s for each frequency) rotations were measured both in normal control animals and a group of animals at 30, 40, 50, 60, 71, and 150 days postinjection sequence (PIS) of streptomycin sulfate . Prior to 30 days PIS, the activity in the nerve was not appropriately modulated during and after rotation . At 30 days PIS and thereafter, the responses resembled those observed in control animals but with systematic changes in parameters of fitted pulse responses and fitted Bode plots as days PIS increased . The return of parameters characterizing the neural dynamics of the semicircular canals were monotonic and could be best described by either linear or exponential functions . After 30 days PIS, the mechanical cupula-endolymph system, the function of which can be inferred from the cupula long time constant (tauL) following step velocity, did not change systematically (tauL = 6.92 +/- 3.96, 8.64 +/- 5.52, 8.35 +/- 4.21, 10.00 +/- 2.79, 9.05 +/- 3.67, 7.05 +/- 2.72; means +/- SD) . However, the mean gain (G) of the HSCPA response to pulse rotation nearly doubled between 30 and 150 days PIS (from 1.31 +/- 0 . 39 to 2.40 +/- 1.04) and returned linearly to control values (G = 2 . 39 +/- 0.77) over this time period {G = 1.33 + 0.009(PIS-30), R2 = 0 . 92, P < 0.05} . Meanwhile, neural adaptation as quantitated using a fractional operator, k, decayed exponentially (single exponential) to an asymptote . The time constant of this exponential was approximately 55 days {k = 0.034 + 0.33e-(PIS-30)/55.4, R2 = 0.99, P < 0.01} . Features of the spontaneous discharge previously shown to be correlated with k changed appropriately . That is, the coefficient of variation (CV) and frequency of firing (FF) decayed and grew asymptotically, respectively . These parameters also exhibited an exponential time course of return to control values from 30 to 150 days PIS {CV = 0.44 + 0.65e-(PIS-30)/21.5, R2 = 0.96, P < 0.01, and FF = 39.97 + 101.42(1 - e-(PIS-30)/32.6), R2 = 0.97, P < 0.01} . The trends of recovery for G, k, and tauL derived from analysis of the pulse response were confirmed by strong positive correlations with best fitted parameters obtained from analysis of the sum-of-sines frequency domain response of HSCPAs . There were statistically significant correlations (r = 0.90, P < 0.05 and r = 0.93, P < 0.05) between parameters (G, k) derived from pulse responses and those (G', k') from sum-of-sines responses, respectively . The cupula time constant based on sum-of-sines' data (tau'L) showed no statistically significant change between 30 and 150 days PIS (P > 0.05, analysis of variance) . Thus the results in present study indicate that both the spontaneous discharge and the driven response to rotation of pigeon HSCPAs recovered their normal physiological status between 30 and 150 days PIS after hair cell death due to aminoglycoside ototoxicity . The recovery was systematic for the parameters chosen to be tested with the exception of the cupula long time constant, tauL . The mechanisms (changes in ciliary dynamics, changes in hair cell ionic currents, changes in bouton terminals, etc.) underlying these changes await further morphophysiological studies.

J Bacteriol, 1998 Dec, 180(24), 6757 - 60
The aadA gene of plasmid R100 confers resistance to spectinomycin and streptomycin in Myxococcus xanthus; Magrini V et al.; Plasmids with the aadA gene from plasmid R100, which confers resistance to the aminoglycosides spectinomycin and streptomycin in Escherchia coli, can be introduced into wild-type Myxococcus xanthus, strain DK1622, by electroporation . Recombinant M . xanthus strains with integrated plasmids carrying the aadA gene acquire resistance to high levels of these antibiotics . Selection for aadA in M . xanthus can be carried out independently of, or simultaneously with, selection for resistance to kanamycin . The kinds and frequencies of recombination events observed between integrative plasmids with aadA and the M . xanthus chromosome are similar to those observed after the transformation of yeast . Cleavage of integrative plasmid DNA at a site adjacent to a region of homology between the plasmid and the M . xanthus genome favors the targeted disruption of M . xanthus genes by allele replacement.

Kekkaku, 1998 Oct, 73(10), 579 - 84
{Clinicopathological study of cases with Mycobacterium szulgai infection}; Iwanaga T et al.; Pulmonary mycobacteriosis is usually caused by Mycobacterium tuberculosis, Mycobacterium avium complex, or Mycobacterium kansasii . There are, however, other slow-growing mycobacteria which can cause pulmonary infection . Mycobacterium szulgai, first reported in 1972, is a scotochromogenic species which can affect human lungs, although human-to-human spread of infection is thought to be unlikely . We have recently treated three cases of middle-aged to elderly persons (45-87 year-old), two of them had underlying diseases (one with intrapulmonary and the other with extrapulmonary) . All patients had constitutional symptoms (cough, sputum, dyspnea), and chest roentgenograms demonstrated either cavitation with scattered nodules or peripheral infiltrates predominantly in upper lobes, resembling pulmonary tuberculosis . In two cases, M . szulgai was identified by using DNA-DNA hybridization method . The in vitro susceptibility of M . szulgai to antimycobacterial drugs was better than that of M . avium complex, and it was resistant only to paraaminosalicylate, cycloserine, and partially to isoniazid . Pulmonary disease of three patients were successfully treated with a combination of multiple antimycobacterial agents including rifampin, ethambutol, isoniazid, or streptomycin.

Am J Otol, 1998 Nov, 19(6), 754 - 7
Cochlear implantation in a patient with profound hearing loss with the A1555G mitochondrial mutation; Tono T et al.; OBJECTIVE: This study aimed to describe the performance of a cochlear implant in a patient with profound hearing loss with the A1555G mitochondrial mutation . SETTING: The study was conducted at two university hospitals . PATIENT: A 50-year-old Japanese man in whom bilateral profound hearing loss developed after administration of streptomycin at the age of 23 participated . The pedigree of the family showed exclusively maternal transmission of hearing impairment . INTERVENTION: Genetic study and auditory rehabilitation with a cochlear implant were performed . RESULTS: The A1555G point mutation was identified from the patient's mitochondrial DNA . Since activation of the implant, the patient has been using it successfully with a monosyllable recognition score of 78% using Japanese word lists for speech audiometry . CONCLUSIONS: The current case indicated that cochlear implantation may be a valuable choice of therapy for the patient with profound hearing loss with the A1555G mutation . The excellent auditory performance with a cochlear implant suggests that hearing loss associated with this mutation is primarily caused by insult to the cochlear tissue containing rich mitochondria (i.e., hair cells or stria vascularis or both), not to the cochlear nerve and its central connections.

Eur Rev Med Pharmacol Sci, 1998 Jan-Feb, 2(1), 21 - 4
Drug-resistance of Mycobacterium tuberculosis in time; Mazzei L et al.; Tuberculosis is heavily worldwide spreading in the last years . More and more signalations seem to indicate that the incidence of drug-resistant Mycobacteria is increasing in almost all industrialized countries . The authors have carried on a study on the percentage of drug-resistant strains of Mycobacterium Tuberculosis (MT) among isolates from patients affected by active pulmonary tuberculosis hospitalized through the years 1992-94 . Out of 59 isolates of MT, 20.3% were drug-resistant: 25% of them to 2 drugs and 16.6% to 3 or more drugs . Resistance to single drug was so distributed: Streptomycin 11.8%, Isoniazid 6.7%, Rifampycin 3.4%, Ethambutol 6.7%, Ansamycin 3.4%, Pyrazinamide 5.0%, Ethionamide 1.7% . These results were confronted with analogous data on MT drug-resistance collected in the same hospital division in the years 1978-82 and 1985-87 . The data analysis shows that actual incidence of drug resistant strains of MT is only slightly decreased but quite similar to that observed in 1978-82, except for Ethambutol, while there is a remarkable reduction vs . 1985-87; in that period, in fact, the highest incidence of drug resistance was recorded . The authors' conclusion is that only little differences were observed in the total amount of resistant strains of MT through 20 years; they also outline that resistance to Ansamycin, most recent out of all tested drugs, is quite similar to that observed for Rifampycin, that is chemically analogous.

J Infect, 1998 Jul, 37(1), 70 - 1
Management of brucella endocarditis of a prosthetic valve; Arslan H et al.; A case of chronic brucella endocarditis of a prosthetic valve is reported . The diagnosis of this infection was established by positive blood cultures and high brucella agglutination titre . The patient was successfully managed by combination of medical therapy (consisting of streptomycin, trimethoprim-sulphamethoxazole, rifampin and tetracycline) and surgery.

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 1997 May, 11(5), 195 - 7
{Effects of streptomycin on ionic currents in isolated outer hair cells of guinea pig cochlea}; Gu F et al.; The effects of streptomycin on ionic currents in outer hair cells isolated from the cochlea of guinea pig were investigated using a whole-cell recording patch-clamp technique . External application of streptomycin (1 mmol/L) caused a decrease of the potassium currents and calcium currents, respectively . The half-maximal inhibition concentration of streptomycin checking the voltage-dependent calcium currents was 56.08 mumol/L, and the ratio of maximal inhibition 21.71% . The present results demonstrate that streptomycin partially irreversibly blocks the voltage-dependent calcium currents in dissociated outer hair cells of guinea pig cochlea in a concentration-dependent manner . The effects of streptomycin of the potassium currents may be, at least in part, the result of the inhibition of Ca2+ influx . It suggests that the inhibition of Ga2+ influx may be one of the ototoxic mechanisms of streptomycin on outer hair cells.

J Bacteriol, 1998 Nov, 180(22), 5954 - 60
In vivo assay of protein-protein interactions in Hin-mediated DNA inversion; Lee SY et al.; In order to form the catalytic nucleoprotein complex called the invertasome in the Hin-mediated DNA inversion reaction, interactions of the DNA-binding proteins Hin and Fis are required . Assays for these protein-protein interactions have been exploited with protein cross-linkers in vitro . In this study, an in vivo assay system that probes protein-protein interactions was developed . The formation of a DNA loop generated by protein interactions resulted in transcriptional repression of an artificially designed operon, which in turn increased the chance of survival of Escherichia coli host cells in a streptomycin-containing medium . Using this system, we were able to assay the Hin-Hin interaction that results in the pairing of the two recombination sites and protein interactions that result in the formation of the invertasome . This assay system also led us to find that an individual Hin dimer bound on a recombination site can form a stable complex with Fis bound on the recombinational enhancer; this finding has never been observed in in vitro studies . Possible pathways toward the formation of the invertasome are discussed based on the assay results for a previously reported Hin mutant.

Indian J Med Res, 1998 Oct, 108, 120 - 7
Evaluation of the BACTEC radiometric method in the early diagnosis of tuberculosis; Venkataraman P et al.; A comparison of the BACTEC radiometric method with the conventional culture and drug susceptibility testing methods on isolates from clinical specimens in pulmonary and extrapulmonary tuberculosis, childhood TB and TB in HIV-infected individuals was undertaken . In the case of pulmonary TB, the rate of isolation of positive cultures was significantly faster with the BACTEC method, with 87 per cent of the positives being obtained by 7 days, and 96 per cent by 14 days . However, while there was no difference in the total number of positive cultures by the two methods in smear positive pulmonary tuberculosis, in smear negative pulmonary TB, the BACTEC method yielded more number of positive cultures . In extrapulmonary TB, HIV-TB and childhood TB, although the BACTEC method did not yield additional positives, the detection of positives was considerably faster than by the conventional methods, in which the degree of growth was also scanty . The agreement in drug susceptibility tests was 94 per cent for streptomycin and isoniazid, 99 per cent for rifampicin and 91 per cent for ethambutol . Further, most of the drug susceptibility test results became available within 8 days by the BACTEC method . By facilitating early diagnosis, the BACTEC method may prove to be cost effective in a population with a high prevalence of tuberculosis, particularly in the extrapulmonary and paucibacillary forms of the disease.

East Afr Med J, 1998 Jun, 75(6), 358 - 63
Contemporary treatment of tuberculosis in HIV prevalent countries in sub-Saharan Africa; Nuwaha F; The HIV pandemic has been worst felt in sub-Saharan Africa . Tuberculosis is an opportunistic disease in the course of HIV infection and in the region, where the prevalence of both M . tuberculosis and HIV are very high, tuberculosis has become a major complication of HIV infection . The annual risk of tuberculosis infection remains high (1.5 to 2.5%) which is more than fifty times compared to the rates in Western Europe and the prevalence of HIV infection in tuberculosis patients ranges between 18 to 67% . More than 35% of the cases in most countries of sub-Saharan Africa are attributed to HIV . The tuberculosis treatment programmes in sub-Saharan Africa are overwhelmed with increasing number of clinical TB . This trend requires re-examination of the treatment strategy used in the region . There is need to replace streptomycin and thiacetazone in treatment regimens; provide effective short-course chemotherapy for all patients irrespective of their HIV status; use more of ambulatory treatment and expand the use of supervised intermittent therapy.

J Mol Cell Cardiol, 1998 Oct, 30(10), 2103 - 10
Phospholipase C inhibitors attenuate arrhythmias induced by kappa-receptor stimulation in the isolated rat heart; Bian JS et al.; To determine whether the phospholipase C (PLC)/inositol 1,4,5 trisphosphate (IP3)/Ca2+ pathway mediates cardiac arrhythmias induced by kappa-opioid receptor stimulation, the effects of U50,488H, a selective kappa-opioid receptor agonist, on cardiac rhythm in a isolated perfused rat heart, intracellular calcium ({Ca2+}i) in a single ventricular myocyte and IP3 production in myocytes were studied in the presence and absence of PLC inhibitors . U50,488H, the effects of which had been shown to be abolished by a selective kappa-receptor antagonist, nor-binaltorphimine, induced arrhythmias dose-dependently and increased both {Ca2+}i and IP3-production in the heart . More importantly, the effects of U50,488H were blocked by PLC inhibitors, neomycin and streptomycin . To further confirm the selectivity of action of the PLC inhibitor, the effects of another PLC inhibitor U73122 and its inactive structural analog, U73343, on cardiac rhythm in the isolated perfused rat heart were compared . The former did, while the latter did not, block the arrhythmogenic effect of U50,488H . We also determined whether the effects of kappa-receptor stimulation involves a pertussis toxin (PTX)-sensitive G-protein . We found that pretreatment with PTX at 4 microg/l for 10 min, a treatment shown to affect PTX sensitive G-protein-mediated functions, attenuated significantly the U50,488H-induced arrhythmias . The present study provides evidence that kappa-receptor stimulation-induced cardiac arrhythmias involves, at least partly, the PLC/IP3/Ca2+ pathway as well as a PTX sensitive G-protein .

Bull Soc Pathol Exot, 1998, 91(3), 199 - 202
{Resistance of mycobacterial tuberculosis complex to the main antibacillary agent in Yaounde, Cameroon}; Bercion R et al.; To evaluate the current prevalence of initial and acquired resistance to the main antituberculosis drugs in Yaounde, isolates of M . tuberculosis complex obtained from sputum cultures of 602 adult patients with pulmonary tuberculosis (516 new cases and 86 old cases) consecutively admitted into the tuberculosis centre of Hopital JAMOT from July 1994 to December 1995 were studied . The susceptibility of isolates to the major antituberculosis drugs was tested by the indirect proportion method . The overall resistance rate (1 or more drugs) was 35.2%, with initial resistance 31.8% (164 of 516) and acquired resistance 55.8% (48 of 86) . Initial resistance to streptomycin was the most frequent (20.5%), followed by isoniazid 12.4%), thiacetazone (5.6%), rifampicine (0.8%) and ethambutol (0.4%) . Initial resistance was noted as 25% to 1 drug, 5.8% to 2 drugs, 0.8% to 3 drugs and 0.2% to 4 drugs . Acquired resistance to isoniazid was the most frequent (45.3%), followed by streptomycin (40.7%), rifampicine (30.2%), thiacetazone (10.5%) and ethambutol (9.3%) . Acquired resistance was found as 13.9% to one drug, 19.8% to 2 drugs, 12.8% to 3 drugs and 9.3% to 4 drugs . A combined resistance to rifampicine and isoniazid in the same patient was noted in 0.8% of the new cases and in 26.7% of the old cases . These high rates af antituberculosis drug resistance in Yaounde underline the urgent need to reestablish a tuberculosis control programme in Cameroon.

Rev Cubana Med Trop, 1996, 48(2), 92 - 7
{Report of drug resistance in strains of Mycobacterium tuberculosis isolated from patients in Iran}; Bahrmand AR et al.; 6,472 clinical samples of patients with tuberculosis suspicion between March, 1993 and March, 1994, were studied . Positive results were obtained in 443 patients; 238 females (53.7%) and 205 males (46.3%) . The predominant age group was that between 30 and 39 years (31.5%) . The cutaneous test of sensitivity to the purified protein derivate (PPD) was positive in 178 patients with a range of 10-14 mm . Abnormal radiological images were found in 222 patients (50.1%) . Higher resistance frequency was detected in Mycobacterium tuberculosis strains among cases suffering from pulmonary tuberculosis . 42 (9.5%) strains were resistant to isoniazid and 31 (7.0%) to streptomycin . Resistance to one drug was observed in 25 isolations (5.4%) . A few strains (1.3%) were resistant to 3 drugs, and 1 of them to 5 drugs . Clinical and epidemiological data suggest that resistance to drugs in tuberculosis is becoming an important problem in the region . The fast diagnosis of this infection and the use of antibiotics with a reduced spectrum may enable the control of this form of tuberculosis.

J Bacteriol, 1998 Oct, 180(20), 5484 - 8
Relationship between spontaneous aminoglycoside resistance in Escherichia coli and a decrease in oligopeptide binding protein; Kashiwagi K et al.; Changes in the amount of oligopeptide binding protein (OppA) in spontaneous kanamycin-resistant mutants of Escherichia coli were investigated . Among 20 colonies obtained from 10(8) cells cultured in the presence of 20 microgram of kanamycin/ml, 1 colony had no detectable OppA and 7 colonies were mutants with reduced amounts of OppA . Sensitivity of wild-type cells to kanamycin increased slightly by transformation of the oppA gene, but the sensitivity of the mutants increased greatly by the transformation . A mutant with no OppA was found to be a nonsense mutant of the oppA gene at amino acid position 166 . In a mutant having a reduced level of OppA, the reduction was due to the decrease in OppA synthesis at the translational level . These mutants were also resistant to other aminoglycoside antibiotics, including streptomycin, neomycin, and isepamicin . Isepamicin uptake activities decreased greatly in these two kinds of mutants . The results support the proposition that aminoglycoside antibiotics are transported into cells by the oligopeptide transport system, and that transport is an important factor for spontaneous resistance to aminoglycoside antibiotics.

