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Ear Nose Throat J, 1991 Jun, 70(6), 393 - 5
Sump catheter drainage of parotid abscess: an alternative to surgery; Berman J et al.; It is a clinical challenge to distinguish patients with parotid abscesses from those with acute sialadenitis . A case of parotid abscess is presented in which a CT scan with intravenous contrast enhancement localized the abscess cavity and guided its aspiration and drainage with an indwelling catheter . By using this percutaneous technique, the need for early surgical intervention by incision and drainage was eliminated . The dense overlying parotid fascia and position of the deep parotid lobe make differentiating between these two clinical entities difficult . Parotid abscesses are readily apparent on computerized tomographic (CT) scanning evaluation with intravenous contrast enhancement, presenting as discrete fluid-filled areas unlike the amorphous appearance of acute sialadenitis . CT scanning with intravenous contrast enhancement has been the preferred radiographic study of choice for evaluating parotid masses or parapharyngeal masses . The treatment of a patient with acute sialadenitis differs from that of a patient with a parotid abscess . Patients with acute sialadenitis will usually respond to vigorous intravenous (IV) hydration, use of sialagogues and appropriate antibiotic coverage . Following a period of conservative treatment with antibiotics and warm soaks, patients with parotid abscesses will usually undergo an incision and drainage procedure, and later, parotidectomy . A case of parotid abscess is presented in which a CT scan with intravenous contrast enhancement localized the abscess cavity and guided its aspiration and drainage with an indwelling catheter . Percutaneous drainage of parapharyngeal abscesses guided by CT has been previously described by Cole . By using this percutaneous technique, the need for early surgical intervention by incision and drainage was eliminated.

Jpn J Antibiot, 1991 Jun, 44(6), 689 - 96
{Pharmacokinetic and clinical studies on flomoxef in the perinatal period in obstetrics and gynecology}; Yamamoto T et al.; Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period in obstetrics and gynecology were performed and the results obtained are summarized as follows: 1 . Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid were determined after intravenous injection of 1 g . The maternal serum concentration was 41.9 micrograms/ml at 16 minutes after administration, and gradually decreased thereafter to 1.36 micrograms/ml at 5 hours 19 minutes . The concentration of FMOX in umbilical cord serum was 17.5 micrograms/ml at 16 minutes after administration, then gradually decreased thereafter, was slightly higher than that in maternal serum after approx . 3 hours and was 2.88 micrograms/ml at 5 hours 19 minutes . The amniotic fluid concentration was 0.31 micrograms/ml at 16 minutes after administration, increased to 7.85-15.8 micrograms/ml at approx . 3 hours, and gradually decreased while maintaining relatively high levels . 2 . One or two grams of FMOX were given by intravenous drip infusion twice daily to 17 patients with perinatal infections for 5 to 7 days . Clinical efficacies were evaluated as excellent in 7 cases and good in 10, suggesting that FMOX was effective in all cases . No subjective side effects were observed in any of the 17 patients . As to abnormal laboratory findings, a minor degree of elevation of GPT was observed in 1 patient and that of GOT.GPT in 1 . No other abnormal changes in laboratory examinations were observed . Considering the above results, we conclude that FMOX is a useful antibiotic in perinatal infections.

Jpn J Antibiot, 1991 Jun, 44(6), 659 - 61
{Clinical studies on flomoxef in pregnant women with infections during the perinatal period}; Iwaki M et al.; Clinical efficacies of flomoxef (FMOX), which is a newly developed oxacephem antibiotic, were evaluated in 14 cases of obstetric and gynecologic infections during the perinatal period . The results were excellent in 6 cases (42.9%) and good in 8 cases (57.1%) . No side effects nor abnormal clinical laboratory test results were observed in mothers or neonates . Thus, FMOX appears to be a useful antibiotic for perinatal infections.

Zentralbl Veterinarmed B, 1991 Jun, 38(4), 283 - 91
Chicken egg antibodies for prophylaxis and therapy of infectious intestinal diseases . V . In vivo studies on protective effects against Escherichia coli diarrhea in pigs; Wiedemann V et al.; A field study and a controlled infection trial showed the protective effect of egg yolk lyophilisate and whole egg lyophilisate against enterotoxic E . coli germs . The lyophilisates were gained from eggs of hens immunized against pilus antigen of porcine-enterotoxic E . coli . In a first field study using egg yolk antibodies, 92% of 299 diarrhea affected piglets were cured . In a further field study diarrhea affected piglets were cured after 3 days by application of egg yolk lyophilisate from immunized hens . Piglets treated only with egg yolk of not immunized hens showed no signs of recovery . The infection trial showed, that whole egg lyophilisate of immunized hens was as successful as a common antibiotic therapy in curing piglets, orally infected with 5 x 10(10) E . coli/feeding and animal . The present data show that chicken egg antibodies can be used for treatment of infectious diarrheal diseases in young animals . So far they represent a good alternative to the common used antibiotic therapy.

AIDS, 1991 Jun, 5(6), 765 - 7
Successful management of intractable cryptosporidial diarrhea with intravenous octreotide, a somatostatin analogue; Kreinik G et al.; A 38-year-old man with AIDS and intractable large-volume diarrhea due to a cryptosporidial infection was successfully treated with intravenous octreotide, a somatostatin analogue . The volume of diarrhea, 10-12 liters with 8-13 movements per day, was reduced to three to four semi-formed to formed stools per day when the patient was treated with 400 micrograms intravenous octreotide daily . The patient's intravenous hyperalimentation was discontinued and he returned to oral feeding . He quickly regained his normal weight and has now resumed his normal activities . For those patients who cannot tolerate subcutaneous administration, intravenous octreotide therapy may not only be life-saving but may also markedly increase the quality of life . Roxithromycin, a macrolide antibiotic, was also administered to this patient with cryptosporidiosis but efficacy was not demonstrated.

Hear Res, 1991 Jun, 53(2), 293 - 311
Cochlear cultures as a model system for studying aminoglycoside induced ototoxicity; Richardson GP et al.; Light and electron microscopy have been used to evaluate the effects of treating mouse cochlear cultures with the ototoxic aminoglycoside antibiotic neomycin sulphate at concentrations of 0.2 mM and greater for periods of up to 1 hour . Neomycin rapidly induces the formation of numerous, membrane filled blisters on the apical surfaces of the sensory hair cells . Such morphological damage is restricted to the hair cells, and is not observed on the surfaces of supporting cells within the organ of Corti . Hair cells in apical-coil cultures are less sensitive than those in basal-coil cultures, and, at any given point along the cochlea, outer hair cells appear to be more extensively damaged by neomycin than inner hair cells . These morphological effects of neomycin are considerably more severe when the drug is applied in calcium/magnesium free saline, and can be blocked by elevating the saline concentration of either calcium or magnesium . The effects can also be blocked by lowering the temperature to 4 degrees C, but not by either K+ depolarization or the lectin Concanavalin A . The potential value of this culture system as a model for studying aminoglycoside induced ototoxicity is discussed.

Heredity, 1991 Jun, 66 ( Pt 3), 357 - 65
Wrinkling of the eye in hybrids between Drosophila virilis and Drosophila lummei is caused by interaction of maternal and zygotic genes; Heikkinen E; Hybrids of Drosophila virilis females and Drosophila lummei males have visible developmental anomalies in external adult structures . Reciprocal hybrids are normal, and the anomalies are not found in other interspecific F1 hybrids of the virilis subgroup . Antibiotic treatments with ampicillin, streptomycin and tetracycline did not cure the syndrome . The genetic basis of the wrinkling of the compound eye was analysed in detail . Both male and female F1 progeny of D . virilis mothers were affected, indicating that wrinkling of eyes is maternally determined . F1 hybrid females produced healthy progeny . Backcross hybrid females (D . virilis x F1) with 16 different combinations of autosomes, either heterozygous or homozygous for D . virilis, were crossed with D . lummei males . It was found that homozygous D . virilis chromosomes 2 and 5 together were necessary to induce the maternal effect . The hybrid zygote responded to the maternal effect when the chromosomes 2, 4 and/or 5 were heterozygous . Elimination of the small sixth (dot) chromosome of D . lummei from the hybrids was correlated with the wrinkling of eyes, but was not the cause, as the two phenomena had a different genetic basis and temperature response . Furthermore, the eyes were wrinkled in flies which presumably had had no D . lummei dot chromosome to lose.

Singapore Med J, 1991 Jun, 32(3), 179 - 82
Infections in the elderly; Owen RE et al.; Infections are a leading cause of morbidity and mortality in the elderly . Altered host defences, a senescent immune system, chronic illnesses, and environmental factors all contribute to the aged's predisposition to infection . Infections can present in atypical fashion contributing to diagnostic and therapeutic delays . Awareness of altered antibiotic absorption, metabolism, and excretion in the elderly is essential to correct antibiotic selection and dosing . Additionally, antibiotic interactions with medications commonly used to treat chronic illnesses should be taken into consideration prior to antibiotic prescribing . Prevention of infectious complications in the elderly requires interest, education, vaccination, and early intervention.

Orthopade, 1991 Jun, 20(3), 244 - 52
{Mid- to long-term results after treatment of 118 cases of periprosthetic infections after knee joint replacement using one-stage exchange surgery}; von Foerster G et al.; From 1976 to 1985, 157 periprosthetic infections after knee arthroplasty were treated surgically at the ENDO-Klinik in Hamburg . Of these, 118 cases underwent one-stage revision arthroplasty using specific antibiotic-loaded cement; 104 were available for analysis after a postoperative follow-up period of 5-15 years . Seventy-six cases were cured as a result of this single operation . This number was increased to 84 by a repeated operation in cases that had failed to respond to therapy . In 20 cases one-stage revision arthroplasty failed in the treatment of periprosthetic infections after replacement of the knee joint.

J R Army Med Corps, 1991 Jun, 137(2), 100 - 3
Third molar surgery: the effect of primary closure, wound dressing and metronidazole on postoperative recovery; Lyall JB; One hundred and forty eight patients with bilateral symmetrically impacted lower third molars entered a clinical crossover trial to compare the effects on postoperative recovery of a Bismuth Iodoform Paraffin Paste (BIPP) socket dressing, primary closure using a resorbable suture (Softgut) and to ascertain if prophylactic metronidazole influenced the outcome . The results reaffirm the surgical principle that contaminated surgical wounds such as third molar sockets are best kept open with a dressing . Attempts at primary closure should be resisted if there is no intention to prescribe antibiotic cover . However, if a suitable antibiotic is taken then primary closure using a resorbable suture can be carried out with confidence . This may reduce the need for outpatient follow up.

J Clin Pharm Ther, 1991 Jun, 16(3), 167 - 76
Pharmacokinetics of tobramycin in pregnant women . Safety and efficacy of a once-daily dose regimen; Bourget P et al.; The pharmacokinetics of tobramycin, an aminoglycoside antibiotic, was investigated after a short intravenous infusion and once-daily dose regimen in two groups of nine pregnant women during the second (Group 1) and the third (Group 2) trimester of pregnancy . During these periods, the risk of infectious diseases is increased . Plasma concentrations of tobramycin were measured by fluorescence polarization immunoassay . The decrease in clearance (21%), at 28 weeks and more of gestation leads to an increase in half-life and the mean residence time (MRT) in the second group (33 and 29% respectively) . The volume of distribution was unchanged in the two groups . No accumulation of the drug was observed in pregnant women . Pharmacokinetic disorders are correlated with the term and moreover with the weight deviation of women, i.e . the growth of the fetus . These findings suggest accumulation of the aminoglycoside antibiotic in the fetus . Moreover, the efficacy and the safety of this therapeutic regimen were excellent . To limit the potential nephrotoxicity and ototoxicity of tobramycin for the mother and the fetus, a once-daily dose regimen seems to be acceptable for the treatment of non-neutropenic pregnant women.

Clin Obstet Gynecol, 1991 Jun, 34(2), 336 - 44
Preventing fetal damage from sexually transmitted diseases; Minkoff HL; The STDs threaten the reproductive health of women in many ways, ranging from premature births through congenital infections and death . An understanding of the natural history of these diseases permits timely interventions which can mitigate the perinatal damage caused by these infections substantially . Ideally, primary prevention or safer sex will be adopted by sexually active women, thereby reducing the morbidity not only for their offspring but for themselves as well . Antiviral therapy is not yet available for minimizing any hazard of fetal exposure to HPV, HSV, HIV, and hepatitis B viral infections . Early antibiotic therapy should reduce the risk of congenital syphilis and any perinatal hazards associated with chlamydial and gonococcal infections.

Aust Fam Physician, 1991 Jun, 20(6), 797, 800, 802 - 4
Conjunctivitis; Hirst LW; Most cases of conjunctivitis are either viral in origin, which makes them extremely contagious and usually self-limited, or bacterial, which usually requires topical antibiotic therapy . Prolonged follicular conjunctivitis should be considered chlamydial in origin and requires systematic antibiotic therapy.

Clin Chest Med, 1991 Jun, 12(2), 245 - 56
Infections with Chlamydia pneumoniae strain TWAR; Thom DH et al.; Chlamydia pneumoniae has recently been recognized as an important cause of respiratory tract disease, including atypical pneumonia . Serosurveys suggest that C . pneumoniae is endemic in most countries and is capable of causing outbreaks and epidemics of pneumonia, especially in countries where the antibody prevalence is relatively low . The population incidence of infection appears to be cyclical, with approximately 4-year cycles in the US (Seattle) and 6-year cycles in Denmark having been demonstrated . Pneumonia caused by the organism is unusual in young children in developed countries but may be an important cause of lower respiratory infections among children in developing and tropical countries . In otherwise healthy adults, C . pneumoniae pneumonia usually can be treated effectively on an outpatient basis . Patients with C . pneumoniae pneumonia often have a gradual onset of symptoms: a sore throat and hoarseness followed by a cough . Auscultatory and radiographic findings usually are prominent, even in patients with mild disease, and a cough and malaise may persist for several weeks or more after appropriate therapy . Microimmunofluorescence serologic testing is available in only a few laboratories . However, the new HL cell line holds promise of making culture and isolation of C . pneumoniae more widely available . Questions remain about the routes of transmission of C . pneumoniae, its incubation period, its role in lower respiratory disease in children in developing countries, the optimal antibiotic therapy, the existence and importance of chronic and latent C . pneumoniae infections, and the organism's association with nonrespiratory tract disease.

J Biochem (Tokyo), 1991 Jun, 109(6), 807 - 10
Neocarzinostatin: interaction between the antitumor-active chromophore and the carrier protein; Takashima H et al.; Conformational analysis of neocarzinostatin, an antibiotic protein with antitumor activity, in its holo-state in solution was carried out by NMR-spectroscopy . The results showed a beta-barrel structure for the carrier protein, in which the chromophore is tightly enwrapped and thus shielded from exposure to the solvent . The three-dimensional structure of this complex led to the proposal of a possible mechanism for the exposure or release of the active principle due to subtle environmental changes, e.g., in pH.

Pediatr Dermatol, 1991 Jun, 8(2), 166 - 8
Treatment of infantile cystic acne with oral isotretinoin: a case report; Arbegast KD et al.; Infantile cystic acne is rare, and its etiology is not clearly defined . Our patient had comedones at 2 months of age that were recalcitrant to multiple-antibiotic regimens . His condition worsened, and he was diagnosed with infantile cystic acne at 10 months of age and started on a trial of oral isotretinoin (Accutane) . A five-month treatment period using doses ranging from 0.36 to 0.67 mg/kg was necessary to achieve adequate control . Oral isotretinoin may be safe and effective in cases of recalcitrant infantile acne, but we advocate close monitoring because of the well-known side effects of oral retinoids.

Probl Vet Med, 1991 Jun, 3(2), 142 - 52
Cleft palate repair; Waldron DR et al.; Cleft palates are congenital or acquired and effect the primary palate (lip) or the secondary (hard and soft) palate . Surgical repair of congenital cleft palate is indicated at an early age . Preservation of maximal tissue and tissue blood supply and a tension-free closure of the defect are requisite for successful repair . Multiple surgical procedures are often performed prior to resolution of this problem . Aspiration pneumonia is often present concurrently and should be treated with appropriate antibiotic therapy.

G Chir, 1991 Jun-Jul, 12(6-7), 393 - 5
{Infectious chemoprophylaxis in colorectal surgery . A multicenter study of imipenem-cilastatin vs . cefuroxime and metronidazole or cefotetan}; Sortini A et al.; The authors report the results of a multicentric clinical study on prevention of surgical infections in colorectal surgery by chemo-antibiotic prophylaxis . This trial was carried on to evaluate the effect of imipenem-cilastatin (1 g i.v . just before operation and 1 g i.v . 3 hours from surgical procedure) vs . cefuroxime + metronidazole (1.5 g + 0.25 g i.v.) or cefotetan (1 g i.v.) given with the same modalities . In 48 patients undergoing colorectal resection (47 with malignant neoplastic disease) 24 were treated with imipenem, 18 with cefuroxime and 6 with cefotetan . In group A (imipenem-cilastatin) the infection rate was 4.2% (1/24 cases), in group B (cefuroxime + metronidazole or cefotetan) postoperative infections were registered in 4 out of 24 cases (16.6%) . This study documented the good results of systemic chemoprophylaxis and the great efficacy of imipenem-cilastatin in colorectal surgery.

Orthopade, 1991 Jun, 20(3), 227 - 38
{Infection of knee endoprosthesis}; Harle A; In knee arthroplasties, infection was and still is the most decisive factor with respect to the end result . Control of infection without removal of the endoprosthesis can be achieved only when an early revision is performed in the first 6 weeks after the arthroplasty . Half-hearted antibiotic medication alone is an unsuitable remedy . Therefore, an infection must be diagnosed without delay and followed up by decisive management . Clinical and laboratory data must be considered together and must supplement each other . Late infections need temporary or permanent removal of the endoprosthesis as a prerequisite for getting rid of the infection . Reimplantation and arthrodesis should be done in a two-stage procedure after the infection is healed . Reimplantation should be restricted to cases in which the infection is definitely under control and in which there is a good bone stock . Arthrodesis is still the treatment of choice, especially in patients with bony defects in the metaphysis of the femur and tibia . Arthrodesis also needs good soft tissue cover, and to prevent a reinfection in this dangerous area we suggest the use of antibiotic-releasing bone plates for stabilisation . External fixation has a high percentage of pintrack infections and often cannot be applied long enough; thus non-unions are the logical consequence.

Arch Int Physiol Biochim Biophys, 1991 Jun, 99(3), 247 - 50
Effects of cefroxadine on L-leucine absorption in rat jejunum; Mendizabal MV et al.; The effect of cefroxadine, an aminocephalosporin (beta lactam antibiotic) on rat intestinal L-leucine transport has been studied . Cefroxadine inhibited the L-leucine uptake by the intestinal mucosa in a dose-dependent fashion . In vivo studies showed that cefroxadine reduced L-leucine absorption . This effect was irreversible . Only the active transport component of the absorption was inhibited . Oxygen consumption of the mucosa was reduced by cefroxadine which inhibited the activity of the basolateral (Na(+)-K+) ATPase also.

Endocrinology, 1991 Jun, 128(6), 3047 - 54
Neomycin mimics the effects of high extracellular calcium concentrations on parathyroid function in dispersed bovine parathyroid cells; Brown EM et al.; We examined the effects of the polycationic antibiotic, neomycin, on the function of dispersed bovine parathyroid cells . Neomycin caused a reversible, dose-dependent inhibition of low calcium (Ca++)-stimulated PTH release, with half-maximal inhibition at 30 microM . Maximal inhibition (with 200 microM neomycin) was not additive with the suppressive effects of high (2 mM) Ca++ . Neomycin also inhibited dopamine-stimulated cAMP accumulation by 90-98% at 100-200 microM, with a half-maximal effect at 40-50 microM . This action was reversible and was blocked by preincubating the cells overnight with 0.5 microgram/ml pertussis toxin . In addition to its suppressive effects on cAMP metabolism and PTH release, neomycin stimulated the accumulation of inositol phosphates and produced a transient increase in the cytosolic Ca++ concentration (Cai) in fura-2-loaded parathyroid cells . The neomycin-evoked spike in Cai persisted despite removal of extracellular Ca++, indicating that it arises from intracellular Ca++ stores . Exposure of cells to elevated magnesium (Mg++) concentrations elicited a similar spike in Cai but blocked the spike in Cai in response to subsequent addition of neomycin and vice versa . Thus, Mg++ and neomycin mobilize Ca++ from the same intracellular store(s) . These results indicate that a polycation, neomycin, closely mimics the effects of polyvalent cations on parathyroid function, suggesting that both agents regulate parathyroid function via similar biochemical pathways.

J Biol Chem, 1991 May 25, 266(15), 9971 - 6
The role of cysteines in polyketide synthases . Site-directed mutagenesis of resveratrol and chalcone synthases, two key enzymes in different plant-specific pathways; Lanz T et al.; Resveratrol and chalcone synthases are related plant-specific polyketide synthases that are key enzymes in the biosynthesis of stilbenes and flavonoids, respectively . The stepwise condensing reactions correspond to those in other polyketide and fatty-acid synthases . This predicts that the two proteins also contain cysteines that are essential for enzyme activity because they bind the substrates . We exchanged, in both enzymes, all of the 6 conserved cysteines into alanine by site-directed mutagenesis and tested the mutants after expression of the proteins in the Escherichia coli heterologous system . Only cysteine 169 was essential in both enzymes, and inhibitor studies suggest that it is the main target of cerulenin, an antibiotic reacting with the cysteine in the active center of condensing enzymes . Most of the other exchanges led to reduced activities . In two cases, the enzymes responded differently, suggesting that the cysteines at positions 135 and 195 may be involved in the different product specificity of the two enzymes . The sequences surrounding the essential cysteine 169 revealed no similarity to the active sites of condensing enzymes in other polyketide synthases and in fatty acid biosynthesis . The available data indicate that resveratrol and chalcone synthases represent a group of enzymes that evolved independently of other condensing enzymes.

Eur J Pharmacol, 1991 May 25, 207(1), 17 - 22
Polymyxin B is a selective and potent antagonist of calmodulin; Hegemann L et al.; Polymyxin B, a cyclic peptide antibiotic, is considered to be a rather selective antagonist of protein kinase C . This drug is therefore widely used to evaluate the involvement of protein kinase C in cellular processes . In the present study, we investigated the effects of polymyxin B on the activity of calmodulin-dependent cyclic 3':5'-nucleotide phosphodiesterase in vitro . The drug potently inhibited this enzyme (IC50 80 nM in the presence of 500 microM Ca2+), while about 200-fold higher concentrations were required to inhibit protein kinase C to the same extent . Phosphodiesterase inhibition was competitive with respect to Ca2+ and calmodulin . Evidence for the formation of a complex between polymyxin B and calmodulin was obtained by polyacrylamide gel electrophoresis under non-denaturing conditions, and by affinity chromatography of calmodulin on polymyxin B-agarose . We therefore suggest that, at least in vitro, polymyxin B is a potent and selective inhibitor of calmodulin.

J Mol Biol, 1991 May 20, 219(2), 145 - 9
Structural alteration in alternating adenine-thymine sequences in positively supercoiled DNA; McClellan JA et al.; An alternating adenine-thymine tract in a relaxed closed circular plasmid was found to become strongly reactive to osmium tetroxide in the presence of actinomycin D . We suggest that this is due to a local overwinding of the alternating tract as a result of positive supercoiling induced by intercalation of the antibiotic at GpC sequences elsewhere in the DNA . We have previously shown that (A.T)n sequences undergo a local underwinding in response to negative supercoiling, and it appears that such sequences are especially torsionally deformable in both directions.

Med J Aust, 1991 May 20, 154(10), 698 - 701
Augmentin-induced jaundice; Wong FS et al.; OBJECTIVE: To alert clinicians to the hepatotoxic potential of Augmentin (amoxycillin and clavulanic acid), a widely prescribed antibiotic, in susceptible patients, and to point out that the hepatic illness may be delayed but serious and protracted . DESIGN AND SETTING: Case reports of patients with Augmentin-induced jaundice referred to the gastroenterology departments in three major teaching hospitals, and a review of cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC) . PATIENTS: Eight patients with nine episodes of Augmentin-induced jaundice personally treated by the authors from March 1988 to February 1990 are described . A further 19 patients reported to ADRAC from May 1987 to November 1989 are discussed . All patient histories were carefully reviewed to ensure that there was a temporal relationship between the course of Augmentin and the onset of the hepatitic illness and that other causes of jaundice were reasonably excluded . RESULTS: Jaundice developed in some of these patients several weeks after drug treatment was completed . The illness may be protracted over many weeks . As yet, there has been no case of progressive disease leading to the liver failure . CONCLUSIONS: The data suggest that a hypersensitivity reaction to clavulanic acid is the likely cause of the jaundice . Therefore, Augmentin, although an important antibiotic, should be reserved for severe infections for which amoxycillin is unsuitable.

Eur J Pharmacol, 1991 May 17, 197(2-3), 187 - 92
A novel glutamate agonist, TAN-950 A, isolated from streptomycetes; Iwama T et al.; A novel antifungal amino acid antibiotic, TAN-950 A ({S}-2-amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid), was found to have affinity for three excitatory amino acid (EAA) receptors and to inhibit {3H}alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ({3H}AMPA), {3H}kainate and {3H}3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ({3H}CPP) binding competitively . It caused excitation of rat hippocampal CA1 neurons in vitro, an effect that was antagonized by an AMPA/kainate antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) . Chemical modification of TAN-950 A brought about a large change in its pharmacological activity . Alkylation at the C-3 position of the isoxazolone ring markedly increased the ability to elicite neuronal firing . This agonistic effect was also antagonized by DNQX . The (R) enantiomer of TAN-950 A had increased selectivity for the N-methyl-D-aspartate (NMDA) receptor subtype . This selectivity was further enhanced by removal of the methylene group from the amino acid moiety . The most potent NMDA agonistic activity was observed with {R}-2-amino-2-(2,5-dihydro-3-methyl-5-oxo-4-isoxazolyl)acetic acid . These derivatives of TAN-950 A might be useful agents for investigating the pharmacological and physiological roles of EAA receptors.

Biochem Biophys Res Commun, 1991 May 15, 176(3), 1473 - 81
BALB/C mouse 3T3 fibroblasts expressing human estrogen receptor: effect of estradiol on cell growth; Gaben AM et al.; Mouse 3T3 fibroblasts (clone A31) were stably transfected with human estrogen receptor (hER) . Among the four sublines expressing functional hER at approximately 10(4) estrogen binding sites/cell, three retained a non-transformed morphology and growth characteristics while the fourth displayed a transformed phenotype (criss-cross growth, lack of density arrest, reduced dependence on exogenous growth factors) . Estradiol (E2) had no effect on the growth of the three non-transformed hER expressing sublines . In contrast, low concentrations (1 to 20 nM) of E2 strongly inhibited the proliferation of the subline with transformed phenotype and high (100 nM) concentrations were toxic in these cells.

Proc Natl Acad Sci U S A, 1991 May 15, 88(10), 4230 - 4
Electroporation by using bipolar oscillating electric field: an improved method for DNA transfection of NIH 3T3 cells; Tekle E et al.; Using the plasmid DNA pSV2-neo (which, when integrated into the cellular genome confers resistance to the antibiotic G418 for selection), we examined and compared the transfection efficiency on NIH 3T3 cells electropermeabilized by applying a sequence of high-frequency unipolar or bipolar square waves or a single square pulse . Results show that a bipolar square wave is, at least, 1.7- and 5.5-fold more efficient than the unipolar square wave and single square pulse, respectively . In the range of electric field strength used for optimum transfection, the survivability of electropermeabilized cells was comparable between the unipolar and bipolar square waves but fell considerably with the single square pulse . Qualitative comparison of cell permeabilization induced by the three types of wave forms and monitored by ethidium bromide uptake revealed that only the bipolar square wave permeabilizes the cell membrane symmetrically at the two hemispheres facing the electrodes . With unipolar square wave or single square pulse, the membrane is permeabilized either on one side or asymmetrically . Taken together, our result suggests that permeabilization of the membrane at multiple sites without affecting cell survivability may account for the improvements in transfection efficiency observed with bipolar oscillating electric fields.