Neurosci Lett, 1998 Aug 7, 252(1), 61 - 4
The role of N-methyl-D-aspartate receptor in the guinea pig inner ear after unilateral labyrinthectomy; Shimogori H et al.; To investigate the role of the N-methyl-D-aspartate (NMDA) receptor in the vestibular periphery, vestibular compensation in the guinea pig was studied following chemical unilateral labyrinthectomy by osmotic pump administration of streptomycin sulfate (SM) with or without D-2-amino-5-phosphonovalerate (D-APV), one of the NMDA receptor antagonists . All animals administrated SM (SM group) or SM and D-APV (SM + D-APV group) showed spontaneous nystagmus and head tilt . The maximum degree of yaw head tilt in the SM + D-APV group was statistically smaller than that in the SM group . Moreover the time constant for head tilt in the SM + D-APV group was statistically shorter than that in the SM group . These results indicate that the NMDA receptor in the vestibular periphery influences vestibular compensation after unilateral labyrinthectomy.

Int J Tuberc Lung Dis, 1998 Sep, 2(9), 743 - 50
Molecular epidemiology of tuberculosis in Cuba outside of Havana, July 1994-June 1995: utility of spoligotyping versus IS6110 restriction fragment length polymorphism; Diaz R et al.; SETTING: Molecular typing has become an important tool for examining the extent of active transmission of tuberculosis . OBJECTIVES: To examine transmission of tuberculosis in Cuba using IS6110 restriction fragment length polymorphism (RFLP) typing and to evaluate the utility of spoligotyping . DESIGN: One hundred and sixty Mycobacterium tuberculosis strains isolated over a one year period in Cuba were subjected to RFLP and spoligotyping . RESULTS: Forty-eight percent of the isolates were found in 19 clusters of strains with identical RFLP patterns . In general, cluster sizes were limited, except for two large institutional outbreaks . Age was strongly inversely correlated to clustering . Most streptomycin-resistant isolates were found in clusters . Fifteen spoligotype clusters comprised 78% of the isolates . Significantly different IS6110 RFLP types subdivided 11 spoligotype clusters, whereas none of the IS6110 clusters were subdivided by spoligotyping . CONCLUSIONS: Considering the short study period, 48% clustering is high, indicating that recent transmission plays an important role in Cuba . Although resistance is still a minor problem, transmission of streptomycin-resistant strains occurs . The high polymorphism observed with IS6110 RFLP indicates that this marker is useful for future molecular epidemiological studies in Cuba . Spoligotyping appeared less suitable for population-based studies.

Int J Tuberc Lung Dis, 1998 Sep, 2(9), 704 - 11
Intensive short course chemotherapy in the management of tuberculous meningitis; Donald PR et al.; SETTING: Short course chemotherapy for tuberculous meningitis (TBM) is advocated by several groups, but relatively few children have been so treated and followed up . METHODS: A prospective, observational study of isoniazid (INH), rifampicin (RMP) and ethionamide (ETH) in a dosage of 20 mg/kg, and pyrazinamide (PZA) 40 mg/kg, all given once daily in hospital for 6 months . Surviving children were followed up for a year after discharge . RESULTS: Ninety five children, 39 (41%) at stage III, 52 (55%) at stage II and 4 (4%) at stage I TBM were studied . Ten (26%) at stage III and 3 (6%) at stage II died before completion of therapy . Five surviving children (6%) moved on discharge and were untraceable; seven children (9%) were lost during follow up and three were inadvertently restarted on antituberculosis therapy . Two children with severe stage III disease died after discharge . One child experienced a probable disease recrudescence 1 month after discharge . Eighteen children (20%) developed a mildly elevated serum bilirubin concentration during the first month of treatment . In five of these children INH, RMP, ETH and PZA were stopped and streptomycin (SM) and ethambutol substituted . In all cases the original treatment was restarted without incident . One child developed overt jaundice after 5 months of treatment due to hepatitis A infection . CONCLUSIONS: Our experience suggests that young children with TBM can be safely treated for 6 months with high doses of antituberculosis agents without overt hepatotoxicity and with a low risk of relapse.

Kekkaku, 1998 Jul, 73(7), 459 - 70
{Chemotherapy for tuberculosis; yesterday, today, and tomorrow--basic and clinical studies}; Aoyagi T; The discovery of streptomycin in 1944 had given rise to great flowering of chemotherapy for tuberculosis . The times which triple treatment of SM.PAS.INH after the temporal time of SM.PAS had been standard regimens on initial treatment had continued for more than twenty years . The shortening of duration for chemotherapy had become possible by the introduction of RFP, and the duration had reduced to one fourth compared with that of the regimens till then by the addition of PZA for two months at the beginning of treatment on the initial treatment cases . In this paper, historical aspects of early and present-day chemotherapy of tuberculosis and the reports of main studies have been summarized, and pharmacokinetics of INH, action of antituberculous drugs in short-course chemotherapy, MDR-TB and biological response modifiers for treatment of tuberculosis, etc . has been reviewed . It is urgently awaited that more new drugs without cross resistance to previous drugs will be developed for the more shortening of the duration and the improvement of the treatment for MDR-TB.

J Clin Microbiol, 1998 Oct, 36(10), 2940 - 3
Evaluation of the ESP culture system II for testing susceptibilities of Mycobacterium tuberculosis isolates to four primary antituberculous drugs; Bergmann JS et al.; The reliability of the ESP Culture System II (herein referred to as ESP II) for testing susceptibilities of Mycobacterium tuberculosis isolates to isoniazid, rifampin, ethambutol, and streptomycin was evaluated by comparing results to those of the method of proportion (MOP), which was considered the reference method, for 20 clinical isolates and 30 challenge strains provided by the Centers for Disease Control and Prevention (CDC) . Clinical isolates also were tested with the BACTEC TB 460 system; these results agreed with those obtained by the MOP for all isolates and all drugs, except the high concentration of isoniazid, for which agreement was 95% . After resolution of discrepancies, levels of agreement between ESP II and MOP for the clinical isolates were 95 and 100%, respectively, for the low and high concentrations of isoniazid, 100% for rifampin and ethambutol, and 95% for streptomycin . For the 30 challenge isolates, ESP II results for both concentrations of isoniazid agreed with the expected results in all cases, whereas agreement was 93% for both rifampin and streptomycin and 90% for ethambutol . All discrepancies with the CDC isolates were due to failure of ESP II to correctly classify resistant strains . By testing isolates yielding discrepant ethambutol and streptomycin results with a lower concentration of both drugs in the ESP II system, agreement increased to 93% for ethambutol and 100% for streptomycin . For the clinical isolates, the times to an ESP II result of susceptible (means +/- standard errors of the means) were 8.47 +/- 0.12 days (range, 7 to 10 days) and 8.73 +/- 0.29 days (range, 5 to 11 days) when the inoculum was prepared from a McFarland equivalent and from a seed bottle, respectively . The time to an ESP II result of resistant varied by drug and method of inoculum preparation, ranging from 5.50 +/- 0.22 days for ethambutol with the inoculum prepared from a McFarland standard to 8 . 0 days for ethambutol with the inoculum prepared from a seed bottle . These data suggest that the ESP II system is a rapid and reliable method for testing susceptibilities of M . tuberculosis isolates to isoniazid and rifampin . Performance, however, may be suboptimal for ethambutol and streptomycin . Testing additional ethambutol-resistant and streptomycin-resistant strains with two concentrations of both drugs is necessary.

Acta Otolaryngol, 1998 Jul, 118(4), 530 - 3
Dose-dependent response of vestibular hair cells of guinea pigs following streptomycin ototoxiation; Nakagawa T et al.; Although the involvement of apoptosis has been suggested in the loss of vestibular hair cells due to aminoglycosides, dose-dependent effects of aminoglycosides have not been determined . We therefore examined dose-dependent effects of streptomycin on the degeneration of hair cells of guinea pig ampullar cristae using TUNEL stain and Hoechst nuclear stain . Streptomycin induced apoptosis of hair cells in a dose-dependent manner . Even following high-dose applications, most of the affected cells showed apoptotic features . Apoptosis may therefore play a predominant role in the deletion of vestibular hair cells affected by aminoglycosides.

Neurochem Int, 1998 Jul, 33(1), 55 - 9
The production of free oxygen radicals and nitric oxide in the rat cochlea; Lopez-Gonzalez MA et al.; Rat cochleas were analysed for free oxygen radicals (FOR) and nitric oxide (NO) production by the chemiluminescent oxidation of luminol . 4Beta-phorbol-12beta-myristate-13alpha-acetate (PMA), a well-known agonist of protein kinase C, induced the release of FOR after a time lag close to 30 s and reverted to basal values in approximately 10 min . Sphingosine inhibited by nearly 50% the response to PMA, whereas staurosporine caused an inhibition of 100% . The incubation of rat cochleas with 0.5 mM arginine potentiated the chemiluminescent reaction induced by PMA causing an additional oxidation of luminol that was inhibited by the NO synthase inhibitor N-methyl-arginine (NMA) . Our results show for the first time the presence in the cochlea of cell populations producing FOR and NO and the real time production following cell activation . This procedure may help to explain the mechanisms involved in ototoxicity, as in the case of streptomycin and gentamicin that enhanced PMA-dependent production of FOR and NO.

Eur J Biochem, 1998 Jul 1, 255(1), 271 - 8
Purification and characterization of two enone reductases from Saccharomyces cerevisiae; Wanner P et al.; Two enone reductases catalyzing irreversibly the enantioselective reduction of alpha,beta-unsaturated carbonyls have been purified 165-fold and 257-fold, respectively, from the cytosolic fraction of Saccharomyces cerevisiae by means of streptomycin sulfate treatment, Sephadex G-25 filtration, DEAE-Sepharose CL-6B chromatography, blue Sepharose CL-6B chromatography and Superdex 200 preparation-grade filtration . One enzyme (E I) was NADPH-dependent, showed a molecular mass of 75 kDa and decomposed under denaturing electrophoretic conditions into two subunits of 34 kDa and 37 kDa . The other enzyme (E II) was NADH linked and the molecular mass estimated by means of Superdex 200 preparation-grade filtration, was 130 kDa . The enzyme decomposed into subunits of 56 kDa and 64 kDa on SDS/PAGE . Both enzymes were most active at pH 4.8 and accepted 1-octen-3-one, 1-hexen-3-one, 3-alken-2-ones, 4-alken-3-ones, 2-cyclohexen-1-ones, 2-alkenals, 2,4-alkadienals, 2-phenyl-2-alkenals, and 2-alkyl-2-alkenals as substrates . Both enzymes showed their highest activities with 1-hexen-3-one and 1-octen-3-one, respectively . The Km values for 1-octen-3-one were estimated as 0.54 mM (E I) and 0.20 mM (E II), respectively . Both enzymes catalyzed the enantioselective reduction of cis- and trans-2-phenyl-2-butenal into (R)-2-phenylbutanal.

Boll Chim Farm, 1998 May, 137(5), 157 - 64
Vitamin D administration to tuberculous children and its value; Morcos MM et al.; Our study was done to assess the value of administration of vitamin D to tuberculous children . The study included twenty four newly diagnosed tuberculous children; eleven males and thirteen females . Their age ranged from one and half to thirteen years . Thirteen patients were extra thoracic type of T.B., while only seven were intrathoracic and the rest were mixed . They were randomly divided into two Groups according to the treatment administered: Group A patients were given Rifampicin, Isoniazid and Streptomycin . Group B received in addition vitamin D . After eight weeks therapy, the patients of each group were evaluated regarding clinical, laboratory, and radiological improvement . Vitamin D level is raised after treatment in both Groups A and B, but this rise is not significant . It also showed insignificant difference between the two groups . Vitamin D level showed very high significant decrease in tuberculous children than matched healthy controls (non tuberculous children) . Calcium was significantly elevated after treatment in Group A whereas no significant change was detected in Group B . Phosphorous was highly significantly elevated after treatment in Group A, whereas in Group B it is just significantly elevated . Alkaline phosphatase level in both groups A and B were slightly decreased after treatment . However, this decrease was not significant . Clinical improvement was more evident in Group B patients (those taking vitamin D) as compared to Group A patients . The same was noted with X-ray and Sonographic findings . We concluded that vitamin D therapy may be of great value in addition to antituberculous drugs in the treatment of tuberculous children, and its use is highly recommended.

Clin Pediatr (Phila), 1998 Jul, 37(7), 433 - 6
Effectiveness of short-course, intermittent chemotherapy for tuberculosis in young infants aged less than 6 months; Kiper N et al.; In order to determine the efficacy of short-course intermittent chemotherapy for tuberculosis in young infants less than 6 months of age, 15 newly diagnosed infants were treated with isoniazid (10-15 mg/kg) and rifampin (10-15 mg/kg), with/without streptomycin (30 mg/kg), daily for 15 days followed by similar doses of isoniazid and rifampin twice a week for another 8.5 months . The follow-up period ranged from 1 to 10 years . No patient demonstrated relapse following the termination of the treatment . These results suggest that short-course, intermittent treatment may be safe and effective for treating tuberculosis in young infants.

Am J Otol, 1998 Jul, 19(4), 478 - 82; discussion 483
Summating potential and action potential ratio in Meniere's disease before and after treatment; Orchik DJ et al.; OBJECTIVE: This study aimed to compare the summating potential and action potential ratio (SP:AP) in patients with Meniere's disease before and after various surgical and medical treatments as an indication of change in endolymphatic hydrops to study the progression of Meniere's disease . STUDY DESIGN: The study design was a retrospective case review . SETTING: The study was conducted at an otology-neurotology referral center . PATIENTS: Eighty-eight ears of 84 patients with Meniere's disease received medical treatment in 18 ears and surgical treatments including endolymphatic shunt in 12 ears, streptomycin perfusion of the lateral semicircular canal in 9 ears, streptomycin perfusion of the middle ear in 33 ears, and dexamethasone perfusion of the middle ear in 16 ears . INTERVENTION: Transtympanic electrocochleography (ECoG) was performed in all patients before treatment and 1-57 months after treatment (mean, 13.5 months) with a 2-year interval in 28 patients . MAIN OUTCOME MEASURE: An enlarged SP:AP ratio (> or = 0.40) was used as the diagnostic criterion for endolymphatic hydrops . RESULTS: Overall, an enlarged SP:AP ratio was found in 75% of ears before treatment and 78% after treatment . The SP:AP ratio, when enlarged, remained enlarged in 91% of ears . A nonenlarged SP:AP ratio before treatment became enlarged after treatment in 41% of ears . In American Academy of Otolaryngology-Head and Neck Surgery stage 1 Meniere's disease (pure-tone threshold average < or = 25 dB), an enlarged SP:AP was found in 58% of ears before treatment and 79% after . Twenty-five (89%) of 28 patients followed for 2 years were free of vestibular symptoms after treatment, and in 22 patients (79%), the SP:AP remained enlarged . The distribution of an enlarged SP:AP ratio was associated with the duration of disease (chi-square = 33.5552, p < 0.01) . CONCLUSIONS: The development of endolymphatic hydrops, as indicated by an enlarged SP:AP, is part of the progression of Meniere's disease . The longer the duration of the disease, the more likely the SP:AP ratio will be enlarged . These findings indicate that endolymphatic hydrops as detected by ECoG was not reversed in this study by the treatments used . Despite the absence of definitive spells of vertigo in most patients, endolymphatic hydrops as evidenced by an enlarged SP:AP ratio persisted.

Int J Tuberc Lung Dis, 1998 Jul, 2(7), 558 - 62
Diagnostic features and therapeutic outcome of erosive and ulcerous endobronchial tuberculosis; Rikimaru T et al.; SETTING AND OBJECTIVE: Erosive and ulcerous endobronchial tuberculosis (EBTB) is distinct from pulmonary tuberculosis in some aspects . We evaluated the clinical features of 56 patients (26 males and 30 females) with EBTB to characterize the clinical features of the disease . RESULTS: The chief complaint in 70% of patients was intractable cough, particularly in those with tracheal tuberculosis . The predominant radiological features were patchy bi-apical infiltrates of variable intensity without cavitation; for six patients, however, plain radiographs revealed no abnormalities . The ulcerous lesions could be classified into three stages: active, healing and scarring . Furthermore, we divided scarring stage into two subtypes, polypoid and non-polypoid . Most of the patients were treated with isoniazid, rifampin, and streptomycin (SM) or ethambutol . Approximately one-third of the patients, not randomly selected, were treated with aerosolized SM and corticosteroids in addition to conventional oral therapy . CONCLUSION: EBTB involves typical clinical and radiographic features . In this uncontrolled series, it was our impression that the period of time to healing of ulcerous lesions seemed to be shorter in those treated with aerosol therapy including streptomycin and corticosteroids.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 1996, 31(5), 280 - 2
{Experimental study of streptomycin on 45Ca intake of otolithic membranes}; Wang E et al.; 45CaCO3 was injected into guinea pigs, and the radioactivity in otolithic membranes of utriculi and sacculi, auditory ossicles and femora was determined by liquid scintillation spectrometry, to study the dynamic effect of streptomycin on calcium content of otolithic membranes, as a means to explore the mechanism of streptomycin ototoxicity . The results showed that otoconium was a dynamic structure which took up 45Ca in a time course generally comparable to that of bone . Saccular otolithic membranes showed greater intake than utricular membranes . The calcium ion concentration of saccular endolymph was greater than that of the utriculus and the two maculas were not identical . Streptomycin may influence 45Ca uptake in the two macular otolithic membranes, causes calcium metabolic disorder and a fall of otolithic calcium content . It is possible that the fluid environments of the endolymph have changed, therefore dysfunction of otolithic organ may occur . This hypothesis may be one of the explanation of the mechanism of streptomycin ototoxicity.

Rev Laryngol Otol Rhinol (Bord), 1997, 118(3), 181 - 2
{Laryngeal tuberculosis: a diagnosis not to be forgotten}; Aouadi A et al.; Tuberculosis of the larynx has become a rarity since the discovery of streptomycin in 1944 . In this article a personal case history is described, together with a review of the literature and an analysis of the main clinical features of tuberculosis of the larynx . The pseudo-tumoural form of tuberculosis is often indicative of the presence of pulmonary tuberculosis, but may also occur in isolation . Histology is often the only definitive diagnostic test.

Biotechnology (N Y), 1995 May, 13(5), 507 - 10
Protease-dependent streptomycin sensitivity in E . coli--a system for protease inhibitor selection; Balint RF et al.; We have developed a bacterial cell system in which the activity of an expressed heterologous protease confers a dominant streptomycin-sensitive (strs) phenotype on the cell . This phenotype owes its high selectivity to the fact that streptomycin (strep) resistance, which is conferred on E . coli by mutants of ribosomal protein S12, is highly recessive to strep sensitivity . Thus, when strep-resistant (strr) strains of E . coli are transformed to co-express the wild-type allele of S12 in addition to the mutant allele, their sensitivity to strep increases by a factor of 100-1000 . Similarly, we found that when the same strr strains were transformed to co-express a heterologous protease and an inactive fusion of S12 with a substrate of the protease, the strep sensitivity of the cells increased approximately 100-fold . This effect was strictly dependent on correct cleavage of the S12 precursor, required only modest levels of expression of protease and substrate, and could be competitively inhibited by co-expression of an alternative substrate gene . This system thus appears to be well-suited to the identification of protease inhibitors, either by selection from libraries of endogenously expressed random peptide-encoding genes, or by screening synthetic or natural products libraries . Protease-dependent dominant phenotypes may be more sensitive and appropriate than the more commonly used recessive phenotypes for proteases which are activating enzymes.

J Physiol, 1998 May 1, 508 ( Pt 3), 793 - 800
Streptomycin inhibition of myogenic tone, K+-induced force and block of L-type calcium current in rat cerebral arteries; Miller AL et al.; 1 . Streptomycin has been demonstrated to inhibit mechanosensitive conductances in a wide variety of cell types, including muscle . The action of streptomycin on rat cerebral arteries that exhibit pressure-induced myogenic response was investigated . 2 . Pressure-induced tone, measured using isobaric myography, in isolated pressurized cerebral arteries was reversibly and concentration-dependently inhibited by streptomycin with an IC50 of 2.6 mM . 3 . Isometric K+-induced force, measured using isometric myography, is supported by voltage-gated Ca2+ entry . Streptomycin reversibly and concentration-dependently inhibited isometric force with an IC50 of 1.71 mM . 4 . Voltage-gated macroscopic inward Ca2+ channel currents were recorded from freshly isolated rat basilar myocytes . These were reversibly and concentration-dependently inhibited by streptomycin with an IC50 of 1.79 and 0.47 mM when 10 and 1.8 mM CaCl2, respectively, was used as the charge carrier . 5 . These data suggest that streptomycin inhibits myogenic tone and K+-induced isometric force largely by blockade of L-type, dihydropyridine-sensitive Ca2+ channels . In conclusion, streptomycin is not useful in the investigation of stretch-activated channels which may underlie the myogenic response of rat small cerebral arteries.

Int J Tuberc Lung Dis, 1998 Jun, 2(6), 499 - 505
Antituberculosis drug resistance surveillance in Kenya, 1995; Githui WA et al.; SETTING: Twenty-two of the 42 administrative districts in Kenya . OBJECTIVE: To determine the prevalence of drug resistance in newly diagnosed patients with pulmonary tuberculosis, to determine possible risk factors associated with resistance, and to establish standard routine surveillance of drug resistance . DESIGN: Cross-sectional study . METHODS: Sputum samples from newly diagnosed patients with smear-positive pulmonary tuberculosis were analysed using standard procedures . RESULTS: Of 638 patients, 85% were culture positive for Mycobacterium tuberculosis . Of 491 patients tested for susceptibility to isoniazid, streptomycin, rifampicin and ethambutol, 90.8% had fully sensitive strains and 9.2% had a strain resistant to one or more drugs . Of 445 patients with no history of previous chemotherapy, 6.3% had a resistant strain . Of 46 patients with a history of previous chemotherapy, 37% had a resistant strain . No resistance to either rifampicin or ethambutol was detected . There was a strong association between previous chemotherapy and resistance . Resistance was not associated with age or sex . High concordance between Kenya's results and those of the Mycobacterium Reference Unit in the UK on both drug-sensitive and drug-resistant strains indicates that clinically significant and comparable data can be obtained from laboratories employing unsophisticated and inexpensive standard procedures . CONCLUSION: Rates of initial drug resistance are still low in Kenya . The increase in acquired resistance to isoniazid requires monitoring.

Clin Infect Dis, 1998 Apr, 26(4), 898 - 902
Clinical features of infections due to Escherichia coli producing heat-stable toxin during an outbreak in Wisconsin: a rarely suspected cause of diarrhea in the United States; Roels TH et al.; In September 1994, a foodborne outbreak of enterotoxigenic Escherichia coli (ETEC) infection occurred in attendees of a banquet in Milwaukee . E . coli was isolated from stool specimens from 13 patients that were comprehensively tested; isolates from five patients were positive for E . coli producing heat-stable toxin, were biochemically identified and serotyped as E . coli O153:H45, and were all resistant to tetracycline, ampicillin, sulfisoxazole, and streptomycin . Diarrhea (100%) and abdominal cramps (83%) were the most prevalent symptoms in 205 cases; vomiting (13%) and fever (19%) were less common . The median duration of diarrhea and abdominal cramps was 6 days and 5 days, respectively . In the United States, health care providers rarely consider ETEC as a possible cause of diarrhea in their patients, and few laboratories offer testing to identify ETEC . Hence, outbreaks of ETEC infection may be underdiagnosed and underreported . As in this outbreak, the relatively high prevalence of diarrhea and cramps lasting > or = 4 days and the low prevalence of vomiting and fever can help distinguish ETEC infection from Norwalk-like virus infection and gastroenteritis due to other causes with incubation times of > or = 15 hours and can provide direction for confirmatory laboratory testing.

J Bone Joint Surg Br, 1998 May, 80(3), 456 - 62
A 15-year assessment of controlled trials of the management of tuberculosis of the spine in Korea and Hong Kong . Thirteenth Report of the Medical Research Council Working Party on Tuberculosis of the Spine.
{A case of isoniazid-induced pneumonitis}
Endo T, Saito T, Nakayama M, Ohse H, Watanabe S, Tamai S, Hasegawa S.

Department of Internal Medicine, National Sanatorium Seiranso Hospital, Ibaraki, JapanA 55-year-old man was given a diagnosis of pulmonary tuberculosis . He was treated with isoniazid (INH), rifampicin (RFP), ethmbutol (EB) and pyrazinamide (PZA) . After three weeks of treatment, he developed fever, dyspnea and dry cough . A chest X-ray taken at that time showed new reticulo-nodular shadows bilaterally and right pleural effusion . Ga scintigram showed strong uptake in both lungs . Transbronchial lung biopsy revealed alveolitis, suggesting drug-induced pneumonitis . Drug lymphocyte stimulation tests for INH, RFP, EB and PZA were negative . Because his symptoms were severe, all drugs were discontinued and daily predonisolone (30 mg) therapy was started . The symptoms and bilateral reticulo-nodular shadows soon resolved . The antituberculosis drugs were changed to streptomycin and levofloxacin, but these were ineffective . Therefore, EB, RFP and PZA, which only rarely induce pneumonitis, were carefully restarted in that order . Pneumonitis did not recur and the pulmonary tuberculosis improved . This clinical course suggests INH-induced pneumonitis.

Zhonghua Jie He He Hu Xi Za Zhi, 1996 Dec, 19(6), 342 - 5
{Detection of M . tuberculosis streptomycin-resistant gene}; Wu X et al.; OBJECTIVE: To observe the mutations of rpsL gene in M . tuberculosis streptomycin-resistant isolates, and to develop a new method for detecting drug resistance . METHOD: Detecting the rpsL genes with PCR-SSCP and analyzing their codons 43 by PCR-RFLP . RESULTS: Strain H37Rv was used as a control . In 22 M . tuberculosis clinical isolates, the rpsL PCR fragments from 5 drug-susceptible isolates had no differences in the SSCP profiles with strain H37Rv, and were restricted by Mbo II . 11 of the 13 streptomycin-resistant isolates showed apparent differences in the SSCP profiles and were not digested with Mbo II . 1 of the 4 other drug-resistant isolates also had apparent SSCP differences and was not digested by Mbo II . CONCLUSIONS: The results suggested that the rpsL gene mutation was frequently observed in M . tuberculosis streptomycin-resistant isolates, and usually situated at codon 43, PCR-SSCP and PCR-RFLP might become a simple, rapid and reliable diagnostic test for drug resistance.

Microbios, 1997, 92(371), 109 - 22
Exogenous isolation of Hgr plasmids from coastal Mediterranean waters and their effect on growth and survival of Escherichia coli in sea water; Lopez-Amoros R et al.; Four self-conjugative plasmids conferring mercury resistance were exogenously isolated from coastal Mediterranean sea water . All the plasmids isolated (93.2, 73.1, 65.2 and 221 kb) showed narrow-spectrum mercury resistance, and no UV resistance; three of them conferred cadmium resistance (Cdr 1.5 mM) and two of them encoded streptomycin resistance (50 micrograms/ml) . Their influence on the survival of the recipient strain Escherichia coli JGL1 in different seawater media was studied and compared with that of two plasmids previously isolated by the same procedure from an epilithic community of the Bristol Channel, Great Britain . A significant negative influence was observed for the largest (221 kb) of the plasmids isolated and one of the epilithic plasmids (239 kb) . The effect of the plasmids on E.coli JGL1 was dependent on the seawater media.

Biol Pharm Bull, 1998 Apr, 21(4), 326 - 9
Isolation and characterization of two plasmids that mediate macrolide resistance in Escherichia coli: transferability and molecular properties; Katayama J et al.; Escherichia coli BM2506 is highly resistant to macrolide antibiotics; it produces macrolide 2'-phosphotransferase II {MPH(2')II} which inactivates such drugs . We investigated the localization and the transfer of the macrolide-resistance determinant that encoded the mphB gene for MPH(2')II in strain BM2506 . Although we detected no clear band of plasmid DNA after agarose gel electrophoresis, transformation analysis using satellite DNA that corresponded to plasmid DNA after CsCl-ethidium bromide gradient centrifugation and restriction analysis of plasmid DNA in transformants showed that strain BM2506 harbored two plasmids, pTZ3721 (84 kb) and pTZ3723 (24 kb), that specified resistance to macrolides, ampicillin, streptomycin, tetracycline and sulfonamide and to macrolides and ampicillin, respectively . Southern hybridization showed that the mphB gene hybridized to both plasmids . Furthermore, pTZ3721 was transferred by conjugation to another strain of E . coli and pTZ3723 was mobilized with a self-transferable plasmid RP1 to other strains of E . coli . Therefore, it appears that the mphB gene is located on two plasmids in BM2506 and can be transferred to other strains of E . coli by conjugation or mobilization.

Kansenshogaku Zasshi, 1998 Mar, 72(3), 238 - 44
{Mycobacterial lung infection in 8 patients with AIDS: clinical and radiological features}; Kawana A et al.; The prevalence of mycobacterial infection in AIDS patients has increased in Japan . This report describes details of the clinical and radiological features of eight AIDS patients with mycobacterial disease (6 with M . tuberculosis infection and 2 with M . kansasii infection) in our hospital during the period from October 1995 through February 1997 . Six of the 8 were men, and two were women . The mean age was 36.5 years . Six were Japanese, one was from Myanmar, and one was Malaysian . The median CD4 positive T lymphocyte counts (CD4 count) at the time of diagnosis of the M . tuberculosis was 75.5 (range 14-569/microliter, and the M . kansasii was 21.5 (range 19-24)/microliter . Clinical findings and symptoms of all patients were non-specific, but almost all patients had a cough and fever . In the radiographic findings, the patients of the M . tuberculosis group presented multiple hilar and mediastinal lymphadenopathy, miliary shadow, and obstructive pneumonia . Both M . kansasii patients showed a multiple infiltration shadow . There were no drug resistant strains in M . tuberculosis except on isolate with moderate resistant . to Streptomycin . These observations suggest that AIDS-associated mycobacterial disease shows atypical clinical and radiological features in some cases, especially in advanced stages of AIDS . Therefore, we need to recognize the characteristics of the clinical and radiological features of the patients with mycobacterial diseases and AIDS.

New Microbiol, 1998 Apr, 21(2), 105 - 11
Characterization of the phenotype conferred by two different rpsL alleles coding for streptomycin dependence; Lagatolla C et al.; Two streptomycin-dependent strains of E . coli B showing different phenotypes were isolated . They carried different rpsL alleles which conferred two levels of dependence on the drug, and showed a different expression when present in heterozygous conditions with other rpsL alleles, coding for sensitivity or resistance on the drug.

Int J Tuberc Lung Dis, 1998 Jan, 2(1), 52 - 5
Should we take a history of prior treatment, and check sputum status at 2-3 months when treating patients for tuberculosis?
Wilkinson D, Bechan S, Connolly C, Standing E, Short GM.
SETTING: Pinetown, South Africa (1975-1983) . OBJECTIVE: To determine the value of previous treatment history and sputum smear examination at 2-3 months in predicting treatment failure and relapse in tuberculosis patients treated with four drugs given twice weekly for six months under direct observation . DESIGN: Four cohort studies among 562 ambulant adults with culture positive pulmonary tuberculosis, designed to test the effectiveness of isoniazid 600-900 mg, rifampicin 600 mg, pyrazinamide 2-3 g, and streptomycin 1-2 g, given twice weekly . The same drug regimen was given to all patients irrespective of previous treatment history . Therapy was not changed if smears remained positive at 2-3 months . RESULTS: Positive predictive values of a history of previous treatment for a positive smear at 2-3 months (18.3%), treatment failure (5.2%), and relapse (9.4%) were poor . Although patients with positive smears at 2-3 months were more likely to fail therapy than patients with negative smears (relative risk=4.5, 95% Confidence Interval {CI}: 1.6-12.8), positive predictive value for treatment failure was only 12.5% . Although relapse was more frequent in patients with positive smears than those with negative smears (9.7% vs 6.2%; P=0.4), most patients who relapsed had been smear negative at 2-3 months (18/21) . CONCLUSION: A four-drug rifampicin-containing regimen can safely be given twice weekly under direct observation to both new and retreatment cases, and the 2-3 month smear examination can safely be omitted.

Int J Tuberc Lung Dis, 1998 Feb, 2(2), 130 - 3
Drug resistant tuberculosis in Estonia; Kruuner A et al.; SETTING: The incidence of drug resistant tuberculosis in Estonia has increased rapidly during the last five to six years . OBJECTIVE: To investigate the drug resistance patterns of Mycobacterium tuberculosis isolated from tuberculosis patients in Estonia . RESULTS: In 1994, 623 cases of tuberculosis were diagnosed in Estonia, 518 new cases with no previous history of tuberculosis, and 105 with a history of previous treatment for tuberculosis . All pulmonary M . tuberculosis isolates from 1994 were analysed for drug susceptibility . Of the 302 new cases (58.3%) that were culture verified, 28% had isolates resistant to one or more of the four drugs tested (isoniazid, rifampicin, streptomycin, ethambutol), and 9% had multi-drug resistant (resistant to at least isoniazid and rifampicin) strains . CONCLUSION: The incidence of drug resistance in M . tuberculosis is high in Estonia.

Int J Tuberc Lung Dis, 1998 Jan, 2(1), 10 - 5
How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis; Mitchison DA; OBJECTIVE: To explore mechanisms by which drug resistance might arise as a result of poor compliance during short course chemotherapy . DESIGN: Four theoretical mechanisms are first described . RESULTS: Examples of the way the mechanisms probably operate are taken from: 1) a study of once-weekly chemotherapy with streptomycin and isoniazid, and 2) the pattern of drug susceptibility in cultures from patients who relapsed after the end of treatment . CONCLUSION: Good compliance is vitally important . The value of a fourth drug in the initial phase of chemotherapy in preventing resistance is questioned . An explanation for mono-resistance to rifampicin in patients with the acquired immune deficiency syndrome (AIDS) is suggested.

Int J Tuberc Lung Dis, 1998 Apr, 2(4), 342 - 3
Tuberculosis due to drug-resistant Mycobacterium bovis in pregnancy; Signorini L et al.; We describe the management practices adopted in a case of pulmonary and extra-pulmonary tuberculosis caused by an isoniazid/pyrazinamide resistant strain of Mycobacterium bovis in a 26-week pregnant woman . She was initially treated with rifampin, isoniazid and ethambutol, pre-term delivery was induced and streptomycin was then added to the regimen . Screening of the new-born revealed no signs of either disease or infection . Isoniazid prophylaxis was not administered and the new-born was vaccinated and isolated from the mother for two months; however she continued to be fed with her mother's milk for the whole period.

Int J Tuberc Lung Dis, 1998 Apr, 2(4), 303 - 11
Drug-resistant tuberculosis in human immunodeficiency virus infected persons in Italy . The Italian Drug-Resistant Tuberculosis Study Group; Angarano G et al.; OBJECTIVE: To describe the prevalence and epidemiological-clinical characteristics of tuberculosis (TB) resistance to first-line drugs in Italian human immunodeficiency virus (HIV)-infected subjects . DESIGN: Prospective, observational multicenter (25 Centers of Infectious Diseases) study . Mycobacterium tuberculosis strains from 167 HIV co-infected subjects with TB (149 new cases, 18 relapses) were tested at a central laboratory for susceptibility to rifampin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E) and streptomycin (S) and for DNA fingerprint type . Drug susceptibility results were related to patients' epidemiological, clinical and laboratory features . RESULTS: Drug resistance patterns among new TB cases were as follows: R = 1%, Z = 6%, S = 8%, H + S = 3%, S + Z = 4% . TB resistant to at least R + H (MDR-TB) was detected in 36% of new cases due to an MDR-TB outbreak which was the largest thus far in Europe, involving 7/25 participating institutions, and was demonstrated by conventional and molecular epidemiology evidence . With multivariate analysis, MDR-TB was associated with hospital exposure to MDR-TB (OR = 39.3, P < 0.001) and previous use of anti-TB drugs (OR = 9.8, P = 0.008) . CONCLUSION: As drug-resistant tuberculosis in Italy is thus far relatively scarce, detection of a large MDR-TB epidemic among HIV-infected subjects was alarming . Aggressive control measures are urgently needed to prevent the spread of MDR-TB throughout the country and among the general population.

Int J Tuberc Lung Dis, 1998 Apr, 2(4), 288 - 95
Nationwide surveillance of drug-resistant tuberculosis in The Netherlands: rates, risk factors and treatment outcome; Lambregts-van Weezenbeek CS et al.; SETTING: The Netherlands, 1993 and 1994 . OBJECTIVE: To determine 1) rates of drug resistance in relation to nationality and country of birth, 2) risk factors for drug resistance, 3) treatment outcome of drug-resistant cases, and 4) rates of primary and acquired drug resistance . DESIGN: Retrospective study of all cases notified with bacillary tuberculosis in The Netherlands in 1993 and 1994 . RESULTS: Drug resistance to one or more drugs was reported in 268 (14.6%) of all 1836 cases, of whom 203 (76%) were foreign born . In Dutch patients rates of isoniazid (H) (2.9%) and streptomycin resistance (3.6%) were lower than in foreign patients (8.6% and 10.6% respectively, P < 0.001) . Multidrug (H and rifampicin {R}) resistance was reported in 0.5% of Dutch-born and 1.4% of foreign cases (P = 0.055) . Rates of acquired resistance to H (11.4%) and HR (5.7%) were higher than rates of primary resistance to these drugs (5.2% and 0.7% respectively, P < 0.05), but the number of retreatment cases was low (6.8% of all cases) . Drug resistance was associated with immigration but not with drug use, homelessness or human immunodeficiency virus (HIV) co-infection . One fifth (20%) of drug-resistant cases was diagnosed by active case finding . Treatment outcome in sensitive and resistant cases was compared . CONCLUSION: These findings suggest that drug resistance is imported, but it is unclear to what extent drug resistance among foreigners has been transmitted or created in The Netherlands . Drug resistance data should be monitored in Dutch and foreign patients separately.