Arch Biochem Biophys, 1991 May 15, 287(1), 180 - 5
Duramycin effects on the structure and function of heart mitochondria . II . Energy conversion reactions; Sokolove PM et al.; The polypeptide antibiotic duramycin has been reported to interact selectively with phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol (Navarro et al., 1985, Biochemistry 24, 4645-4650) . PE is a major component of mitochondrial membranes . Duramycin was used to probe the role of PE in mitochondrial energy conversion reactions with the following results: (i) Duramycin uncoupled mitochondrial respiration, decreasing the respiratory control ratio to 1 at 5 microM . At concentrations of duramycin in excess of 10 microM, ADP addition inhibited electron transport . (ii) Duramycin inhibited oxidative phosphorylation (C50 less than 2 microM) . (iii) Duramycin stimulated mitochondrial ATP hydrolysis modestly . The antibiotic was 7- to 16-fold less effective in this regard than concentrations of carbonylcyanide p-trifluoromethoxyphenylhydrazone (F-CCP) which produced comparable uncoupling . (iv) Duramycin inhibited uncoupled ATPase activity (C50 = 8 microM) . Inhibition of the ATPase activity of intact mitochondria was blocked by 1 mM MgCl2 and 5 mM CaCl2; inhibition persisted in sub-mitochondrial particles assayed in the presence of 3 mM MgCl2 . The effects on mitochondrial function of free fatty acids (FFA) and duramycin are similar in many respects . It is suggested that duramycin, like FFA, uncouples via a nonclassical mechanism, possibly by disrupting intramembrane H+ transfer between redox and ATPase complexes . In addition, interaction of duramycin, either direct or indirect, with the F0 moiety of the mitochondrial ATPase and with one or more components of the respiratory electron transport chain is proposed.

Surg Gynecol Obstet, 1991 May, 172(5), 351 - 6
A randomized clinical trial of ampicillin, gentamicin and clindamycin versus cefotaxime and clindamycin in children with ruptured appendicitis; Schropp KP et al.; This prospective, randomized, double-blind study compares the efficacy, safety and cost-effectiveness of ampicillin, gentamicin and clindamycin (AGC) or cefotaxime and clindamycin (CC) for the treatment of children with complicated appendicitis . Ninety-seven children were randomized . Forty-seven were assigned to the AGC regimen and 50 received CC . Forty-two patients in the AGC group had an appropriate therapeutic outcome, whereas 48 of 50 children who received CC completed the trial successfully (p = NS) . There were no differences between the groups with reference to the duration of antibiotic administration, fever, leukocytosis or length of hospitalization . Complications of therapy were uncommon and neither regimen demonstrated a significant advantage from an economic standpoint . We concluded that, in childhood, complicated appendicitis can be treated with either CC or AGC with equal efficacy.

Biochemistry, 1991 May 7, 30(18), 4421 - 31
Steady-state fluorescence and molecular-modeling studies of tomaymycin-DNA adducts; Barkley MD et al.; The interaction of tomaymycin and 8-O-methyltomaymycin with calf thymus DNA was studied by steady-state fluorescence techniques . The 8-phenolic proton of tomaymycin has a pK = 8.0, and the phenolate anion is essentially nonfluorescent . However, the fluorescence of the DNA adduct does not decrease until pH greater than 10.5, when the DNA double helix denatures . Acrylamide quenches the fluorescence of the free antibiotic with a quenching rate constant kq = 7 x 10(9) M-1 s-1 . In DNA adducts, the quenching rate constant is reduced about 50-fold, indicating that the aromatic ring of the drug is shielded from the solvent . The four possible binding modes of the antibiotics were modeled on a 6-mer duplex by molecular mechanics calculations in the absence and presence of water and counterions . The modeling studies show that the antibiotic is buried in the minor groove in all binding modes, with the 8-substituent pointing away from the DNA core . Three or five waters are displaced from the minor groove, depending on the orientation of the drug on the DNA.

DICP, 1991 May, 25(5), 542 - 5
The role of corticosteroids in infants and children with bacterial meningitis; Bahal N et al.; Bacterial meningitis continues to be a cause of substantial morbidity in infants and children . Hearing impairment is the most common sequela of this disease . Corticosteroids have been used in an attempt to reduce the incidence of meningitis-induced hearing loss . Some studies have demonstrated a decrease in the incidence of hearing impairment in patients treated with cefuroxime plus dexamethasone compared with cefuroxime alone . Similar data are lacking for other frequently used antibiotics . Based on these studies, the use of dexamethasone should be considered in infants and children greater than two months of age with suspected bacterial meningitis . Critical issues including the timing of steroid initiation in relation to antibiotic therapy and the appropriate antibiotic-corticosteroid regimen must be addressed . Studies should be performed to define the exact role of corticosteroids in the treatment of bacterial meningitis . Until additional data are available, we recommend the use of dexamethasone in pediatric patients older than two months of age with bacterial meningitis.

J Gen Intern Med, 1991 May-Jun, 6(3), 216 - 22
Utilization of hospital resources by alcoholic and nonalcoholic patients: a prospective study; Niquille M et al.; OBJECTIVE: To measure any difference in the utilization of hospital resources between alcoholic patients and nonalcoholic patients (controls) in a department of internal medicine . DESIGN: Prospective comparative study . Alcoholics were identified as patients with Michigan Alcoholism Screening Test (MAST) scores of greater than or equal to 8 . Controls were defined as patients with MAST scores of less than or equal to 4, and matched with alcoholics for sex, age, and time of admission . The length of stay, as well as several indicators of utilization of diagnostic and therapeutic procedures, was used for the comparison of resource utilization . SETTING: General wards of internal medicine of a 1,000-bed city and teaching hospital in Lausanne, Switzerland . PARTICIPANTS: One hundred and three alcoholic patients and 103 controls aged 20-75 years, admitted from September 1, 1988, to March 18, 1989 . RESULTS: Alcoholics had the same lengths of stay (16 days), durations of intravenous infusions (six days), and durations of bladder catheterization (one day) . Statistically nonsignificant differences were found between alcoholics and nonalcoholics regarding the charges for routine laboratory examinations {693 vs . 734 Swiss francs (Sfrs)}, antibiotic therapies (218 vs . 145 Sfrs), and x-ray procedures (568 vs . 774 Sfrs; p = 0.06) . The average number of electrocardiograms (two vs . five; p less than 0.005) and the duration of intensive care unit (ICU) stay (one vs . two days; p less than 0.05) were significantly lower for alcoholics than for controls . A total hospital charges index was also lower for alcoholics than for controls (11,900 Sfrs vs . 12,800 Sfrs), but not significantly . CONCLUSION: The authors' results suggest that alcoholics do not use more hospital resources per admission than do nonalcoholics . Moreover, alcoholics tend to use less frequently some procedures, such as the ICU, electrocardiography, and x-ray examinations . Several hypotheses are developed to explain these results in relation to those of previous studies, which showed more use of medical care by alcoholics than by nonalcoholics.

Anat Rec, 1991 May, 230(1), 136 - 45
Potentiation of cochlear hair cell loss by acoustic stimulus and gentamicin in the guinea pig; Bhattacharyya TK et al.; We explored the possibility of synergism between a pure-tone stimulus and gentamicin in causing cochlear injury by analyzing hair cell loss . Guinea pigs receiving daily injections of gentamicin (200 mg/kg body wt.) for 1 week were exposed to a 2 kHz tone (95 dB SPL, 2 hours daily) . Surface preparations of the spiral organ were studied by phase contrast microscopy, and the extent of hair cell loss in the entire organ of Corti was recorded in cytocochleograms . Gentamicin by itself was slightly ototoxic, damaging the innermost row of outer hair cells, whereas exposure to sound alone caused no hair cell loss . Combined antibiotic and acoustic exposure produced extensive cochlear damage . A few animals showed massive hair cell degeneration and collapse of the organ of Corti, except in the apical turn . The site of damage was possibly determined by the frequency of the sound stimulus . Thus, an intermittent tonal stimulus such as that used in the present experiment can be harmless by itself, but causes injury to cochlear hair cells in guinea pigs when administered in combination with gentamicin.

J Am Acad Dermatol, 1991 May, 24(5 Pt 2), 898 - 902
Follicular accentuation of leukocytoclastic vasculitis in an HIV-seropositive man . Report of a case and review of the literature; Weimer CE Jr et al.; Palpable purpura in a follicular localization developed in association with acute epididymitis in a white man who was seropositive for the human immunodeficiency virus (HIV) . Biopsy specimens revealed a leukocytoclastic vasculitis with follicular accentuation . With antibiotic therapy the vasculitis resolved, but it recurred during repeated episodes of the epididymitis . Follicular accentuation of skin disease is often seen in HIV-seropositive patients . Leukocytoclastic vasculitis with a follicular localization may be the presenting skin manifestation of HIV infection.

Mol Gen Genet, 1991 May, 226(3), 418 - 24
Stable transformation of the moss Physcomitrella patens; Schaefer D et al.; We report the stable transformation of Physcomitrella patens to either G418 or hygromycin B resistance following polyethylene glycol-mediated direct DNA uptake by protoplasts . The method described in this paper was used successfully in independent experiments carried out in our two laboratories . Transformation was assessed by the following criteria: selection of antibiotic-resistant plants, mitotic and meiotic stability of phenotypes after removal of selective pressure and stable transmission of the character to the offspring; Southern hybridisation analysis of genomic DNA to show integration of the plasmid DNA; segregation of the resistance gene following crosses with antibiotic-sensitive strains; and finally Southern hybridisation analysis of both resistant and sensitive progeny . In addition to stable transformants, a heterogeneous class of unstable transformants was obtained.

Head Neck, 1991 May-Jun, 13(3), 208 - 12
Isolated sphenoid sinus disease; Rothfield RE et al.; Isolated sphenoid sinus disease is an unusual entity that is encountered infrequently . With advances in antibiotic therapy and imaging techniques, the nature of isolated sphenoid sinus disease has significantly changed . More tumors and less inflammatory disorders are being encountered . We have retrospectively reviewed the medical records of patients who had undergone sublabial transseptal sphenoidotomy for isolated sphenoid sinus disease at Allegheny General Hospital for Pittsburgh between January 1985 and July 1989 . Thirteen patients were identified with isolated sphenoid sinus disease who were successfully managed with sublabial transseptal sphenoidotomy . This approach allows maximal visualization and safety with minimal morbidity.

Angiology, 1991 May, 42(5), 404 - 7
Bacterial infection and peripheral vascular disease; Ciuffetti G et al.; Whole blood filterability was monitored in 16 nondiabetic peripheral vascular disease (PVD) patients within forty-eight hours of onset of bacterial infection, after ten to seventeen days antibiotic therapy and again, ten days later, after convalescence . The whole blood filterability rate was constantly disturbed before infection in these patients; the impairment worsened significantly (as was expected during infection), but after convalescence the whole blood filterability rate did not return to preinfection levels . This further significant impairment in whole blood filterability was inversely correlated with a reduction in the patients' pain-free walking time as determined by a standard treadmell test performed after convalescence and compared with their average times before infection.

Medicine (Baltimore), 1991 May, 70(3), 188 - 97
Pyogenic infection of the sacroiliac joint . Case reports and review of the literature; Vyskocil JJ et al.; Three cases of pyogenic sacroiliitis are described, and the English literature from 1878 to 1990 reviewed, for a total of 166 cases . In 1 patient the source of infection was identified at the site of an intravenous line; 1 patient had 2 risk factors for developing the disease (pregnancy and intravenous drug use); and a third patient had no source of infection and no associated risk factors . The diagnosis of pyogenic sacroiliitis was made in each patient by history, physical examination, and positive skeletal scintigraphy or computed tomography of the sacroiliac joint . The infectious agent causing septic arthritis was identified by fine-needle aspiration of the sacroiliac joint under fluoroscopic guidance . Two of the 3 patients also had an open biopsy of the sacroiliac joint--one to confirm the organism causing septic arthritis, and the other for surgical drainage of the infected sacroiliac joint . Cultures from all 3 patients grew organisms uncommon for this disease, and all were treated for 6 weeks with intravenous antibiotics . In all patients pain diminished after treatment . Pyogenic sacroiliitis is a relatively rare condition (1-2 cases reported/year) that may be clinically difficult to diagnose unless the clinician is familiar with the disease . A prompt diagnosis can prevent significant morbidity and reduce serious complication . Major predisposing factors include intravenous drug use, trauma, or an identifiable focus of infection elsewhere, but 44% of patients have no predisposing or associated factors identified . Most patients present with an acute febrile illness with pain in the buttocks and pain on movement that stresses the affected sacroiliac joint . There is no specific blood test which points to the diagnosis of pyogenic sacroiliitis, although the erythrocyte sedimentation rate may be greater than 100 mm/hr . The diagnostic procedure of choice is bone scan with attention to the early perfusion phase, which usually localizes the affected sacroiliac joint . Unilateral involvement is the rule . In patients whose blood cultures fail to reveal a causative organism, fluoroscopic guided fine-needle aspiration of the sacroiliac joint under general anesthesia may help to identify the organism . If all cultures are negative, open biopsy of the sacroiliac joint may be required . Open biopsy should also be done if sequestration or an abscess is formed, or if the patient fails to respond to antibiotic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Hepatology, 1991 May, 13(5), 962 - 9
Involvement of cell calcium and transmembrane potential in control of hepatocyte volume; Khalbuss WE et al.; This study examined the role of hepatocyte calcium and cytoskeleton in activation of hyposmotic stress-induced increases in hepatocyte transmembrane potential and control of cell volume . Hepatocyte transmembrane potential was measured by glass microelectrodes in mouse liver slices before and after exposure to hyposmotic medium . Hepatocytes were loaded with tetramethylammonium by briefly exposing liver slices to nystatin, a cation poreforming antibiotic . Changes in hepatocyte steady-state water volume were determined by changes in intracellular tetramethylammonium activity measured with tetramethylammonium-sensitive, double-barrel micro-electrodes 4 min after exposure to hyposmotic medium . Hyposmotic stress of 74% of the control osmolality (approximately 280 mOsm) hyperpolarized hepatocyte transmembrane potential by 1.83 times the control hepatocyte transmembrane potential, and cell water volume increased by a factor of 1.19 . The Ca2+ channel blocker verapamil (100 mumol/L) completely inhibited hyposmotic stress-induced hyperpolarization of hepatocyte transmembrane potential . This inhibitory effect diminished at doses of 37.5 or 50 mumol/L, but even these hyperpolarizations were decreased significantly compared with control . Hyposmotic stress during added verapamil dosage (50 mumol/L) also resulted in 23% greater cell swelling compared with control . Ca(2+)-free medium plus ethylene glycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid (5 mmol/L) inhibited hyposmotic stress-induced increases in hepatocyte transmembrane potential and resulted in 16% greater cell swelling compared with control . Calmodulin inhibitors trifluoperazine (100 mumol/L) and promethazine (100 mumol/L) inhibited the hyperpolarization of hepatocyte transmembrane potential caused by hyposmolality, as did 3,4,5-trimethoxybenzoate 8-(N,N-diethylamino)octyl ester) (50 mumol/L), which inhibits mobilization of Ca2+ from intracellular stores . Cytochalasin B (50 mumol/L), which disrupts microfilaments, also inhibited hyperpolarization of hepatocyte transmembrane potential with osmotic stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Arch Intern Med, 1991 May, 151(5), 1010 - 1
Aortitis caused by Mycobacterium fortuitum; Schlossberg D et al.; Aortic valve replacement was complicated by sternal wound infection with Mycobacterium fortuitum . The wound was treated with debridement and antibiotic therapy . Five months later the patient developed fever, and blood cultures yielded M fortuitum . At surgery, aortitis with pseudo-aneurysm formation was encountered . Mycobacterium fortuitum grew from the aortic lesion . This is the first report of M fortuitum causing aortitis, although this organism is known to infect sternal wounds and mediastinum . Mediastinal infection can progress despite a normal wound appearance . Its manifestations may be delayed and may include infections of the aorta as well as of the sternum and mediastinum.

J Fam Pract, 1991 May, 32(5), 504 - 7
Endocarditis prophylaxis in a primary care clinic; Madlon-Kay DJ; BACKGROUND . Primary care physicians often make decisions about the use of endocarditis prophylaxis (EP) . Compliance with American Heart Association (AHA) recommendations has been found to be poor in hospitalized patients and in a dental school clinic . The purpose of this study was to examine the use of endocarditis prophylaxis in a primary care clinic . METHODS . The problem list of all adult patients seen in a primary care clinic in 1989 was reviewed for diagnoses that might require EP . Eighty-four charts were identified and reviewed . RESULTS . Sixty-five percent of the study patients had documentation in their charts about the need for EP . Mitral valve prolapse was the most frequent diagnosis . The physicians recommended EP for most patients with mitral valve prolapse regardless of whether there was documented mitral insufficiency . Endocarditis prophylaxis was most commonly prescribed for dental procedures . Six patients received prophylaxis for procedures for which the AHA does not recommend prophylaxis . Only 19% of the antibiotic regimens prescribed were entirely consistent with the AHA 1984 guidelines . The most common deviation from the AHA guidelines was continuing oral antibiotics too long . CONCLUSIONS . Compliance with the AHA 1984 recommendations, although better than reported in other settings, was less than optimal in this primary care clinic . Family physicians should consider whether EP is indicated in any patient with cardiac disease . If prophylaxis is indicated, then such a recommendation should be clearly documented in the chart . Family physicians need to be familiar with the 1990 AHA recommendations.

Chest, 1991 May, 99(5), 1294 - 5
Pneumonia preceding respiratory failure . A rare, easily misleading clinical manifestation in adult Arnold-Chiari malformation; Tsao TC et al.; A 47-year-old woman was admitted for bilateral lower lobe pneumonia with respiratory distress . Two episodes of respiratory failure developed despite improvement of pneumonia after antibiotic chemotherapy . Loss of consciousness and quadriplegia accompanied the last episode of respiratory failure . Arnold-Chiari malformation type 1 was diagnosed and a suboccipital craniectomy was performed . The neuromuscular and respiratory disorders greatly improved after operation . We believe that ACM 1 should be considered when an adult develops unexpected respiratory failure after improvement of the primary pulmonary condition . This disease is potentially treatable by surgical management, and if it is misdiagnosed, will be fatal.

Plast Reconstr Surg, 1991 May, 87(5), 861 - 6; discussion 867-8
Ulcerated anogenital hemangioma of infancy; Achauer BM et al.; Ten female infants were referred for symptomatic hemangiomas in the anogenital area . (One had had steroid treatment prior to consultation.) The natural history of these lesions is well known . Virtually all will spontaneously involute over a period of years . However, the lesions reported were particularly troublesome because of repeated ulcerations and subsequent pain . Prior treatment had been local wound care with antibiotic ointment and Telfa-type dressings . After referral from a family practitioner or pediatrician, argon laser treatment was performed in an outpatient setting . Eight of the 10 patients were treated with local anesthesia, and 2 had general anesthesia . All lesions healed in 1 to 5 weeks . No patients referred during this period were excluded from this series . All who received treatment were included . All the lesions involuted following treatment . In our estimation, the final result is identical to what may be expected after spontaneous involution of an ulcerated or infected hemangioma . The major difference is that involution occurred in a few weeks in laser-treated patients rather than a period of months or years . Ulcerated hemangiomas of the anogenital area have significant morbidity that can be efficiently avoided with the use of argon laser therapy . Lesions of the anogenital area have a strong predilection for females.

Clin Immunol Immunopathol, 1991 May, 59(2), 246 - 55
Daunomycin treatment prevents clinical expression of experimental autoimmune myasthenia gravis; Christadoss P et al.; Myasthenia gravis (MG) is an autoimmune neuromuscular disease, characterized by muscle weakness and electrophysiological abnormality . No treatment which would reliably induce permanent clinical remission of MG is yet available . The therapeutic efficacy and toxic effect of daunomycin (Dm), an antibiotic of the rhodomycin group, was evaluated in murine experimental autoimmune MG . Low dosage Dm treatment effectively prevented the development of muscle weakness and its associated electrophysiological abnormality, without inducing detectable toxicity and global immunosuppression.

Neurol Neurochir Pol, 1991 May-Jun, 25(3), 343 - 8
{Results of surgical treatment of multiple brain abscesses--3 case reports}; Wrobel-Wisniewska G et al.; On the basis of three cases of multiple cerebral abscesses, the authors showed that an attempt at conservative treatment could be ineffective and should, therefore, be closely monitored with CT scanning . If surgery is not avoidable one should excise those abscesses with which cause a mass effect as antibiotic therapy may be insufficient.

Biopolymers, 1991 May, 31(6), 803 - 11
The solution structure of the lantibiotic gallidermin; Freund S et al.; The 21-peptide amide antibiotic gallidermin is a potential therapeutic against acne disease . It belongs to the class of polycyclic lanthionine and alpha,beta-didehydroamino acids containing polypeptides, which were named "lantibiotics." The structural gene of the recently elucidated lantibiotic gallidermin encodes a precursor peptide containing Ser, Thr, and Cys residues in the C-terminal prolantibiotic part, and an unusually hydrophilic leader peptide . The ribosomally synthesized pregallidermin is posttranslationally modified and processed to a complex peptide antibiotic with four sulfide rings and two unsaturated residues . The complete solution structure of gallidermin was determined in trifluoroethanol: water (95:5) and dimethylsulfoxide by two-dimensional 1H-nmr at 500 MHz, using a combination of double quantum filtered correlated spectroscopy, homonuclear Hartman-Hahn, and nuclear Overhauser enhancement spectroscopy experiments . Using a total number of 152 distance constraints from NOEs and 14 torsional constraints, derived from coupling constants, we obtained a screwlike solution structure of gallidermin . Restrained molecular dynamics simulations yielded a set of five converging structures with an atomic rms difference of 1.7 A for the backbone atoms, not dependent on the starting structure . The spatial structure model is in excellent agreement with the amphiphilic and channel-forming properties of gallidermin on membranes and its tryptic cleavage at the exposed site between residues 13 and 14.

J Neurosurg, 1991 May, 74(5), 734 - 7
The morbidity of long-term seizure monitoring using subdural strip electrodes; Wyler AR et al.; The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes . Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery . In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae . In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections . There were no other instances of major morbidity or mortality in either group of patients . The total morbidity rate for both serious and minor complications was 0.85%.

Paediatr Indones, 1991 May-Jun, 31(5-6), 123 - 35
The behaviour of health care providers in managing diarrheal disease in Palembang City, south Sumatera, Indonesia; Ismail R et al.; A study on knowledge, attitude and practice of health care providers in Palembang had been conducted at the end of 1989 and beginning of 1990 . Four approaches were carried out: (1) by recording the help obtained by cases who consulted researchers for further help for the same diarrheal diseases (DD) episode, (2) by studying the medical records of DD cases admitted to three hospitals, (3) by studying prescriptions dispensed by three pharmacies and (4) by focus group discussions . The findings were analysed to evaluate the achievement of the Indonesian Diarrheal Diseases Control Program (CDD) . ORT, avoiding antimotility drugs and appropriated feeding have been accepted and practiced by the providers in Palembang . The target of promotion now is to support the acquisition of these behaviours to be implemented as a routine habit of the providers and as a part of the ongoing system of health care delivery system . Specifically the danger of loperamide promotion to the policy on antimotility must be stressed . Rapid iv rehydration and avoiding surface precipitating agents have been accepted, but are not practiced consistently yet due to practical considerations . It seems that there is no impact at all of CDD towards the rate of antibiotic therapy in DD . Besides intensifying the campaign, enforcing group pressure, may be we have to elaborate more the perception of health care provider as a practitioner, and conforming the strategy of the CDD campaign towards the findings . Health education had not been practiced effectively yet . Morale and value system of the providers are important for the success of this program . In general the medical-technic aspect of the CDD has been accepted by the providers, but there is still a lot to do in communicating them to be adopted as an effective behaviourPIP: In late 1989 and early 1990, researchers conducted a knowledge, attitude, and practice study of health care providers in Palembang City, Indonesia to determine the behavior of health care providers in managing diarrheal disease (DD) cases . Overall health care provides knew, accepted, and practiced oral rehydration therapy (ORT), but they still considered antibiotics as a major method to manage DD . Even though they tended to avoid using antimotility drugs, some continued to prescribe loperamide . This could be due to a campaign by manufacturers and some reports on benefits and safety of loperamide use in DD . Health care providers tended to advise continued appropriate feeding during diarrhea . This finding surprised many who assumed that most providers semistarved DD cases . Most health care providers felt that medical and nursing schools did not train and motivate them well enough to do health education on a community basis . They did provide health education on a physician-patient basis, however . Since health care providers were motivated to preserve and elevate their self image, they did not fully implement the concept and knowledge that the Indonesian Diarrheal Diseases Control Program (CDD) had promoted . Even though the CDD induced health care providers to accept ORT, avoidance of antimotility drugs, and appropriate feeding, health care providers reached the behavior frozen state . Thus public health professionals needed to remotivate them to induce more change . They should use scientific reasoning to promote behavior change such as stressing the importance of nutrient sufficiency during diarrheal diseases . They can convince identification figures (more senior, well positioned providers) to accept new behaviors . Lastly they can apply social pressure on health care providers via the mass media .

J Antimicrob Chemother, 1991 May, 27(5), 647 - 54
Reappraisal of amoxycillin absorption kinetics; Westphal JF et al.; Interest in the intestinal absorption mechanisms of drugs has increased because transepithelial passage across the gut does not necessarily follow a passive diffusion process . Amoxycillin, like other amino-beta-lactam antibiotics, has been demonstrated in vitro to use the dipeptide carrier-mediated system in rodent small intestine . In order to assess the in-vivo relevance of these data, we applied the Loo-Riegelman method for a reappraisal of amoxycillin absorption kinetics in healthy human volunteers . The results showed evidence of a saturable carrier-mediated uptake of this antibiotic . With respect to the in-vitro data previously published, the dipeptide carrier system would appear to be the most likely transport mechanism.

J Antimicrob Chemother, 1991 May, 27(5), 627 - 38
Comparative activities of amoxycillin, amoxycillin/clavulanic acid and tetracycline against Chlamydia trachomatis in cell culture and in an experimental mouse pneumonitis; Beale AS et al.; The activity of amoxycillin, amoxycillin/clavulanic acid and two tetracycline antibiotics was investigated against three strains of Chlamydia trachomatis in vitro . McCoy cells were infected and single doses of antibiotic administered 24 h after infection . The percentage of infected cells was calculated at intervals up to 72 h after infection . Amoxycillin and clavulanic acid, alone and in combination, reduced the incidence of inclusion formation of all three strains . Particularly good activity was observed against the laboratory-adapted strain C . trachomatis Sa2f and a clinical isolate C . trachomatis LB1, where a progressive reduction in numbers of inclusions was observed with time . Minocycline and oxytetracycline were the most active agents tested . In an experimental animal model, mice were inoculated intranasally with C . trachomatis MoPn (ATCC VR123) which caused a fatal pneumonia within 16 days, and treated orally for four days commencing at 24 h after infection . At doses producing clinically achievable serum concentrations, amoxycillin (10 mg/kg), amoxycillin/clavulanic acid (10 + 5 mg/kg) and minocycline (5 mg/kg) all protected the mice over a 21-day period . The majority of the animals treated with clavulanic acid alone (20 mg/kg) survived the infection . Treatment with oxytetracycline was less effective, a dose of 160 mg/kg being required to protect 70% of the mice . The results indicate that amoxycillin and amoxycillin/clavulanic acid were more effective against C . trachomatis MoPn in vivo than might be predicted from in-vitro data, suggesting that amoxycillin/clavulanic acid may have potential for the treatment of polymicrobial infections involving C . trachomatis.