Probl Tuberk, 1998, (1), 28 - 30
{Complications of polychemotherapy for renal tuberculosis}; Kul'chavenia EV et al.; The paper analyzes the incidence of adverse reactions caused by tuberculostatics used in the treatment of renal tuberculosis by follow-ups of 117 patients . Current polychemotherapy for renal tuberculosis has been found to be complicated by drug intolerance in 40.1% of cases . Intermittent intravenous injection of tuberculostatics causes side effects in 36.8% of patients while conventional treatment does in 59.1% . Pyrazinamide, streptomycin, and ethambutol are most toxic to patients with renal tuberculosis . There is a higher likelihood of drug intolerance in females with bilateral nephrotuberculosis complicated by chronic renal failure.

Nephron, 1998, 78(3), 319 - 22
Crescentic glomerulonephritis due to rifampin treatment in a patient with pulmonary atypical mycobacteriosis; Ogata H et al.; A 64-year-old male was treated continuously with rifampin, isoniazid and streptomycin for pulmonary atypical mycobacteriosis, Mycobacterium kansasii . Five weeks after beginning the treatment, the patient suddenly developed acute renal failure . A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis with moderate interstitial changes . Serum antirifampin antibody was detected, and the cessation of rifampin treatment was followed by a rapid spontaneous recovery of the patient's renal function . This is, to our knowledge, the first case of rapidly progressive crescentic glomerulonephritis associated with rifampin treatment where circulating antirifampin antibody is demonstrated and the renal function spontaneously improved after discontinuing rifampin treatment.

ORL J Otorhinolaryngol Relat Spec, 1998 Jan-Feb, 60(1), 1 - 3
Expression of fibroblast growth factor receptor in adult mouse utricle damaged by streptomycin sulfate; Yamashita H et al.; The expression of fibroblast growth factor (FGF) receptor was investigated in adult mouse utricles damaged by streptomycin sulfate using confocal laser scanning microscopy (CLSM) . The nerve endings in the mouse utricles could be detected by the immunoreactivity of neurofilament by CLSM . In the utricles of control adult mice, little expression of FGF receptor could be detected by a method of double staining for FGF receptor and neurofilament immunoreactivities . However, the expression of FGF immunoreactivity increased in the nerve endings of the damaged utricles . This result suggests that FGF is probably related to the synaptic plasticity in the adult mouse utricles.

Mol Gen Genet, 1998 Feb, 257(3), 299 - 307
Transcript analysis of the tobacco plastid operon rps2/atpI/H/F/A reveals the existence of a non-consensus type II (NCII) promoter upstream of the atpI coding sequence; Miyagi T et al.; The plastid ATP synthase complex is composed of nine subunits, of which six are encoded in the plastome . The plastid-encoded genes are arranged in two transcriptional units: atpB/E and atpI/H/F/A . We have recently reported that besides containing four -10 and -35 consensus-type (CT) promoters, the atpB/E operon also contains a non-consensus type (NCII) promoter that alone is responsible for its expression in non-photosynthetic plastids . As the functionality of ATP synthase requires expression of all nine subunits, NCII promoter-driven transcription of the atpI/H/F/A operon is to be expected in non-photosynthetic plastids . Therefore, a detailed transcriptional analysis of this operon was carried out using RNA samples from tobacco leaf, cultured cells (BY-2) and seedlings grown on streptomycin and spectinomycin; which contain chloroplasts, translationally active non-photosynthetic plastids and translationally inactive plastids, respectively . We identified a total of three transcription initiation sites (TIS) and four transcript processing sites in the non-coding regions of this operon . Our results also demonstrate that rps2 is co-transcribed with the atpI/H/F/A genes . One of the TIS (-208 atpI) is characterized by an NCII type promoter, while other two primary transcripts (-131 atpI and -384 atpH) initiate from CT promoters . In non-photosynthetic plastids the atpI/H/F/A-specific transcript pool seems to be solely contributed by initiation at the -208 atpI (NCII type) promoter, because transcripts from CT promoters do not accumulate in these plastid types.

Gene, 1998 Jan 30, 207(2), 167 - 70
Construction of a yeast expression system with positive selection for gene insertion in the absence of a specific phenotype; Hashimoto Y et al.; A positive-selection system of cloned inserts in Escherichia coli has been devised using a streptomycin-resistant (Smr) gene and streptomycin-dependent (Smd) E . coli . A vector, pHA394, based on the yeast expression vector pAM82 has the Smr gene, which inactivates streptomycin (Sm) and invalidates the streptomycin dependence, resulting in a very low transformation efficiency . Replacement of the Smr gene by the recombinant vector allows high-frequency transformation . This system was applied to the lysozyme gene . After the yeast secretion signal was fused to the lysozyme gene using an intermediate vector, pHA474, the Smr gene of pHA394 was replaced by the fusion gene, followed by transformation of Smd E . coli . Analysis of the transformants showed that the plasmid gene contained 100% of the lysozyme gene.

Trans R Soc Trop Med Hyg, 1997 Nov-Dec, 91(6), 707 - 8
HIV testing and tuberculosis treatment outcome in a rural district in Malawi; Banerjee A et al.; PIP: Unusually high mortality rates have been recorded among HIV-infected tuberculosis patients in urban Africa 6 and 12 months after initiation of tuberculosis treatment--a trend that impedes efforts to achieve the 85% cure rate target set by the World Health Organization . This study investigated tuberculosis treatment outcomes in relation to HIV serostatus in a rural district of Malawi (Ntcheu) . All 205 smear-positive pulmonary tuberculosis patients newly diagnosed in the district in 1995 received 2 months of daily supervised streptomycin, rifampicin, isoniazid, and pyrazinamide in the hospital followed by 6 months of isoniazid and thiacetazone at home . HIV testing, offered to all tuberculosis patients, was accepted by 110 (54%), 73 (66%) of whom were HIV-positive . By the end of treatment, 126 patients (61%) had been cured and 56 (27%) had died . Significantly fewer HIV-positive patients or patients who declined HIV testing were cured (59% and 55%, respectively) than those who agreed to testing and were HIV-negative (84%) . The mortality rate was 29% among patients who tested HIV-positive, 8% among those with a negative test result, and 34% among patients who declined HIV testing . Acceptance of HIV testing improved over the course of the study period in response to changes in counseling techniques, especially clarification that blood taken for HIV testing would not be used for transfusions . Overall, these findings suggest that, in areas where HIV infection is prevalent, an 85% tuberculosis cure rate may be unrealistic .

Acta Physiol Pharmacol Ther Latinoam, 1997, 47(4), 197 - 202
Risk factors for hepatotoxicity induced by antituberculosis drugs; Devoto FM et al.; To evaluate the risk factors involved in antituberculosis treatment-induced hepatotoxicity . In a retrospective study we analyzed the rate of drug-induced hepatotoxicity in a sample of 456 patients . Patients received a combination of drugs including isoniazid, rifampin, pirazinamide and streptomycin or ethambutol . The association among hepatotoxicity and several risk factors (age, sex, alcoholism and HIV infection) was studied by univariate methods, stratified analysis and the multiple logistic regression model . Signs of liver injury were found in 9.86% of the treated patients . In the logistic model, the adjusted odds ratios (OR) and significance were found as follows: a) for alcoholism, OR = 17.31 (95% CI: 6.35-47.16), p < 0.001; b) for HIV infection, OR = 3.23 (95% CI: 1.47-7.11), p = 0.003 and c) for female sex, OR = 2.44 (95% CI: 1.22-4.86), p = 0.011 . Age was not significantly associated with hepatotoxicity . Alcoholism, HIV infection and female sex were associated with an increased risk of hepatotoxicity in this study.

Acta Otolaryngol, 1998 Jan, 118(1), 74 - 9
The process of otoconia formation in guinea pig utricular supporting cells; Harada Y et al.; In order to clarify the mechanism of otoconia formation, the pathway of calcium transport in the utricular supporting cells was investigated . Potassium pyroantimonate (PA) precipitation, which indicates the localization of calcium ions, was seen not only in otoconia but also in supporting cell cytoplasm . In the latter, deposits of PA were detected in the secretory granules and endoplasmic reticulum (ER) . These deposits were not present in cells pretreated with ethylene glycol-O,O,-bis (2-aminoethyl)-N,N,N',N'-tetra-acetic acid (EGTA) . Exposure of the supporting cells to streptomycin sulfate (SM) increased the number of lysosomes . These lysosomes contained many small deposits of PA . The remaining granules and ER in cytoplasm also contained small deposits of PA . The findings suggest that otoconia are formed by the vestibular supporting cells in which calcium ions might be transported via ER-secretory granule-lysosome-cytoplasmic protrusion.

Am J Trop Med Hyg, 1998 Feb, 58(2), 190 - 1
Early clinical response to different therapeutic regimens for human brucellosis; Malik GM; Seventy-three cases of acute brucellosis were studied in relation to fever duration and hospital stay following different drug combinations, including gentamicin plus cotrimoxazole, rifampicin plus doxycycline, rifampicin plus cotrimoxazole, rifampicin plus tetracycline, streptomycin plus doxycycline, doxycycline plus cotrimoxazole, tetracycline plus cotrimoxazole, and tetracycline plus streptomycin . No statistical significant difference was found between these combinations regarding early clinical response in human brucellosis.

Circ Res, 1998 Mar 9, 82(4), 430 - 7
Role of ion channels and exchangers in mechanical stretch-induced cardiomyocyte hypertrophy; Yamazaki T et al.; We have previously reported that stretching of cardiomyocytes activates the phosphorylation cascade of protein kinases, including Raf-1 kinase and mitogen-activated protein (MAP) kinases, followed by an increase in protein synthesis partly through enhanced secretion of angiotensin II and endothelin-1 . Membrane proteins, such as ion channels and exchangers, have been postulated to first receive extracellular stimuli and evoke intracellular signals . The present study was performed to determine whether mechanosensitive ion channels and exchangers are involved in stretch-induced hypertrophic responses . Neonatal rat cardiomyocytes cultured on expandable silicone dishes were stretched after pretreatment with a specific inhibitor of stretch-sensitive cation channels (gadolinium and streptomycin), of ATP-sensitive K+ channels (glibenclamide), of hyperpolarization-activated inward channels (CsCl), or of the Na+-H+ exchanger (HOE 694) . Pretreatment with gadolinium, streptomycin, glibenclamide, and CsCl did not show any inhibitory effects on MAP kinase activation by mechanical stretch . HOE 694, however, markedly attenuated stretch-induced activation of Raf-1 kinase and MAP kinases by approximately 50% and 60%, respectively, and attenuated stretch-induced increase in phenylalanine incorporation into proteins . In contrast, HOE 694 did not inhibit angiotensin II-and endothelin-1-induced Raf-1 kinase and MAP kinase activation . These results suggest that among many mechanosensitive ion channels and exchangers, the Na+-H+ exchanger plays a critical role in mechanical stress-induced cardiomyocyte hypertrophy.

Ann Acad Med Singapore, 1997 Sep, 26(5), 647 - 50
Molecular techniques in the diagnosis of drug-resistant tuberculosis; Alcaide F et al.; In the last few years, there has been considerable progress in our understanding of the mechanisms of action and resistance to anti-tuberculosis agents . To date, there is information about 11 genes involved in resistance to all major anti-tuberculous drugs in Mycobacterium tuberculosis . Mutations in katG, inhA and ahpC genes are found in up to 90% of isoniazid-resistant strains, rifampin resistance is associated (> 96%) with rpoB mutations, pyrazinamide resistance with pncA mutations (72% to 97%), ethambutol resistance with mutations in embB (47% to 65%), streptomycin resistance with rrs or rpsL mutations (70%), and fluoroquinolone resistance with gyrA substitutions (75% to 94%) . Additional genes and mechanisms may play a role, particularly in association with lower levels of resistance . Based on this growing set of information, genotypic analysis of resistance is becoming a real possibility, and novel tests are being developed . Issues such as effectiveness, cost-efficiency, and appropriate setting for the implementation of these techniques are not yet established.

Rinsho Shinkeigaku, 1997 Oct, 37(10), 895 - 9
{A case of multiple intracranial tuberculoma diagnosed by open brain biopsy}; Sakuma R et al.; To provide histological diagnoses of brain diseases, CT-guided stereotactic brain biopsy (CT-SBB) has been widely used because of its less invasive technique compared with open brain biopsy (OBB) . However, CT-SBB is not always diagnostic . We report a case of multiple intracranial tuberculoma whose diagnosis was not made by CT-SBB but by OBB . The patient is a 46-year-old man with insulin-dependent diabetes mellitus who had been receiving immunosuppressive agents (azathioprine, cyclosporin, and prednisolone) after renal transplantation for diabetic renal failure for 9 years . He gradually developed febrile, headache and unsteady gait . Brain MRI demonstrated multiple intracranial lesions involving left fronto-temporal and right parietal lobes, left cerebellar hemisphere, and the fourth ventricle . Although the MRI findings were consistent with those of previously reported cases of intracranial tuberculoma, other conditions, such as malignant lymphoma and toxoplasmosis, were not ruled out . Therefore, CT-SBB targeting the left temporal lobe lesion was done for definitive diagnosis, but it revealed only mild perivascular infiltration of mononuclear cells and hemorrhage . He was transferred to our clinic for further evaluation . On examination, mild truncal and limb ataxia on the left were noted in addition to the neurological findings corresponding to diabetic retinopathy and neuropathy . Despite vigorous laboratory examinations, including repeated bacterial cultures and PCR of cerebrospinal fluid, no evidence of tuberculous infection was obtained . A tentative diagnosis of multiple intracranial tuberculoma was made, and anti-tuberculous drugs (isoniazid 400 mg, ethambutol 750 mg, and pyrazinamide 1.5 g) were administered . Since his symptoms deteriorated because of ventricular dilatation resulting from the enlarged lesion in the fourth ventricle after a temporary clinical improvement, VP-shunting and OBB from the left temporal lobe lesion were done . The excised lesion was firmly encapsulated and the histological examination revealed typical pathology of tuberculoma . Ziehl-Neelsen staining and PCR for Mycobacterium tuberculosis of the biopsied specimen were also positive . Further administration of increased doses of anti-tuberculous drugs (isoniazid 600 mg, ethambutol 500 mg, pyrazinamide 2.0 g and intramuscular injection of streptomycin 0.3 g twice a week) eventually ameliorated the symptoms and shrank the lesions . In case of intracranial tuberculoma, the needle of CT-SBB may not penetrate the firm capsule of tuberculoma and only the surrounding brain tissue may be obtained as in the present case . Therefore, it is recommended to consider OBB from the beginning for definitive diagnosis of intracranial tuberculoma . Paradoxical worsening of the clinical and laboratory findings of tuberculosis in spite of appropriate anti-tuberculous therapy as seen in the present case has been described in both pulmonary and extra-pulmonary tuberculosis . The phenomenon, called transient worsening, could happen and we have to keep it in mind during the treatment of intracerebral tuberculoma.

Otolaryngol Clin North Am, 1997 Dec, 30(6), 1051 - 9
The role of dexamethasone or streptomycin perfusion in the treatment of Meniere's disease; Shea JJ Jr; There is ample clinical and animal evidence that, in most patients, Meniere's disease is an immune-mediated disorder in a small, misplaced, malfunctioning endolymphatic sac that causes endolymphatic hydrops, the essential pathology of this disease . If this is so, then the potent anti-inflammatory steroids are the ideal first treatment for Meniere's disease and other immune-mediated diseases of the inner ear, and streptomycin perfusion is the ideal second treatment for those who do not respond to dexamethasone perfusion . The diagnosis, selection of patients, and details of operation with the results are presented . Results have been good with relief of dizzy spells and preservation of hearing in most patients after dexamethasone perfusion and relief of dizzy spells in those patients not responding to the dexamethasone perfusion by streptomycin perfusion.

Otolaryngol Clin North Am, 1997 Dec, 30(6), 1097 - 100
Bilateral Meniere's disease . Treatment with intramuscular titration streptomycin sulfate; Graham MD; Most patients with bilateral Meniere's disease treated with streptomycin sulfate titration therapy and followed over the long term have either improvement or relief of their disabling vertigo . Although persistent post-treatment disequilibrium occurs not infrequently, it is mild in the most patients . Stabilization or improvement of hearing occurs in most patients, and the authors have not encountered hearing loss to date as a result of streptomycin sulfate titration therapy . There seems to be considerable separation between the vestibulotoxic and cochleotoxic doses of streptomycin sulfate intramuscularly when administered in humans.

Int J Tuberc Lung Dis, 1997 Dec, 1(6), 502 - 8
Tuberculosis control in remote districts of Nepal comparing patient-responsible short-course chemotherapy with long-course treatment; Jochem K et al.; SETTING: A tuberculosis programme in hill and mountain districts of Nepal supported by an international non-governmental organisation (NGO) . OBJECTIVE: To evaluate under programme conditions the effectiveness of unsupervised monthly-monitored treatment using an oral short-course regimen . DESIGN: In this prospective cohort study, outcomes for new cases of smear-positive tuberculosis starting treatment over a two-year period in four districts in which a 6-month rifampicin-containing regimen was introduced as first-line treatment (subjects) were compared to outcomes for similarly defined cases in four districts where a 12-month regimen with daily streptomycin injections in the intensive phase continued to be used (controls) . RESULTS: Of 359 subjects started on the 6-month regimen, 85.2% completed an initial course of treatment compared to 62.8% of 304 controls started on the 12-month regimen (P < 0.001); 78.8% of subjects and 51.0% of controls were confirmed smear-negative at the end of treatment (P < 0.001) . The case-fatality rate during treatment was 5.0% among subjects and 11.2% among controls (P = 0.003) . Among those whose status was known at two years, 76.9% of subjects were smear-negative without retreatment, compared to 60.9% of controls (P < 0.001) . CONCLUSION: In an NGO-supported tuberculosis control programme in remote districts of Nepal, patient-responsible short-course therapy supported by rapid tracing of defaulters achieved acceptable outcomes . Where access and health care infrastructure are poor, district-level tuberculosis teams responsible for treatment planning, drug delivery and programme monitoring can be an appropriate service model.

Otolaryngol Head Neck Surg, 1998 Feb, 118(2), 261 - 6
Titration streptomycin therapy in Meniere's disease: long-term results; Balyan FR et al.; As soon as the use of streptomycin was started for the treatment of tuberculosis, its ototoxic effect was discovered . Initial reports demonstrated that streptomycin was successful in reducing vestibular responses while preserving cochlear activity . Streptomycin sulfate has been used for almost half a century for the treatment of vertigo in patients with Meniere's disease . At the Gruppo Otologico, Piacenza, Italy, between 1987 and 1995 we treated 16 patients with either bilateral Meniere's disease or with Meniere's disease in their only hearing ear, adopting the titration streptomycin therapy protocol of Graham et al . Three patients with follow-up periods of less than 2 years were not included in this study . The ages of the patients ranged from 36 to 64 years with a mean of 49.2 years . The patients were observed for 2 to 8.8 years . The dose of administered streptomycin varied from 14 to 49 gm . Episodic vertigo was totally relieved in all of the patients after initial treatment, whereas hearing remained the same or was improved when compared with the pretreatment levels . Five of the patients experienced recurring vertigo during a period of 4 to 24 months after initial treatment . Oscillopsia persisted in two patients and ataxia in darkness persisted in another two patients . Hearing was unchanged in 14 ears, improved in 2 ears, and worsened in 4 ears at the last follow-up evaluation . The overall outcome indicated that intramuscular titration streptomycin therapy seems to be one of the most important therapeutic options in the treatment of disabling vertigo in patients with either bilateral Meniere's disease or Meniere's disease in an only hearing ear.

Genetics, 1998 Jan, 148(1), 457 - 69
Epigenetic instability and trans-silencing interactions associated with an SPT::Ac T-DNA locus in tobacco; English JJ et al.; Progeny of tobacco line 2853.6, which carries a streptomycin phosphotransferase (SPT) gene interrupted by the maize element Activator (Ac), were selected for streptomycin resistance (Spr) because of germinal Ac excision . Some events gave rise to Spr alleles that were unstable and exhibited a mottled phenotype on streptomycin-containing medium due to somatic loss of SPT function . This instability was most pronounced in one particular line, Spr12F . Other Spr alleles rarely exhibited silencing of SPT . Streptomycin-sensitive, homozygous Spr12F plants were recovered, and crosses were performed with other, more stable Spr lines . A high proportion of the resulting heterozygous progeny were silenced for SPT expression . The silenced state was heritable even after the Spr12F allele segregated away . No correlation could be made between silencing and methylation of the SPTgene . Structural analysis of allele Spr12F showed that the SPT gene from which Ac had excised was flanked by direct repeats of Ac . A search was carried out among 110 additional Spr alleles for new independent unstable alleles, and four were identified . All of these alleles also carried an SPT gene flanked by direct repeats of Ac . Thus, there is a strong correlation between this structure and instability of SPT expression.

AIDS, 1998 Jan 22, 12(2), 191 - 5
A survey of drug-resistant Mycobacterium tuberculosis and its relationship to HIV infection; Spellman CW et al.; OBJECTIVE: To compare the prevalence of drug-resistant tuberculosis disease among patients with and without HIV infection . DESIGN: An historical prospective evaluation of patients with culture-proven tuberculosis reported between January 1988 and December 1995 . SETTING: A major metropolitan county public health department . PATIENTS: A total of 802 consecutive culture-positive tuberculosis patients were eligible for inclusion in the study . HIV serologic testing and drug susceptibilities were completed on 741 (92%) eligible patients . Of these patients, 646 tested HIV-negative and 95 (12.8%) tested HIV-positive . Patients not tested for HIV (n = 59) and without drug susceptibilities (n = 2) were excluded from the analyses . Outpatient management was based on a policy of universal directly observed therapy . MAIN OUTCOME MEASURES: Patient HIV status, initial drug resistance and acquired drug resistance . Isolates were characterized for resistance to isoniazid, rifampin, rifabutin, ethambutol, streptomycin, capreomycin, kanamycin and ethionamide . Determination of initial resistance was based on the first available susceptibility study and acquired resistance on subsequent susceptibility studies . RESULTS: Initial drug resistance was found in 55 (8.5%) HIV-negative patients and four (4.2%) HIV-positive patients . Acquired drug resistance occurred in five (0.8%) HIV-negative patients and one (1.1%) HIV-positive patient . These differences were not statistically significant . CONCLUSIONS: HIV infection is not a risk factor for drug-resistant tuberculosis . Increased drug resistance in HIV infected tuberculosis patients reflects a failure of tuberculosis control in the underlying population.

Int J Tuberc Lung Dis, 1997 Aug, 1(4), 309 - 13
Survey of primary drug resistance of Mycobacterium tuberculosis in Casablanca, Morocco; el Baghdadi J et al.; SETTING: In 1990, a 6-month short-course regimen (2 SHRZ/4 RH) was introduced for the treatment of tuberculosis in Morocco . OBJECTIVE: To assess the efficacy of the national tuberculosis control programme, a prospective study of primary drug resistance was conducted from April 1992 to July 1994 in Casablanca . DESIGN: A total of 402 strains isolated from 402 patients living in Casablanca with no previous history of tuberculosis was included in the study . RESULTS: The overall rate of primary drug resistance to at least one drug was 23.9%; it was 19.7% to streptomycin, 11.4% to isoniazid, and 8.2% to both streptomycin and isoniazid . The rates of resistance to rifampicin and ethambutol were both less than 1% . The survey was divided into two periods of 14 months each . The rates of primary drug resistance increased from 21.1% to 27.6% during these two periods (Odds Ratio {OR} 1.43; 95% Confidence Interval {CI} 0.88 to 2.32); this increase occurred only for streptomycin (15.9% to 24.7%, OR 1.73; 95% CI 1.02 to 2.93) . CONCLUSION: The rate of primary drug resistance of Mycobacterium tuberculosis in Casablanca has risen in recent years to an ominous level . Urgent measures are needed in order to interrupt this trend.

Int J Tuberc Lung Dis, 1997 Jun, 1(3), 225 - 30
Antituberculosis drug resistance in immigrants to Alberta, Canada, with tuberculosis, 1982-1994; Manns BJ et al.; SETTING: Provincial Tuberculosis Service, Alberta, Canada . OBJECTIVE: To estimate resistance rates of Mycobacterium tuberculosis to antituberculosis drugs in relation to previous treatment, country of origin, age and duration of residence in Canada . DESIGN: Retrospective chart review of all culture-positive tuberculosis diagnosed between 1982 and 1994 in immigrants to Alberta . RESULTS: A total of 753 immigrants with culture-positive tuberculosis were studied; 131 patients (17.4%, 95% Confidence Interval {CI} 14.7, 20.1) had strains resistant to one or more of the first-line medications (isoniazid {INH}, rifampin {RIF}, ethambutol {EMB}, pyrazinamide {PZA}, and streptomycin {SM}) . Initial and secondary resistance rates were 16.4% and 30.3%, respectively (P = 0.003, Odds ratio {OR} 2.2, 95% CI 1.3, 3.8) . Resistance occurred in 22.2% of patients 40 years of age and under, and in 13.8% of those over 40 years of age (P = 0.005, OR 1.8, 95% CI 1.2, 2.6) . Resistant M . tuberculosis was isolated from 20.4% of those who had lived in Canada for less than 15 years, and in 9.0% of those who had immigrated to Canada more than 15 years before diagnosis (P < 0.001; OR 2.4, 95% CI 1.3, 4.2) . Resistance rates to individual medications in all immigrants were as follows: INH 9.9% (95% CI 7.8, 12.0), RIF 0.8% (95% CI 0.2, 1.4), EMB 1.9% (95% CI 1.0, 2.8), PZA 1.9% (95% CI 0.3, 3.5), and SM 12.9% (95% CI 10.4, 15.4) . Immigrants from Vietnam, China, and the Philippines had tuberculosis strains that were resistant to one or more of the first line medications in 30.2%, 21.8%, and 15.5% of cases, respectively (P = 0.04) . CONCLUSION: In industrialized countries such as Canada where most cases of tuberculosis are diagnosed among the foreign-born, drug resistance surveys continue to be an important part of an effective tuberculosis control program.

Graefes Arch Clin Exp Ophthalmol, 1998 Jan, 236(1), 52 - 60
Synergistic effect of electric pulses and bleomycin on cultured rabbit subconjunctival fibroblasts; Oshima Y et al.; BACKGROUND: The combined effect of electric pulses (EP) and antiproliferative agents on the proliferation of rabbit Tenon's capsule fibroblasts was investigated . METHODS: Rabbit Tenon's capsule fibroblasts were cultured . Some of these cells were exposed to various intensities of EP alone (500-2500 V/cm) . Other cells were then exposed for 30 min to an antiproliferative agent: bleomycin (BLM; 0.0005-50 mumol/l), mitomycin C (MMC; 0.0005-50 mumol/l), 5-fluorouracil (5-FU; 0.05-5000 mumol/l), or streptomycin (SM; 0.0005-50 mumol/l) with or without EP (2000 V/cm, 99 mus, eight pulses) . Cell proliferation was assessed by cell counting on day 3 and by a 3H-thymidine uptake assay . DNA fragmentation was assessed by flow-cytometric analysis and agarose gel electrophoresis . RESULTS: A significant reduction in the cell number was observed only at 2500 V/cm (P < 0.05) . BLM, MMC and 5-FU treatment inhibited cell proliferation in a dose-dependent manner either with or without EP (ID50: BLM alone, 0.029 mumol/l; BLM and EP, 0.00022 mumol/l; MMC alone, 41.6 mumol/l; MMC and EP, 27.5 mumol/l; 5-FU alone, 1045 mumol/l; 5-FU and EP, 690.2 mumol/l; P < 0.05) . EP treatment induced an inhibitory effect of BLM on cell proliferation which was 100 times more prominent than BLM alone (0.0005 mumol/l of BLM alone 103.4 +/- 4.4%, 0.0005 mumol/l of BLM and EP 26.0 +/- 4.4%; P = 0.021) . BLM treatment with EP also augmented the apoptotic-like DNA fragmentation in both a flow-cytometric DNA histogram and agarose gel-electrophoresis . CONCLUSION: EP treatment enhanced the inhibitory effect of BLM on the cell proliferation of Tenon's capsule fibroblasts of rabbits . The combination of electric pulses and antiproliferative drug treatments may therefore reduce the necessary dose of antiproliferative agents in filtering surgery.

FEMS Microbiol Lett, 1998 Jan 1, 158(1), 127 - 32
Expression of the mouse metallothionein-I gene conferring cadmium resistance in a transgenic cyanobacterium; Ren L et al.; This paper reports the construction of a transgenic strain of cyanobacterium aimed at removing heavy metal pollution in waters . The mouse metallothionein-I (mMT-I) gene was inserted in the vector pRL-439 downstream of the strong psbA promoter . The resulting plasmid pRL-MT was ligated at the EcoRI site of the shuttle vector pKT-210 to generate the shuttle expression vector pKT-MT . This recombinant plasmid was introduced into Anabaena sp . PCC 7120 by triparental conjugative transfer . After selection on streptomycin, a stable transgenic Anabaena strain was obtained . The presence of the mMT-I gene was confirmed by DNA/DNA hybridization and its expression was demonstrated by immunodetection with specific antibodies . A metal tolerance experiment showed that this transgenic Anabaena strain had acquired higher metal resistance.

Int J Tuberc Lung Dis, 1997 Apr, 1(2), 152 - 8
Short-course chemotherapy in the treatment of Pott's paraplegia: report on five year follow-up; Rajeswari R et al.; OBJECTIVE: To assess the efficacy of 9-month short-course chemotherapy (SCC) and to study the pattern of neurological recovery in patients with Pott's paraplegia . DESIGN: Patients with recent onset of spastic paraplegia due to clinically and radiologically active spinal tuberculosis involving vertebral bodies of level D4-L1 were treated with streptomycin, rifampicin, isoniazid and ethambutol daily for the first 2 months, followed by rifampicin plus isoniazid twice weekly for the next 7 months . The study was conducted in 2 phases . In the first phase 10 patients were admitted to the open trial where all patients had undergone modified Hong Kong surgery in addition to chemotherapy . In the next phase 23 patients enrolled in the study were randomly allocated to receive either chemotherapy alone or surgery plus chemotherapy . All the patients were followed for 5 years from the start of treatment . A scoring system was devised to predict neurological recovery . RESULTS: In all, 33 patients were admitted and treated with SCC . Thirteen patients were allocated to the chemotherapy (CHEM) regimen; of these 3 patients had to be operated upon for clinical deterioration; the remaining 20 had surgery plus chemotherapy; 4 were excluded for various reasons, leaving 29 patients in the analysis . None relapsed requiring treatment . CONCLUSION: A combination of surgery (when indicated) and SCC of 9 months' duration is effective in the treatment of Pott's paraplegia . All patients had neurological recovery by the end of 9 months; 8 recovered with chemotherapy alone . Complete motor recovery was seen in 62% by the 3rd month and 90% by the 6th month.

Int J Tuberc Lung Dis, 1997 Feb, 1(1), 64 - 7
Primary resistance to anti-tuberculosis drugs in Addis Ababa, Ethiopia; Demissie M et al.; OBJECTIVE: To obtain current, representative information on current drug resistance patterns in Addis Ababa, Ethiopia . DESIGN: A cross-sectional study whereby 167 isolates were tested for susceptibility to the anti-tuberculosis drugs commonly used in the country (isoniazid, thiacetazone, rifampicin, streptomycin and ethambutol) . All hospitals, health centres and 6 of the 9 clinics in Addis Ababa were included in the study . RESULT: Overall primary drug resistance was found to be 15.6% (26/167) . Primary resistance to two or more drugs was 7.2% (12/167) . The highest rate of primary resistance was to streptomycin (10.2%) followed by isoniazid (8.4%) . Resistance to rifampicin was low (1.8%, 3/167) and to ethambutol nil . Multiple drug resistance in combinations with rifampicin was low . CONCLUSION: To prevent further development and spread of resistance, universal use of standard treatment protocol, control of the circulation of anti-tuberculosis drugs, training of health workers, expansion of strictly supervised short-course treatment and establishing a nation-wide and regular surveillance system are recommended.

Int J Tuberc Lung Dis, 1997 Feb, 1(1), 44 - 51
Randomised controlled clinical trial of short course chemotherapy in abdominal tuberculosis: a five-year report; Balasubramanian R et al.; OBJECTIVES: To assess and compare the efficacy of a 6-month short-course chemotherapy regimen (SCC) with that of a 12-month standard regimen in the treatment of abdominal tuberculosis . DESIGN AND SUBJECTS: A total of 193 adult patients with evidence of abdominal tuberculosis were randomly allocated to one of two daily regimens: 1) a 6-month SCC regimen with rifampicin, isoniazid and pyrazinamide for 2 months followed by rifampicin with isoniazid for another 4 months (6R series) and 2) and 12-month standard regimen of ethambutol and isoniazid with streptomycin supplemented for 2 weeks (12E series) . Surgery was undertaken only for patients suspected to have obstruction or perforation of the intestine . RESULTS: A total of 163 (85 6R, 78 12E) patients were available for efficacy analysis after exclusion of 30 patients for various reasons . At the end of treatment clinical status was normal in 84 (99%) in 6R patients and in 73 (94%) in 12E patients . Of these, 147 patients completed follow-up for 5 years; none had relapsed requiring treatment for abdominal tuberculosis . CONCLUSION: A 6-month SCC regimen has been found to be as effective as the standard 12-month regimen in the treatment of all forms of abdominal tuberculosis.

J Pediatr, 1997 Dec, 131(6), 863 - 8
Outbreak of drug-resistant tuberculosis with second-generation transmission in a high school in California; Ridzon R et al.; BACKGROUND: In spring 1993, four students in a high school were diagnosed with tuberculosis resistant to isoniazid, streptomycin, and ethionamide . METHODS: To investigate potential transmission of drug-resistant tuberculosis, a retrospective cohort study with case investigation and screening by tuberculin skin tests and symptom checks was conducted in a high school of approximately 1400 students . Current and graduated high-school students were included in the investigation . DNA fingerprinting of available isolates was performed . RESULTS: Eighteen students with active tuberculosis were identified . Through epidemiologic and laboratory investigation, 13 cases were linked; 8 entered 12th grade in fall 1993; 9 of 13 had positive cultures for Mycobacterium tuberculosis with isoniazid, streptomycin, and ethionamide resistance, and all 8 available isolates had identical DNA fingerprints . No staff member had tuberculosis . One student remained infectious for 29 months, from January 1991 to June 1993, and was the source case for the outbreak . Another student was infectious for 5 months before diagnosis in May 1993 and was a treatment failure in February 1994 with development of rifampin and ethambutol resistance in addition to isoniazid, streptomycin, and ethionamide . In the fall 1993 screening, 292 of 1263 (23%) students tested had a positive tuberculin skin test . Risk of infection was highest among 12th graders and classroom contacts of the two students with prolonged infectiousness . An additional 94 of 928 (10%) students tested in spring 1994 had a positive tuberculin skin test; 22 were classroom contacts of the student with treatment failure and 21 of these had documented tuberculin skin test conversions . CONCLUSION: Extensive transmission of drug-resistant tuberculosis was documented in this high school, along with missed opportunities for prevention and control of this outbreak . Prompt identification of tuberculosis cases and timely interventions should help reduce this public health problem.

Laryngorhinootologie, 1997 Sep, 76(9), 519 - 22
{Intravenous gentamicin therapy in bilateral Menière disease}; Jahnke K et al.; BACKGROUND: The treatment of severe forms of bilateral Meniere's disease remains an especially challenging task . Similar problems also occur in debilitating Meniere's disease in the only hearing ear . The intramuscular titration therapy with streptomycin has been the means of choice since 1984 to minimize the risk of total hearing loss in cases of severe bilateral disease . METHOD: Since 1989 we have treated six out of 21 cases of bilateral Meniere's disease by intravenous application of 2 x 120 mg gentamicin in Ringer's solution for several days . Additionally we reported on two cases in 1988 . Only minor amounts of gentamicin were applied to sedate the function of both vestibular organs while avoiding damage to the cochlea . RESULTS: In two cases hearing approved approximately about 10 dB, in two cases hearing remained stable, and in two cases hearing worsened about 10 dB . Five of six patients showed minor excitability in caloric tests on both sides, they did not complain of vertigo attacks one to five years after therapy . CONCLUSION: Given that only very small amounts of gentamicin are applied to sedate the function of the vestibular organ while causing almost no damage to the cochlea, this method seems to be an excellent means for treatment of bilateral Meniere's disease . Patients do not experience severe problems with equilibrium afterwards, and the treatment can be repeated as often as necessary.