J Antimicrob Chemother, 1991 May, 27(5), 607 - 17
The effects of minocycline and tetracycline on the mitotic response of human peripheral blood-lymphocytes; Ingham E et al.; The effects of minocycline and tetracycline on the mitotic response of human peripheral blood lymphocytes was investigated in vitro . The effects of the antibiotics on the mitotic response of purified lymphocytes stimulated with Interleukin-1 beta varied according to the individual from whom the lymphocytes were obtained . At concentrations above those reported to be present in serum during conventional therapy (2-8 mg/l), there was a tendency for both minocycline and tetracycline to suppress the mitotic response . Minocycline was superior to tetracycline in this respect . However, at physiological concentrations the antibiotics either had no significant effect, suppressed the mitotic response (minocycline at 2 mg/l with one of six donors), or enhanced the mitotic response (tetracycline at 2 and 8 mg/l with four of six donors) . The stimulatory effect of tetracycline was not demonstrated when lymphocytes were cultured in whole blood for up to seven days with the antibiotic alone . Similar effects of the antibiotics were observed when mononuclear cell fractions isolated from six donors were stimulated with an optimal concentration of phytohaemagglutinin (PHA) . Stimulation of lymphocytes in whole blood cultures with PHA in the presence of minocycline and tetracycline revealed that, under these culture conditions, the antibiotics could suppress the mitotic response of lymphocytes at physiological doses with cells from a majority of donors.

Pathol Biol (Paris), 1991 May, 39(5), 500 - 2
{Binding of cefuroxime to macromolecules from bronchitic sputum in patients with chronic bronchitis}; Lhermitte M et al.; Cefuroxime binding to soluble bronchial macromolecules has been performed in vitro with preparations obtained from ten patients . Cefuroxime at various concentrations have been added to soluble macromolecules (10 g/l) . Free cefuroxime has been obtained by equilibrium dialysis and measured by HPLC . Results show that cefuroxime binding is about 30% of total antibiotic.

Pathol Biol (Paris), 1991 May, 39(5), 410 - 9
{Uptake of ofloxacin by Escherichia coli}; Pechinot A et al.; The uptake of ofloxacin by Escherichia coli NIHJ-JC2 was determined by a sensitive and convenient method using high-performance liquid chromatography (HPLC) with a fluorometric detection (sensitivity level: 1 ng/ml) . Concentrations of ofloxacin were measured in bacteria after contact with 5 micrograms/ml of antibiotic for 1, 2, 3, 5, 10, 20 and 30 min . Ofloxacin uptake was rapid, 70% of broth concentration occurring within the first min and 96% after 5 min; then it reached a plateau which was 1.16 times as high as the broth concentration.

J Chir (Paris), 1991 May, 128(5), 243 - 6
{Gas gangrene . Clinical considerations, prognosis and therapeutic prospects in our experience}; Cristoferi G et al.; The prognosis of gas gangrene is changing as the means of treatment become more accurate and are implemented earlier . The authors, in their work referring to 10 cases of gas gangrene, point out to the extreme fastness of debridement and immediate exeresis, of wide-spectrum antibiotic protection and of caloric balance, associated to a treatment using trace elements . The importance of hyperbaric oxygen therapy seems to be increasingly proven with time . Lastly, in their general experience of treatment, the authors suggest the use of a specific frequency soft laser therapy, which might speed up the process of tissue repair.

Rinsho Ketsueki, 1991 May, 32(5), 475 - 80
{Domain structure of human von Willebrand factor, and its modulators involved in the platelet adhesion process in vitro}; Fujimura Y et al.; von Willebrand factor (vWF), a macromolecular glycoprotein synthesized in endothelial cells and megakaryocytes circulates in blood as heterogenous multimers and plays a critical role in the formation of platelet plugs . vWF is composed of an identical subunit with a molecular weight (MW) of 270 kDa, which is held together by disulfide bonds . Functional domains of vWF for factor VIII, heparin, platelet glycoprotein (GP) Ib, collagen, and GP IIb/IIIa locate in this order from the N-to C-terminus of subunit . The GP Ib binding domain is cryptic in normal circulation and only becomes expressed when vWF is associated with the subendothelial matrix or with fibrin . In vitro, an antibiotic ristocetin or the snake venom botrocetin isolated from Bothrops jararaca mimics the active component of subendothelial matrix and causes the binding of vWF to GP Ib . To elucidate the mechanism of in vitro process of vWF-GPIb binding, we describe here the isolation and characterization of two distinct forms of botrocetin . Since ristocetin is a heavily glycosylated proteoid, it is hard to characterize the structure on the basis of amino acid analysis . The apparent MW of the one-chain botrocetin was 28 kDa before and 32 kDa after reduction of disulfide bonds, while that of the two-chain botrocetin was 27 kDa before and 15/14.5 kDa after reduction . Amino acid composition of the two species revealed a similar high content of potentially acidic residues (greater that 60 Asx and Glx residues/molecules) but significant differences in the content of Cys and Phe residues . The N-terminal sequence of the one-chain was Ile-Ile/Val-Ser-Pro-Pro-Val-Cys-Gly-Asn-Glu-.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Otorrinolaringol Esp, 1991 May-Jun, 42(3), 177 - 9
{Monopolar endoscopic coagulation in posterior epistaxis}; Bernal Sprekelsen M; Most cases of severe nasal bleeding are treated by anterior and posterior packing of the nose . The permanence of the packing makes necessary an antibiotic therapy and sedation of restless patients . Extraction of the packs may lead to new bleedings from original vessel, but also from granulation tissue which may grow onto the nasal pack . The present paper offers an alternative treatment of severe nasal bleeding with the monopolar coagulation under endoscopic control, avoiding anterior and posterior nasal packing.

Pharm Res, 1991 May, 8(5), 570 - 5
Nonisothermal stability assessment of stable pharmaceuticals: testing of a clindamycin phosphate formulation; Kipp JE et al.; The stability of an antibiotic formulation (clindamycin phosphate in dextrose), which is stable at room temperature, was assessed by nonisothermal kinetic analysis at elevated temperatures . A preliminary study, conducted to establish apparent rate order, verified the appropriateness of a first-order kinetic model . The test formulation was then heated linearly from 70 to 90 degrees C over 12 hr . Data (drug concentration, temperature, and time) were fitted to the first-order model using nonlinear least-squares regression . Arrhenius parameter estimates obtained from three nonisothermal trials, and rate constants at 25 degrees C derived by extrapolation, demonstrated acceptable reproducibility and were in agreement with values derived from isothermal experiments at 30, 45, 55, 65, and 75 degrees C . First-order rate constants obtained from studies conducted for 20 months at 25 degrees C were in accord with isothermal and nonisothermal results.

Endoscopy, 1991 May, 23(3), 133 - 5
Bridging of benign choledochal stenoses by endoscopic retrograde implantation of mesh stents; Foerster EC et al.; A prospective study of a new stent for bridging choledochal stenoses was performed in seven patients (5 females, 2 males, age range 49-80 years) with benign bile duct stenosis or bilioduodenal fistula in whom conventional bougienage (3 patients) and/or month-long implantation of plastic prostheses (7 patients) failed because of reocclusion . The self-expanding mesh stents (Wallstent) were implanted by duodenoscopy in six patients . In one patient with a B-II stomach, the stent could only be inserted by the percutaneous transhepatic route . All prostheses were inserted endoscopically without complications . At follow-up after an average of eight months prosthesis-related complications were found in only one patient; there was no case of prosthesis occlusion . One patient with a bilioduodenal fistula of unknown origin developed fever and sepsis three days after implantation and subsequently a liver abscess which resolved on repeated drainage and antibiotic therapy . Although definitive interpretation of the results requires a longer follow-up period, on the basis of the present data endoscopic reconstructive splinting of benign choledochal stenosis would appear to be a promising technique.

Vet Clin North Am Small Anim Pract, 1991 May, 21(3), 545 - 51
Performing a complete canine semen evaluation in a small animal hospital; Johnston SD; Normal dog semen ranges in volume from 1 to 30 mL per ejaculate and contains 300 million to 2 billion sperm, of which more than 70% are progressively motile and morphologically normal . Dog semen should contain fewer than 10,000 bacteria per mL; higher numbers are indication of an infection of the male reproductive tract and usually are associated with cytologic evidence of inflammation (neutrophils in semen sediment) and with decreased progressive motility and decreased numbers of morphologically normal sperm . Measurement of pH of seminal plasma of dogs with infection of the reproductive tract may provide information on determining the choice of antibiotic . Measurement of seminal plasma alkaline phosphatase in azoospermic dogs is an indicator of tubular patency to the level of the epididymides.

Jpn J Surg, 1991 May, 21(3), 348 - 51
Liver abscess as the initial manifestation of colonic Crohn's disease: report of a case; Kotanagi H et al.; Liver abscess is a rare complication of Crohn's disease and in most of the reported cases, the diagnosis of Crohn's disease preceded that of liver abscess . We report herein a case in which a liver abscess was the initial clinical manifestation of Crohn's disease in a 36 year old man who presented with high fever and weakness . The diagnosis of liver abscess was established by abdominal ultrasonography, computed tomography and an arterial blood culture . The abscess was resolved with antibiotic therapy alone and during the drug therapy, a barium enema examination was performed which revealed a stricture at the transverse colon . Resection of the transverse colon was performed and macroscopic and microscopic examination of the resected specimen established the diagnosis of Crohn's disease . The liver abscess was thus speculated to be secondary to the inflamed bowel . Although rare, Crohn's disease should be included in the differential diagnosis of diseases causing liver abscess.

Postgrad Med J, 1991 May, 67(787), 446 - 9
Granulomatous enteropathy in common variable immunodeficiency: a cause of chronic diarrhoea; Mike N et al.; Gastrointestinal disease is a well recognized feature in patients with common variable immunodeficiency, and is often due to infection with a variety of organisms . Symptoms usually improve with appropriate antibiotic therapy and replacement gammaglobulin . We describe three middle-aged female patients with common variable immunodeficiency who had protracted diarrhoea and weight loss . Despite extensive investigation no infectious cause was found . All patients had granulomas distributed throughout the gastrointestinal tract, but no features of inflammatory bowel disease . There was a poor response to gammaglobulin replacement therapy, antibiotics or symptomatic treatment . We suggest that granulomatous enteropathy is another gastrointestinal manifestation of common variable immunodeficiency.

Clin Exp Dermatol, 1991 May, 16(3), 210 - 1
Treatment of the depressed and dysmorphophobic acne patient; Hull SM et al.; Sixteen patients with minimal facial acne but with symptoms of dysmorphophobia related to their acne were treated with isotretinoin, 0.5 mg/kg/day, (n = 5); 1 mg/kg/day (n = 11) for 16 weeks . All 16 had previously received long-term antibiotic therapy with no 'perceived' improvement in their acne . Formal psychiatric assessment was not possible through lack of cooperation . Fourteen of 16 patients derived benefit from isotretinoin therapy in that all 14 were subsequently satisfied with the cosmetic results achieved . However, the incidence of relapse was greater than that for a control group, 14 requiring additional therapy in the form of antibiotics or further isotretinoin (seven patients) within 20 months of completing the original course . Patients with acne and dysmorphophobia represent an important group of patients who benefit from treatment with isotretinoin; if possible this should be in conjunction with psychotherapy.

Arch Biochem Biophys, 1991 May 1, 286(2), 569 - 73
Location of the disulfide bonds in the antitumor protein neocarzinostatin; Kuromizu K et al.; Two disulfide bonds in the antitumor antibiotic neocarzinostatin were determined chemically . The peptic and peptic/thermolytic peptides from the native protein were isolated by gel filtration and ion-exchange chromatography followed by reverse-phase HPLC . The cystine peptides obtained were oxidized separately by performic acid treatment and further separated by HPLC into cysteic acid peptides . Sequence analyses of the isolated peptides revealed the location of the disulfide bonds at Cys37-Cys47 and Cys88-Cys93.

Rapid Commun Mass Spectrom, 1991 May, 5(5), 252 - 4
Direct evidence for degradation of esperamicin A1 with thiol confirmed by fast-atom bombardment mass spectrometry; Takayama M et al.; A degradation of esperamicin A1, which is a potent antitumor antibiotic having DNA-cleaving activity, was studied by fast-atom bombardment (FAB) mass spectrometry . It was proved that the degradation easily occurs via the thiol group(s) in the matrix solution and not by a FAB-induced reaction . It was concluded that from the FAB mass spectra of all non-volatile compounds, the molecular weight should be determined by using at least two chemically different matrices.

Int J Pancreatol, 1991 May, 8(4), 379 - 86
Clinical regression of infected pancreatic necrosis . Case report; Faintuch J et al.; Infected pancreatic necrosis was diagnosed clinically and radiologically in a patient admitted for acute pancreatitis . As free gas in the pancreatic area was recognized, antibiotic therapy (ceftriaxone) was empirically introduced, while surgical drainage was being planned . After the second week, the patient rapidly started to improve, to the point that he could be discharged home without operation . Control CT-scans and general laboratory tests, at this phase and later on, confirmed a still enlarged gland but free of infection or ongoing inflammation . Cholelithiasis, which had been identified in an early ultrasound scan, was electively treated by cholecystectomy 2 mo after the onset of pancreatitis, in the absence of sepsis, and with uneventful recovery . This case illustrates the rare possibility of spontaneous regression of infected necrotic pancreatitis, without any type of operation or nonoperative drainage.

J Pharm Pharmacol, 1991 May, 43(5), 297 - 302
The influence of Myrj 59 on the solubility, toxicity and activity of amphotericin B; Tasset C et al.; The effect of Myrj 59 (a polyoxyethyleneglycol derivative of stearic acid) on amphotericin B (Am B) solubility, toxicity and activity has been investigated . We showed that Myrj 59 could solubilize the antibiotic . Moreover, it also decreased and abolished the haemolytic activity of the drug by increasing the resistance of the red blood cells and impairing the interaction of Am B with the cellular membrane cholesterol, but it did not modify the in-vitro antifungal activity of the drug . On the other hand, Myrj 59 did not decrease the acute in-vivo toxicity of the drug (LD50 and nephrotoxicity) . In a previous study we have shown that a polyoxyethleneglycol derivative of cholesterol could solubilize Am B and was able to decrease the in-vitro and in-vivo toxicity of the antibiotic without altering its in-vitro antifungal activity . The results of the present study suggest that the cholesterol moiety of the surfactant is not necessary to decrease the in-vitro lytic activity of the drug but could play a role in the reduction of the in-vivo toxicity.

Chem Pharm Bull (Tokyo), 1991 May, 39(5), 1199 - 212
Synthesis and biological activity of (S)-2-amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A) derivatives; Tamura N et al.; (S)-2-Amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A (1)) is a novel amino acid antibiotic which shows a high affinity for glutamate receptors of the central nervous system . To improve the affinity for glutamate receptors, the structure-activity relationships of TAN-950 A derivatives 6a--o, 15a--o were investigated . Optically active TAN-950 A analogs 15a--h were synthesized starting with methyl (S)- and (R)-N-Boc-pyroglutamate (8) via acylation at the C-4 position followed by isoxazolone formation with hydroxylamine and subsequent deprotection reactions . The lactam 16, prepared from (RS)-aminoadipic acid, and dimethyl esters 19 of (R)- and (S)-aspartic acid were converted to (RS)-3-methyl-homo-TAN-950 A (15i) and optically active nor-TAN-950 A derivatives 15j--o, respectively, utilizing a similar sequence of reactions . Most of TAN-950 A derivatives 6a--o, 15a--o showed an affinity for glutamate receptors . The 3-alkyl derivatives 15b, d--g, especially, showed a high affinity for the quisqualate subtype-receptor and had a strong activating effect on the hippocampal neurons (glutamate agonistic activity) . The (R)-enantiomer 15a of TAN-950 A had increased selectivity for the N-methyl-D-aspartate (NMDA) subtype-receptor . This selectivity was further enhanced by removal of the methylene group in the amino acid moiety of 15a . The most potent and selective NMDA agonistic activity was observed with (R)-3-methyl-nor-TAN-950 A (15m).

Biotechnology (N Y), 1991 May, 9(5), 450 - 4
Piezoelectric cell growth sensor; Ebersole RC et al.; We have developed a reusable piezoelectric sensor that enables rapid characterization of cell viability and response to cell-affecting agents . This is accomplished via a novel polymer transduction principle that involves reaction of a pH-sensitive amphoteric polymer with metabolically generated acid . Subsequent adhesion of the protonated polymer to the transducer surface causes a decrease in the sensor resonant frequency corresponding to the cell metabolic rate . This disclosure provides the first example of a piezoelectric sensor capable of detecting metabolic responses of viable cells . The sensor provides real-time measurement of cell metabolism and division rates, and antibiotic sensitivity . This technology provides the basis for an advanced piezoelectric sensor that does not require immobilized biological receptors and can be miniaturized without compromising signal-to-noise factors.

Biochemistry, 1991 Apr 30, 30(17), 4290 - 7
Mithramycin blocks transcriptional initiation of the c-myc P1 and P2 promoters; Snyder RC et al.; The c-myc protooncogene plays an important role in the regulation of cellular proliferation . Mithramycin, a DNA binding antibiotic which binds G-C-rich DNA, inhibits c-myc expression in both differentiating and nondifferentiating cells . The G-C-rich nature of the c-myc promoter suggests that mithramycin may act by directly inhibiting promoter function . The mithramycin binding sites in the c-myc promoter regions were determined by DNAse I footprinting . Particularly prominent mithramycin binding is noted in the regions just 5' of the P1 and P2 promoter TATA boxes . Gel retardation experiments performed in the presence of mithramycin demonstrate that drug binding can prevent the formation of discrete complexes between HeLa cell nuclear proteins and c-myc promoter DNA fragments . Mithramycin also directly blocks the binding of the transcription factor Sp1 to the P1 promoter region . In vitro run-off transcription demonstrates that mithramycin can completely inhibit the in vitro function of both the P1 and P2 promoters . These data suggest that mithramycin inhibits transcription of the c-myc protooncogene by blocking the binding of important regulatory factors, thus preventing formation of the c-myc transcription initiation complex.

Nucleic Acids Res, 1991 Apr 25, 19(8), 1925 - 31
A novel BK virus-based episomal vector for expression of foreign genes in mammalian cells; De Benedetti A et al.; A composite mammalian cell-E . coli shuttle vector was developed based on the human papova virus BK and pSV-neo . The vector contains a dioxin-responsive enhancer (DRE) controlling a mouse mammary tumor virus (MMTV) promoter for the inducible expression of inserted genes . In human cells the vector replicates episomally, presumably utilizing the BKV rather than the SV40 origin, and expresses the BK T/t antigens . A deletion in the late BK region precludes the expression of the core/capsid proteins VP1, VP2, and VP3, thereby preventing the infectious lytic cycle . HeLa cells which were transfected with this vector and selected for resistance to the antibiotic G418 maintained the construct primarily in episomal form during more than one year of continuous culture, with little or no integration into the host genome . Transformed cells cultured in higher concentrations of G418 contained higher copy numbers of the vector . This permits one to vary the dosage of an inserted gene easily and reversibly without the need of conventional amplification techniques and clonal analysis . Using a chloramphenicol acetyl transferase (CAT) reporter gene inserted downstream of the MMTV promoter, we found that CAT expression was greater in clones with higher vector copy number . CAT expression was inducible with 2,3,7,8-tetrachlorodibenzo-p-dioxin, but inducibility was found to be inversely proportional to the copy number . Transformation of bacteria with plasmid molecules retrieved from the mammalian host was efficient, making this vector well adapted for the screening of cDNA libraries for the ability to express a phenotype in mammalian cells . Moreover, DNA sequences were stable during long-term passage in mammalian cells; vector passaged continuously for more than one year retained fully functional bacterial genes for resistance to chloramphenicol and ampicillin.

Biochemistry, 1991 Apr 16, 30(15), 3733 - 8
Induction of heat-labile sites in DNA of mammalian cells by the antitumor alkylating drug CC-1065; Zsido TJ et al.; CC-1065 is a very potent antitumor antibiotic capable of covalent and noncovalent binding to the minor groove of naked DNA . Upon thermal treatment, covalent adducts formed between CC-1065 and DNA generate strand breaks {Reynolds, R . L., Molineux, I . J., Kaplan, D.J., Swenson, D.H., & Hurley, L.H . (1985) Biochemistry 24, 6228-6237} . We have shown that this molecular damage can be detected following CC-1065 treatment of mammalian whole cells . Using alkaline sucrose gradient analysis, we observe thermally induced breakage of {14C}thymidine-prelabeled DNA from drug-treated African green monkey kidney BSC-1 cells . Very little damage to cellular DNA by CC-1065 can be detected without first heating the drug-treated samples . CC-1065 can also generate heat-labile sites within DNA during cell lysis and heating, subsequent to the exposure of cells to drug, suggesting that a pool of free and noncovalently bound drug is available for posttreatment adduct formation . This effect was controlled for by mixing {3H}thymidine-labeled untreated cells with the {14C}thymidine-labeled drug-treated samples . The lowest drug dose at which heat-labile sites were detected was 3 nM CC-1065 (3 single-stranded breaks/10(6) base pairs) . This concentration reduced survival of BSC-1 cells to 0.1% in cytotoxicity assays . The generation of CC-1065-induced lesions in cellular DNA is time dependent (the frequency of lesions caused by a 60 nM treatment reaching a plateau at 2 h) and is not readily reversible . The induction of heat-labile sites in cellular DNA was confirmed by gel electrophoretic analyses of the damage to intracellular simian virus 40 (SV40) DNA in SV40-infected BSC-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

FEMS Microbiol Lett, 1991 Apr 15, 63(2-3), 247 - 50
Cloning of nocardioform DNA conferring the ability to inactivate rifampicin; Andersen SJ et al.; A novel mechanism of resistance to rifampicin has recently been reported in which this antibiotic is inactivated . Here we describe the cloning of DNA from a nocardiofrom strain conferring this ability to inactivate rifampicin . Cloning was on the basis of complementation, as an increased resistance to the antibiotic . The genetic information was on a 8.3-kb BglII fragment.

Proc Natl Acad Sci U S A, 1991 Apr 15, 88(8), 3155 - 9
Lymphocytes as cellular vehicles for gene therapy in mouse and man; Culver K et al.; The application of bone marrow gene therapy has been stalled by the inability to achieve stable high-level gene transfer and expression in the totipotent stem cells . We show that retroviral vectors can stably introduce genes into antigen-specific murine and human T lymphocytes in culture . Murine helper T cells were transduced with the retroviral vector SAX to express both neomycin-resistance and human adenosine deaminase genes . These cells were expanded in culture and selected for expression of neomycin resistance with G418 . The gene insertion, selection, and culture expansion did not alter antigen specificity or growth characteristics of the T cells in vitro . To determine if cultured T cells might be used for gene therapy, their persistence and continued expression of the introduced genes was evaluated in nude mice transplanted with the SAX-transduced T cells . G418-resistant cells could be readily recovered from the spleens of recipients of transduced T cells for several months . In addition, recovered cells continued to produce human adenosine deaminase . Based on these observations, we studied cultured human tumor-infiltrating lymphocytes as a candidate cell for a trial of gene transfer in man . Exponential cultures of interleukin-2-stimulated tumor-infiltrating lymphocytes were efficiently transduced with the neomycin-resistance gene using the retroviral vector N2 . Gene insertion and subsequent G418 selection did not substantially alter the growth characteristics, interleukin 2 dependence, membrane phenotype, or cytotoxicity profile of the transduced T cells . These studies provided a portion of the experimental evidence supporting the feasibility of the presently ongoing clinical trials of lymphocyte gene therapy in cancer as well as in patients with adenosine deaminase deficiency.

Proc Natl Acad Sci U S A, 1991 Apr 15, 88(8), 3047 - 51
Selective abstraction of 2H from C-5' of thymidylate in an oligodeoxynucleotide by the radical center at C-6 of the diradical species of neocarzinostatin: chemical evidence for the structure of the activated drug-DNA complex; Meschwitz SM et al.; Use has been made of the mechanism of DNA deoxyribose damage by the ene-diyne-containing chromophore of the antitumor antibiotic neocarzinostatin to provide chemical evidence for the structure of the activated drug-DNA complex . Radical centers at C-2 and C-6 of the diradical form of the glutathione-activated chromophore abstract hydrogen atoms from C-1' of the C residue and C-5' of the T residue in AGC.GCT to generate a bistranded lesion consisting of an abasic site at C and a strand break at T . This laboratory has proposed a molecular model for the drug-DNA interaction in which the naphthoate moiety of the chromophore intercalates between A.T and G.C, placing the diradical core in the minor groove, so that the radical centers at C-6 and C-2 are close to C-5' of T and C-1' of C, respectively . To determine which radical center abstracts one of the hydrogen atoms from C-5', the self-complementary oligodeoxynucleotide GCAGCGCTGC was synthesized with 2H at both 5' positions of the T residue and treated with glutathione-activated chromophore . Sequencing-gel electrophoresis showed that drug attack was limited to the T and C residues and that abstraction of 2H from C-5' exhibited a small isotope selection effect of 1.25 . 1H NMR spectroscopic examination of the reacted chromophore, isolated by HPLC, indicated that 2H was selectively abstracted by C-6, providing experimental corroboration of the model and further elucidating the chemical mechanism . Since direct strand breakage at the T residue exceeds (44% more) abasic site formation at the C residue, other models of drug-DNA interaction leading to only single-strand breaks are also considered.

Biochem Pharmacol, 1991 Apr 15, 41(8), 1241 - 8
Inhibition of bleomycin-induced cellular DNA strand scission by 1,10-phenanthroline; Byrnes RW et al.; Inhibition by 1,10-phenanthroline of cellular DNA strand scission induced by the antitumor antibiotic bleomycin in Ehrlich ascites tumor cells was studied . DNA alkaline elution was performed on cells after 1-hr bleomycin treatments . Pretreatment for 24 hr with initial 1,10-phenanthroline concentrations of 0.2 nmol/10(5) cells, which depletes cells of ferritin iron by 80%, had no consistent effect on bleomycin strand breakage . However, simultaneous treatment with 3.1 nmol of 1,10-phenanthroline/10(5) cells and with bleomycin concentrations from 5 to 25 microM decreased both apparent double-stranded breaks and random breakage . When cells were treated with both 3.1 nmol of 1,10-phenanthroline/10(5) cells and 25 microM bleomycin, washed free of both drugs, and incubated at 35 degrees for 1 hr, the resulting breakage was equivalent to that found in cells treated with bleomycin only . When the combination treatment was extended to 4 hr, cell washing and reincubation resulted in increased strand scission, as compared with strand scission in cells treated with bleomycin only . Growth inhibition by bleomycin was not affected appreciably by temporary suppression of DNA strand breakage activity.

N Z Med J, 1991 Apr 10, 104(909), 138 - 9
Viral and bacterial infection in childhood: the value of C reactive protein; Stanley TV et al.; In 199 children with acute infections admitted to an acute general paediatric ward, the serum C reactive protein (CRP) level, using a simple latex agglutination kit, was compared with standard haematological parameters in distinguishing children with viral and bacterial infections . CRP levels proved superior to any haematological parameters singly or in combination in distinguishing these groups . A CRP level of 1:4 identified all but 13% of children with viral infections and excluded all but 15% of children with bacterial infections . The sensitivity of the test was 87%, the specificity 85% . The positive and negative predictive values were 95% and 74% respectively . Combined haematology, using total white cell count, total neutrophil count and percentage neutrophils, misclassified 26% of patients . CRP estimation could potentially help reduce unnecessary antibiotic prescription and shorten hospitalisation in febrile children . Its use in a general practice setting deserves further study.

Biochim Biophys Acta, 1991 Apr 8, 1077(2), 192 - 6
Identification of koningic acid (heptelidic acid)-modified site in rabbit muscle glyceraldehyde-3-phosphate dehydrogenase; Sakai K et al.; The sesquiterpene antibiotic koningic acid (heptelidic acid) has been previously demonstrated to modify glyceraldehyde-3-phosphate dehydrogenase in specific manner, probably by binding to the sulfhydryl residue at the active site of the enzyme (Sakai, K., Hasumi, K . and Endo, A . (1988) Biochim . Biophys . Acta 952, 297-303) . Rabbit muscle glyceraldehyde-3-phosphate dehydrogenase labeled with {3H}koningic acid was digested with trypsin . Reverse-phase HPLC revealed that the label is associated exclusively with a tryptic peptide having 17 amino acid residues . Microsequencing and fast atom bombardment mass spectrometry demonstrated that the peptide has the sequence Ile-Var-Ser-Asn-Ala-Ser-Cys-Thr-Thr-Asn-Cys-Leu-Ala-Pro-Leu-Ala-Lys . In comparison to the amino acid sequence of glyceraldehyde-3-phosphate dehydrogenase from other species, this peptide is in a highly conserved region and is part of the active site of the enzyme . The cysteine residue corresponding to the Cys-149 in the pig muscle enzyme, which has been shown to be an essential residue for the enzyme activity, was shown to be the site modified by koningic acid . Structural analyses of the reaction product of koningic acid and L-cysteine suggested that the epoxide of koningic acid reacts with the sulfhydryl group of cysteine residue, resulting in a thioether.

Biochemistry, 1991 Apr 2, 30(13), 3295 - 303
Effects of mutations of the bulged nucleotide in the conserved P7 pairing element of the phage T4 td intron on ribozyme function; Schroeder R et al.; The P7 element of group I introns contains a semiconserved "bulged" nucleotide, a C in group IA introns (nt 870 in the td intron) and an A in group IB introns {Cech, T.R . (1988) Gene 73, 259-271} . Variants U870, G870, and A870, isolated by a combination of in vitro and in vivo genetic strategies, indicate that C and A at position 870 are consistent with splicing whereas U and G are not . Although mutants G870 and U870 could be activated in vitro by increasing the Mg2+ concentration, their Km for GTP at pH 7 was 20-100-fold elevated, and they were unable to undergo site-specific hydrolysis . The dependence of the mutants on high guanosine concentrations could be substantially overcome by an increase in pH, suggesting that a tautomeric change, which makes U and G mimic C and A, is responsible for restoring function . In contrast to the striking Km effect, Vmax for the mutants differed by less than a factor of 2 from the wild type . Furthermore, streptomycin, an aminoglycoside antibiotic that competes with guanosine for its binding site, inhibited splicing of the U870 and G870 constructs at least as well as of the C870 and A870 variants, indicating that the guanosine-binding site of the mutants is proficient at interacting with a guanidino group . While our experiments argue against a hydrogen-bonding interaction between the C6-O of the cofactor and C4-NH2 of the bulged nucleotide, they are consistent with other models in which the C4-NH2 and/or N3 groups of the bulged C are involved in establishing an active ribozyme.

Kansenshogaku Zasshi, 1991 Apr, 65(4), 400 - 22
{A comparative study between cefpirome (CPR) and ceftazidime (CAZ) in respiratory tract infections}; Soejima R et al.; Efficacy and safety of a new injectable cephem antibiotic, cefpirome sulfate (hereafter, CPR), against respiratory tract infections were examined and compared with those of a control drug, ceftazidime (hereafter, CAZ) . As a rule, CPR 0.5 g twice a day, 1.0 g twice a day, or CAZ 1.0 g twice a day (hereafter CPR 0.5 g group, CPR 1.0 g group, and CAZ group) was administered for 14 days and the following results were obtained . 1 . The total number of cases was 470 (155 cases in the CPR 0.5 g group, 160 cases in the CPR 1.0 g group, and 155 cases in the CAZ group) . Among them 390 cases were subjected to analyses of clinical efficacy by the efficacy evaluation committee (131 cases in the CPR 0.5 g group, 131 cases in the CPR 1.0 g group and 128 cases in the CAZ group) . 2 . Efficacy rates determined by the efficacy evaluation committee were 82.4% (108/131) for the CPR 0.5 g group, 81.7% (107/131) for the CPR 1.0 g group, and 83.6% (107/128) for the CAZ group . Efficacy rates determined by the physician in charge were 82.0% (105/128) for the CPR 0.5 g group, 80.5% (99/123) for the CPR 1.0 g group, and 88.5% (108/122) for the CAZ group . No statistically significant difference was observed among the 3 groups . In evaluation of equivalency, clinical efficacy for the CPR 0.5 g group and the CPR 1.0 g group determined by the clinical efficacy evaluation committee was proved to be statistically equivalent to that for the CAZ group . 3 . In patients with pneumonia, efficacy rates determined by the efficacy evaluation committee were 87.1% (61/70) for the CPR 0.5 g group, 80.7% (71/88) for the CPR 1.0 g group, and 78.9% (56/71) for the CAZ group . Efficacy rates determined by the physician in charge were 85.3% (58/68) for the CPR 0.5 g group, 80.7% (67/83) for the CPR 1.0 g group, and 86.2% (56/65) for the CAZ group and no statistically significant difference was observed among the 3 groups . In patients with chronic respiratory tract infection, efficacy rates determined by the efficacy evaluation committee were 77.0% (47/61) for the CPR 0.5 g group, 83.7% (36/43) for the CPR 1.0 g group, and 89.5% (51/57) for the CAZ group . Efficacy rates determined by the physician in charge were 78.3% (47/60) for the CPR 0.5 g group, 80.0% (32/40) for the CPR 1.0 g group, and 91.2% (52/57) for the CAZ group . No statistically significant difference was observed among the 3 groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Acta Paediatr Scand, 1991 Apr, 80(4), 486 - 7
Unusual cause of methadone poisoning; Gayle MO et al.; A child with respiratory distress was found to have been given an antibiotic which was reconstituted with methadone . A delay in standard emergency room management led to a delay in diagnosis and treatment.

Z Lebensm Unters Forsch, 1991 Apr, 192(4), 328 - 34
{Statistical evaluation of residue data for the assessment of predicted values (half-life, withdrawal time) as an example of toltrazuril and enrofloxacin in trout}; Brinkman B et al.; The half-lives and withdrawal times of the veterinary drugs Toltrazuril and Enrofloxacin in trout have been assessed by statistical analysis . Confidence intervals were computed using a normal distribution of residual data and an empirical distribution by the Bootstrap method . Both methods produced similar statistics for the two drugs . Simulation of the residue data according to the regression lines of the decay curves has shown that the Bootstrap method is better for use when the residue patterns are not distributed normally . Using confidence intervals, a statistical mean of withdrawal times can be assessed . Taking into account the decays of the individual antibiotics in all treated trout, tolerance intervals for the regression lines are obtained: the calculated 10-20% longer withdrawal time includes values for which the antibiotic concentration in 95% of the treated trout is decreased below the tolerance level of Toltrazuril or Enrofloxacin.

J Appl Physiol, 1991 Apr, 70(4), 1650 - 4
Polymyxin B inhibits contraction-stimulated glucose uptake in rat skeletal muscle; Young JC et al.; Glucose transport in muscle is activated by contractile activity, an effect that persists in the postexercise state . Polymyxin B, a cyclic decapeptide antibiotic, inhibits the stimulation of glucose uptake in isolated muscle by contractile activity but also decreases tension development in electrically stimulated muscle . The purpose of this study was to determine whether polymyxin B also inhibits contraction-stimulated glucose uptake after in vivo administration of the drug and to examine the relationship between the effects of polymyxin B on tension development and its effects on contraction-stimulated glucose uptake . When polymyxin B was administered to rats in vivo, glucose uptake in muscle after electrical stimulation was decreased, despite the same amount of tension developed as in control rats, indicating an effect of polymyxin B on glucose transport independent of tension development . Our results also indicate that the postexercise increase in glucose uptake is a function of the tension developed by prior contractions . When muscles were perfused with medium containing polymyxin B, this relationship was disrupted . These results provide evidence that polymyxin B causes a decrease in muscle glucose uptake independent of its effects on tension development . The extent to which its effects on glucose uptake are also the result of a diminution in contractile force is uncertain.

Res Commun Chem Pathol Pharmacol, 1991 Apr, 72(1), 39 - 51
Fluxes and accumulation of tetracyclines by human blood cells; Gabler WL; Tetracyclines (Tc's) have anti-inflammatory properties unrelated to their antibiotic activities . Their anti-inflammatory property, in part, results from the ability of members of this family of antibiotic to inhibit neutrophil functions . There are marked differences in the ability of different Tc's to suppress neutrophils which may relate to their ability to cross the plasma membrane . To gain insight into the mechanism of Tc inhibition of neutrophils and the reason for the differences in antineutrophil effect of Tc's, we studied the flux and sequestration of Tc's in blood cells . Using centrifugation and a dibutylphthalate scrubber system we found that doxycycline (Dc) was rapidly taken up by blood cells reaching intracellular concentrations several times that found in the medium . Dc also rapidly effluxed when antibiotic loaded cells were placed in drug free medium . While Ca2+, Mg2+ nor protein separately were effective inhibitors of Dc influx, when divalent cations and proteins were combined Dc uptake was markedly suppressed . Tc uptake by blood cells ranked Dc greater than chlortetracycline = tetracycline greater than oxytetracycline, a ranking similar to that reported for neutrophil inhibition by members of the Tc family, suggesting that intracellular accumulation of drug is an important facet of Tc suppression of neutrophil function.

Oral Surg Oral Med Oral Pathol, 1991 Apr, 71(4), 496 - 8
Cefadroxil in the management of facial cellulitis of odontogenic origin; Hanna CB Jr; The objectives of this prospective single-blind trial were to compare the efficacy and safety of cefadroxil, 1 gm/day, and cephalexin, 250 mg four times a day, in the treatment of facial cellulitis of odontogenic origin . One hundred sixteen patients were screened for sensitivity to the assigned antibiotic and then randomly assigned treatment groups . Fifty-eight (100%) of the cefadroxil-treated patients and 57 (98%) of the cephalexin-treated patients were considered cured . Adverse reactions were noted in only two cefadroxil-treated patients and one cephalexin-treated patient . One patient from each group discontinued therapy prematurely; the patient who discontinued cephalexin was the only treatment failure in this study . This study found that cefadroxil administered once a day was therapeutically equivalent to cephalexin given four times a day.

Nippon Kyobu Geka Gakkai Zasshi, 1991 Apr, 39(4), 458 - 62
{A case report of pulmonary sequestration (Pryce I) associated with infective endocarditis}; Sugimoto T et al.; We experienced a case of pulmonary sequestration of Pryce type I associated with infective endocarditis (IE) . A 19-old-man had prolonged high fever of 39 degrees C against antibiotic therapy . He was referred to our hospital because of the positive blood culture and abnormal echocardiographic findings, which were severe aortic regurgitation with vegetations clinging the aortic cusps . In addition, his chest X-ray film showed mass lesion behind the cardiac shadow, and continuous murmur was auscultated on this portion . The left pulmonary arteriography revealed no arterial distribution to the left lower lobe, while aortography showed an aberrant artery arising from the descending aorta entering into this lobe . One month after aortic valve replacement for IE, left lower lobectomy and amputation of the aberrant artery were performed successfully . Pathologically, inflammatory changes of the aortic valve and proliferations of intimal and medial wall of the aberrant artery were shown . However, alveo-bronchial structure of the resected lobe was normal . Diagnosis, complications and surgical management of pulmonary sequestration were discussed.

Semin Thorac Cardiovasc Surg, 1991 Apr, 3(2), 116 - 8
The potential power output for skeletal muscle to provide cardiac assistance; Badylak SF; It is clear that autologous skeletal muscle offers a potential power source, free of invasive tubes and wires and without the need for immunosuppressive or antibiotic therapy, with the capability of assuming at least 25% to 50% of the natural heart's workload . The application of this power source as either a heart wrap in CMP procedures or as an assist ventricle in SMV designs is not only possible, but in fact, reality in the case of CMP procedures . Optimization of these applications requires continued research, but offers renewed hope for patients with CHF who currently depend on indefinite pharmacologic therapy, the total artificial heart, or the too few donor hearts for transplantation.

Indiana Med, 1991 Apr, 84(4), 252 - 3
Prophylaxis for recurrent cellulitis complicating venous and lymphatic insufficiency; Pauszek ME; Serious cellulitis, a common acute illness, frequently is associated with underlying venous and lymphatic compromise . The process is easily treated but, when recurrent, is associated with significant morbidity . Local measures, such as support hose and elimination of tinea pedis, have a role in its therapy but do not uniformly prevent recurrence . Prophylactic antibiotic therapy modeled after rheumatic fever prophylaxis can be effective in the prevention of this process.

Clin Pharmacokinet, 1991 Apr, 20(4), 293 - 310
Pharmacokinetics of newer drugs in patients with renal impairment (Part I); Fillastre JP et al.; Many drugs are eliminated via the renal route and the usual dose must be modified in patients with severe renal impairment . This review is an attempt to supply physicians with the more recent data on pharmacokinetic studies of new drugs administered in uraemic patients . The review is in 2 parts: the first indicates the results of studies on the pharmacokinetics of antibiotic agents, antifungal, antiviral and antiulcer drugs, and nonsteroidal anti-inflammatory drugs . Special mention is made of epoetin (recombinant human erythropoietin) . It was not possible to give all the information collected from the recent literature: since mild renal failure has little effect on the fate of a drug, pharmacokinetic data obtained in patients with a creatinine clearance (CLCR) of more than 50 ml/min has been omitted . Both the text and tables give recommendations for treating patients with moderate renal insufficiency (CLCR of about 50 ml/min), more severe renal impairment (CLCR between 10 and 50 ml/min) and end-stage renal failure with a very low creatinine clearance (below 10 ml/min) . It was not possible to give uniform recommendations (i.e . reducing the dose while maintaining the same interval, or giving the same dose and prolonging the interval) . This article follows the recommendations of the authors, which may vary for drugs in similar classes.

Clin Pediatr (Phila), 1991 Apr, 30(4 Suppl), 36 - 41; discussion 49
Infrared, thermistor, and glass-mercury thermometry for measurement of body temperature in children with cancer; Shenep JL et al.; Body temperature is often the sole determinant of whether or not the neutropenic cancer patient is admitted to the hospital for empiric antibiotic therapy . Recently developed infrared tympanic thermometers offer rapid readings, but their accuracy has not been established . We studied two infrared thermometers (FirstTemp and Thermoscan) and a thermistor (IVAC) in children with cancer . Mean infrared measurements did not differ significantly between right and left ear canals, and the mean IVAC temperature did not differ significantly from the left to the right axilla (P greater than 0.05, paired t test) . IVAC predictive mode mean temperature was 0.2 degrees C lower than monitor mode mean temperature in the axilla (P less than 0.0001), but 0.1 degree C higher than monitor mode orally (P less than 0.0001) . Aiming the infrared instrument at the tympanic membrane using an ear tug resulted in a 0.2 degree C higher mean temperature than casual placement in the ear canal (P less than 0.0001) . After compensation for the mean difference in reference oral glass-mercury versus test instrument temperatures, the FirstTemp, Thermoscan, and oral and axillary predictive mode IVAC measurements yielded sensitivities for the detection of fever of 84%, 84%, 82%, and 86%; specificities of 100%, 99%, 100%, and 100%; positive predictive values of 100%, 93%, 100%, and 100%; and negative predictive values of 95%, 98%, 98%, and 98%, respectively . We conclude that each of these instruments detects fever with comparable reliability . Infrared instruments are especially attractive alternatives due to their time efficiency.

J R Soc Med, 1991 Apr, 84(4), 193 - 5
Persisting incidence and mortality of sinogenic cerebral abscess: a continuing reflection of late clinical diagnosis; Chalstrey S et al.; Seventy-four verified cases of cerebral abscess seen in the Regional Neurosurgical Centre at Addenbrookes Hospital, Cambridge between 1965 and 1987 were reviewed . During that time no decline in incidence or change in the associated mortality was found to occur . ENT disease, taken as a whole, represented the most common source (40%) while acute frontal sinusitis (23%) proved to be the most common single underlying cause . Cerebral abscesses of sinogenic origin in particular were diagnosed late, with a deteriorating conscious level being the precipitating event in 94% of cases . Over 80% of such patients had presented initially to a non-ENT department with acute frontal headache where neither the underlying frontal sinusitis nor the developing intracranial complication had been suspected . These findings might explain why the incidence and mortality associated with cerebral abscesses of sinogenic origin, have changed little in the last 25 years despite improvements in diagnostic imaging, surgical technique and antibiotic therapy . We recommend that the diagnosis of acute frontal sinusitis be considered in any patient who presents with acute frontal headache, particularly if symptoms are unilateral . Furthermore, we stress that early confirmation of intracerebral complications by computerized axial tomography (CT) scanning continues to depend entirely upon an early clinical diagnosis which should result from a high level of clinical suspicion in patients who develop intracranial symptoms in the presence of known acute frontal sinus infection.

Todays OR Nurse, 1991 Apr, 13(4), 9 - 14
Infection control and the future . Continuing and emerging trends; Hiestand S et al.; One might believe that technological advancements, prophylactic antibiotic therapy, and ambulatory surgical trends would have appreciably altered infection statistics . Unfortunately, although economic pressures have shortened inpatient days and stimulated a major shift to outpatient surgical procedures, these changes did little to reduce surgical wound infection rates . Not only are they occurring more often, in more debilitated patients, but they are also becoming increasingly virulent, difficult, and costly to manage . When one considers the effects of surgical wound infection, and the added expense and inconvenience to both patient and hospital, it is logical to assume that OR nurses will take a proactive role in implementing new methods of prevention . The expanded role of the perioperative nurse specialist has helped to improve the quality of intraoperative care . Many positive clinical and technological changes in medical devices and infection control products have helped patient care . Any technological changes in the future must be made on the basis of a rational plan to improve patient care by decreasing surgical wound infection . Changes will occur on the basis of what is in the best long-range interest of the patient . The challenge for today's OR nurse, the medical community, and the health-care industry is to adapt to the needs of a rapidly changing health-care delivery environment . The future holds great promise . The expertise of the OR nurse, as clinician and manager, will be in greater demand as change continues to challenge professionals.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Cancer, 1991 Apr 1, 47(6), 889 - 92
Anti-drug monoclonal antibodies antagonize toxic effect more than anti-tumor activity of doxorubicin; Balsari A et al.; Monoclonal antibodies (MAbs) able to bind epitope(s) of drug molecule can interfere with the biologic action of the drug . This is known and already exploited in some instances of practical relevance, as in the reversal of the digoxin effect . Similar antidotal action is exhibited by MAbs reacting with a cytotoxic antibiotic, doxorubicin (DXR), and in such a way as to induce differential neutralization of drug action . Indeed, within certain limits, the cytotoxic action of DXR in vitro as well as in vivo is more effectively neutralized on normal than on tumor cells, with consequent increase in therapeutic index.

Chest, 1991 Apr, 99(4), 928 - 33
High-resolution ultrafast chest CT in the clinical management of febrile bone marrow transplant patients with normal or nonspecific chest roentgenograms; Barloon TJ et al.; Plain chest roentgenograms may be normal or show nonspecific abnormalities during the frequent febrile episodes that occur in patients after bone marrow transplantation . In this group, ultrafast 10-mm and 3-mm high-resolution CT scans were prospectively performed in 33 patients to determine if useful information was provided that either changed the patient's clinical management or added confidence to the clinical diagnosis . The 36 symptomatic episodes that occurred in 33 patients included fever in 20 episodes and fever combined with cough, dyspnea, chest pain, or rales in 16 . Fourteen chest roentgenograms were interpreted as normal, and 22 were interpreted as demonstrating nonspecific changes; however, none of the roentgenograms was considered helpful in that they did not provide sufficient information for further management . In 2 of 14 episodes in patients with normal chest roentgenograms and in 9 of 22 episodes in patients with nonspecific chest roentgenograms, CT scanning resulted in a change in clinical management that included performing bronchoscopy, increasing or changing antibiotic coverage, starting white blood cell transfusions, requesting surgical biopsy, or a combination of these . In 1 of 14 episodes in patients with normal chest roentgenograms and in 8 of 22 episodes in patients with nonspecific roentgenograms, CT added confidence to the diagnosis . In the remaining 16 episodes, CT scans provided no additional information . We conclude that in many instances, noncontrast ultrafast chest CT scans can provide information that may either change a patient's clinical management or more clearly establish the extent of pulmonary disease.

J Am Coll Cardiol, 1991 Apr, 17(5), 1177 - 82
Treatment of complicated prosthetic aortic valve endocarditis with annular abscess formation by homograft aortic root replacement; Glazier JJ et al.; The outcome of 30 consecutive patients with active aortic prosthetic valve endocarditis and root abscesses treated by the technique of homograft aortic root replacement with reimplantation of the coronary arteries is detailed . The principles of this technique are the removal of all abscesses and infected areas likely to drain into the infected mediastinum, excision of infected tissues down to healthy noninfected tissue and replacement with an antibiotic-impregnated homograft aortic root . All patients had evidence of progressive cardiac failure and ongoing sepsis . Mean patient age (+/- SD) at the time of operation was 42 +/- 18 years . The mean number of previous aortic valve replacements per patient was 1.6 +/- 0.7; 14 patients (47%) had undergone greater than or equal to 2 previous replacements . At operation, aortic root abscesses were found in all patients; abscess extension to adjacent structures and partial valve dehiscence had occurred in 23 . In-hospital death occurred in 9 (30%) of the 30 patients . The 21 hospital survivors have been followed up for a mean of 66 +/- 42 months (range 9 to 144) . Overall, 17 (81%) of the 21 hospital survivors have remained free of major adverse events (recurrence of endocarditis, need for reoperation or death) . The results of our study suggest that homograft aortic root replacement should be considered favorably in the treatment of patients with aortic prosthetic valve endocarditis and root abscesses.

Biochem Int, 1991 Apr, 23(6), 1107 - 15
A new class of potent, slowly reversible dehydropeptidase inhibitors; Parsons WH et al.; Dehydrodipeptide analogs whose scissile carboxamide has been replaced with a PO(OH)CH2 group have been found to be potent inhibitors of the zinc protease dehydrodipeptidase 1 (DHP-1, renal dipeptidase, EC 3.4.13.11) . The best of these inhibitors, compound 25 (Ki = 0.52 nM), is two hundred times more potent than cilastatin 2 which is used clinically as a component of the broad-spectrum antibiotic combination Primaxin . Compound 25 is a tight binding inhibitor exhibiting slow binding kinetics with a remarkably slow off rate from DHP-1 (half life greater than 8 hours) . The kinetics of its binding are consistent with a simple on-off mechanism whereas the less active D-enantiomer 26 appears to bind in an initial loose complex with the enzyme which slowly rearranges to a tighter complex (Ki = 83 nM).

DICP, 1991 Apr, 25(4), 348 - 50
Evaluation of an imipenem/cilastatin target drug program; Abel SR et al.; This article describes an imipenem/cilastatin (I/C) target drug program . The program, developed following completion of a drug usage evaluation study, was designed to improve I/C dosing, reduce central nervous system (CNS) adverse effects, and reduce antibiotic costs . Following completion of an inservice education program for the medical and pharmacy professional staffs, ongoing monitoring of I/C usage was accomplished through the pharmacy-based drug-dosing service . Pharmacists evaluated I/C dosage based upon culture/sensitivity results and indicators of renal function . If deemed inappropriate, the pharmacist contacted the prescribing physician with a dosage recommendation . Two hundred ten courses of I/C therapy were prescribed in the nine-month period following implementation of the target drug program; 26 cases (12 percent) required dosage adjustment . The incidence of CNS adverse effects including seizures decreased from 15 to 1 percent (p = 0.0015) . A $6033 drug cost avoidance also resulted from pharmacist intervention.

J Pharm Sci, 1991 Apr, 80(4), 338 - 40
Characterization of the aqueous decomposition products of (+)1,2-bis(3,5-dioxopiperazinyl-1-yl)-propane (ICRF-187) by liquid chromatographic and mass spectral analysis; Burke TG et al.; High-performance liquid chromatography (HPLC) and fast atom bombardment mass spectrometry (FAB-MS) were employed to separate and identify the aqueous decomposition products of (+)1,2-bis(3,5-dioxopiperazinyl-1-yl)-propane (ICRF-187; 1), a drug active against several forms of human cancer and which also has recently been shown to display potent cardioprotective activity in patients treated with the antitumor antibiotic doxorubicin . Two reversed-phase HPLC columns were used to separate the hydrolysis products of 1, a Waters muBondapak phenyl column and an LKB Spherisorb ODS2 column . Incubation of 20 microM 1 in phosphate-buffered saline (PBS) at 37 degrees C for 21 h resulted in 47% decomposition, with three hydrolysis products detected (compound 2, Waters column retention time (RT) = 3.7 min, observed monoisotopic protonated molecular ion (MH+) m/z value of 305.1; compound 3, RT = 4.1 min, MH+ m/z value of 287.1; compound 4, RT = 4.8 min, MH+ m/z value of 287.1) . The RT and MH+ m/z values for 1 were 17.1 min and 269.1, respectively . Based on the FAB-MS data, 2 corresponds to ICRF-198, the polar diacid diamide derivative of 1, while peaks 3 and 4 represent the monoacid monoamide derivatives of 1 . Using B/E linked scan daughter FAB-MS analysis, 3 displayed a prominent fragment with a m/z value of 160, indicating that it corresponds to the monoacid monoamide derivative of 1, with the methyl group adjacent to the hydrolyzed ring . Compound 4, displaying a fragment with a m/z value of 142 in its B/E linked scan daughter ion spectrum, corresponds to the monoacid monoamide derivative of 1, with the methyl group adjacent to the closed ring.

Contraception, 1991 Apr, 43(4), 317 - 23
The lack of interaction between temafloxacin and combined oral contraceptive steroids; Back DJ et al.; In view of the considerable debate concerning the possible failure of contraception in women taking broad spectrum antibiotics, we have examined a group of 12 women aged 22-32 in a controlled study . Each woman had been on long-term therapy with oral contraceptive steroids (OCS) containing ethynylestradiol (EE2) and levonorgestrel (Ng) for at least 6 months and all were in good general health . Blood samples were taken about 11.0 hours after dosing with their OCS on days 5, 6, 7 and 8 of their contraceptive cycle, for measurement of EE2, Ng, FSH and LH by radioimmunoassay . In addition blood samples were taken on days 19, 20 and 21 of the contraceptive cycle for assay of progesterone concentrations in plasma . The study was repeated in the next cycle of use of their OCS during which they took temafloxacin, a broad spectrum quinolone antibiotic in a dose of 600 mg twice daily for 7 days starting on day 1 of the cycle . All women completed the study satisfactorily as judged by diary cards, tablet counts and plasma temafloxacin concentrations . In the early part of the study some nausea and headaches were seen due to taking temafloxacin on an empty stomach but these effects were not seen when the antibiotic was later given with food . There was no evidence of any interaction between temafloxacin and the OCS . The plasma concentration of EE2 was 61.4 +/- 21.1 pg/ml in the control cycle and 68.5 +/- 26.6 pg/ml in the temafloxacin cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: In view of the considerable debate concerning the possible failure of contraception in women taking broad spectrum antibiotics, the authors examined a group of 12 women ages 22-32 in a controlled study . Each had been on longterm therapy with oral contraceptives (OCs) containing ethinyl estradiol (EE) and levonorgestrel (Ng) for at least 6 months and all were in good general health . Blood samples were taken about 11.0 hours after dosing with OCs on days 5, 6, 7, and 8 of their contraceptive cycle, for measurement of EE2, Ng, FSH, and LH by radioimmunoassay . In addition, blood samples were taken on days 19, 20, and 21 of their contraceptive cycle for assay of progesterone concentrations in plasma . The study was repeated in the next cycle of OC use during which the patients took temafloxacin, a broad spectrum quinoline antibiotic in a dose of 600 mg twice daily for 7 days, beginning on day 1 of the cycle . All women completed the study satisfactorily as judged by diary cards, tablet counts, and plasma temafloxacin concentrations . In the early part of the study, some nausea and headaches were experienced; this was due to the taking of the drug on an empty stomach . When the antibiotic was administered with food, this problem was no longer a concern . There was no evidence of any interaction between temafloxacin and OCs . The plasma concentration of EE2 was 61.4 +or- 21.2 pg/ml in the control cycle and 68.5 +or- 26.6 pg/ml in the temafloxacin cycle . The plasma progesterone concentration was 0.53 +or- 0.1 ng/ml in the control cycle and 0.6 +or- 0.24 ng/ml in the temafloxacin cycle (p0.01) . No woman demonstrated any significant rise in plasma FSH or LH concentrations during temafloxacin therapy . The authors conclude that there is no evidence for a systematic interaction between temafloxacin and OCs and that there is no need for use of alternative contraceptive methods in women taking OCs who are also being treated with temafloxacin . author's modified

Minerva Stomatol, 1991 Apr, 40(4), 273 - 6
{The clinical efficacy of roxithromycin in patients with acute odontogenic infections}; Panattoni E et al.; The clinical efficacy of a macrolide antibiotic, roxithromycin, was evaluated in 24 patients affected by acute odontogenic infections . Patients were treated with a first dose of 300 mg p.o . which was followed by 150 mg p.o . 12-hourly for the following two days . Total responses were evaluated by an arbitrary scale . The results showed that an excellent and good response was obtained in 99.96% of treated patients . On the basis of clinically compared data and the drug safety it may be concluded that roxithromycin can be successfully used in the treatment of odontogenic infections.