J Antibiot (Tokyo), 1997 Oct, 50(10), 847 - 52
Involvement of afsA in A-factor biosynthesis as a key enzyme; Ando N et al.; The afsA gene of Streptomyces griseus has been postulated to encode a key enzyme for A-factor biosynthesis from primary metabolites commonly present in Streptomyces strains . Escherichia coli cells harboring afsA under the control of the T7 promoter specified distinct A-factor activity in the culture broth, as determined by induction of streptomycin production and aerial mycelium and spore formation in an A-factor-deficient S . griseus mutant strain . Production of the substance(s) having A-factor activity was inhibited by cerulenin, an inhibitor of fatty acid biosynthesis . These observations suggest that afsA encodes a key enzyme in the A-factor biosynthetic pathway in which a beta-keto acid derived from fatty acid biosynthesis and a glycerol derivative serve as precursors.

J Clin Microbiol, 1997 Dec, 35(12), 3325 - 7
Reliability of mycobacteria growth indicator tube for testing susceptibility of Mycobacterium tuberculosis to ethambutol and streptomycin; Bergmann JS et al.; The reliability of mycobacterial growth indicator tubes (MGIT) for testing susceptibility of Mycobacterium tuberculosis to ethambutol and streptomycin was evaluated by comparing MGIT results to those obtained by the radiometric BACTEC TB system and the method of proportion . The method of proportion was considered the reference method . To resolve discrepancies, all three testing methods were repeated . For the 74 isolates evaluated, initial ethambutol results agreed by all three methods for 64 (86.5%) of them; 58 were susceptible and 6 were resistant . MGIT and method-of-proportion results agreed for 67 isolates, and BACTEC results agreed with method-of-proportion results for 71 (P = 0.096) . Initial streptomycin results obtained by all three methods agreed for 69 (93.2%) isolates: 55 were susceptible and 14 were resistant . MGIT and method-of-proportion results were concordant for 69 isolates, and BACTEC and method-of-proportion results agreed for 73 (P = 0.049) . The mean times to MGIT results were 5.58 +/- 0.10 days (range, 3 to 9 days) for ethambutol and 5.47 +/- 0.11 days (range, 3 to 9 days) for streptomycin, compared to a mean of 7.41 +/- 0.20 days (range, 4 to 12 days) for both drugs with the BACTEC system (P < 0.001).

Biochem Biophys Res Commun, 1997 Nov 26, 240(3), 536 - 9
Recombinant Mycobacterium aurum expressing Escherichia coli beta-galactosidase in high throughput screening of antituberculosis drugs; Srivastava R et al.; Mycobacterium aurum is considered a surrogate of M . tuberculosis and recently has been proposed as test organism in high throughput screening of antituberculosis drugs (3) . In this investigation, we suggest use of a recombinant M . aurum expressing E . coli lacZ gene, in which beta-galactosidase production is the reporter system as recently reported by us (6) . The assay is based on production of beta-galactosidase in presence of drugs during growth . Enzyme production was inhibited within 4 h by frontline antimycobacterial drugs like streptomycin, rifampicin, isoniazid, ethambutol, ofloxacin, and sparfloxacin at their MICs . The assay could be performed conveniently in 96-well microtiter plate format.

J Med Genet, 1997 Nov, 34(11), 904 - 6
Familial streptomycin ototoxicity in a South African family: a mitochondrial disorder; Gardner JC et al.; The vestibular and ototoxic effects of the aminoglycoside antibiotics (streptomycin, gentamycin, kanamycin, tobramycin, neomycin) are well known; streptomycin, in particular, has been found to cause irreversible, profound, high frequency sensorineural deafness in hypersensitive persons . Aminoglycoside ototoxicity occurs both sporadically and within families and has been associated with a mitochondrial DNA (mtDNA) 1555A to G point mutation in the 12S ribosomal RNA gene . We report on the molecular analysis of a South African family with streptomycin induced sensorineural deafness in which we have found transmission of this same predisposing mutation . It is now possible to identify people who are at risk of hearing loss if treated with aminoglycosides in the future and to counsel them accordingly . In view of the fact that aminoglycoside antibiotics remain in widespread use for the treatment of infections, in particular for tuberculosis, which is currently of epidemic proportions in South Africa, this finding has important implications for the family concerned . In addition, other South African families may potentially be at risk if they carry the same mutation.

Hear Res, 1997 Nov, 113(1-2), 224 - 34
Mechanotransduction of hair bundles arising from multicellular complexes in anemones; Mire P et al.; Sea anemones are among the simplest animals to use hair bundles to detect vibrations . Although we previously found anemone bundles to be morphologically similar to vertebrate hair bundles, only indirect evidence implicated anemone bundles in mechanotransduction . Here, we test mechanotransduction of these bundles using loose-patch current recording from apical membranes of cells at the base of deflected bundles . Step bundle deflection results in graded membrane currents that are inward in some cells (positive) and outward in other cells (negative) . Positive responses range from 5 to 30 pA, abruptly saturate with stronger stimuli, and increase in duration with prolonged deflections . Negative responses range from 10 to 150 pA, show a logarithmic relation to stimulus strength, and attenuate with prolonged deflections . Additionally, responses are reversibly inhibited by streptomycin . We present a model for anemone bundle mechanotransduction modified from the gating spring model for vertebrate mechanotransduction . Because anemone bundles comprise stereocilia arising from a multicellular complex, we propose that supporting cells on opposite sides of a bundle function as oppositely polarized hair cells . Thus, deflection induces ion channels to open in cells on one side of the complex, while allowing channels to close in cells on the opposite side of the complex.

Kekkaku, 1997 Sep, 72(9), 507 - 13
{Relationship between streptomycin susceptibility and rpsL mutations of Mycobacterium tuberculosis strains}; Fukuda M et al.; The relationship between streptomycin (SM) susceptibility and rpsL mutations of Mycobacterium tuberculosis strains was studied . Of 18 clinically isolated SM-resistant M.tuberculosis strains, mutation was suspected in 9 strains (50%) with SM MICs of > or = 256 micrograms/ml by PCR-single strand conformation polymorphism targeting rpsL gene . On the other hand, using PCR-direct sequence method, amino acid substitution caused by single nucleotide point mutation in rpsL gene was demonstrated in 11 out of 18 strains (61%) . The same amino acid substitution at codon 43 (Lys-->Arg) was observed in all 11 strains with SM MICs of > or = 256 micrograms/ml . In addition, PCR products obtained from these 11 strains could not be cut by a restriction enzyme, Mbo II, while H37Rv strain and the other 32 strains with SM MICs of < 256 micrograms/ml were cut into 2 fragments . In conclusion, our results suggest that highly SM-resistant M.tuberculosis strains with MICs of > or = 256 micrograms/ml could be rapidly and easily detected by the restriction enzymatic method.

Mol Gen Genet, 1997 Aug, 255(6), 549 - 60
Molecular analysis of the ribosomal L11 protein gene (rplK = relC) of Streptomyces griseus and identification of a deletion allele; Kawamoto S et al.; The rplK (= relC) gene, which codes for ribosomal protein L11, was cloned from Streptomyces griseus IFO13189 using a screening procedure based on polymerase chain reaction amplification of a gene segment that subsequently allowed the isolation of the complete gene from a gene library . rplK lies between the nusG gene, encoding a protein involved in antitermination of transcription, and the rplA gene, which encodes the ribosomal protein L1 . Comparison of the rplK gene sequences of the wild-type strain and the presumed relC mutant strain 3-3 (originally isolated as a thiopeptin-resistant isolate) revealed a 12-bp deletion within the rplK gene from the mutant, flanked by a 4-bp repeat sequence in the corresponding region in the wild type . When the wild-type rplK gene was propagated on a low-copy-number vector in the relC mutant 3-3, the ability to produce guanosine 5'-diphosphate 3'-diphosphate, streptomycin, and submerged spores was completely restored to parental levels . The impaired ability to form aerial mycelium was, however, unaffected . Western blotting analysis showed that the ribosomes from the relC mutant 3-3 incorporate the mutant L11 protein normally, although the level of incorporation is approximately one-third that of the wild-type L11 protein in ribosomes of the parent strain . Propagation of the mutant rplK gene in the wild-type strain resulted in marked defects in growth, streptomycin production, and aerial mycelium formation, indicating that the mutant L11 protein exerts certain negative effects in the cells.

Nippon Jibiinkoka Gakkai Kaiho, 1997 Sep, 100(9), 927 - 36
{Formation and calcium incorporation of giant otoconia of the guinea pig after streptomycin intoxication}; Zhang DM; The mechanisms for the formation and fate of giant otoconia following streptomycin (SM) intoxication were investigated in adult pigmented guinea pigs by scanning electron microscopy . Calcium turnover into otoconia has also been studied by using tetracycline as a tracer . The administration of SM induced the reduction of otoconia with the formation of giant otoconia . The giant otoconia had a multifaceted morphology in their early developmental period . This type of otoconia showed entire fluorescence indicating existence of calcium uptake . They then grew up to the transitional type and finally to the cylindrical type . The giant otoconia were thought to be formed mainly by dissolution of normal otoconia due to the loss of environmental calcium followed by recrystallization as giant crystals . The transitional type of giant otoconia showed less calcium ion uptake and the removal of calcium from the giant otoconia caused their quick disappearance . These phenomena might be closely related to the otoconial dynamics which may regulate calcium ion homeostasis of endolymph.

J Neurophysiol, 1997 Oct, 78(4), 1913 - 27
Electrophysiological properties of vestibular sensory and supporting cells in the labyrinth slice before and during regeneration; Masetto S et al.; The whole cell patch-clamp technique in combination with the slice preparation was used to investigate the electrophysiological properties of pigeon semicircular canal sensory and supporting cells . These properties were also characterized in regenerating neuroepithelia of pigeons preinjected with streptomycin to kill the hair cells . Type II hair cells from each of the three semicircular canals showed similar, topographically related patterns of passive and active membrane properties . Hair cells located in the peripheral regions (zone I, near the planum semilunatum) had less negative resting potentials {0-current voltage in current-clamp mode (Vz) = -62.8 +/- 8.7 mV, mean +/- SD; n = 13} and smaller membrane capacitances (Cm = 5.0 +/- 0.9 pF, n = 14) than cells of the intermediate (zone II; Vz = -79.3 +/- 7.5 mV, n = 3; Cm = 5.9 +/- 1.2 pF, n = 4) and central (zone III; Vz = -68.0 +/- 9.6 mV, n = 17; Cm = 7.1 +/- 1.5 pF, n = 18) regions . In peripheral hair cells, ionic currents were dominated by a rapidly activating/inactivating outward K+ current, presumably an A-type K+ current (IKA) . Little or no inwardly rectifying current was present in these cells . Conversely, ionic currents of central hair cells were dominated by a slowly activating/inactivating outward K+ current resembling a delayed rectifier K+ current (IKD) . Moreover, an inward rectifying current at voltages negative to -80 mV was present in all central cells . This current was composed of two components: a slowly activating, noninactivating component (Ih), described in photoreceptors and saccular hair cells, and a faster-activating, partially inactivating component (IK1) also described in saccular hair cells in some species . Ih and IK1 were sometimes independently expressed by hair cells . Hair cells located in the intermediate region (zone II) had ionic currents more similar to those of central hair cells than peripheral hair cells . Outward currents in intermediate hair cells activated only slightly more quickly than those of the cells of the central region, but much more slowly than those of the peripheral cells . Additionally, intermediate hair cells, like central hair cells, always expressed an inward rectifying current . The regional distribution of outward rectifying potassium conductances resulted in macroscopic currents differing in peak-to-steady state ratio . We quantified this by measuring the peak (Gp) and steady-state (Gs) slope conductance in the linear region of the current-voltage relationship (-40 to 0 mV) for the hair cells located in the different zones . Gp/Gs average values (4.1 +/- 2.1, n = 15) from currents in peripheral hair cells were higher than those from intermediate hair cells (2.3 +/- 0.8, n = 4) and central hair cells(1.9 +/- 0.8, n = 21) . The statistically significant differences (P < 0.001) in Gp/Gs ratios could be accounted for by KA channels being preferentially expressed in peripheral hair cells . Hair cell electrophysiological properties in animals pretreated with streptomycin were investigated at approximately 3 wk and approximately 9-10 wk post injection sequence (PIS) . At 3 wk PIS, hair cells (all zones combined) had a statistically significantly (P < 0.001) lower Cm (4.6 +/- 1.1 pF, n = 24) and a statistically significantly (P < 0.01) lower Gp(48.4 +/- 20.8 nS, n = 26) than control animals (Cm = 6.2 +/- 1.6 pF, n = 36; Gp = 66 +/- 38.9 nS, n = 40) . Regional differences in values of Vz, as well as the distribution of outward and inward rectifying currents, seen in control animals, were still obvious . But, differences in the relative contribution of the expression of the different ionic current components changed . This result could be explained by a relative decrease in IKA compared with IKD during that interval of regeneration, which was particularly evident in peripheral hair cells . (ABSTRACT TRUNCATED)

Probl Tuberk, 1997, (4), 55 - 7
{Pulmonary tuberculosis and acquired immunodeficiency syndrome in Ukraine (first communication)}; Feshchenko II et al.; The epidemiological HIV infection situation in the Ukraine in the past 4 years is analyzed . In patients with AIDS, the clinical manifestations of tuberculosis are atypical; prolonged intoxication, negative tuberculin tests, no bacterial isolation in half the cases . These patients should be treated with 4 - 5 antituberculous drugs, by taking into account the fact that only long-term continuous therapy may yield a positive effectPIP: In the Ukraine, the first case of HIV infection was reported in 1987 and, by the end of 1992, the number rose to 112 cases, 12 of which developed AIDS . By mid-1996, about 4500 HIV-positive cases were known to exist and there were 73 known AIDS patients, of which 40 died . Another cause for concern is the resurgence of tuberculosis (TB) and, in particular, TB in combination with HIV infection . There were 177.8 double infection cases/100,000 population in the country according to recent statistical data versus 38.7 TB cases/100,000 population in the general population . The first 8 cases of double infection were reported in 1991 . TB is commonly treated with the following drugs: 5-10 mg/kg isoniazid; 10 mg/kg ethambutol or 25 mg/kg pyrazinamide; 15 mg/kg streptomycin or 15 mg/kg kanamycin . AIDS is treated with azidothymidine, dextransulfate, and by the implantation of lymphocytes for the restoration of immune function . The observation period of the 8 patients infected with TB and HIV lasted from 4-5 months to 2 years, during which time intensive therapy consisted of 4-5 preparations . Post-TB sequelae, such as fibrous inflammation in the lungs, should be treated with 5 mg/kg isoniazid for 3 months twice a year . The traditional diagnosis of TB relies on negative TB tests, atypical X-ray images, and the presence of Mycobacterium tuberculosis in more than 50% of the patients .

Vojnosanit Pregl, 1997 May-Jun, 54(3), 217 - 21
{Tonsillo-pharyngeal form of tularemia}; Trnjak Z et al.; Clinical, laboratory and serologic features of tonsillopharyngeal form of tularemia in 14 patients were analyzed in the study . The disease was ignored under the diagnosis of typical tonsillopharyngitis followed by cervical lymphadenopathy . Routine laboratory analyses results were non-specific and didn't reveal the disease etiology, while microagglutination test (MAT) of F . tularensis in the second week of disease was positive in 86% of patients . Skin tularin test was positive in all the tested patients during the first week of the disease . The best results in the treatment were achieved by administration of streptomycin and doxycycline . Well timed therapy prevented the lymph nodes colliquation, disease recurrence and infection generalization . The authors point out the significance of this clinical form of tularemia in the differential diagnosis of tonsillopharyngitis and cervical lymphodenopathy.

Nihon Kyobu Shikkan Gakkai Zasshi, 1997 Jun, 35(6), 681 - 6
{Adenocarcinoma of the lung associated with acute promyelocytic leukemia and miliary tuberculosis}; Kakemizu N et al.; A 44-year-old man was admitted to the hospital because of acute promyelocytic leukemia . A nodular shadow (2.5 cm in diameter) was seen in the right upper lung field on a chest roentgenogram . During the administration of combination chemotherapy for the leukemia, diffuse granular shadow appeared in all lung fields . Transbronchial lung biopsy findings indicated tuberculosis . The patient was given streptomycin, isoniazid, rifampicin and ethambutol, but the nodular show enlarged and a pleural effusion appeared on the right side . Cytologic examination of the pleural effusion revealed adenocarcinoma . Similar findings were obtained from a second transbronchial lung biopsy . The frequency of association of lung cancer and other malignancy is about 4% . The incidences of primary lung cancer found during the course of active tuberculosis, active pulmonary tuberculosis found during the course of primary lung cancer, and tuberculosis found during the course of acute leukemia are 0.9 to 1.4%, 0.4 to 4.3%, and 2.4 to 4.5%, respectively . To our knowledge, this is the first case in Japan in which adenocarcinoma of the lung was associated with acute promyelocytic leukemia and tuberculosis.

ORL J Otorhinolaryngol Relat Spec, 1997 Sep-Oct, 59(5), 263 - 8
Effect of streptomycin on the otoconial layer of the guinea pig; Takumida M et al.; The effects of streptomycin on the otoconial layer of the adult guinea pig were investigated using scanning electron microscopy . Administration of streptomycin induced a reduction of otoconia with formation of giant otoconia . These phenomena reached their maximum 4 weeks after the cessation of streptomycin intoxication in the utricle and between 2 and 6 weeks after in the saccule . Otoconia began to recover in the utricle 4 weeks and in the saccule 6 weeks after the cessation of streptomycin intoxication with an increasing number of small otoconia . Eight or 10 weeks after the cessation of streptomycin intoxication, the otoconial layer has completely recovered in both the utricle and saccule.

J Mol Biol, 1997 Aug 29, 271(4), 566 - 87
A new model for the three-dimensional folding of Escherichia coli 16 S ribosomal RNA . III . The topography of the functional centre; Mueller F et al.; We describe the locations of sites within the 3D model for the 16 S rRNA (described in two accompanying papers) that are implicated in ribosomal function . The relevant experimental data originate from many laboratories and include sites of foot-printing, cross-linking or mutagenesis for various functional ligands . A number of the sites were themselves used as constraints in building the 16 S model . (1) The foot-print sites for A site tRNA are all clustered around the anticodon stem-loop of the tRNA; there is no "allosteric" site . (2) The foot-print sites for P site tRNA that are essential for P site binding are similarly clustered around the P site anticodon stem-loop . The foot-print sites in 16 S rRNA helices 23 and 24 are, however, remote from the P site tRNA . (3) Cross-link sites from specific nucleotides within the anticodon loops of A or P site-bound tRNA are mostly in agreement with the model, whereas those from nucleotides in the elbow region of the tRNA (which also exhibit extensive cross-linking to the 50 S subunit) are more widely spread . Again, cross-links to helix 23 are remote from the tRNAs . (4) The corresponding cross-links from E site tRNA are predominantly in helix 23, and these agree with the model . Electron microscopy data are presented, suggestive of substantial conformational changes in this region of the ribosome . (5) Foot-prints for IF-3 in helices 23 and 24 are at a position with close contact to the 50 S subunit . (6) Foot-prints from IF-1 form a cluster around the anticodon stem-loop of A site tRNA, as do also the sites on 16 S rRNA that have been implicated in termination . (7) Foot-print sites and mutations relating to streptomycin form a compact group on one side of the A site anticodon loop, with the corresponding sites for spectinomycin on the other side . (8) Site-specific cross-links from mRNA (which were instrumental in constructing the 16 S model) fit well both in the upstream and downstream regions of the mRNA, and indicate that the incoming mRNA passes through the well-defined "hole" at the head-body junction of the 30 S subunit.