Antibiot Khimioter, 1991 Apr, 36(4), 30 - 2
{Variability of ceftazidime pharmacokinetics in children with suppurative-septic diseases}; Manuilov KK et al.; Marked variability of the ceftazidime pharmacokinetics (Cmax and T1/2) was observed in 3 newborns and 2 infants with purulent septic infections . The patients were under complex treatment in a reanimation unit (artificial pulmonary ventilation, infusions) . It was recommended to perform the treatment with monitoring the antibiotic plasma concentrations to prevent the drug failure because of the changes in the distribution and excretion patterns . The use of HPLC for the purpose is advisable.

Arq Bras Cardiol, 1991 Apr, 56(4), 269 - 73
{Fatal active rheumatic disease . Study of 13 necropsy cases}; Velloso LG et al.; PURPOSE--To study the clinical features of a group of patients with fatal acute rheumatic fever (ARF) . PATIENTS AND METHODS--Thirteen patients with ARF, the ages ranged between 4.5 and 25 (mean 14) years . Eight patients were male . Patients were studied in two groups: group A of those 14 year-old or younger (8 cases), and group B of those older than 15 years (5 cases) . RESULTS--Clinical presentation was fever and severe heart failure in all patients . In group A, it was the first attack of ARF in 5 patients . The time elapsed between beginning of symptoms and hospital admission ranged between 10 and 90 (mean 40) days . Mitral insufficiency occurred in all patients . The blood leukocyte count was greater than 10000 per mm3 in six cases . Atrioventricular block occurred in one case . Valvular vegetations were detected on echocardiogram in 4 cases . Two patients received antibiotic therapy . Surgical treatment of the valvular heart disease was carried on in one patient . In group B, it was the first ARF attack in 2 cases, the time elapsed between beginning of the symptoms and hospital admission ranged between 4 and 60 (mean 21) days . Leukocyte count greater than 10000 por mm3 occurred in 4 cases . Atrioventricular block was diagnosed in one case . Valvular vegetations on echocardiogram were detected in 2 patients . In two cases, the treatment was antibiotic therapy . Three patients were operated on . CONCLUSION--ARF may still be fatal, even in the first attack or in patients in the third decade of life . Other diagnoses are frequently considered, due to the intense clinical and laboratorial manifestations.

Eur J Cell Biol, 1991 Apr, 54(2), 291 - 8
Effects of daunomycin on the microtubular network: a cytochemical study on a human melanoma cell line; Molinari A et al.; The interaction of daunomycin (DAU), an anthracyclinic antibiotic employed as antitumoral agent, with microtubules, has been investigated by cytochemical and morphological methods on a human melanoma cell line (H14) . Results obtained indicated that DAU was able to modulate the microtubule reassembly in cells treated with colcemid; such an effect proved to be dose-dependent . In particular, it has been observed that a low dose of DAU (0.05 microM) seemed to favor the microtubule reassembly whereas a higher dose (0.10 microM) impaired this process . In addition, when the anthracyclinic antibiotic was employed together with colcemid, both the cell detachment and the depolymerization of microtubules induced by the mitotic poison were hampered . These effects were dose-dependent and were better accomplished when DAU was used at an equimolar or at higher dose than that employed for the antimicrotubular agent . Moreover, the treatment of cells with DAU alone induced the stabilization of the microtubules, making them more resistant to the action of antimicrotubular agents . This effect could in part explain the antagonistic action exerted by DAU against colcemid . These observations seem to confirm that the microtubular network is an important target involved in the mechanism of action of the anthracyclinic antibiotics.

J Biomol Struct Dyn, 1991 Apr, 8(5), 989 - 1025
Design and synthesis of sequence-specific DNA-binding peptides; Grokhovsky SL et al.; Design, synthesis and DNA binding activities of two peptides containing 32 and 102 residues are reported . A nonlinear 102-residue peptide contains four modified alpha helix-turn-alpha helix motifs of 434 cro protein . These four units are linked covalently to a carboxyterminal crosslinker containing four arms each ending with an aliphatic amino group . From CD studies we have found that in aqueous buffer in the presence of 20% trifluoroethanol the peptide residues assume alpha-helical, beta-sheet and random-coiled conformations with the alpha-helical content of about 16% at room temperature . Upon complex formation between peptide and DNA, a change in the peptide conformation takes place which is consistent with an alpha - beta transition in the DNA binding alpha helix-turn-alpha helix units of the peptide . Similar conformation changes are observed upon complex formation with the synthetic operator of a linear peptide containing residues 7-37 of 434 cro repressor . Evidently, in the complex, residues present in helices alpha 2 and alpha 3 of the two helix motif form a beta-hairpin which is inserted in the minor DNA groove . The last inference is supported by our observations that the two peptides can displace the minor groove-binding antibiotic distamycin A from poly(dA).poly(dT) and synthetic operator DNA . As revealed from DNase digestion studies, the nonlinear peptide binds more strongly to a pseudooperator Op1, located in the cro gene, than to the operator OR3 . A difference in the specificity shown by the non-linear peptide and wild-type cro could be attributed to a flexibility of the linker chains between the DNA-binding domains in the peptide molecule as well as to a replacement of Thr-Ala in the peptide alpha 2-helices . Removal of two residues from the N-terminus of helix alpha 2 in each of the four DNA-binding domains of the peptide leads to a loss of binding specificity.

Curr Genet, 1991 Apr, 19(4), 243 - 8
Interactions between chromosomal omnipotent suppressors and extrachromosomal effectors in Saccharomyces cerevisiae; Ono B et al.; Chromosomal omnipotent suppressor mutations recovered in psi+ strains of Saccharomyces cerevisiae were brought into psi- cytoplasm . SUP46, SUP138 and SUP139 acted as dominant omnipotent suppressors in the psi- cytoplasm though their suppressor activity was substantially reduced . SUP46 and SUP138 conferred recessive thermosensitivity and antibiotic sensitivity in psi- cytoplasm as in psi+ cytoplasm . On the other hand, sup111 through sup115, which acted as recessive omnipotent suppressors in the psi+ cytoplasm, manifested no, or very low, suppressor activity in the psi- cytoplasm . They, however, still enhanced the efficiency of the SUP29 tRNA suppressor in psi- cytoplasm . A multicopy plasmid carrying the wild-type SUP35 gene enhanced the efficiency of sup111 in psi- cytoplasm.

Z Gastroenterol, 1991 Apr, 29(4), 146 - 52
{Percutaneous drainage of liver and splenic abscess}; Schwerk WB et al.; 42 patients with solitary (n = 34) and multiple (n = 8) abscesses of the liver (n = 36) and the spleen (n = 6) were treated with ultrasound guided percutaneous interventions . 38 patients (90%) underwent a total of 97 closed abscess aspirations using needles of 0.9 and 1.3 mm in diameter . In 4 cases (10%) percutaneous catheter drainage was performed . Intravenous antibiotics were used in all cases . Those patients with closed abscess aspiration additionally received local injection of aminoglycosides into the cavity . 40 out of the 42 patients could be treated successfully by percutaneous methods for a cure rate of 95.2% . Percutaneous drainage failure occurred in 2.4% . One patient with multiple liver abscesses and catheter drainage died from myocardial infarction (hospital mortality 2.4%) . Complications of ultrasound-guided interventions included two minor bleedings, requiring no therapy, and one pleural empyema (complication rate 7.1%) . There were no treatment related lethal complications . These results indicate that abscesses of the liver and the spleen up to 10 cm in diameter can be effectively treated by closed (repetitive) needle aspiration and antibiotic therapy with a relatively low rate of complications . About half of our patients with abscesses of more than 10 cm received percutaneous catheter drainage . On the basis of our experience surgical drainage of liver abscesses and splenectomy in splenic abscesses should be restricted to those cases with percutaneous drainage failure.

Eur J Clin Microbiol Infect Dis, 1991 Apr, 10(4), 368 - 77
Role of quinolones in surgical prophylaxis; Mandell LA; The general principles involved in the use of chemoprophylaxis in surgery, the selection of patients at risk, and the choice of antibiotic agents are reasonably well established . While a good deal of data exist regarding commonly used prophylactic regimens, very little data are available on the role of quinolones in surgical prophylaxis . The literature dealing with this area is reviewed, and studies on the use of quinolones in biliary, colorectal, urologic, orthopedic and vascular surgery are discussed . The data suggest that generally the quinolones are as efficacious as the other antibiotics with which they were compared, and in the case of urologic surgery the results using quinolones were better than those in non-treated controls . Single-dose prophylaxis was regularly shown to be as effective as multiple dose regimens . Further clinical trial data are necessary before any firm conclusions can be drawn regarding the role of quinolones in surgical prophylaxis.

J Egypt Soc Parasitol, 1991 Apr, 21(1), 87 - 9
A case of complicated anthroponotic cutaneous leishmaniasis in Al Baha, Saudi Arabia; Morsy TA et al.; A complicated case of ACL, which showed feverish and widely disseminated ulcers over the face was successfully treated with systemic antibiotic and pentostam as intralesional injections.

Hautarzt, 1991 Apr, 42(4), 233 - 6
{Photoallergic reaction to olaquindox}; Hochsattel R et al.; Olaquindox, an antibiotic belonging to the quinoxaline group, is a growth promoter used in pig breeding . A farmer developed a photoallergic contact eczema to it, which progressed to a persistent light reaction . Besides this, we found a photosensitivity to chlorpromazine, a tranquillizer that is also used in pig breeding . In addition, after using potent light-protective drugs containing UV-A and UV-B filters, this patient developed a (photo)allergy to different filter substances . The photoallergy to olaquindox was caused by mixing a food additive containing olaquindox with the pigswill for both young and adult animals . We point out the dangers (potent photoallergen, cancer induction) resulting from the widespread use of this substance in the EC.

Boll Chim Farm, 1991 Apr, 130(4), 128 - 32
Absorption of some cephalosporins by rectal route in rabbits; Bahia MF; In order to obtain an effective alternative to parenteral administration of several cephalosporins, experiments were carried out in rabbits by rectal route . The suppositories of cefotaxime (CTX), ceftazidime (CAZ) and cefoxitin (CFX) in association with surface active sodium lauryl sulfate (SLS), release the antibiotic for absorption . Based on the positive results of the comparative plasmatic levels, this dosage appears to be applicable to humans too.

Acta Med Okayama, 1991 Apr, 45(2), 89 - 94
Peplomycin-induced DNA repair synthesis in permeable mouse ascites sarcoma cells; Zhang B et al.; DNA repair synthesis induced in permeable mouse ascites sarcoma cells by peplomycin, an antitumor antibiotic, was studied . Mouse ascites sarcoma (SR-C3H/He) cells were permeabilized with a low concentration of Triton X-100 in an isotonic condition . Permeable cells were treated with an appropriate concentration of peplomycin to introduce single-strand breaks in permeable cell DNA . DNA repair synthesis in peplomycin-treated permeable cells was measured by incubating the cells with four deoxynucleoside triphosphates in an appropriate buffer system . The DNA repair synthesis was enhanced by ATP and NaCl at near physiological concentrations . More than 90% of DNA synthesis in the present system depended on the peplomycin-treatment . The repair nature of the DNA synthesis was confirmed by a BrdUMP density shift technique . The repair patches were largely completed and ligated in the presence of ATP . Analyses using selective inhibitors for DNA polymerases showed that both DNA polymerase Beta and aphidicolin-sensitive DNA polymerases (DNA polymerase alpha and/or delta) were involved in the repair DNA synthesis.

Am Rev Respir Dis, 1991 Apr, 143(4 Pt 1), 855 - 64
Protected bronchoalveolar lavage . A new bronchoscopic technique to retrieve uncontaminated distal airway secretions; Meduri GU et al.; We tested the effectiveness of protected bronchoalveolar lavage (PBAL), performed through a protected transbronchoscopic balloon-tipped (PBT) catheter, in collecting distal airway secretions with a minimal degree of contamination . The PBAL had less than or equal to 1% squamous epithelial cells in 91% of specimens and an absence of bacterial growth in 59% of patients without pneumonia . Using a threshold of 10(4) cfu/ml we had one false positive result in 33 patient without pneumonia and one false negative in 13 patients with pneumonia . Quantitative bacterial cultures of the PBAL specimens had a diagnostic sensitivity of 97% and a specificity of 92%, with a positive predictive value of 97% and a negative predictive value of 92% . The diagnostic efficiency was 96% . The presence of intracellular organisms in much greater than or equal to 2% of the recovered alveolar cells (Giemsa stain) was seen in all but two patients with pneumonia (on corticosteroids) and in none of the patients without pneumonia . Gram stains of the PBAL specimens were positive in all but one patient with pneumonia and negative in all but one patient without infection (patient with endobronchial narrowing secondary to neoplasm with false positive cultures) . Either the Giemsa or the Gram stain was positive in all patients with pneumonia, allowing early and accurate diagnosis of lower respiratory tract infection before the results of cultures were available . The time off antibiotic therapy before bronchoscopy did not affect the result of PBAL cultures, contrary to what we observed for the protected brush specimen.

J Hosp Infect, 1991 Apr, 17(4), 303 - 6
A randomized prospective study to compare ceftizoxime with cephradine as single dose prophylaxis in elective cholecystectomy; Skipper D et al.; This study compares the efficacy of ceftizoxime with that of cephradine as single agent prophylaxis in elective cholecystectomy . The incidence of purulent wound infection was low in both groups (ceftizoxime 1/99; cephradine 2/92) . No adverse reactions to the trial antibiotics occurred in either group . Ceftizoxime is a safe, effective, convenient and well-tolerated antibiotic for use as single agent prophylaxis in elective cholecystectomy . However, because it has no demonstrable advantage over cephradine and is three times as expensive, its routine use is not justified.

J Ind Microbiol, 1991 Apr, 7(3), 163 - 74
Expression of polyketide biosynthesis and regulatory genes in heterologous streptomycetes; Strohl WR et al.; There are now several examples showing that hybrid secondary metabolites can be produced as a result of interspecies cloning of antibiotic biosynthesis genes in streptomycetes . This paper reviews examples of hybrid secondary metabolite production, and examines the underlying biochemical and regulatory principles leading to the formation of hybrid anthraquinones by recombinant anthracycline-producing streptomycetes carrying actinorhodin biosynthesis genes . An anthraquinone, aloesaponarin II, was produced by cloning the actI, actIII, actIV, and actVII genes (pANT12) of actinorhodin biosynthesis pathway from Streptomyces coelicolor in anthracycline producing streptomycetes . Streptomyces galilaeus strains 31 133 and 31 671, aclacinomycin and 2-hydroxyaklavinone producers, respectively, formed aloesaponarin II as their major polyketide product when transformed with pANT12 . Subcloning experiments indicated that a 2.8-kb XhoI fragment containing only the actI and actVII loci was necessary for aloesaponarin II biosynthesis by S . galilaeus 31 133 . When S . galilaeus 31 671 was transformed with the actI, actVII, and actIV genes, however, the recombinant strain produced two novel anthraquinones, desoxyerythrolaccin and 1-O-methyldesoxyerythrolaccin . When S . galilaeus 31 671 was transformed with only the intact actIII gene (pANT45), aklavinone was formed exclusively . These experiments indicate a function for the actIII gene, which is the reduction of the keto group at C-9 from the carboxyl terminus of the assembled polyketide to the corresponding secondary alcohol . The effects of three regulatory loci, dauG, dnrR1, and asaA, on the production of natural and hybrid polyketides were also shown.

Vet Rec, 1991 Mar 23, 128(12), 278 - 80
Prophylactic medication of feedlot calves with tilmicosin; Schumann FJ et al.; The parenteral administration to calves of the antibiotic tilmicosin either on arrival at a feedlot or 72 hours later was evaluated in a group of 308 steer calves . The calves were allotted to 24 pens so that there were eight replicates of the two medicated groups and eight replicates of the control group . The need for veterinary treatment was reduced significantly (P less than 0.05) during the first month of the feeding period in the two medicated groups . The medicated groups had an improved average daily weight gain (P less than 0.01) over the trial period compared with the non-medicated animals . This improved average daily gain by the medicated groups was not reduced when animals with respiratory disease were excluded from the calculations . The medicated groups also had an improved feed conversion efficiency (P less than 0.01) over the first 60 days of the feeding period compared with the non-medicated animals.

Schweiz Med Wochenschr, 1991 Mar 23, 121(12), 397 - 412
{GM-CSF and G-CSF: cytokines in clinical application}; Ruef C et al.; Leukopenia or pancytopenia as a result of bone marrow dysfunction are manifestations of various diseases or complications of therapeutic regimens . The spectrum of diseases associated with leukopenia is wide and includes congenital as well as acquired neutropenias secondary to conditions such as myelodysplastic syndromes, AIDS, malignant tumors with or without chemotherapy-enhanced neutropenia, bone marrow transplantation or therapeutic or accidental radiation . The morbidity and mortality of infectious diseases is greatly enhanced during neutropenic phases . Over the last few years attempts have been made to shorten the duration and lessen the severity of neutropenia in patients with the above conditions by administration of Granulocyte Macrophage Colony Stimulating Factor (G-CSF) . Both cytokines were successfully tested in phase I and II trials . Treatment with GM-CSF or G-CSF results in a dose-dependent increase of the neutrophil count . GM-CSF also increases the number of eosinophils and monocytes in peripheral blood . The effect of both cytokines on the neutrophil count is transient as long as the underlying disease persists . This prompted the institution of maintenance therapy, which has been successfully used with either cytokine . Long-term treatment is usually well tolerated and results in a reduction in the frequency of infections as well as in the duration of antibiotic treatments . Side effects of GM-CSF or G-CSF are usually mild and include fever, myalgia, bone pain, and erythema . A number of patients developed dyspnea, hypotension, sweating, flushing and erythema after the first dose of GM-CSF in each treatment cycle . This first-dose reaction occurs more frequently after intravenous than reactions were reported with G-CSF . Some patients with myelodysplastic syndrome progressed to acute myeloic leukemia during or after treatment with GM-CSF or G-CSF . Most of these patients presented with an increased fraction of blasts in the bone marrow, which preceded the treatment with the colony stimulating factors . Since GM-CSF and possibly G-CSF may increase the risk of developing acute leukemia in patients with myelodysplastic syndrome, it appears prudent to limit the use of these cytokines in patients with this disease . The subcutaneous route of administration appears to be preferable to intravenous administration, since the incidence and severity of side effects are reduced . While many questions concerning dosage, long-term therapy and combination therapy still remain unanswered, the information presented in this review concerning the clinical use of these cytokines warrants an optimistic outlook.

Biochim Biophys Acta, 1991 Mar 18, 1063(1), 60 - 6
The nature of the conductance increase induced by filipin in cholesterol-containing planar lipid bilayers; Krawczyk J et al.; The effects of the polyene antibiotic filipin on the conductance and permeability of planar lipid bilayers were investigated under voltage-clamp conditions . The membrane conductance of lipid bilayers containing no cholesterol was not affected by filipin . In the presence of cholesterol containing lipid bilayers, filipin induced a 10(4)-10(5)-fold increase in transmembrane conductance . This conductance increase was dependent on the ionic species present in solution, decreasing in the following order: GCsCl greater than GNaAc greater than GKCl greater than GNaCl greater than CaCl2 greater than GNa2SO4 greater than GBaCl2 greater than GMgCl2 . Reversal potential measurements in simple biionic conditions revealed the following relative permeability sequence: PK greater than PCl greater than PNa approximately Pac approximately PBa greater than PCs greater than PMg approximately PCa greater than Psulphate . The filipin-sterol mediated increase in membrane conductance was independent of the membrane potential . The increase in membrane current following a step alteration in membrane potential occurred instantaneously and had no dependence on the previous value of the holding membrane potential . We propose that the filipin-sterol complex forms ion channels in lipid membranes . These channels are found in a single configuration (open state) and select preferentially monovalent cations or anions over divalent ions . Our experimental results are discussed in relation to the effects of other polyene antibiotics on the membrane permeability, and also in relation to experimental problems previously reported with the use of filipin in planar lipid bilayers.

Ugeskr Laeger, 1991 Mar 18, 153(12), 840 - 4
{Proved self-poisoning . A 10-year case load from an intensive care unit}; Fisker NJ et al.; During the period 1.1.1979-31.12.1988, a total of 2.023 admissions (involving 1.511 patients) occurred on account of deliberate self-poisoning in the Intensive Care Unit of the Anaesthetic Department of Odense Hospital . No significant alterations were observed in the female/male ratio or in the average age, during this period . Duration of hospitalization in the Intensive Care Unit showed a decrease . The frequencies of cases of poisoning with barbiturates showed a decrease while poisonings with acetaminophen, alcohol and chemical-technical agents showed increasing frequencies . Poisoning with benzodiazepines, neuroleptics, polycyclic antidepressive drugs, dextropropoxyphen or acetylsalicylic acid occurred with unaltered frequency . Treatment consisted mainly of endotracheal intubation, artificial ventilation, circulatory therapy, forced alkaline diuresis, haemodialysis and antibiotic therapy . The frequency of forced alkaline diuresis decreased during the period while circulatory therapy, haemodialysis, antibiotic therapy and treatment with antidotes were employed increasingly frequently . The acute lethality was 1.6% . It is concluded that treatment was mainly symptomatic and concentrated on ensuring respiratory and circulatory functions and that the acute lethality is unchanged and will probably not be lowered further . The "Scandinavian method" is thus still the cornerstone in the treatment of poisoning and is responsible for the continued low acute lethality.

Ann Intern Med, 1991 Mar 15, 114(6), 472 - 81
Lyme disease: recommendations for diagnosis and treatment; Rahn DW et al.; The incidence and the endemic range of Lyme disease in the United States have increased steadily since the disease was originally recognized in Lyme, Connecticut, in 1975 . Because of the varied clinical manifestations of this illness and the use of unstandardized serologic testing methods, diagnosis is often uncertain and treatment outcomes are often difficult to evaluate . The antibiotic regimens that are commonly used in clinical practice have changed rapidly . They show much regional variation with little critical comparison of treatment results . The clinical diagnosis and the literature on the treatment of the various stages of Lyme disease are reviewed . The reported data are supplemented with recommendations based on 15 years of clinical experience with this illness.

Hosp Pract (Off Ed), 1991 Mar 15, 26(3), 83 - 6, 90-1
Acute diverticulitis: diagnosis and management; Van Ness M et al.; A high index of suspicion is required for early detection of complications, most commonly diverticular abscess and colovesical fistula . Appropriate antibiotic therapy should cover a wide range of potential pathogens.

Biochemistry, 1991 Mar 5, 30(9), 2483 - 94
The DNA sequence at echinomycin binding sites determines the structural changes induced by drug binding: NMR studies of echinomycin binding to {d(ACGTACGT)}2 and {d(TCGATCGA)}2; Gilbert DE et al.; The complexes formed between the cyclic octadepsipeptide antibiotic echinomycin and the two DNA octamers {d(ACGTACGT)}2 and {d(TCGATCGA)}2 have been investigated by using one- and two-dimensional proton NMR spectroscopy techniques . The results obtained for the two complexes are compared to each other, to the crystal structures of related DNA-echinomycin complexes, and to enzymatic and chemical footprinting results . In the saturated complexes, two echinomycin molecules bind to each octamer by bisintercalation of the quinoxaline moieties on either side of each CpG step . Binding of echinomycin to the octamer {d(ACGTACGT)}2 is cooperative so that only the two-drug complex is observed at lower drug-DNA ratios, but binding to {d(TCGATCGA)}2 is not cooperative . At low temperatures, both the internal and terminal A.T base pairs adjacent to the binding site in the {d(ACGTACGT)}2-2 echinomycin complex are Hoogsteen base paired (Gilbert et al., 1989) as observed in related crystal structures . However, as the temperature is raised, the internal A.T Hoogsteen base pairs are destabilized and are observed to be exchanging between the Hoogsteen base-paired and an open (or Watson-Crick base-paired) state . In contrast, in the {d(TCGATCGA)}2-2 echinomycin complex, no A.T Hoogsteen base pairs are observed, the internal A.T base pairs appear to be stabilized by drug binding, and the structure of the complex does not change significantly from 0 to 45 degrees C . Thus, the structure and stability of the DNA in echinomycin-DNA complexes depends on the sequence at and adjacent to the binding site . While we conclude that no single structural change in the DNA can explain all of the footprinting results, unwinding of the DNA helix in the drug-DNA complexes appears to be an important factor while Hoogsteen base pair formation does not.

Biochemistry, 1991 Mar 5, 30(9), 2444 - 8
Bleomycin-dependent damage to the bases in DNA is a minor side reaction; Gajewski E et al.; The antitumor antibiotic bleomycin degrades DNA in the presence of ferric ions and H2O2 or in the presence of ferric ions, oxygen, and ascorbic acid . When DNA degradation is measured as formation of base propenals by the thiobarbituric acid assay, it is not inhibited by superoxide dismutase and scavengers of the hydroxyl radical or by catalase (except that catalase inhibits in the bleomycin/ferric ion/H2O2 system by removing H2O2) . Using the technique of gas chromatography/mass spectrometry with selected-ion monitoring, we show that DNA degradation is accompanied by formation of small amounts of modified DNA bases . The products formed are identical with those generated when hydroxyl radicals react with DNA bases . Base modification is significantly inhibited by catalase and partially inhibited by scavengers of the hydroxyl radical and by superoxide dismutase . We suggest that the bleomycin-oxo-iron ion complex that cleaves the DNA to form base propenals can decompose in a minor side reaction to generate hydroxyl radical, which accounts for the base modification in DNA . However, hydroxyl radical makes no detectable contribution to the base propenal formation.

Zentralbl Hyg Umweltmed, 1991 Mar, 191(2-3), 117 - 58
{Hygiene barriers in the hospital--psychological aspects}; Bergler R; This study was made necessary due to the great extent of hospital infections (720,000 cases) in the Federal Republic of Germany and the fact that the nosocomial infection is the most common infectious disease . Starting with a theoretical explanatory model of hygiene behaviour in clinics, 25 senior physicians, 38 assistant doctors, 31 members of the nursing staff and 20 members of the cleaning personnel and domestic staff in university clinics (surgery, orthopaedics, anaesthesia, gynaecology, paediatrics) were examined in a two-stage sociopsychological investigation . To be checked was the hypothesis that the quality and intensity of hygiene behaviour in clinics rises with the extent of personal hygiene sensitivity, knowledge about hygiene essentials, hygiene risks, causes of infection and possibilities of prophylaxis, exemplary and supervisory behaviour on the part of principals and staff in the clinic, as well as the absoluteness, succinctness, clinic-specificity and compulsoriness of rules of hygiene . General findings: (1) During training hygiene was a subject which did not arouse much interest; 57% admit big deficiencies in training; 60.4% of all those asked saw a big lack of information concerning basic knowledge of hospital hygiene, use of non-reusable materials, disinfection of endoscopes, laser probes etc., antibiotic therapy and strategy, development of resistant germs and their disinfection, ways and chains of infection, asepsis in the operating theatre, disposal of contaminated material, rules of hygiene in dealing with HIV-patients, sterilization of implants etc . (2) Doctors and nursing staff assume a relatively high incidence of hospital infections in their own clinic and in their wake an increase in psychological strain on the part of the patients, as well as higher costs in the health service . The most common hygiene deficiencies are lack of space and storage rooms, no separation of septic and aseptic patients, deficiencies in toilets and bathrooms, inadequate personal hygiene behaviour of staff, lack of protective clothing or no regular change of clothing, shortcomings in disinfection, incorrect use of syringes, stethoscopes, etc., no sterile dressings for wounds, no systematic hygiene control and no official consequences for wrong behaviour.(ABSTRACT TRUNCATED AT 400 WORDS)

Poult Sci, 1991 Mar, 70(3), 600 - 4
Folate deficiency in chicks fed diets containing practical ingredients; Pesti GM et al.; Development of folate deficiency was evaluated in young chicks fed diets containing corn and soybean meal as major constituents . Folic acid deficiency, as indicated by retarded growth and feed efficiency, could be produced in 18-day-old chicks . Chicks fed the basal diet had increased growth when given supplements of either folic acid, choline Cl, or DL-methionine, but not vitamin B12 . Relative liver size (grams per 100 g of body weight) was reduced by a methionine or methionine plus choline supplement in two experiments but by folic acid in only one of two experiments . Plasma hemoglobin was reduced by folic acid or a methionine and choline supplement after 42 days on the diets . Folic acid deficiency can be produced in young chicks with a diet based on practical ingredients . Purified diets or very high levels of antibiotic feeding are not necessary to produce folic acid deficiency as long as low levels of methionine and choline are present in the basal diet.

Int J Artif Organs, 1991 Mar, 14(3), 150 - 3
Septicemia in long-term jugular hemodialysis catheters; eradicating infection by changing the catheter over a guidewire; Carlisle EJ et al.; By convention, septicemia occurring from an infected vascular catheter is treated with antibiotics and removal of the catheter . This approach, used with surgically implanted long-term catheters would be expected to result in loss of the vascular access site . During a 57 month period, we treated 21 episodes of septicemia secondary to infection of long term indwelling double lumen jugular venous catheters in our hemodialysis unit . Seventeen of 21 episodes were managed successfully by changing the catheter over a guidewire, thus preserving the access site . No relapse was observed after the antibiotic therapy was stopped . Only four patients required complete removal of the catheter and subsequent use of another site.

J Vet Pharmacol Ther, 1991 Mar, 14(1), 51 - 60
Development of an analytical method for cephapirin and its metabolite in bovine milk and serum by liquid chromatography with UV-VIS detection and confirmation by thermospray mass spectometry; Tyczkowska KL et al.; Metabolites of the cephapirin beta-lactam antibiotic have not previously been reported in bovine milk . The principal metabolite was tentatively identified as desacetylcephapirin by liquid chromatography with UV-VIS photodiode array (LC/UV-VIS PDA), and liquid-chromatography-mass-spectrometric (LC-MS) detection . Synthetic desacetylcephapirin was prepared by incubation of cephapirin in bovine milk and serum at 37 degrees C . Also, a method for determining cephapirin in bovine milk and serum was developed . The detection limits for cephapirin and desacetylcephapirin were estimated to be 10 and 50 micrograms/kg, respectively, for LC/UV-VIS PDA, and 100 and 500 micrograms/kg for LC-MS.

Eur J Radiol, 1991 Mar-Apr, 12(2), 120 - 3
Ultrasound; a method of brain abscess drainage monitoring; Goraj B et al.; Ultrasound guided percutaneous aspiration was performed in fourteen patients with multiple brain abscesses . A bone defect in the skull served as the site of needle insertion and served to sonographically evaluate the abscesses . Antibiotic therapy was administered in all cases . Repeat drainage was required in 5 cases . There were no complications . In 10 patients complete improvement without CNS lesions was achieved . Three patients suffered from headaches and seizures for a period of 6 weeks following the aspiration . One patient with multiple otogenic abscesses died in spite of multiple efforts to drain the abscesses . Our results demonstrate sonography to be very effective for monitoring brain abscess drainage and follow-up.

Biopharm Drug Dispos, 1991 Mar, 12(2), 149 - 62
Distribution kinetics of netilmicin in human blister fluid: effect of renal impairment; Lanao JM et al.; The pharmacokinetics of netilmicin in plasma and blister fluid were compared in 10 healthy volunteers with normal renal function and 10 voluntary patients with varying degrees of renal impairment . Netilmicin kinetics in plasma were characterized by an open two-compartment kinetic model . For the study of the kinetics of the antibiotic in blister fluid a specific kinetic distribution model was employed . In the healthy volunteers the plasma kinetics of netilmicin showed a behaviour similar to that of other aminoglycoside antibiotics, although a high blister/plasma partition coefficient was obtained, with a mean value of 4.27 +/- 1.65 . The transfer of netilmicin in blister fluid governed by the constants K1b/Vb and Kbl had mean values of 0.19 +/- 0.09 h-1 l-1 and 0.25 +/- 0.10 h-1, respectively . In the patients with renal impairment plasma and blister fluid antibiotic levels showed a progressive accumulation . In these patients the affinity of netilmicin for blister fluid was significantly altered . The blister/plasma partition coefficient in this group of patients had a mean value of 2.65 +/- 1.33; the decrease being statistically significant (p = 0.023) with respect to the value obtained in the healthy volunteers . Similarly, the exit constant of netilmicin from blister fluid (Kb1) showed a statistically significant increase (p = 0.035) in the patients with renal impairment . The findings point to a loss of affinity of netilmicin for blister fluid as a result of renal impairment . Linear and logarithmic relationships were established between some pharmacokinetic parameters and creatinine clearance . Dosage schedules are proposed for netilmicin in patients with renal impairment.

World J Surg, 1991 Mar-Apr, 15(2), 235 - 9
Necrotizing lesions of soft tissues: a review; Patino JF et al.; Necrotizing lesions of the soft tissues are grave entities not infrequently seen in daily surgical practice . They may occur with epidemic proportions after natural disasters, representing a serious challenge to the surgeon since they are characteristically associated with high mortality rates unless an early diagnosis is made and prompt aggressive surgical management is initiated . Necrotizing fasciitis is the currently accepted generic term to encompass into a single category the diverse syndromes of progressive gangrenous infections of the skin and subcutaneous tissues . Necrotizing fasciitis must be viewed as a clinical entity rather than a specific type of infection: it is a clinical infection most commonly caused by a mixed aerobic/anaerobic synergistic polymicrobial combination . Zygomycetes may appear as major causal organisms (mucormycosis) and they should be actively searched for . Initial diagnosis of necrotizing fasciitis is established through the characteristic physical signs . Gram stain, and, in some doubtful cases, through frozen-section tissue biopsy . Aggressive and urgent radical debridement is the key to survival, combined with wide-spectrum antibiotic therapy.

World J Surg, 1991 Mar-Apr, 15(2), 162 - 9
Hepatic abscess; Donovan AJ et al.; Hepatic abscess--amebic or pyogenic--can be diagnosed with great accuracy by either ultrasonography or computed tomographic (CT) scanning . Ultrasound is the modality of choice and will detect almost 100% of abscesses . Confirmation of a diagnosis of amebic liver abscess is made by the indirect hemagglutination test that should be positive in almost 100% of cases . Cultures of pus from the abscess and from the blood must be obtained in cases of pyogenic liver abscess . A positive culture of pus from the abscess has been achieved in 90% of cases . Ultrasound or CT guidance is utilized in aspiration of a hepatic abscess . In the treatment of an amebic liver abscess, metronidazole is the amebicide of choice . Open drainage is contraindicated . For cases that fail to respond to therapy with amebicides, closed drainage guided by CT or ultrasound is performed . Secondary bacterial infection of an amebic liver abscess is an extremely rare event . The identification and determination of the antibiotic sensitivity of organisms responsible for pyogenic liver abscess is a crucially important step . Unless a celiotomy is necessary to correct an intraabdominal process or the abscess is extremely large, the initial treatment of pyogenic liver abscess is a 2 week course of appropriate antibiotics followed by a 1 month course of oral antibiotics . The majority of pyogenic liver abscesses will respond to such treatment . If drainage of a pyogenic abscess is required, the preferable technique is with a percutaneous CT- or ultrasound-directed catheter.(ABSTRACT TRUNCATED AT 250 WORDS)

Ophthalmic Surg, 1991 Mar, 22(3), 150 - 2
Nocardia asteroides infection following scleral buckling; King LP et al.; We report a case of delayed external ocular Nocardia asteroides infection following scleral buckling for rhegmatogenous detachment . Surgical removal of the exoplant material allowed isolation and identification of the organism . Topical and systemic antibiotic therapy following exoplant removal yielded a favorable result.

Fam Pract Res J, 1991 Mar, 11(1), 75 - 81
Acute bronchitis in children: building a clinical definition; Vinson DC; Much about acute bronchitis in children is uncertain, even its definition . This study was undertaken to help build a clinical definition to serve as a guide for further research . Charts of 180 children 1 to 12 years old were reviewed . Each had received a diagnosis of acute bronchitis (54 patients), upper respiratory infection with a cough (128 patients), or a new diagnosis of asthma (26 patients) during the previous 12 months . A history of sputum production (odds ration 25.0, p = 0.0001), the finding of rales or rhonchi on examination (OR 11.6, p less than 0.0001), and a past history of lower respiratory illness (OR 3.0, p = 0.01) were associated with a diagnosis of acute bronchitis, but fever and duration of illness were not . In addition, the diagnosis of acute bronchitis was strongly associated with a prescription for an antibiotic . In a child with a cough, acute bronchitis is more likely to be diagnosed if there is a history of sputum production, rales or rhonchi on examination, and a past history of lower respiratory disease.

J Intraven Nurs, 1991 Mar-Apr, 14(2), 91 - 9
Performance of a new softening expanding midline catheter in home intravenous therapy patients; Fontaine PJ; This pilot study was performed to evaluate the performance of a midline catheter as an alternative to the conventional short peripheral catheters and central venous lines used to administer intravenous therapy to the patients at Caremark Homecare before this study . The midline catheters were inserted in home care patients primarily diagnosed with osteomyelitis and infections, for the delivery of approximately 16 days of I.V . antibiotic therapy . Midline catheter performance was compared with the published data on peripheral catheters and central venous lines because there are no other midline catheters available for clinical use that could be used as a study control . Through this pilot study, the importance of adequate dilution of medications and treatment of early aseptic mechanical phlebitis were realized . Also, a variety of patient types was found to be suited to the use of a midline catheter (wide range of age, weight, venous access, and diagnoses) . These findings served as a basis for the ongoing formal study . The low complication rate, insertion ease, and suitability of a wide variety of patient types makes the midline catheter a better alternative to peripheral catheters or central venous lines for intermediate-length I.V . therapies of 1 to 6 weeks.

Transfusion, 1991 Mar-Apr, 31(3), 212 - 7
Infection or suspected infection after hip replacement surgery with autologous or homologous blood transfusions; Murphy P et al.; Homologous blood transfusions have been associated in both animals and humans with an increased risk of acute postoperative infectious complications . Eighty-four patients who underwent hip replacement surgery and were transfused with 2 or 3 units of blood were analyzed to determine whether those receiving homologous transfusions had different outcomes than those receiving autologous blood only . Only patients free of other risks for postoperative infection were studied . Those receiving homologous blood had a 32 percent (16/50) rate of proven or suspected infections, which was significantly higher than the 3 percent (1/34) rate in patients receiving autologous blood (p = 0.0029) . Wound infections accounted for only a minority (6/17) of the proven or suspected infections, which suggests that nonsurgical factors contributed to these complications . The patients identified as being infected required significantly more antibiotic therapy (mean, 7.6 days) and lengthier hospital stays (mean, 15.5 days) than the patients who remained free of evidence of infection (means: 2.3 days of antibiotics and 12.3 days in the hospital) (p = 0.0001 for each variable) . Other potential risk factors for infection, such as duration of surgical procedure, advanced patient age, amount of blood loss, type of anesthesia, surgeon performing the operation, use of a cemented versus porous-coat prosthesis, leukocytopenia, anemia, and underlying medical diagnosis, did not account for the differences in infection rates seen in those receiving homologous and autologous transfusions . These results confirm previous reports of an increased risk of postoperative infection in patients receiving homologous transfusions . Homologous transfusion may contribute to an increased risk of infection by immunologic modulation of the recipient.(ABSTRACT TRUNCATED AT 250 WORDS)

J Med Chem, 1991 Mar, 34(3), 1193 - 201
Synthesis and copper-dependent antimycoplasmal activity of amides and amidines derived from 2-amino-1,10-phenanthroline; de Zwart MA et al.; A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency . Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentration of 40 microM all compounds appeared to be very active against Mycoplasma gallisepticum K154 . The most active compounds were found in the amide series and show growth inhibition in the nanomolar range . These compounds are 4 times more active than tylosin, a macrolide antibiotic, which is used therapeutically in veterinary practice . In the presence of copper, amides derived from 3 are more active than corresponding amidines . Increased activity following derivatization of 3 may be due to the presence of a third coordination site for copper in the title compounds . Evaluation of biological data revealed that antimycoplasmal activity of amides derived from 3 is dependent on lipophilicity . For these amides a good linear correlation was found between antimycoplasmal activity and hydrophobic fragmental values for substituents considered . This quantitative structure-activity relationship study indicated that antimycoplasmal activity was increased upon a decrease of these hydrophobic fragmental values.

Am J Med Sci, 1991 Mar, 301(3), 221 - 30
Gonococcal endocarditis: twenty-five year experience; Jackman JD Jr et al.; Gonococcal endocarditis is a devastating albeit rare complication of disseminated gonorrhea . It virtually disappeared as a disease entity with the advent of antibiotic therapy . Recently, it has reappeared with surprisingly high frequency for unclear reasons . Since 1983, the authors have observed six episodes of this disease in five patients, the largest series reported to date . It is predominantly a disease of young people without underlying valvular heart disease . Characteristic clinical features include a high frequency of congestive heart failure and nephritis and a proclivity for aortic valve involvement, commonly with associated ring abscess, and large vegetations . Genitourinary symptoms, arthralgias, and rash are uncommon . Previously undescribed features include involvement of all four valves simultaneously, recurrence on an aortic valve prosthesis, and a high frequency of terminal complement deficiencies . Precipitous hemodynamic deterioration despite appropriate therapy is not uncommon, and overall mortality rate remains an alarming 19%.

Am J Emerg Med, 1991 Mar, 9(2 Suppl 1), 7 - 10; discussion 33-4
Allergic histories and reactions of patients treated with digoxin immune Fab (ovine) antibody . The Digibind Study Advisory Panel; Kirkpatrick CH; Seven hundred seventeen adult patients with life-threatening digitalis intoxication were treated with Fab fragments of ovine antidigoxin immunoglobulin G (IgG) . Results of the efficacy of treatment and adverse effects were collected with standard report forms . Eighty-two (11%) of the patients were recorded as having histories of allergy (71 patients) and/or asthma (11 patients) . Of the "allergic" subjects, 35 described reactions to antibiotics, 19 to other medications, 3 to foods, and 2 to pollens; in 12 subjects the etiologic agent was not specified . Six subjects had adverse reactions that were probably or possibly due to allergy to components of the antibody preparation . Of these 4 (5%; 95% confidence interval (Cl) 1.8% to 12%) occurred in the 82 subjects with histories of allergy or asthma and 3 (9%; 95% Cl 1.8% to 23%) of these occurred in the 35 persons with histories of allergy to an antibiotic . In contrast, only 2 (0.3%; 95% Cl 0.04% to 1.1%) similar reactions occurred in the 635 subjects with no histories of allergy or asthma . All reactions responded to symptomatic treatment . The authors conclude that treatment of digitalis intoxication with ovine antidigoxin IgG-Fab (Digibind) is generally well tolerated and allergic reactions are rare . However, there is a significantly increased risk of reactions in patients with histories of allergy or asthma.

Ann Emerg Med, 1991 Mar, 20(3), 253 - 7
Management of acute pyelonephritis in an emergency department observation unit; Israel RS et al.; STUDY OBJECTIVES: To determine whether moderately to severely ill patients with acute pyelonephritis can be treated successfully on an outpatient basis, and whether any aspect of history, physical examination, or initial laboratory data predicts failure of outpatient therapy and the need for hospitalization . DESIGN: Retrospective chart review of all patients with a diagnosis of acute pyelonephritis seen during a three-year period . SETTING: Emergency department observation unit of an urban teaching hospital serving residents of the city and county of Denver . TYPE OF PARTICIPANTS: Women between the ages of 15 and 50 with symptoms, physical examination, and initial laboratory data consistent with a diagnosis of pyelonephritis . INTERVENTIONS: Patients received IV antibiotics, rehydration, analgesics, and antiemetics in an observation unit for up to 12 hours, when they were either admitted to the hospital or discharged home on oral antibiotics . MEASUREMENTS AND MAIN RESULTS: Sixty-three of 87 patients (72%) with acute pyelonephritis were managed successfully as outpatients, nine (22%) were hospitalized directly from the observation unit because they were considered to be too ill to go home, and five (6%) returned with persistent symptoms after ED therapy and were hospitalized . No clinical or laboratory variable predicted success or failure of ED observation unit therapy at the time of initial presentation . CONCLUSION: In selected patients, the observation unit may be used to initiate therapy for acute pyelonephritis . Those with an adequate clinical response to initial treatment may be discharged on oral antibiotic therapy with appropriate follow-up.

J Am Coll Cardiol, 1991 Mar 1, 17(3), 590 - 8
Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study; Hickey AR et al.; An observational surveillance study was conducted to monitor the safety and effectiveness of treatment with Digoxin Immune Fab (Ovine) (Digibind) in patients with digitalis intoxication . Before April 1986, a relatively limited number of patients received treatment with digoxin-specific Fab fragments through a multicenter clinical trial . Beginning with commercial availability in July 1986, this study sought additional, voluntarily reported clinical data pertaining to treatment through a 3 week follow-up . The study included 717 adults who received Digoxin Immune Fab (Ovine) . Most patients were greater than or equal to 70 years old and developed toxicity during maintenance dosing with digoxin . Fifty percent of patients were reported to have a complete response to treatment, 24% a partial response and 12% no response . The response for 14% of patients was not reported or reported as uncertain . Six patients (0.8%, 95% confidence interval 0.3% to 1.8%) had an allergic reaction to digoxin-specific antibody fragments . Three of the six had a history of allergy to antibiotic drugs . Twenty patients (2.8%, 95% confidence interval 1.7% to 4.3%) developed recrudescent toxicity . Risk of recrudescent toxicity increased sixfold when less than 50% of the estimated dose of antibody was administered . A total of 215 patients experienced posttreatment adverse events . The events for 163 patients (76%) were judged to result from manifestations of underlying disease and thus considered unrelated to Fab treatment . Digoxin-specific antibody fragments were generally well tolerated and clinically effective in patients judged by treating physicians to have potentially life-threatening digitalis intoxication.

Obstet Gynecol, 1991 Mar, 77(3), 416 - 20
The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone; Neely JL et al.; Doxycycline and other antibiotics have been implicated in oral contraceptive (OC) failure, but information is sparse and studies of a doxycycline-OC interaction are nonexistent . Because an interaction between doxycycline and OCs, especially those containing low-dose estrogen, could result in an unplanned and unwanted pregnancy, a controlled clinical trial of the effects of doxycycline on OC hormone concentrations was performed . Twenty-four women aged 18-35 years were recruited as volunteers from among the patients seen in a University-based family planning clinic . While they were on a steady dose of the OC Ortho-Novum 1/35, serum concentrations of ethinyl estradiol, norethindrone, and endogenous progesterone were measured on days 18, 19, and 20 of the menstrual cycle (control phase) . These measurements were repeated on days 18, 19, and 20 of the following menstrual cycle while the patient was taking doxycycline, 100 mg twice daily (treatment phase) . No statistically significant differences in serum levels of ethinyl estradiol, norethindrone, or endogenous progesterone were seen between the control and treatment phases . However, there was large inter-patient and intra-patient variability in ethinyl estradiol and norethindrone levels . No elevations of endogenous progesterone occurred to suggest ovulation during antibiotic administration in either phase . It is not known what effects longer or earlier administration of doxycycline during the OC cycle would have on serum hormone concentrations or ovulation . Pregnancies attributed to failure of OCs because of tetracycline use could in fact be due to other causes or could represent a true interaction that only manifests itself in a small proportion of women at risk.

Cardiologia, 1991 Mar, 36(3), 247 - 9
{Prosthetic valve endocarditis caused by Gemella haemolysans}; Morea P et al.; Reported herein is the case of a 47 year old man with mitral and aortic bioprosthetic valves who developed endocarditis . Blood cultures turned out to be positive for Gemella haemolysans, a commensal of the upper respiratory tract . Proper antibiotic therapy was immediately started according to antibiogram, and continued after the acute stage of the disease had been overcome . The aortic prosthesis appeared much more to be incompetent at Doppler and aortography (from 2/4 to 3/4) . At surgery, the gross appearance of the explanted xenograft was consistent with infective endocarditis . The case is described for the rarity of the etiology: only 6 cases of infective endocarditis from Gemella haemolysans are reported in the literature, but this is the first involving a prosthetic valve.

Int J Dermatol, 1991 Mar, 30(3), 218 - 9
The use of mupirocin before skin surgery; Czarnecki DB et al.; Presumed skin cancers were excised from 46 consecutive outpatients without antibiotic cover . A purulent wound developed in ten patients . Similar, but contaminated lesions were excised from 40 patients, but mupirocin ointment was used before surgery . Not one purulent wound developed out of 45 excisions.

Antibiot Khimioter, 1991 Mar, 36(3), 39 - 42
{Comparative study of the effect of daunorubicin and its nitroxyl derivative on in vitro function of rat liver mitochondria}; Volk SE et al.; The effect of rubomycin (daunorubicin) and its nitroxyl derivative, ruboxyl, on respiration and oxidative phosphorylation of the rat liver mitochondria was comparatively studied . It was shown that ruboxyl had a more pronounced uncoupling effect than rubomycin, especially during respiration in the presence of the glutamate mixture with malate . Unlike rubomycin, ruboxyl in concentrations of 0.05 to 0.5 mM induced stimulation under metabolic conditions rather than respiration . When the antibiotic concentration increased ruboxyl started to inhibit the respiration as compared to the control and the inhibition level appeared to be higher than that induced by rubomycin . Possible mechanisms for decreasing rubomycin toxicity by its modification with the nitroxyl radical are discussed.

Minerva Stomatol, 1991 Mar, 40(3), 125 - 7
{Juvenile osteomyelitis and osteopetrosis . A case report}; Battaglia MA et al.; A case of mandibular osteomyelitis in a child affected by osteopetrosis is presented . Systemic antibiotic therapy was ineffective and surgery was required to obtain a partial control of infection.

Arzneimittelforschung, 1991 Mar, 41(3), 257 - 9
Pharmacokinetics of cefotiam in plasma, parotid saliva and mixed saliva in healthy adults; Zerfowski M et al.; Cefotiam (Spizef; CAS 61622-34-2) at a dose of 2 g was administered intravenously to 10 young, healthy, male volunteers . Multiple simultaneous blood, parotid saliva, and mixed saliva samples were collected for 7 h . The antibiotic assay was carried out by high-pressure liquid chromatography . Significant salivary cefotiam concentrations were found for 2 to 4 h, potentially inhibitory to a wide array of pathogens commonly isolated from the upper aerodigestive tract . Salivary cefotiam concentrations were correlated to plasma levels (p less than 0.01), but saliva/plasma ratios varied considerably . It is unlikely that passive diffusion is the applicable transfer mechanism for cefotiam secretion into saliva.

J Gen Virol, 1991 Mar, 72 ( Pt 3), 609 - 16
Analysis of Fv-1 restriction in two murine embryonal carcinoma cell lines and a series of differentiated derivatives; Heitman CK et al.; We have used antibiotic-resistant retrovirus vectors rescued by Fv-1-sensitive murine leukaemia viruses (MuLV) to examine the Fv-1 phenotype of two undifferentiated embryonal carcinoma (EC) cell lines derived from teratocarcinomas of mouse strain 129 . In addition, a set of EC cell-derived differentiated cell lines was analysed . Restriction of both B-tropic and endogenous N-tropic virus is characteristic of the Nr-type restriction reported in mouse strain 129 . However, results indicate that Fv-1 restriction is not expressed in the PCC4.aza1R EC cell line . In contrast, the F9 EC cell line showed a strong restriction of the B-tropic pseudotyped vector but failed to restrict endogenous N-tropic pseudotypes . The Fv-1 gene thus seems to be differentially expressed in two EC cell lines derived from the same mouse strain . Furthermore, the selective restriction of B-tropic but not endogenous N-tropic MuLV in F9 cells suggests that these activities function independently of each other . Analysis of PCC4.aza1R-derived differentiated cell lines revealed that three fibroblast cell lines derived by retinoic acid-induced differentiation were also phenotypically silent for Fv-1 . However, a pre-adipocyte line established following simultaneous exposure to retinoic acid and 5-azacytidine showed strong restriction of both B-tropic and endogenous N-tropic MuLV . Although additional data suggest that there is no correlation between the differentiated pre-adipocyte phenotype and Fv-1 expression, our results nonetheless show that Nr restriction can be observed in some derivatives of PCC4.aza1R cells, presumably by activating expression of the Fv-1 gene.

Endocrinology, 1991 Mar, 128(3), 1359 - 68
The interaction of signal transduction pathways in FRTL5 thyroid follicular cells: studies with stable expression of beta 2-adrenergic receptors; Tsuzaki S et al.; Multiple signal transduction pathways interact in FRTL5 cells to promote thyroid follicular cell differentiated function and cell proliferation . In these cells, TSH is a tissue-specific mitogen that promotes DNA synthesis primarily through activation of adenylate cyclase . To further test the role of adenylate cyclase in regulating cell growth and differentiated function we have introduced into FRTL5 the human beta 2-adrenergic receptor (BAR) complementary DNA and have studied the ability of isoproterenol, alone and in combination with insulin-like growth factor I (IGF-I), to stimulate cAMP accumulation, iodide transport, {3H}thymidine incorporation into DNA, and cell growth . Wild-type FRTL5 were infected with a PLJ retroviral construct containing the BAR in either a sense (FRTL BAR) or antisense (FRTL RBAR) orientation, and cell populations were selected on the basis of resistance to the antibiotic geneticin . FRTL BAR expressed approximately 1.3 x 10(5) high affinity binding sites per cell for the beta 2-specific ligand, CGP-12177, while neither FRTL5 wild-type nor RBAR cells demonstrated any specific binding . FRTL BAR had significantly higher levels of intracellular cAMP, {3H}thymidine incorporation, and iodide uptake in the absence of added isoproterenol than FRTL RBAR or wild-type cells . In FRTL BAR, but not RBAR cells, isoproterenol stimulated a dose-dependent accumulation of cAMP, iodide uptake, {3H}thymidine incorporation, and cell growth . FRTL BAR and RBAR cells were equally responsive to TSH and to IGF-I . Isoproterenol enhanced the ability of IGF-I to stimulate {3H}thymidine incorporation in BAR but not RBAR cells . Isoproterenol partially inhibited the ability of TSH to stimulate cAMP generation and DNA synthesis . These studies demonstrate that activation of adenylate cyclase through the BAR introduced into FRTL5 cells by retroviral infection reproduces the range of biological effects in these cells stimulated by TSH and suggest that activation of adenylate cyclase is sufficient to stimulate thyroid differentiated function and cell growth . FRTL BAR cells will provide an interesting model system with which to study the heterologous regulation of both TSH and BARs through activation of a common signal transduction pathway, adenylate cyclase.

FASEB J, 1991 Mar 1, 5(3), 338 - 43
A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits; Wakabayashi G et al.; Despite antibiotic therapy, the septic shock syndrome continues to have a high mortality . Tumor necrosis factor (TNF) and interleukin 1 (IL 1), two polypeptide cytokines produced during sepsis, are thought to mediate the hypotension and tissue damage of shock . In the present studies, rabbits were infused with Escherichia coli organisms to produce shock . The IL 1 receptor antagonist (IL 1ra), which competes with IL 1 for occupancy of the IL 1 cell-surface receptors without agonist properties, was given 15 min before the bacterial infusion and during the subsequent 4 h . In saline-treated controls, hypotension was sustained for 4 h and death occurred for two of five rabbits; in rabbits treated with the IL 1ra, however, blood pressure was only transiently decreased, returned to pre-E . coli levels, and no deaths occurred . The associated leukopenia was also reduced by treatment with the antagonist (P less than 0.05) . Histological examination of lung tissues showed reduced infiltrating neutrophils in the IL 1ra treatment group . Despite the attenuated responses in animals treated with the IL 1ra, circulating TNF and IL 1 levels were nearly identical in both groups . We conclude that specific blockade of IL 1 at the receptor level demonstrates an essential role for this cytokine in the pathogenesis of septic shock.