Ann Otol Rhinol Laryngol, 1997 Aug, 106(8), 643 - 8
Audiologic features of hearing loss due to the 1,555 mutation of mitochondrial DNA; Tsuiki T et al.; We proved a 1,555 mutation of mitochondrial DNA in one member of each of three families with familial streptomycin hearing loss, and report the pedigrees and audiologic features . DNA was extracted by the standard method . The 1,555 A to G mutation was identified in all three patients and confirmed by direct sequencing of the polymerase chain reaction products by a cycle sequencing method . On audiograms, the hearing loss was sensorineural, bilateral, and symmetric, showing a high-tone loss or a profound loss particularly in the high-tone range, and the "symmetry law" of Langenbeck was applicable . The superimposed audiograms of members of one family did not cross themselves, proving the applicability of the "never-cross principle of audiograms."

Acta Otolaryngol, 1997 Jul, 117(4), 538 - 44
Formation and fate of giant otoconia of the guinea pig following streptomycin intoxication; Takumida M et al.; Formation and fate of abnormal (giant) otoconia of the guinea pig following streptomycin intoxication were investigated using scanning electron microscopy . The giant otoconia formed as multifaceted morphology in their early developmental period . They grew up the the transitional type and finally to the cylindrical type . It has been suggested that the giant otoconia found following streptomycin intoxication may be formed mainly by dissolution of normal otoconia due to the loss of environmental calcium, followed by recrystallization as giant crystals . These phenomena seemed to be closely related to the otoconial dynamics which may regulate calcium ion homeostasis of the endolymph.

Int J Dev Neurosci, 1997 Jul, 15(4-5), 387 - 99
Ionic currents in regenerating avian vestibular hair cells; Masetto S et al.; By applying the conventional whole-cell patch-clamp technique in combination with the slice procedure, we have investigated the properties of avian semicircular canal hair cells in situ . Passive and active electrical properties of hair cells from control animals have been compared with those of regenerating hair cells following streptomycin treatment (that killed almost all hair cells) . Regenerating type II hair cells showed patterns of responses qualitatively similar to those of normal hair cells . However, parameters reflecting the total number of ionic channels and the surface area of type II hair cells changed during recovery-suggesting that new hair cells came from smaller precursors which (with time) reacquired the same electrophysiological properties as normal hair cells . Finally, we have investigated the ionic properties of a small sample of type 1 hair cells . Ionic currents of regenerating type I hair cells did not show, at least in the temporal window considered (up to 10 weeks from the end of the streptomycin treatment), the typical ionic currents of normal type I hair cells, but expressed instead ionic currents resembling those of type II hair cells . The possibility that regenerating type I hair cells can transdifferentiate from type II hair cells is therefore suggested.

ORL J Otorhinolaryngol Relat Spec, 1997 Jul-Aug, 59(4), 209 - 14
Selective chemical vestibulectomy . Preliminary results; Ecke U et al.; In an attempt to destroy the peripheral vestibular labyrinth selectively in patients suffering from intractable vertigo as a result of end-stage Meniere's disease, 25 patients underwent selective chemical vestibulectomy between 1989 and 1994 . As part of the procedure a certain quantity of streptomycin was placed between the bony and the membranous part of the lateral semicircular canal . The dosage of streptomycin used for successful ablation of vertigo varied between 250 and 100 micrograms . Within 12 months following the procedure all patients experienced a tremendous improvement in their overall condition . In spite of the fact that some patients noted an overall hearing improvement, increased cochlear thresholds were observed in a number of patients, which could not be ignored . The aim of this report is to detail the reliability of control of vertigo, conservation of hearing, and change in disability 12 months after surgery in the 23 patients (of 25) available for follow-up.

Microbiology, 1997 Jul, 143 ( Pt 7), 2135 - 43
A spectinomycin resistance determinant from the spectinomycin producer Streptomyces flavopersicus; Lyutzkanova D et al.; The spectinomycin (sp) resistance determinant from Streptomyces flavopersicus was cloned into Streptomyces lividans using the plasmid vector pIJ699 . A plasmid, pDGL15, with a 3.65 kb insert from S . flavopersicus conferring resistance to Sp was isolated . DNA sequence analysis of the 3651 1 bp DNA insert revealed four open reading frames (ORFs) . The amino acid sequence deduced from one ORF (SpcN) showed a high degree of similarity to an aminoglycoside phosphotransferase (StrN) and from a second one (SpcR) to a regulatory protein (StrR) of the streptomycin biosynthesis gene cluster from S . griseus . The two other ORFs were incomplete and the deduced amino acid sequences showed similarities to an amidinotransferase encoded in the streptomycin biosynthesis gene cluster of S . griseus and to the transposase of IS112, respectively . Expression of the spcN gene in E . coli under the control of tac promoter conferred Sp resistance to the cells . An enzymic assay confirmed that the gene product of spcN is an ATP-dependent aminoglycoside phosphotransferase which phosphorylates Sp and actinamine, the aminocyclitol moiety of Sp.

Biochem Biophys Res Commun, 1997 Jun 27, 235(3), 602 - 5
beta-Galactosidase reporter system in mycobacteria and its application in rapid antimycobacterial drug screening; Srivastava R et al.; Pathogenic mycobacteria are generally slow growing organisms and it takes several weeks to evaluate inhibitors of growth . Therefore, for rapid screening of the inhibitors of mycobacterial growth, a beta-galactosidase reporter system has been described which utilises a recombinant Mycobacterium smegmatis mc(2)155 expressing E . coli lacZ gene as the test organism . The assay is based on production of beta-galactosidase in presence of drugs during growth . A correlation between beta-galactosidase production and colony forming ability of mycobacteria was obtained . beta-galactosidase production was inhibited within 6 h by front line standard antimycobacterial drugs like streptomycin, rifampicin, isoniazid, ethambutol, pyrazinamide and ofloxacin at their reported MICs . The assay was performed on mycobacterial cells permeabilized with chloroform and sodium dodecyl sulfate.

J Commun Dis, 1997 Jun, 29(2), 121 - 5
V . cholerae 01 outbreak in remote villages of Shimla district, Himachal Pradesh, 1994; Bora D et al.; An outbreak of V . cholerae 01 occurred in remote villages of Rohru tehsil, district Shimla, Himachal Pradesh, during June-July 1994 . Seven villages were affected . Overall attack rate was 16.4 per cent in surveyed villages . Attack rate in children < 5 was significantly high . Suspected source was spring water contaminated from open air defaecation . V . cholerae was resistant to co-trimoxazole and streptomycin.

Addiction, 1997 Jun, 92(6), 657 - 66
Sir Austin Bradford Hill: medical statistics and the quantitative approach to prevention of disease; Wilkinson L; Sir Austin Bradford Hill (1897-1991), son of a prominent medical physiologist, was destined for the study of medicine when World War I intervened . He chase to enlist as a pilot in the Royal Navy Air Service . Having contracted tuberculosis on his way to the Dardanelles, Hill was 'sent home to die' . In spite of the odds he recovered; but with no chance of working in physically taxing fields such as medicine or science . Advised and encouraged by Major Greenwood, he carved out for himself a career in medical statistics, first at the Medical Research Council and subsequently at the London School of Hygiene and Tropical Medicine, where his inspired teaching helped to shape the development of medical research in the second half of the twentieth century . He is particularly remembered for the way he made medical statistics an essential part of modern epidemiology, a new phase in an epidemiology concerned with chronic as well as with infectious diseases . At the same time, he introduced randomization where therapies-beginning with streptomycin in tuberculosis-could be evaluated in large-scale clinical trials . Perhaps his best known achievement is his design of the smoking and lung cancer trials, carried out with Richard Doll who later extended-and still extends-the trials which so convincingly have linked addiction to tobacco to patients' later problems with cancers and with coronary heart disease.

Cardiovasc Res, 1997 Jun, 34(3), 493 - 503
Effect of streptomycin on wall-stress-induced arrhythmias in the working rat heart; Salmon AH et al.; OBJECTIVE: To assess whether streptomycin, an inhibitor of mechano-sensitive cation channels, has an effect on arrhythmias-induced by an increase of ventricular wall stress in the rat heart . METHODS: The isolated working rat heart preparation was used . Arrhythmias were induced by increasing the afterload (i.e., aortic pressure) against which the left ventricle (LV) pumped for 20 s . This led to an increase of LV pressure, stretch of the LV and an increase in LV wall stress . The number of ventricular premature beats induced by each afterload step was compared in the absence and presence of streptomycin, a compound known to block mechano-sensitive cation channels in the heart . RESULTS: Perfusion with 200 microM streptomycin caused a significant reduction in wall-stress-induced arrhythmias . The effect of streptomycin on arrhythmias reached steady-state within 10 min of application . In the presence of streptomycin, arrhythmias elicited by a 40 mmHg afterload increase were reduced to 38% of control . Arrhythmias induced by an 80 mmHg afterload increase were reduced to 61% of control . Complex arrhythmias (ventricular tachycardia) induced by an afterload increase were also reduced in the presence of 200 microM streptomycin . There was no change in inotropic state with streptomycin, as assessed either by cardiac output or by maximum developed LV pressure . Streptomycin 50 microM (a typical therapeutic plasma concentration in patients) had no effect on wall-stress-induced arrhythmias . CONCLUSIONS: The results were inconsistent with streptomycin acting by modulating inositol phosphate production, or altering the level of intracellular calcium or inotropic state . The anti-arrhythmic effect of streptomycin appears more consistent with inhibition of mechano-sensitive cation channels, suggesting that these ion channels might be involved in causing wall-stress-induced arrhythmias.

J Mol Cell Cardiol, 1997 Jun, 29(6), 1629 - 37
Resting tension participates in the modulation of active tension in isolated guinea pig ventricular myocytes; Cazorla O et al.; We studied active and passive properties of intact isolated guinea-pig ventricular myocytes in auxotonic conditions . Cells were attached using carbon fibres . The passive properties of the myocytes, in the presence of the stretch-activated channel blocker streptomycin sulphate, could be separated into two groups: stiff cells (stiffness slope = 2.88 +/- 0.93 nN/micron3, n = 63 cells) and compliant cells (stiffness slope = 0.91 +/- 0.35 nN/micron3, n = 52 cells) . The study and the localization of the different kind of cells indicated that endocardium is mainly constituted of stiff cells (80%) while the epicardium contained more compliant cells (60%) . When a longitudinal strain was applied to compliant cells, an increase in resting tension, diastolic sarcomere length and active tension were observed . On the other hand, in stiff cells, it induced an increase in resting tension and active tension with little change of diastolic sarcomere length . In both kinds of cells, strain had no effect on Ca2+ transient amplitude and shape . Plotting active tension v diastolic sarcomere length also clearly showed two separated populations of cells, corresponding to stiff and compliant cells . The results of the two groups of cells when plotting active tension v resting tension could not be distinguished . We conclude that resting tension is an important factor in the modulation of active tension by stretch in addition to interfilament lattice spacing or sarcomere length.

World J Surg, 1997 Jun, 21(5), 516 - 9
Management of mycobacterial cervical lymphadenitis; Kanlikama M et al.; The treatment results of mycobacterial cervical lymphadenitis in 69 patients between 1990 and 1993 are reviewed . All patients underwent surgical procedures consisting of total excision or selective nodal dissection for lymphadenopathies and curettage for fluctuant cases, followed by antituberculous chemotherapy applied according to the likely or proved mycobacterial species . For this purpose, three or four drugs (including isoniazid, rifampin, ethambutol, and streptomycin) were used for 12 to 18 months . The cure rate was 100% after a minimum follow-up of 3 years . Clinical features, treatment modes, and guidelines for management are discussed.

Antimicrob Agents Chemother, 1997 Jun, 41(6), 1385 - 8
Isolation of a gene encoding a novel spectinomycin phosphotransferase from Legionella pneumophila; Suter TM et al.; A gene capable of conferring spectinomycin resistance was isolated from Legionella pneumophila, the agent of Legionnaires' disease . The gene (aph) encoded a 36-kDa protein which has similarity to aminoglycoside phosphotransferases . Biochemical analysis confirmed that aph encodes a phosphotransferase which modifies spectinomycin but not hygromycin, kanamycin, or streptomycin . The strain that was the source of aph demonstrated resistance to spectinomycin, and Southern hybridizations determined that aph also exists in other legionellae.

Trop Med Int Health, 1997 May, 2(5), 422 - 7
Urban epidemic of bubonic plague in Majunga, Madagascar: epidemiological aspects; Boisier P et al.; After an absence of 62 years, an epidemic of plague occurred in the harbour city of Majunga (Madagascar) from July 1995 to March 1996, following sporadic cases in March and May 1995 . By 15 March 1996, 617 clinically suspected cases of bubonic plague had been notified . Laboratory testing was carried out for 394 individuals: 60 (15.2%) were confirmed to have bubonic plague and 48 (12.2%) were considered as presumptive cases . The incidence was significantly higher in males in all age groups and in both sexes in the 5-19 age group . Twenty-four deaths were related to plague, but early treatment with streptomycin has confirmed its effectiveness insofar as the case-farality ratio was only 8.7% among confirmed and presumptive cases admitted to hospital . The difficulty of clinically diagnosing bubonic plague was affirmed . The disease met favourable conditions through the poverty and low level of hygiene prevalent in most parts of Majunga.

Acta Otolaryngol, 1997 May, 117(3), 376 - 81
Effect of streptomycin intoxication on vestibular nerve regeneration and posture recovery; Kadir A et al.; The action of streptomycin sulfate (SM) on the regenerative process of the vestibular nerve and posture recovery was studied, using bull frogs . The vestibular nerve was sectioned in various conditions with intact endorgan or with SM intoxication . When the nerve was sectioned with the hair cells left intact, the nerve regenerated well and body balance recovered to normal . However, when neural regeneration was blocked, recovery was incomplete . SM intoxication resulted in various degrees of hair cell damage . Degree of posture recovery correlated well with the number of hair cells . When the nerve was sectioned after damaging the hair cell, the nerve failed to regenerate and posture recovery was incomplete . These results suggest that the degree of posture recovery depends on hair cell function and neural regeneration . Furthermore, neural regeneration is strongly influenced by hair cell function.

Plant J, 1997 May, 11(5), 907 - 19
Increased Ac excision (iae): Arabidopsis thaliana mutations affecting Ac transposition; Jarvis P et al.; The maize transposable element Ac is highly active in the heterologous hosts tobacco and tomato, but shows very much reduced levels of activity in Arabidopsis . A mutagenesis experiment was undertaken with the aim of identifying Arabidopsis host factors responsible for the observed low levels of Ac activity . Seed from a line carrying a single copy of the Ac element inserted into the streptomycin phosphotransferase (SPT) reporter fusion, and which displayed typically low levels of Ac activity, were mutagenized using gamma rays . Nineteen mutants displaying high levels of somatic Ac activity, as judged by their highly variegated phenotypes, were isolated after screening the M2 generation on streptomycin-containing medium . The mutations fall into two complementation groups, iae1 and iae2, are unlinked to the SPT::Ac locus and segregate in a Mendelian fashion . The iae1 mutation is recessive and the iae2 mutation is semi-dominant . The iae1 and iae2 mutants show 550- and 70-fold increases, respectively, in the average number of Ac excision sectors per cotyledon . The IAE1 locus maps to chromosome 2, whereas the SPT::Ac reporter maps to chromosome 3 . A molecular study of Ac activity in the iae1 mutant confirmed the very high levels of Ac excision predicted using the phenotypic assay, but revealed only low levels of Ac re-insertion . Analyses of germinal transposition in the iae1 mutant demonstrated an average germinal excision frequency of 3% and a frequency of independent Ac re-insertions following germinal excision of 22% . The iae mutants represents a possible means of improving the efficiency of Ac/Ds transposon tagging systems in Arabidopsis, and will enable the dissection of host involvement in Ac transposition and the mechanisms employed for controlling transposable element activity.

Hear Res, 1997 May, 107(1-2), 53 - 66
Hair bundles of sea anemones as a model system for vertebrate hair bundles; Watson GM et al.; Sea anemones are marine invertebrates that use hair bundles to detect swimming movements of prey . Prey are captured by nematocysts (stinging capsules) that discharge into the prey . To further characterize anemone hair bundles and to compare hair bundles in anemones with hair bundles in vertebrates, we investigated fine structure and cytochemistry of anemone hair bundles . In addition, using a biological assay based on counting nematocysts discharged into vibrating test probes, we examined sensitivity of vibration detection to aminoglycoside antibiotics, Ca(2+)-free seawater, and amiloride . Like vertebrate hair bundles, anemone hair bundles are composed of stereocilia, possess lateral linkages between stereocilia whose preservation for transmission electron microscopy is enhanced by ruthenium red, and possess tip links morphologically similar to vertebrate tip links . Furthermore, vibration-dependent discharge of nematocysts is reversibly inhibited by 10(-4) M streptomycin and abolished by brief exposure to Ca(2+)-free seawater . However, unlike vertebrate hair bundles, anemone hair bundles appear to be insensitive to amiloride since vibration-dependent discharge of nematocysts is unaffected by up to mM amiloride . Thus, anemone hair bundles may serve as a useful model system for vertebrate hair bundles with the interesting feature of being insensitive to amiloride.

Nat Biotechnol, 1997 May, 15(5), 432 - 5
Efficient hammerhead ribozyme and antisense RNA targeting in a slow ribosome Escherichia coli mutant; Chen H et al.; We have evaluated inhibition of the plasmid-born chloramphenicol acetyl transferase gene (CAT) by the hammerhead ribozyme and antisense RNA in Escherichia coli where the translation and transcription rates have been modified . Whereas neither antisense nor the hammerhead had an inhibitory effect on CAT activity in wild-type E . coli, both reduced the level of the messenger RNA and the activity of the CAT gene by almost 60% in a slow ribosome mutant . Streptomycin, which increases the speed of translation in this mutant strain, restored full CAT activity . The level of CAT activity expressed from a T7 RNA polymerase promoter was not affected by the presence of either antisense RNA or the hammerhead ribozyme . When the target gene was expressed from a chromosomal locus in wild-type E . coli, both antisense RNA and the hammerhead ribozyme showed some inhibitory activity, but the level of inhibition was significantly increased in the slow ribosome strain . This bacterial system offers a unique entry to the study of cellular factors which mediate the activity of ribozymes in vivo.