Rev Clin Esp, 1991 Mar, 188(4), 193 - 6
{Snake bites in our environment . A biannual review of 7 cases}; Angles R et al.; The clinical picture, treatment and evolution of seven patients presenting snake bites are analyzed . Local symptoms were constant, with a spontaneous favorable evolution in 7 to 10 days . The most relevant systemic manifestations were coagulation anomalies which appeared in two patients . Treatment always included local wound care, antitetanicum antibiotic and anticoagulant prophylaxis with specific antiophidic serum in five patients.

Chem Res Toxicol, 1991 Mar-Apr, 4(2), 203 - 13
Determination of the structural features of (+)-CC-1065 that are responsible for bending and winding of DNA; Lee CS et al.; Analysis of the anomalous migration in electrophoretic mobilities of (+)-CC-1065-modified oligomers following ligation reveals that (+)-CC-1065 induces DNA bending and winding of the helix . (+)-CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis . This drug selectively bonds covalently to N3 of adenine and lies in the minor groove of DNA, reacting in a highly sequence-selective manner . Structurally, (+)-CC-1065 consists of three subunits: two identical pyrroloindole units (subunits B and C) and a third subunit containing the DNA-reactive cyclopropane ring (subunit A) . While the bonding reaction is the main determinant of DNA sequence selectivity of (+)-CC-1065, binding interactions between the inside edge substituents of the B and C subunits and the floor of the minor groove of DNA can modulate or fine tune this sequence selectivity, {Hurley, L . H., Lee, C.-S., McGovern, J . P., Mitchell, M . A., Warpehoski, M . A., Kelly, R . C., & Aristoff, P . A . (1988) Biochemistry 27, 3886-3892} . The A subunit of (+)-CC-1065 is responsible for the bending of DNA, and close van der Waals contacts between the inside edge of (+)-CC-1065 and the floor of the minor groove of DNA cause winding equivalent to about 1 base pair per alkylation site and stiffening of DNA . The magnitude of DNA bending induced by (+)-CC-1065 and related compounds is about 14-19 degrees, which is equivalent to that produced by an adenine-thymine tract of about 5-6 base pairs in length . Experiments using oligomers containing both an adenine tract and a unique (+)-CC-1065 bonding site approximately one helix turn apart demonstrate that the directionality of drug-induced bending is in toward the minor groove and the locus of bending is about 2-3 base pairs to the 5'-side of the covalently modified adenine . A circularization efficiency assay shows that the optimum size of circles produced by (+)-CC-1065 and related drugs is between 168 and 180 base pairs . These results are discussed in relation to the molecular basis of the DNA sequence selectivity of (+)-CC-1065, and the (+)-CC-1065-induced DNA bending is compared with the intrinsic bending associated with adenine tracts . Since (+)-CC-1065 induces effects on local DNA structure that appear similar to those produced naturally by adenine tracts and certain DNA binding proteins, the relevance of this phenomenon to biological effects of (+)-CC-1065 and related drugs is considered.

Ann Gastroenterol Hepatol (Paris), 1991 Mar-Apr, 27(2), 51 - 5
{A case of Whipple's disease with ankylosing spondylarthritis treated with trimethoprim-sulfamethoxazole}; Blaison D et al.; We report the case of a patient, suffering from Whipple's disease and HLA B27 positive ankylosing spondylitis with syndesmophytes and erosive discopathy . Since spinal radiographic aspects of spondylitis due to Whipple's disease are unusual, we are debating on their relation . We, then, took an interest in the treatment given to this patient: trimethoprim-sulfamethoxazole which would now appear to be the best antibiotic for Whipple's disease.

Chem Phys Lipids, 1991 Mar, 57(2-3), 327 - 40
Polymorphic phospholipid phase transitions as tools to understand peptide-lipid interactions; Tournois H et al.; The effect of peptides on bilayer----non-bilayer phase transitions can be used as a tool to investigate the molecular aspects of peptide-lipid interactions . In this contribution the action on membranes of the peptide antibiotic gramicidin A and the bee venom component melittin are compared . Although the known structures and locations of these peptides upon membrane binding are very different, their actions on membranes show striking parallels . A general model is proposed that explains the seemingly complex peptide-lipid interactions by making use of simple concepts.

West Indian Med J, 1991 Mar, 40(1), 33 - 6
Pott's puffy tumour and subdural empyema following frontal sinusitis; Holder J et al.; A previously healthy 17-year-old lad presented with purulent sinusitis and subsequently developed subdural empyema in association with Pott's puffy tumour . Complete resolution occurred with an intensive antibiotic regime and drainage of the subgaleal space.

Chem Res Toxicol, 1991 Mar-Apr, 4(2), 241 - 52
Molecular recognition between oligopeptides and nucleic acids: DNA binding selectivity of a series of 1,2,4-triazole-containing lexitropsins; Rao KE et al.; The synthesis of a series of 1,2,4-triazole-containing oligopeptide lexitropsins related to the natural antitumor antibiotic distamycin is described . The binding properties of these new agents to both native DNAs and synthetic polydeoxyribonucleotides were determined by UV absorption and circular dichroism studies . The DNA binding and sequence selectivity of these agents have been determined by complementary strand MPE footprinting on two restriction fragments of pBR322 DNA . The lexitropsins bearing one 1,2,4-triazole moiety bind to AT sequences like distamycin but also tolerate GC sites . However, 3, which contains two contiguous 1,2,4-triazole moieties, appears not to recognize AT stretches and demands two consecutive GC bases in the middle of a four-base recognition site . The triazole lexitropsins avoid ATTT (4264-4267) and AAAA (4273-4276) to which distamycin binds strongly to the EcoRI/Hind III fragment . Determination of pKa values indicates the 1,2,4-triazole units are protonated under physiological conditions . The avoidance of AT stretches and the recognition of GC base sites by 3 suggest molecular recognition in these cases is determined, not by electrostatic effects, but rather by invoking a hydrogen bond between the triazole 4-nitrogen and G-2NH2 in the minor groove.

Zh Vopr Neirokhir Im N N Burdenko, 1991 Mar-Apr, (2), 13 - 6
{The antiblastic properties of reumycin (experimental research)}; Romodanov SA et al.; The work deals with the results of study of the antineoplastic activity of a Soviet produced antineoplastic antibiotic reumycin in relation to 35 glial tumors of various degrees of malignancy in primary cultures and in heterotransplantation under the capsule of kidneys in mice . In tissue cultures 71.5% of gliomas were sensitive to reumycin, in the subcapsular test 75% of tumors proved to be reumycin sensitive with fluctuations of inhibited growth of heterotransplants within a range of 27-75% . Among the reumycin resistant tumors, the cultures of one of the glioblastomas showed stimulation of proliferation, which justifies the necessity for testing the individual sensitivity of the tumor to reumycin in each concrete patient.

Appl Microbiol Biotechnol, 1991 Mar, 34(6), 749 - 55
Genetic analysis of the phosphinothricin-tripeptide biosynthetic pathway of Streptomyces viridochromogenes Tü494; Alijah R et al.; Streptomyces viridochromogenes Tu494 produces the antibiotic phosphinothricyl-alanyl-alanine (Ptt) . Ptt-non-producing mutants were isolated following N-methyl-N'-nitro-N-nitrosoguanidine (NTG) or UV light treatment of spore suspensions . In co-synthesis and bioconversion experiments the mutational blocks in the biosynthetic pathway were localized . The mutant NTG1 was analysed in detail . This mutant acts as a secretor for all other mutants . From bioconversion experiments with presumptive precursors circumstantial evidence was obtained that NTG1 is mutated in a gene involved in the alanylation of N-acetyl-demethyl-phosphinothricin . Using a cosmid gene library the DNA region complementing the defective gene of mutant NTG1 was isolated on a 4-kb BamHI fragment . Subcloning experiments showed that a 3-kb BglII/BamHI fragment is sufficient for complementation of mutant NTG1.

Clin Ter, 1991 Feb 28, 136(4), 273 - 8
{Clinical experience with imipenem-cilastatin in intensive therapy}; Verre M et al.; The authors describe their experience with imipenem-cilastatin in 36 patients in critical conditions due to multiresistant bacterial infections . The efficacy and tolerability of the antibiotic are stressed.

Rev Fr Gynecol Obstet, 1991 Feb 25, 86(2 Pt 2), 191 - 4
{Clinical aspects and complementary tests in pelvic congestive states}; Loffredo V; Pelvic congestion syndrome is common to three pathologies: premenstrual syndrome, intermenstrual syndrome and chronic pelvic fibrous congestion syndrome . The two first syndromes are well-known . They are periodical and hormonal treatment is relevant in premenstrual syndrome (all forms of progesterone and provascular treatment) . Chronic pelvic congestion syndrome or fibrous congestion is linked with fibrous changes of the subperitoneal cellular tissue after more or less lasting chronic congestion . It is sometimes secondary to low noised and unknown sepsis (Bret and De Brux fibro-sclerous pelviperitonis) . It is usually linked with the traumatical rupture of cellular pelvic tissue from obstetrical etiology (Masters and Allen syndrome) . In varicocele, uterine plexus and ilio-lumbar ligament, hormonal action has been suggested . Three signs overnite polymorphic clinical study: deep dyspareunia, moving cervix, uterus retroversion . But primitive or secondary congestion is only in fact evoked by coelioscopy even with its limits . When coelioscopy is negative, hysterophlebography will be achieved and will visualize sometimes extremely pelvic plexus vasodilatation . As function of findings lesions, treatment lays down 3 principles: first principle not to abuse with surgery except in case of testing patent ligamentary lesions . Second principle to prescribe a polyvalent general treatment with triade antibiotic, antiinflammatory and phlebotonic drugs . Third principle to be preventive by improving obstetrical exercise as usually this syndrome succeeds to a more or less traumatic delivery.

Eur J Pharmacol, 1991 Feb 25, 206(2), 155 - 8
The inhibition of {125I}omega-conotoxin GVIA binding to neuronal membranes by neomycin may be mediated by a GTP-binding protein; Stumpo RJ et al.; omega-Conotoxin GVIA (omega-CT) has been reported to block calcium currents at the L- and N-type calcium channels . In neuronal membranes omega-CT, and the aminoglycoside antibiotic neomycin, have been shown to inhibit {125I}omega-CT binding, presumably acting at the N-type calcium channel . We demonstrate here that the concentration curve for neomycin sulfate inhibition of {125I}omega-CT binding is shifted to the right by GTP analogues or fluoride, increasing the IC50 for neomycin . {125I}omega-CT binding is unaffected by these agents and in competition studies the potency of omega-CT, Ca2+, or La3+ is not modulated by GTP analogues or fluoride . These results indicate that the inhibition of {125I}omega-CT binding by neomycin may be mediated by a GTP binding protein.

Proc Natl Acad Sci U S A, 1991 Feb 15, 88(4), 1431 - 5
Demonstration of a pronounced effect of noncovalent binding selectivity on the (+)-CC-1065 DNA alkylation and identification of the pharmacophore of the alkylation subunit; Boger DL et al.; Studies on the structural origin of the DNA alkylation selectivity of the antitumor antibiotic (+)-CC-1065 are detailed . The sites of alkylation of double-stranded DNA were examined for simple derivatives of 7-methyl-1,2,8,8a-tetrahydrocycloprop{1,2-c}pyrrolo{3,2-e}indol- 4(5H)-one (CPI), (+)-CC-1065, and agents incorporating the parent 1,2,7,7a-tetrahydrocycloprop{1,2-c}indol-4-one (CI) left-hand subunit . The CI subunit of the agents is a much more reactive alkylating agent than the natural CPI alkylation subunit of CC-1065 . Consequently, simple derivatives of CI were found to alkylate double-stranded DNA under milder conditions than were simple derivatives of CPI, and the marked similarities in the CI and CPI DNA alkylation profiles illustrate that CI represents the minimum pharmacophore of CPI . Comparisons of the DNA alkylation profiles of (+)-N-butyloxycarbonyl-CPI, (+)-N-acetyl-CPI, and (+)-CC-1065 revealed distinctions in the CPI and (+)-CC-1065 sites of alkylation, whereas the incorporation of the reactive CI electrophile into an analog of CC-1065 (CI-CDPI2) (CDPI, N3-carbamoyl-1,2-dihydro-3H-pyrrolo{3,2-e}indole-7-carboxylic acid) provided an agent that possesses the characteristic CC-1065 DNA alkylation profile (site selectivity and relative site intensity) . These observations suggest that the noncovalent binding selectivity of the agents may restrict the number of available DNA alkylation sites and play a productive role in controlling the sequence-selective alkylation by effectively delivering the electrophile to A + T-rich minor groove regions of DNA possessing accessible adenine N-3 alkylation sites . In turn, the noncovalent binding selectivity may be derived from preferential binding within the narrower, sterically more accessible A + T-rich minor groove of double-stranded DNA.

J Biol Chem, 1991 Feb 15, 266(5), 3113 - 7
Repair of alkali-labile sites within the mitochondrial DNA of RINr 38 cells after exposure to the nitrosourea streptozotocin; Pettepher CC et al.; Studies were initiated to investigate whether mechanisms exist within mitochondria to repair damage incurred by mitochondrial DNA after exposure to alkylating toxins . A clonal isolate from a rat insulinoma cell line was utilized to measure the formation and repair of alkali-labile sites within the mitochondrial genome after exposure to the alkylating antibiotic streptozotocin . Alkali-labile sites were formed in mitochondrial DNA in a dose-dependent fashion . Eight hours after exposure to the toxin, 55% of the lesions were removed . The level of repair increased to 70% after 24 h . In comparison, only 46% of N7-methylguanines were removed across the entire cellular genome . These studies demonstrate that streptozotocin causes appreciable mitochondrial DNA damage in a dose-dependent manner and provide the first evidence that a repair mechanism for alkali-labile sites is present within the mitochondrion.

Biochemistry, 1991 Feb 5, 30(5), 1364 - 72
DNA-nogalamycin interactions; Egli M et al.; The anthracycline antibiotic nogalamycin differs from the more common daunomycin-type anthracyclines by substitution on both ends of the intercalating chromophore, giving nogalamycin the approximate shape of a dumbbell . The chromophore of daunomycin is substituted on only one end . In nogalamycin, the positively charged amino sugar substituent of daunomycin is replaced by an uncharged nogalose sugar and a methyl ester group . The other end of nogalamycin, where daunomycin is unsubstituted, is fused to a bicyclo amino sugar with a positively charged dimethylamino group . Much larger DNA fluctuations are required for intercalative entry of nogalamycin than for entry of daunomycin . This report describes the X-ray crystal structure of the complex between nogalamycin and the self-complementary DNA hexamer d(me5CGTsAme5CG) . The DNA contains cytosines methylated at the 5-positions and a phosphorothioate linkage at the TpA step . Nogalamycin intercalates at the terminal CpG steps and interacts with both strands in both grooves of the DNA . Large conformational adjustments in both nogalamycin and the DNA are necessary to form a stable, intercalative complex . The interactions of the bases with the nogalamycin substituents lead to sliding of bases relative to each other along the normal to Watson-Crick hydrogen bonds . The planarities of base pairs surrounding the intercalation site are distorted . The backbones of the two strands are distorted asymmetrically by nogalamycin with large deviations from standard B-DNA geometry . The complex between nogalamycin and DNA illustrates the conformational flexibility of DNA . The hydrogen-bonding interactions between nogalamycin and DNA do not suggest a sequence-specific binding of the drug, although additional secondary effects might lead to differences between various intercalation sites.

Can J Microbiol, 1991 Feb, 37(2), 122 - 7
Two new genes (smhA and lytE) apparently functionally related to the murH gene of Escherichia coli; Dai DX et al.; The murH mutant of Escherichia coli exhibits temperature-sensitive growth and lysis at the restrictive temperature . Temperature-resistant derivatives of the mutant occurred at a frequency of about 3 X 10(-6) . All of the seven independent isolates examined were shown to be pseudorevertants carrying extragenic suppressors of murH, which mapped at 24.5 min on the linkage map . One allele, apparently representing a new locus, designated smhA, was characterized further . The smhA mutation by itself conferred no recognizable phenotype . However, smhA suppressed the temperature-sensitive lysis phenotype of the murH mutant . The smhA mutant acquired a spontaneous mutation in another new gene, designated lytE, which was mapped at 25 min . The lytE mutation by itself conferred a temperature-sensitive lysis phenotype indistinguishable from that of the murH mutant . The lytE mutation was suppressed by smhA as well as by another suppressor of murH designated smhB . The suppressor activity of smhA was apparently relatively specific in that smhA failed to prevent lysis caused by either mutational or antibiotic-induced blocks in peptidoglycan synthesis . The possibility that the smhA and lytE genes are functionally related to murH is considered.

Bol Med Hosp Infant Mex, 1991 Feb, 48(2), 112 - 6
{Evaluation of primary cicatrization of anastomosis of small intestine (experimental study in guinea pigs)}; Silva-Cuevas A et al.; The healing process carried out during the first 72 hours of the anastomotic line of the small intestine has not been satisfactorily studied . This is a time during which intestinal transit is evaluated and oral feeding is given without being really sure whether there is resistance to rupture and if the open surgical technique favors local infection . For this study, 120 guinea pigs submitted to end-to-end anastomosis were used, 30 with continuous sutures and 30 with separate stitches, who were examined 24, 48 and 72 hours after the surgery, plus another group similarly evaluated immediately after the surgery, finding that rupture resistance is greater immediately after surgery than 48 or 72 hours later and that in these, the inflammatory process is greater and a more positive number of cultures are found . The antibiotic orally and parenterally administered did not do away with the infection but did limit further complications.

J R Coll Surg Edinb, 1991 Feb, 36(1), 41 - 4
Practical surgical audit: a morbidity profile; Cale AR et al.; A prospective study of 248 patients admitted consecutively under the care of a single surgeon was performed and data on a variety of patient details were collected daily during the period of their hospitalization . Analysis of the data identified four quantifiable indices of morbidity, namely duration of hospitalization, duration of intravenous infusion, analgesic requirement and antibiotic administration, which can be combined arithmetically and used to produce a morbidity profile . The use of such a profile may allow comparisons to be made between different units if applied to specific conditions and permit a more accurate assessment of overall patient morbidity than can be presently done using mortality rates.

Int J Pediatr Otorhinolaryngol, 1991 Feb, 21(1), 15 - 20
Preventing perioperative obstruction of tympanostomy tubes: a prospective trial of a simple method; Cunningham MJ et al.; The intraluminal obstruction of tympanostomy tubes by hemorrhage incurred in the perioperative period is not a rare problem . The exact frequency, however, is unknown and methods of prevention have not been studied . We prospectively investigated a method of unilaterally coating one grommet with antibiotic ointment in 128 children undergoing bilateral tympanostomy tube placement; the contralateral tube was not treated . We established the incidence of intraluminal obstruction by blood in untreated grommets to be 4.7% . The incidence of hemorrhagic obstruction of the coated tubes was less (2.3%) but did not achieve statistical significance (P less than 0.20) . The technique of antibiotic ointment application to the tympanostomy tube at the time of surgery was not sufficiently efficacious to justify routine use.

Int J Artif Organs, 1991 Feb, 14(2), 87 - 91
Intraperitoneal thrombolytic agents in relapsing or persistent peritonitis of patients on continuous ambulatory peritoneal dialysis; Murphy G et al.; Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients . In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences . The treatment failed in eight other patients, who had their peritoneal catheters removed . Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter . Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances . Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis . Post-instillation peritoneal fluid cell counts and cultures should be monitored . Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis.

Harefuah, 1991 Feb 1, 120(3), 129 - 30
{Conservative treatment of CSF leakage after lumbosacral operations}; Waisman M et al.; CSF leakage through a postoperative lumbosacral wound is an uncommon complication . It may result from excessive traction on nerve roots, or direct trauma or laceration at operation, causing inadvertent opening of the dura (1,4) . Other reasons for this complication are residual bone spikes postlaminectomy, traumatic myelography puncture (2), and improper suture of dural defects . We examined 8 patients who had postoperative CSF leakage as the sole complication of lumbosacral spinal operations . They were all treated conservatively with bed rest in the Trendelenburg position, antibiotic coverage, watertight skin suturing and daily subcutaneous puncture . Each patient had been operated on for a different condition.

Tijdschr Kindergeneeskd, 1991 Feb, 59(1), 36 - 9
{Purulent pericarditis in children . A continuously life-threatening disease}; Morshuis WJ et al.; Acute purulent pericarditis in children is usually fatal, if not recognized and adequately treated . The history of three children with acute purulent pericarditis is presented . In every septic child who presents with signs of right heart decompensation, acute purulent pericarditis should be seriously considered . Echocardiography is essential for the diagnosis . If possible, diagnostic pericardiocenthesis should be performed . Experience of the last years suggests that excellent results can be obtained when adequate surgical drainage and antibiotic therapy are combined.

Dtsch Tierarztl Wochenschr, 1991 Feb, 98(2), 47 - 50
Flavomycin effects on performance of beef bulls and nutrient digestibility in wethers; De Schrijver R et al.; For 28 weeks a feeding experiment was conducted to determine the effects of dietary flavomycin on performance of beef bulls . In the first and second half of the trial, 40 animals (average initial weight 352 kg) had free access to corn silage or beet pulp, respectively, both supplemented with an appropriate concentrate containing 0 or 10 mg/kg of the antibiotic . Daily flavomycin intake was 39 to 46 mg when the animals were on the corn silage diet and 51 to 54 mg when they were fed the beet pulp diet . The animals fed the corn silage-based diet supplemented with flavomycin showed a non-significant improvement of daily gain (1.4%) and feed conversion (2.3%) . When the beet pulp-based diet was fed, flavomycin significantly increased daily gain (15.2%, P less than 0.002) and feed conversion efficiency (9.1%, P less than 0.03) . For the overall feeding experiment the positive effect of flavomycin feeding was 6.7% on body weight gain (P less than 0.09) and 5.2% on feed conversion (P less than 0.13) . Flavomycin did not affect carcass yield of beef bulls . Also the effect of flavomycin on diet digestibility was studied in wethers fed a mixture of beet pulp and concentrate, containing 0 or 10 ppm flavomycin . No significant effect from the antibiotic on digestion of dry matter, crude protein, fibre, fat, ash and N-free extract was observed.

Acta Anaesthesiol Scand, 1991 Feb, 35(2), 97 - 104
Postoperative pulmonary complications and lung function in high-risk patients: a comparison of three physiotherapy regimens after upper abdominal surgery in general anesthesia; Christensen EF et al.; The effect of three postoperative regimens of respiratory therapy on pulmonary complications and lung function was compared in high-risk patients . Fifty-one patients were randomized to: 1) conventional chest physiotherapy alone (PHYS), 2) chest physiotherapy and positive expiratory pressure (PEP), or 3) chest physiotherapy with both positive expiratory pressure and inspiratory resistance (RMT) . Treatments were given twice daily by a physiotherapist and self-administered . The incidence of postoperative pulmonary complications (PPC) was respectively, 71%, 76% and 65% in the PHYS-, PEP- and RMT-groups . The incidence of PPC requiring treatment with antibiotic, bronchodilator or supplementary oxygen according to the existing clinical practice was 47%, 47% and 29% . The incidence of atelectasis was 65%, 64% and 60% and of pneumonia 29%, 35% and 6% . There was no difference between the groups, except for a tendency to a lower frequency of pneumonia in the RMT-group . Postoperatively forced vital capacity (FVC) decreased to mean 54%, forced expired volume in 1 s to 48% and functional residual capacity to 76% of preoperative values . Arterial oxygen tension (PaO2) declined to mean 8.1 kPa and arterial saturation (SaO2) to 89% . There was no difference between the groups except for FVC, PaO2 and SaO2 (P = 0.008, P = 0.008 and P = 0.002), which showed the least decrease in the RMT-group . None of the regimens could be considered as satisfactory concerning the prevention of PPC, but RMT seemed to be the most efficient . Insufficient self-administration of treatment was probably one of the causes of the overall high incidence of PPC in this study.

J R Army Med Corps, 1991 Feb, 137(1), 35 - 7
Space infections of the head and neck--the "new" clinical picture; Evans DG et al.; A series of 12 neck space infections admitted to a military hospital in Germany in a 12 month period are presented . This represents an incidence of 1:1000 for the age group studied . The reappearance of the retropharyngeal abscess which has been rare since the widespread use of antibiotics, along with the generally high incidence of this group of infections, is probably a result of the more discriminating use of antibiotics in primary health care . The pitfalls in diagnosis and the preferred antibiotic cover are discussed.

Arch Mal Coeur Vaiss, 1991 Feb, 84(2), 269 - 71
{Brucella endocarditis on Starr aortic valve prosthesis}; Kamoun S et al.; The authors report the case of a 22 year old patient with brucella endocarditis on a Starr-Edwards aortic valve prosthesis implanted 5 years previously . Six blood cultures were positive for Brucella melitensis biovar I . Antibiotic therapy associating Rifampicin and Tetracycline and then Rifampicin and Ofloxacine did not prevent abscess formation and valve dehiscence . The poor haemodynamic status and persistent infection led to replacement of the valve prosthesis . Culture of the infected prosthesis grew a colony of brucella melitensis resistant to fluoro-quinolones . Valve replacement and antibiotic therapy led to clinical improvement and constant apyrexia with a 12 month follow-up . Brucella endocarditis on a valve prosthesis is a very rare occurrence . The combination of valve replacement and antibiotic therapy is usually required.

Gene, 1991 Feb 1, 98(1), 129 - 34
An expression vector for the phytopathogenic fungus, Ustilago maydis; Kinal H et al.; We have constructed an expression vector for the phytopathogenic fungus Ustilago maydis . This vector, pUXV, expresses genes located downstream from a U . maydis glyceraldehyde-3-phosphate dehydrogenase promoter . Plasmid pUXV also contains a selective marker gene conferring resistance to the antibiotic hygromycin B and a U . maydis autonomously replicating sequence, UARS, allowing high transformation efficiency . Expression of a cDNA from the toxin-encoding region of the U . maydis virus P6 in pUXV resulted in as much killing activity as from viral particles when evaluated by killer plate assay . Plasmid pUXV preserves essential sequences from pUC12 and is therefore a shuttle vector for U . maydis and Escherichia coli.

J Reprod Med, 1991 Feb, 36(2), 113 - 7
CO2 laser for suppurative hidradenitis of the vulva; Sherman AI et al.; Chronic suppurative hidradenitis is a disease of the apocrine glands occurring predominantly in the axillae of the anogenital region . Treatment, to date, has been frustrating . Prolonged antibiotic therapy and multiple incisions and drainage have been the usual form of therapy, but those surgical procedures leave patients with ugly scars; retracted, hypertrophic skin edges; and pitted, indurated and disfiguring abscesses . The only successful treatment to date has been wide excision of the entire apocrine gland-bearing tissues, such as radical vulvectomy, which often necessitates grafts to cover the surgically exposed areas . That has left patients with unsatisfactorily functioning vaginas and a mutilated appearance . Recently we instituted the use of the CO2 laser to treat these patients with the goal of eradicating the suppurative sinus tracts and the infected apocrine glands without removing large volumes of adjacent, unaffected tissue . Over the past eight years we treated 11 patients who had extensive, chronic hidradenitis of the anogenital area with the CO2 laser . The use of laser therapy for these patients has produced effective and less-mutilating results . Such treatment has been a successful option for treating this debilitating disease.

Clin Pediatr (Phila), 1991 Feb, 30(2), 88 - 92
Underdiagnosis and undertreatment of chronic sinusitis in children; Richards W et al.; A review of outpatients diagnosed with sinusitis during the previous year by the allergy services of Childrens Hospital of Los Angeles and Kaiser Permanente, Orange County, revealed 34 patients who had protracted discomforting and debilitating symptoms . The mean duration of symptoms was approximately six months (range 1-14 months) . None had been previously diagnosed as having sinusitis or received appropriate treatment . Although all were referred for evaluation of allergic rhinitis and/or asthma, approximately 1/3 were found to have neither of these conditions . Among patients who had asthma, their asthmatic symptoms were aggravated by the sinusitis . All patients eventually responded favorably to appropriate antibiotic therapy . Earlier diagnosis and appropriate therapy would have foreshortened the course of this very discomforting condition . In recent years, we have observed a marked increase in the number of patients referred with the chief complaint of "worsening allergy" and who were subsequently found to have sinusitis . Most of the patients experienced significant incapacitation for protracted periods before a correct diagnosis was made and treatment instituted . In all but a few cases, prompt and sustained improvement followed appropriate therapy . The purpose of this report is to present a retrospective review of 34 illustrative cases.