J Clin Microbiol, 1997 May, 35(5), 1287 - 9
Determination of drug susceptibility of Mycobacterium tuberculosis through mycolic acid analysis; Garza-Gonzalez E et al.; In the present work a rapid method to determine the susceptibility of Mycobacterium tuberculosis to isoniazid and streptomycin by determining levels of mycolic acids by high-performance liquid chromatography (HPLC) was developed . Mycobacterial growth kinetics in the presence and absence of antituberculosis drugs was characterized by evaluating the total area corresponding to mycolic acid peaks (TAMA) . Results show a linear relationship between the logarithm of CFU per milliliter and TAMA and show that it is possible to detect growth inhibition of M . tuberculosis in the presence of isoniazid or streptomycin by using HPLC in 3 and 4 days, respectively.

FEMS Microbiol Lett, 1997 Apr 15, 149(2), 265 - 72
Properties of C-terminal truncated derivatives of the activator, StrR, of the streptomycin biosynthesis in Streptomyces griseus; Thamm S et al.; The StrR protein is a DNA-binding protein activating the transcription of streptomycin biosynthesis of Streptomyces griseus N2-3-11 and Streptomyces glaucescens . A putative helix-turn-helix motif located between amino acid positions 207 and 227 of the StrR protein was identified as a prerequisite for its DNA-binding properties . Although, C-terminal truncated StrR proteins were able to interact with StrR-binding sites, they failed to activate transcription from the StrR-dependent promotor strB1p . Therefore, the C-terminal domain of StrR seemed to be necessary for its function as transcriptional activator.

Mol Cell Probes, 1997 Apr, 11(2), 123 - 6
Geographic variation of the predictive values of genomic mutations associated with streptomycin resistance in Mycobacterium tuberculosis; Dobner P et al.; Specific mutations associated with resistance to streptomycin (SM) in Mycobacterium tuberculosis suggest themselves for its rapid prediction . However, as with any diagnostic test, their predictive values are dependent on their prevalences . In this report, SM resistance associated mutations in the rrs and rpsL genes of 25 SM resistant isolates from Germany and 25 SM resistant isolates from Sierra Leone were characterized and compared . Mutations in the rrs gene were infrequent in isolates from both localities (20% and 12%, respectively) and thus of limited predictive values . In contrast, rpsL mutations were found in 48% of the German isolates but only in 24% of the isolates from Sierra Leone . It is concluded that the predictive values of mutations in this gene may vary significantly with the origin of the samples under investigation.

Microbiology, 1997 Apr, 143 ( Pt 4), 1077 - 86
Expression analysis of the ssgA gene product, associated with sporulation and cell division in Streptomyces griseus; Kawamoto S et al.; The ssgA gene of Streptomyces griseus B2682, when present in high copy number, results in both suppression of sporulation and fragmented growth of mycelia . Western analysis with polyclonal antibodies against the gene product (SsgA) revealed a close correlation between SsgA accumulation and the onset of sporulation in wild-type cells . The protein was only detected in the cytoplasm . Certain developmental mutants of S . griseus (afs, reIC and brgA) which are defective in aerial mycelium formation in solid culture and submerged spore formation in liquid culture failed to accumulate SsgA . The SsgA protein appeared shortly (1 h) after nutritional shift-down of strain B2682 cells . afs mutant cells sporulated and expressed SsgA only when A-factor was present both before and after nutritional shift-down . Introduction of the ssgA gene in a low-copy-number vector into strain B2682 resulted in fivefold overexpression of SsgA, and was accompanied by fragmented growth of mycelia and suppression of submerged spore formation (in liquid culture) and aerial mycelium formation (in solid culture) . Streptomycin production was not inhibited . In a control experiment, a nonfunctional ssgA gene possessing a frameshift mutation near its N-terminus had no effect on either growth or sporulation . It is proposed that the ssgA gene product plays a role in promoting the developmental process of S . griseus.

J Bacteriol, 1997 Apr, 179(8), 2748 - 52
A mutation at proline-115 in the A-factor receptor protein of Streptomyces griseus abolishes DNA-binding ability but not ligand-binding ability; Onaka H et al.; A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) and its specific receptor protein (ArpA) are required for streptomycin production and aerial mycelium formation in Streptomyces griseus . A mutant strain HO1 that produced streptomycin and formed aerial mycelium and spores was derived from an A-factor-deficient mutant, S . griseus HH1 . The phenotypes of mutant HO1 were found to result from a single amino acid replacement of ArpA; the proline residue at position 115 in the wild-type ArpA was replaced by serine, yielding mutant ArpA (P115S) . The mutant ArpA (P115S) was still able to form a homodimer and possessed A-factor-binding ability but lost the ability to bind DNA . The properties of P115S suggest that ArpA consists of two independently functional domains, one for A-factor binding and one for DNA binding, and that proline-115 plays an important role in DNA binding . This is in agreement with the idea that A-factor binding to the COOH-terminal domain of ArpA causes a subtle conformational change of the distal NH2-terminal DNA-binding domain, resulting in dissociation of ArpA from DNA.

Acta Otolaryngol, 1997 Mar, 117(2), 219 - 21
A study on temperature dependent vestibular potential: effect of long lasting thermal stimulus and aminoglycoside agent; Suzuki M et al.; Effect of temperature changes on the vestibular receptor was studied using isolated posterior semicircular canals (PSC) of bull frogs . Cupula was removed from the crista . PSC was placed in the inner compartment of the double chamber . Warm or cool water was filled in the outer compartment to change the temperature of the inner compartment . Changes of the spontaneous discharge were recorded from the ampullary nerve . When cooled, the discharge temporarily increased, followed by a gradual decrease . When warmed, it temporarily decreased and then increased, forming response curves of a mirror image . After addition of streptomycin, the temperature dependent response disappeared . These results suggest that the semicircular canal receptor is activated by direct temperature effects.

Semin Respir Infect, 1997 Mar, 12(1), 61 - 7
Tularemia pneumonia; Gill V et al.; Tularemia pneumonia may complicate the various clinical presentations of tularemia, or present as an uncommon zoonosis . Approximately 200 cases of tularemia are reported in the United States per year, and 10% to 20% present with pneumonia either as a primary event or as a complication of ulceroglandular or typhoidal tularemia . Tularemia pneumonia also occurs with the other tularemic forms, glandular, oculoglandular, and oropharyngeal tularemia as a result of secondary bacteremic spread to the lungs . Pneumonia usually occurs within 2 days to months after infection . The mortality rate of primary tularemic pneumonia and pneumonia complicating typhoidal tularemia is high . The clinical and roentgenographic presentations of tularemia pneumonia are highly variable and is one of the zoonotic atypical pneumonias . Tularemic pneumonia may mimic fungal and bacterial pneumonias, tuberculosis, or malignancy . The diagnosis of tularemic pneumonia should be considered in any patient presenting with an atypical pneumonia with the finding of an ulcer and/or lymphadenopathy and a history of outdoor activity . Serum agglutination tests and ELISA are the basis of serological diagnosis . Francisella tularensis can be cultured from the sputum, skin ulcer, pleural fluid, and the lymph nodes, but cultures should not be obtained because of the danger to laboratory personnel . The drug preferred for treatment of tularemic pneumonia is streptomycin for 1 to 2 weeks.

Genetics, 1997 Mar, 145(3), 771 - 6
Multiple origins of a mitochondrial mutation conferring deafness; Hutchin TP et al.; A point mutation (1555G) in the smaller ribosomal subunit of the mitochondrial DNA (mtDNA) has been associated with maternally inherited traits of hypersensitivity to streptomycin and sensorineural deafness in a number of families from China, Japan, Israel, and Africa . To determine whether this distribution was the result of a single or multiple mutational events, we carried out genetic distance analysis and phylogenetic analysis of 10 independent mtDNA D-loop sequences from Africa and Asia . The mtDNA sequence diversity was high (2.21%) . Phylogenetic analysis assigned 1555G-bearing haplotypes at very divergent points in the human mtDNA evolutionary tree, and the 1555G mutations occur in many cases on race-specific mtDNA haplotypes, both facts are inconsistent with a recent introgression of the mutation into these races . The simplest interpretation of the available data is that there have been multiple origins of the 1555G mutation . The genetic distance among mtDNAs bearing the pathogenic 1555G mutation is much larger than among mtDNAs bearing either evolutionarily neutral or weakly deleterious nucleotide substitutions (such as the 4336G mutation) . These results are consistent with the view that pathogenic mtDNA haplotypes such as 1555G arise on disparate mtDNA lineages which because of negative natural selection leave relatively few related descendants . The co-existence of the same mutation with deafness in individuals with very different nuclear and mitochondrial genetic backgrounds confirms the pathogenicity of the 1555G mutation.

Gene, 1997 Feb 28, 186(2), 197 - 200
A sensitive reporter gene system using bacterial luciferase based on a series of plasmid cloning vectors compatible with derivatives of pBR322; Manen D et al.; We present a series of plasmid cloning vectors that are derived from a mutant of pSC101 possessing an elevated number of copies per genome equivalent . These vectors are compatible with any plasmid replicating from a pBR322 origin and use spectinomycin and/or streptomycin as a selective marker . They can be used whenever the simultaneous presence of several plasmids in the cell is desired . We use this vector system for the constitutive expression of the genes that are responsible for the production of the aldehyde substrate of bacterial luciferase . Transcription from promoters carried on a second plasmid can thus be measured within the living cell over a range of 3 orders of magnitude using bacterial luciferase as a reporter gene.

Nippon Jibiinkoka Gakkai Kaiho, 1997 Feb, 100(2), 253 - 63
{The mechanism of formation of the otoconia in the utricular supporting cells of the guinea pig}; Mori N; The mechanism of formation of the otocania in the utricular supporting cells of the guinea pig was investigated by means of an organ culture system using the potassium pyroantimonate (PA) precipitation method . The utricular otoconia and the secretory granules and mitochondria in the utricular supporting cells immediately after removal from the animal were positive to PA . When the specimens were treated with ethylene-glycol-0, 0-bis (2-aminoethyl)-N, N, N', N'-tetraacetic acid (EGTA) as a chelater prior to the PA staining, almost all deposits disappeared . This indicates that calcium is the main ion precipitated by the PA method . The utricules of the guinea pig were exposed to 30 mg of streptomycin sulfate per ml for 3 days in culture . The number of large lysosomes which contained vesicles and myeloid bodies in the supporting cells increased . On the other hand, the secretory granules were reduced in the cytoplasm of the supporting cells . Acid phosphatase activity in the lysosomes and the Golgi apparatus decreased . As a result of the PA treatment, these large lysosomes, especially the vesicles which were in them, contained a large quantity of calcium ion . From these findings, I conclude that the mechanism of formation of otoconia is as follows: The area of formation of otoconia is the supporting cells . Globular substances are the precursors of otoconia, and they contain calcium ion which was taken into the supporting cells . These globular substances are made in close relationship among the endplasmic reticula, secretory granules and lysosomes . They are secreted from the supporting cells and form the mature otoconia on the otoconial membrane.

Otolaryngol Head Neck Surg, 1997 Feb, 116(2), 189 - 92
Prospective randomized study of thrice weekly six-month and nine-month chemotherapy for cervical tuberculous lymphadenopathy; Yuen AP et al.; The aim of this study is to compare the efficacy of a thrice weekly 6-month regimen, 4S3H3R3Z3/2H3R3 (which consists of an initial 4 months of streptomycin (S), isoniazid (H), rifampicin (R), and pyrazinamide (Z) followed by 2 months of isoniazid and rifampicin), with a thrice weekly 9-month regimen, 4S3H3R3Z3/5H3R3 (which consists of an initial 4 months of streptomycin, isoniazid, rifampicin, and pyrazinamide followed by 5 months of isoniazid and rifampicin), in the treatment of cervical tuberculous lymphadenopathy . A total of 113 patients were recruited between August 1987 and December 1993 . Twenty-two patients were excluded from the analysis because of defaulting treatment or modification of regimen . Ninety-one patients were included in the analysis . Forty-three patients were given the 6-month regimen, and 48 patients were given the 9-month regimen . Two (5%) patients of the 6-month regimen and one (2%) patient of the 9-month regimen had primary failure after completion of treatment (relative risk, 2.23; 95% confidence interval, 0.21 to 23.76) . Of the 88 patients who had initial clinical remission after completion of treatment, the 5-year actuarial remission rates were 89% for the 6-month regimen and 90% for the 9-month regimen (Wilcoxon, p = 0.44) . There were no significant differences of both primary failure rate and 5-year actuarial remission rate of the two regimens . The 6-month regimen is recommended as the initial treatment of tuberculous lymphadenopathy.

J Med Genet, 1997 Feb, 34(2), 169 - 72
Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity; Pandya A et al.; Irreversible hearing loss is a catastrophic complication of treatment with aminoglycoside antibiotics such as streptomycin, gentamycin, and kanamycin . Many kindreds showing a matrilineal pattern of inheritance of this trait have been described in China where the widespread use of aminoglycoside antibiotics accounts for approximately 25% of profound deafness in some districts . Because of the characteristic inheritance pattern, mitochondrial DNA (mtDNA) mutations were postulated to be the cause of the deafness in these pedigrees . In 1993 it was shown that an A to G substitution at base pair 1555 of the mitochondrial 12S ribosomal RNA gene was the only mutation common to all the families with aminoglycoside ototoxicity . We ascertained three Mongolian pedigrees from the School for the Deaf and Blind in Ulaanbaatar, all of which contained multiple affected subjects with streptomycin induced deafness in a pattern consistent with matrilineal transmission . Amplified mtDNA, obtained from transformed lymphoblastoid cell lines using previously described primers, showed the A to G point mutation in the 12S rRNA gene in two of the three families by restriction analysis as well as direct sequencing . No other example of this substitution was found among 400 control samples from Mongolians with normal hearing . We have thus confirmed the clinical relevance of the 1555 A to G mitochondrial mutation in the 12S rRNA gene by identifying it in affected subjects with familial aminoglycoside ototoxicity in another ethnic group . In countries where aminoglycosides are widely used, genetic counselling and screening of high risk families before the use of these drugs could have a dramatic effect on the incidence of deafness.

Endocrinology, 1997 Feb, 138(2), 764 - 70
Thyroid hormones regulate the onset of osmotic activity of rat liver mitochondria after birth; Almeida A et al.; The effect of thyroid hormone deprivation on the osmotic activity of liver mitochondria from early newborn rats was studied . Experimentally induced hypothyroidism prevented the increase in the osmotic activity of mitochondria observed immediately after birth . Osmotic activity was restored by T4 and T3 treatment to hypothyroid newborns but not when this treatment was supplemented with cycloheximide . Under the same circumstances, streptomycin had no effect . Hypothyroidism abolished the change in the slope of the osmotic curve (plot of inverse absorbance of mitochondrial suspensions incubated in sucrose solutions vs . inverse sucrose concentration) observed in mitochondria from euthyroid newborns at 110-120 mOsm sucrose, suggesting that hypothyroidism prevents the formation of tight physical connections between mitochondrial outer and inner membranes . Thyroid hormone deprivation increased the passive permeability of the mitochondrial inner membrane to protons, resulting in a decreased respiratory control ratio . Hypothyroidism prevented the sharp decrease in the affinity of mitochondria for ATP observed in euthyroid newborns immediately after birth . These results corroborate our previous suggestion (Endocrinology, 1995, 136:4448) that, during the early neonatal period, thyroid hormones control the synthesis of some nucleus-coded protein(s) involved in the assembly of F0,F1-ATPase.

Biochemistry (Mosc), 1997 Jan, 62(1), 71 - 6
Purification and characterization of citrate synthase from Methylobacterium extorquens--a methylotrophic producer of polyhydroxybutyrate; Belova LL et al.; Citrate synthase (citrate oxaloacetate-lyase, CoA-acetylating; EC 4.1.3.7, CS) was isolated and purified to homogeneity from a methylotrophic producer of polyhydroxybutyrate (PHB), Methylobacterium extorquens 15 . The purification procedure includes streptomycin sulfate treatment of cell-free extract, ammonium sulfate fractionation, two steps of hydrophobic chromatography, and ion-exchange chromatography . The specific activity of the final enzyme preparation was 24 U/mg protein . The enzyme has apparent molecular weight 260 kD and consists of four 66-kD subunits . The enzyme shows a sigmoid saturation curve with CoASA (h = 1.3) . Kinetic parameters are: K(m) = 84 microM for CoASA; K(m) = 12 microM for oxaloacetate; Vmax = 29.7 mumoles/min per mg protein . KCl at concentrations up to 80 mM activates the CS . ATP exerts a significant inhibitory effect on the enzyme activity, whereas NAD(P)H, isocitrate, alpha-ketoglutarate, ADP, acetoacetyl-CoA, glyoxylate, and glutamate have no influence . A possible role of the CS in coordinated control of CoASA transformation through the tricarboxylic acid cycle and PHB biosynthesis in this methylotroph is discussed.

Eur Arch Otorhinolaryngol, 1997, 254(3), 153 - 7
Cell death caused by the acute effects of aminoglycoside and zinc in the ampullary cristae of guinea pigs; Nakagawa T et al.; We reported that apoptosis occurred in the guinea pig vestibular hair cells after chronic aminoglycoside treatments . In the present study, we used in situ nick-end labeling to determine whether apoptosis was also induced by the acute effects of aminoglycosides in guinea pig ampullar cristae . In addition, we evaluated the effect of zinc supplements upon these ototoxic treatments . After a local application of streptomycin directly to the round window, we found labeled bodies in the vestibular hair cells . The zinc supplement increased the number of labeled bodies resulting in severe hair cell loss . These findings indicate that the acute effects of aminoglycosides also induce apoptosis of the vestibular hair cells, and that zinc enhances aminoglycoside ototoxicity . Consequently, we propose that an interaction with ion channels may play a key mechanism in the processes of apoptosis affecting the vestibular hair cells.

Mol Gen Mikrobiol Virusol, 1997, (1), 8 - 14
{The effect of various physiological and genetic factors on the transition process of enterotoxigenic strains of Escherichia coli into uncultured state}; Chetina EV; Factors accelerating the transfer of enterotoxigenic E . coli strains in unculturable state have been revealed . These factors were illumination, aeration, hypertonic conditions of the microcosm, and exposure to cobalt chloride . Enterotoxigenic E . coli cells were seeded in solid nutrient media from microcosms with 0.9% NaCl solution for the longest time . The rate of transfer in unculturable forms of the examined bacteria changed depending on the medium of preliminary culturing and the phase of culture growth . Effects of mutations in some chromosome genes on the rate of transfer of bacteria in unculturable state were studied . Switching off the chromosomal genes gltB, livJ, and ompR accelerated the transfer of bacteria in unculturable forms . The vegetative functions of uncultured forms of the model enterotoxigenic strain IG187 recover in the presence of low concentrations of streptomycin or chloramphenicol.

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