Mol Reprod Dev, 1991 Feb, 28(2), 158 - 68
Distribution of filipin-sterol complexes in the plasma membrane of stallion spermatozoa during the epididymal maturation process; Lopez ML et al.; The presence and distribution of cholesterol in mature and immature epididymal spermatozoa was analyzed using filipin as a cytochemical tool in freeze-fracture replicas and thin section preparations . The polyenic-antibiotic filipin formed complexes with 3, beta -OH sterols, producing characteristic protrusions, or pits, that were heterogeneously distributed in the plasma membrane of stallion spermatozoa, revealing a specific organization in a functionally specialized area of the gamete . The acrosomal region of the sperm head presented a significantly higher density of filipin sterol complexes than the postacrosomal region, which was usually free of these complexes . The plasma membrane of the flagellum also showed filipin sterol complexes randomly distributed in freeze-fracture replicas . The strong filipin labeling observed in the membrane of spermatozoa obtained from the caput region of the epididymis decreased significantly during epididymal passage . The significance of these changes is not completely understood, but they might contribute to establishing the molecular organization necessary for sperm transit and storage in the epididymis as well as to development of motile spermatozoa that are able to fertilize the oocyte and induce normal embryonic development.

J Steroid Biochem Mol Biol, 1991 Feb, 38(2), 219 - 25
Effect of the progestogens, gestodene, 3-keto desogestrel, levonorgestrel, norethisterone and norgestimate on the oxidation of ethinyloestradiol and other substrates by human liver microsomes; Back DJ et al.; A number of different progestogens, levonorgestrel (LNG), norethisterone (NET), gestodene (GSD), desogestrel (DG) and norgestimate (NORG) are used in combination with the oestrogen ethinyloestradiol (EE2) in oral contraceptive steroid preparations . All the progestogens are acetylenic steroids and previous studies have indicated the potential of acetylenic steroids to cause mechanism-based or "suicide" inactivation of cytochrome P-450 . We have compared the effects of the different progestogens on EE2 2-hydroxylation (a reaction catalyzed by enzymes from the P-450IIC, P-450IIIA and P-450IIE gene families) and also the oxidative metabolism of other drug substrates (cyclosporin, diazepam, tolbutamide) by human liver microsomes . On coincubation with EE2 as substrate, GSD, 3-keto desogestrel (3-KD, the active metabolite of desogestrel) and LNG produced some concentration-dependent inhibition of EE2 2-hydroxylation (maximum 32% inhibition at 100 microM 3-keto desogestrel) . Ki values determined for GSD and 3-KD were 98.5 +/- 12.3 and 93.2 +/- 10.3 microM (mean +/- SD; n = 4), respectively . Preincubation of progestogens in a small volume (50 microliters) incubation for 30 min in the presence of an NADPH-generating system enhanced the inhibitory potential of all the steroids (at 100 microM, inhibition was for GSD 39%, 3-KD 46%, LNG 46%, NET 51% and NORG 43%) . Inhibitory effects were therefore comparable and also similar to the macrolide antibiotic troleandomycin . The most marked inhibition seen was of diazepam N-demethylation and hydroxylation by GSD (71 and 57%, respectively) and 3-KD (62 and 50%, respectively) . In preincubation studies involving cyclosporin as the substrate, the order of inhibitory potency was GSD greater than 3-KD greater than NET greater than LNG for production of both metabolite M17 and M21 . The results of the study indicate that all the progestogens in common use have the propensity to inhibit a number of oxidative pathways but there is little evidence for one progestogen being more markedly inhibitory than others.

Dis Colon Rectum, 1991 Feb, 34(2), 151 - 5
A comparison between single and double dose intravenous Timentin for the prophylaxis of wound infection in elective colorectal surgery; Cuthbertson AM et al.; A prospective, randomized, single-blind, controlled clinical trial was undertaken to determine whether two doses of systemic Timentin provided superior prophylaxis against postoperative sepsis in elective colorectal surgery compared with a single dose of the same antibiotic . Timentin, a combination of ticarcillin and clavulanic acid was administered intravenously (3.1 g) at the commencement of operation to all patients, and this was repeated after 2 hours in those patients randomized to receive a second dose . The wound infection rate was 11 percent in the 143 patients completing follow-up and receiving a single dose, and 13 percent in the 128 patients receiving two doses of Timentin (P greater than 0.05) . The rates of postoperative septicemia 3 vs . 4 percent and intra-abdominal abscess 5 vs . 8 percent were similar . Multivariate analysis of the factors likely to affect postoperative would infection rate demonstrated an association with the type of hospital, public or private, wound infection rate 16 and 6 percent, respectively (P less than 0.01), and the surgeon group defined by the number of patients contributed greater than 25 or less than 25, wound infection rate 6 and 18 percent, respectively (P less than 0.05) . We concluded that a single dose of intravenous Timentin was as effective as two doses for prophylaxis against surgical infection and that the surgeon group and the hospital in which the operation took place were statistically significant predictors of postoperative wound infection.

Arch Surg, 1991 Feb, 126(2), 149 - 56
Clinical spectrum of fungal infections after orthotopic liver transplantation; Castaldo P et al.; During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%) . Candida species accounted for 83.5% of cases . Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16) . The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation . Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications . Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%) . Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.

Neurology, 1991 Feb, 41(2 ( Pt 1)), 239 - 44
Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study; Giuseffi V et al.; To identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls . Ninety percent of the IIH patients were women; the mean age was 33 . Obesity and recent weight gain were much more common among patients than controls . Symptoms most commonly reported by IIH patients were headache (94%), transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%) . Daily occurrence of these symptoms was much more common among patients than controls . Controls also reported these and other IIH symptoms, but at lower frequencies . Several conditions previously associated with IIH were no more common in patients than controls including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives . We conclude that previous studies of IIH, mostly uncontrolled and retrospective, have underestimated the frequency of symptoms in IIH patients and reported chance and spurious associations with common medical conditions and medications . The profile of a young obese woman with headaches and either TVO or ICN should alert the clinician to the diagnosis of IIH, especially when the symptoms occur daily.

Crit Care Med, 1991 Feb, 19(2), 171 - 5
Reliability of the bronchoscopic protected catheter brush in the diagnosis of pneumonia in mechanically ventilated patients; Rodriguez de Castro F et al.; OBJECTIVE: To assess the usefulness of the telescoping plugged catheter in the diagnosis of nosocomial pneumonia . DESIGN: Prospective study . PATIENTS: A total of 103 ventilated patients with suspected pneumonia were prospectively studied over 20 months . RESULTS: The quantitative cultures of the protected brush specimen detected pulmonary bacterial infection (greater than 10(3) cfu/mL) in 49 (47.5%) patients . Subsequent follow-up confirmed pneumonia in 41 patients; in only one patient was a positive protected brush specimen culture established as a false-positive result . There were 54 patients with less than 10(3) cfu/mL and the diagnosis was excluded in 36 of them . We identified eight patients with false-negative protected brush specimen cultures . The results obtained by this technique allowed us to modify treatment in 49 (47.5%) patients . CONCLUSIONS: The telescoping plugged catheter demonstrated significant bacterial infection in a relatively small proportion of patients in whom bacterial lung infection was suspected . This technique can be safely performed and is a sensitive and specific method to establish the cause of pneumonia, thus allowing specific treatment and the avoidance of inappropriate antibiotic therapy.

Plast Reconstr Surg, 1991 Feb, 87(2), 268 - 75
Aesthetic augmentation of the posterior mandible; Whitaker LA; The posterior mandible begins just behind the mental nerve and second bicuspid bilaterally, extends to the posterior edge of the ramus, and then runs superiorly to the zygomatic arch . Augmentation of the posterior mandible is possible by use of a synthetic implant that is tailored individually to each patient's specific needs . Implant plant thickness varies from 4 to 8 mm, with an average thickness of 6 mm . Careful preoperative planning is done based on an aesthetic assessment of the amount of highlighting desired, thickness of the soft tissues, and the use of life-size photographs and cephalometric and Panorex x-rays . A pattern is cut, and the implant is carved to fit the patient . Insertion of the material after careful tailoring to the individual patient's own mandibular size and configuration requires a generous posterior lower buccal sulcus incision . Antibiotic irrigation and systemic antibiotics are essential, and careful closure in two layers completes the procedure . One implant in the series extruded in a patient who had had radiation therapy, and one patient required repositioning of the implant . Otherwise, in 22 patients there were no infections or permanent morbidity . The procedure seems to be a realistic and safe one for both the youthful and aging face, as demonstrated in patients in this series, with ages varying from 16 to 40 years.

Antibiot Khimioter, 1991 Feb, 36(2), 39 - 41
{Combined etiological and pathogenetic therapy of urogenital Ureaplasma-Chlamydia-gonococcal infection in men}; Bukharovich MN et al.; One hundred and sixteen males with mixed Ureaplasma ++, chlamydial and gonorrheal urethritis were treated . 22 of them suffered from recent torpid urethritis and 94 were chronic patients including those with complications . The diagnosis was confirmed by the laboratory tests . The patients were subjected to complex treatment with immunostimulation (by the gonorrhea vaccine, methyluracil and pyrogenal), local therapy and the use of antibiotic combinations on day 8: gentamicin (0.84 g per treatment course) and doxycycline (2.1 g per treatment course) . The treatment course was equal to 14 days . Favourable etiological and clinical results were observed in 114 patients . The recovery was confirmed by 3-fold verification . A high efficacy of the developed method studied clinically was stated.

J Antibiot (Tokyo), 1991 Feb, 44(2), 192 - 9
Synthesis and cytostatic properties of daunorubicin derivatives, containing N-phenylthiourea or N-ethylthiourea moieties in the 3'-position; Preobrazhenskaya MN et al.; A series of phenylthiourea and ethylthiourea derivatives of daunorubicin and its congeners was prepared by reaction of the 3'-amino group of the antibiotic with phenylisothiocyanate or ethylisothiocyanate . S-Methylation yielded S-methylisothiouromium salts which when reacted with amines resulted in an intramolecular cyclization with the participation of the neighboring 4'-OH group . The structures and predominant conformations of the thiourea derivatives and daunorubicino(3'-N,4'-O-d)oxazolines were determined by 1H and 13C NMR . Cytostatic activities of the thiourea and oxazoline derivatives were compared with the cytostatic activities of N-methylurea and N-methyl-N-nitrosourea containing daunorubicin and its congeners . Carminomycin derivatives were endowed with the highest cytostatic activity.

J Pharmacobiodyn, 1991 Feb, 14(2), 82 - 6
Effect of carrier-mediated transport system on intestinal fosfomycin absorption in situ and in vivo; Ishizawa T et al.; Intestinal absorption mechanism of fosfomycin (FOM), a water-soluble and small molecular antibiotic, at the clinical dose level was examined by both in situ single-pass perfusion technique of rat small intestine and oral administration in rat in vivo . Analyzing the luminal concentration-dependence of FOM absorption rates in situ by the equation composed of two terms of carrier transport of Michaelis-Menten type and simple-diffusion, apparent Michaelis constant (Kt), maximal transport velocity (Jmax), and first-order diffusive absorption clearance (Kd) were 1.13 mM, 2.54 nmol/min/cm length, and 0.551 microliters/min/cm length, respectively . At the low FOM concentration in the lumen (0.1 mM), its absorption was reduced to about 60% of the control by inorganic phosphate ion at 1.0 mM in the same manner as the uptake in brush border membrane vesicles of rat small intestine (BBMVs) in vitro . Both the glycol form of FOM at 10 mM, the hydrolyzed metabolite of FOM in the stomach juice, and FOM itself at 10 mM reduced FOM absorption by about 50%, indicating the metabolite to be transported by the same carriers as those of FOM . At the higher FOM concentration (5 mM), its absorption was not reduced by any inhibitor described above . No inhibitory effect of 50 mM phosphate ion on FOM absorption following the oral dosing of 20 mg/kg FOM was found . It was concluded that FOM absorption at the clinical dose (10-20 mg/kg) is barely inhibited by the carrier-mediated system via phosphate transport system observed in the in vitro BBMVs.

Br Heart J, 1991 Feb, 65(2), 97 - 9
Doppler ultrasound and the silent ductus arteriosus; Houston AB et al.; A clinically undetectable, small ductus arteriosus was identified by Doppler ultrasonography in 21 individuals . Infants were excluded from the study and no patient had pulmonary hypertension . Persistence of the ductus arteriosus is likely to be more common than shown by less sensitive diagnostic methods . Some patients considered to have infective endocarditis with a normal heart may have a silent ductus arteriosus . Evidence of such an association would justify ligation or antibiotic cover as prophylactic measures.

Clin Nucl Med, 1991 Feb, 16(2), 84 - 6
Multiple foci of increased accumulation of Ga-67 citrate in a horseshoe kidney . Differentiation of infection from nephroblastomatosis; Glass T et al.; In the proper clinical setting, Ga-67 citrate appears to be a highly valuable radionuclide which may be used to differentiate an infectious process in the kidney from nephroblastomatosis . The authors present the case of a 7-year-old boy with multiple well-circumscribed foci of intense Ga-67 citrate accumulation in a horseshoe kidney . After a 2-week course of antibiotic therapy, the kidney showed significant improvement.

Rev Med Chil, 1991 Feb, 119(2), 183 - 8
{Emphysematous pyelonephritis: 3 cases}; Alvo M et al.; We report 3 patients who developed emphysematous pyelonephritis . All were diabetic females over 50 years of age with unilateral necrotizing pyelonephritis . Intra and perirenal gas was demonstrated and all patients had infection by E coli . X ray and ultrasound studies allowed the diagnosis . Antibiotic therapy was unsuccessful and all patients had to be operated on.

Riv Eur Sci Med Farmacol, 1991 Feb-Apr, 13(1-2), 51 - 60
{A new anti-inflammatory-analgesic-antipyretic, morniflumate, in the treatment of chronic recurring bronchitis}; Melica A et al.; To assess the therapeutic effects of morniflumate, a new non-steroidal anti-inflammatory drug, a controlled study versus imidazole-2-hydroxybenzoate, both combined with amoxicillin, and antibiotic therapy alone was carried out on 60 patients, aged 18 to 60 with flare-ups of chronic bronchitis . After administering morniflumate, all the clinical parameters assessed (objective auscultation, cough, expectoration, exertional dyspnoea, chest pain, hyperthermia) had improved . The modifications observed in this group were greater and earlier when compared to those of the control groups . No significant variations of laboratory parameters nor any particular side-effects were reported.

Mol Microbiol, 1991 Feb, 5(2), 289 - 98
The stringent response in Streptomyces coelicolor A3(2); Strauch E et al.; The stringent response was elicited in the antibiotic producer Streptomyces coelicolor A3(2) either by amino acid depletion (nutritional shiftdown) or by the addition of serine hydroxamate; both led to increased levels of ppGpp and to a reduction in transcription from the four promoters of the rrnD rRNA gene set . Analysis of untreated batch cultures revealed elevated ppGpp levels at the end of exponential growth, preceding the onset of antibiotic production . The effect of provoking the stringent response on antibiotic production in exponentially growing cultures was assessed by S1 nuclease mapping of actIII, an early gene of the actinorhodin biosynthetic cluster . Expression of actIII occurred after nutritional shiftdown, but not after treatment with serine hydroxamate . Although the need for ppGpp in triggering antibiotic production remains equivocal, ppGpp synthesis alone does not appear to be sufficient to initiate secondary metabolism in S . coelicolor A3(2).

Antimicrob Agents Chemother, 1991 Feb, 35(2), 351 - 7
Endotoxin-tobramycin additive toxicity on renal proximal tubular cells in culture; Joly V et al.; Aminoglycoside-induced renal damage is enhanced in animals with Escherichia coli pyelonephritis . Bacterial endotoxin is liberated during antibiotic therapy . The toxic effect of endotoxin and tobramycin, alone or in combination, was investigated in primary cultures of rabbit proximal tubular cells grown to confluence in serum-free medium . Sodium-dependent uptakes of Pi and alpha-methylglucopyranoside (MGP) and enzymatic activities (lactate dehydrogenase {LDH} released as a marker of cell necrosis and gamma-glutamyltransferase {GGT} and N-acetyl-beta-D-glucosaminidase {NAG} present in the homogenate as markers of brush border membrane and lysosome integrity) were measured . Cells were exposed to (i) endotoxin (20 mg/liter), tobramycin (1 mM), or endotoxin plus tobramycin for 48 h, or (ii) endotoxin (100 mg/liter), tobramycin (4 mM), or endotoxin plus tobramycin for 72 h . Endotoxin alone did not alter Pi uptake, but tobramycin inhibited Pi uptake through a decrease in Vmax . The effect was not enhanced by the combination of endotoxin and tobramycin . Endotoxin and tobramycin alone exerted no significant effect upon MGP uptake, but strong inhibition of the Vmax was observed after exposure to a combination of endotoxin plus tobramycin, without alteration of the Km . Endotoxin decreased residual GGT activity in the cell homogenate . Tobramycin increased LDH release in the medium and NAG activity in the homogenate . Endotoxin plus tobramycin resulted in an additive effect upon LDH and NAG activities . In conclusion, by disturbing apical membrane integrity, endotoxin increased tobramycin toxicity in vitro in the absence of serum hormonal mediator.

J Antibiot (Tokyo), 1991 Feb, 44(2), 218 - 24
Biosynthesis of the streptovaricins: 3-amino-5-hydroxybenzoic acid as a precursor to the meta-C7N unit; Staley AL et al.; {Carboxy-14C}-3-amino-5-hydroxybenzoic acid (AHBA) has been shown to be incorporated by Streptomyces spectabilis to the extent of greater than 0.1% (35: 1 dilution) in the ansamycin antibiotic streptovaricin C, the major component of the streptovaricin complex . When {carboxy-13C}AHBA was similarly administered, C-21 (quinone methide carbonyl at 188.3 ppm) of streptovaricin C was specifically labeled (at twenty one times natural abundance) . In preparation for the 13C incorporation study the 13C NMR spectrum of streptovaricin C was investigated, making extensive use of short- and long-range HETCOR . These assignments revise some of those proposed earlier for streptovaricin C.

Int J Radiat Biol, 1991 Feb, 59(2), 397 - 408
An in vitro 125IUdR-release assay for measuring the kinetics of cell death; Schneiderman MH et al.; A radionuclide release assay for measuring the in vitro kinetics of cell death has been developed . CHO cells were labelled for 24 h with 3.0 hBq/ml of {125I} iododeoxyuridine (125IUdR) and the fate of the labelled cells and their progeny was monitored at daily intervals by measuring the rate of 125I release . Prelabelling with 125IUdR did not alter the plating efficiency, the doubling time or the selection of mitotic cells . The rate of 125I release from labelled (but otherwise untreated) CHO cells was approximately equal to 4% day . Treatment with a lethal dose of X-rays (30 Gy), heat (46 degrees C, 1 h), cold (-90 degrees C, 1 h) or the antibiotic Geneticin (300 micrograms/ml, continuously) resulted in the release of greater than 99% the 125I activity associated with the cells . Cell death was rapid after heating or freezing, and delayed after treatment with X-rays or Geneticin . The results illustrate the efficacy of the 125I release assay for measuring the kinetics of cell death in mammalian tissue culture cells.

Mol Biochem Parasitol, 1991 Feb, 44(2), 233 - 43
Tunicamycin-resistant variants from five species of Leishmania contain amplified DNA in extrachromosomal circles of different sizes with a transcriptionally active homologous region; Katakura K et al.; Twelve independent variants were selected from five species of Leishmania for resistance to tunicamycin by exposure of cultured promastigotes to increasing concentrations of this antibiotic, an inhibitor of the microsomal N-acetylglucosamine-1-phosphate transferase in the dolichol pathway of N-glycosylation . All variants obtained from all species, as found previously with Leishmania amazonensis, contain amplified chromosomal DNA exclusively as extrachromosomal circles . These circular amplicons hybridize with amplified DNAs cloned previously from tunicamycin-resistant Leishmania amazonensis, but not with those from Leishmania resistant to other drugs . The amplicons from tunicamycin-resistant cells vary with different species in size from 30 to 70 kb, but all share a homologous region of 20 kb . Multiple independent transcripts are overexpressed from this region . Elevation of the microsomal glycosyltransferase activity is demonstrated in these variants from representative species . The results thus provide further evidence that this enzyme is overexpressed due to amplification of the gene in these cells . The consistent observation of this event in all cases studied also suggests that this is the predominant, if not the only mechanism of tunicamycin resistance in Leishmania.

Biochem Biophys Res Commun, 1991 Jan 31, 174(2), 878 - 84
Structural flexibility of Aib-containing peptides: the N-terminal tripeptide of trichotoxin; Gessmann R et al.; The sequence Aib-Gly-Aib which corresponds to the N-terminus of the microheterogeneous peptide antibiotic trichotoxin has been studied crystallographically in the context of different protecting groups . Peptides Ac-Aib-Gly-Aib-OH (A) and Z-Aib-Gly-Aib-OH (B) form beta-turns . Both peptides show a remarkable conformational flexibility forming a large variety of beta-turns of different types.

Clin Ter, 1991 Jan 31, 136(2), 101 - 6
{Use of pefloxacin in boutonneuse fever}; Di Lascio G et al.; On the basis of previous studies, the authors tested pefloxacin, a new generation quinolone, for the treatment of Mediterranean spotted fever . Treatment with this drug brought about complete recovery with rapid subsidence of clinical symptoms and normalization of instrumental and laboratory parameters . This antibiotic should therefore be listed as one of the agents suitable for combatting rickettsial infections and its use should be encouraged in view of its easy handling, excellent compliance and the possibility for oral administration.

Nucleic Acids Res, 1991 Jan 25, 19(2), 257 - 64
Sequence-specific cleavage of double-stranded DNA caused by X-ray ionization of the platinum atom in the Pt-bis-netropsin--DNA complex; Grokhovsky SL et al.; An analog of the antibiotic netropsin containing two netropsin-like fragments linked covalently via a platinum atom has been synthesized . DNase I and hydroxyl radical footprinting studies have shown that this compound binds at selective sites on a DNA restriction fragment with a known nucleotide sequence . After X-ray irradiation of Pt-bis-netropsin--DNA complexes a platinum-mediated cleavage of DNA is observed at specific DNA sites . This enables one to determine the location of the synthetic ligand on the DNA with a precision of about one nucleotide . The cleavage activity seems to be related to the emission of Auger electrons from the platinum atom that cause rupture of the deoxyribose residues on the two DNA strands near the position of the platinum atom in the complex.

Rev Prat, 1991 Jan 21, 41(3), 235 - 8
{Preparation for digestive endoscopies}; Rey JF; Endoscopic examinations are extremely valuable methods of exploration or even treatment in hepato-gastroenterology . Preparation for these examinations may be very simple in the case of oesophago-gastroduodenoscopy, since all that is required of the patients is to be fasting . In exploration of the colon, preparation is longer and more meticulous, and its quality will to a great extent condition the quality of the diagnosis obtained . Whenever endoscopic examinations are complemented by treatment, the precautions to be taken are sometimes more important and may amount to preoperative evaluation, including prophylactic antibiotic therapy . Pre-endoscopic preparation must also take into account some particular cases, such as patients with cardiac valve or children . The general practitioner plays a very important role in informing his patients about to undergo an endoscopic exploration or treatment . He must also tell them that precautions must be taken after endoscopy, notably in case of non-general anaesthesia.

Pol Tyg Lek, 1991 Jan 21-28, 46(4-5), 71 - 3
{Gentamicin may have an influence on the effectiveness of peritoneal dialysis}; Czyzewska K et al.; An effect of gentamicin on urea and uric acid transfer through peritoneum was studied in rabbits in vitro . It was found that gentamicin decreases urea transfer by approximately 30% . Its effect on uric acid transfer was transient so as mean values of this parameter did not differ statistically before and after antibiotic administration . It may be assumed that gentamicin decreases permeability of peritoneum for certain low molecules of endogenic origin . Such an effect may prove unfavourable when peritoneal dialysis efficiency is concerned.

Biochim Biophys Acta, 1991 Jan 17, 1088(1), 119 - 26
Localization and characterization of a temporally regulated promoter from the Streptomyces aureofaciens 2201 plasmid pSA 2201; Farkasovsky M et al.; An RNA polymerase-binding 167 bp HinfI fragment from a low-copy Streptomyces plasmid pSA 2201 has been shown to have promoter activity in vivo using a promoter-probe vector . This promoter (A1) is probably involved in expression of the genes responsible for the production of an antibiotic compound, found to be located on this plasmid . A 2600 nucleotides (nt) long transcript starting from this promoter has been identified by Northern hybridization analysis . The transcription start point has been determined using high-resolution S1 mapping and confirmed by in vitro transcription analysis with purified S . aureofaciens 2201 RNA polymerase . The A1 promoter shows no homology in the -10 and -35 consensus sequence of the typical bacterial promoters, and expression from this promoter is temporally dependent on the phase of growth having the maximum transcription activity in the stationary phase.

Arch Otolaryngol Head Neck Surg, 1991 Jan, 117(1), 103 - 5
Focal myositis . A new cause for the pediatric neck mass; Isaacson G et al.; Focal myositis is an inflammatory pseudotumor of skeletal muscle that may involve the head and neck . It can closely mimic either a neoplastic or infectious process . We present the case of a 7-year-old boy with a 2-week history of a painful, unilateral neck swelling, fever, and torticollis . He failed to respond to antibiotic therapy and required an open neck exploration . An incisional biopsy of the indurated, inflammatory tissue adherent to his sternocleidomastoid muscle showed focal myositis . Focal myositis is an unusual, but important possibility in the differential diagnosis of any neck mass and especially one in a child . Although its cause is unknown, it is a self-limited disease and neither excisional biopsy nor radical resection is justified.

Chest, 1991 Jan, 99(1), 84 - 8
The diagnostic utility of the antibody-coated bacteria test in intubated patients; Wunderink RG et al.; PURPOSE: Pilot study to determine if the presence of antibody-coated bacteria (ACB) in sputum specimens obtained from endotracheal tube suctioning would aid in the diagnosis of lower respiratory tract infection (LRTI) . PATIENTS AND METHODS: All endotracheally intubated and mechanically ventilated patients for a two-month period were recruited for study . The diagnosis of LRTI was based on a clinical suspicion sufficient enough to start or change antibiotic therapy . Specimens were obtained by blind endotracheal tube suctioning . After processing, sputum smears were stained with fluorescein-labelled antibody to the Fc portion of IgG, IgM, and IgA . More than five fluorescein-labelled bacteria per oil immersion field were considered positive smears . RESULTS: Seventy-one specimens were obtained from 36 patients . Eighteen specimens were positive in 12 patients, all of whom had LRTI . No specimen was positive in patients not diagnosed as having LRTI . The ACB test was positive in 12 of 25 patients with LRTI . Patients with LRTI but negative ACB were more likely to have received prior antibiotic therapy (p less than 0.001) . ACB was positive prior to the clinical diagnosis of LRTI in seven of nine patients (av 4.1 days, range 2-6 days) and converted to negative in three specimens obtained seven or more days after starting appropriate antibiotics, while in three specimens it remained positive three-six days post treatment initiation . CONCLUSIONS: The ACB test appears to be highly specific for the presence of LRTI in intubated patients . Sensitivity of the test may be adversely affected by prior antibiotic therapy . A positive ACB test may predict the subsequent development of LRTI . Further study is warranted.

Int J Clin Monit Comput, 1991-92, 8(4), 263 - 9
A strategy for development of computerized critical care decision support systems; East TD et al.; It is not enough to merely manage medical information . It is difficult to justify the cost of hospital information systems (HIS) or intensive care unit (ICU) patient data management systems (PDMS) on this basis alone . The real benefit of an integrated HIS or PDMS is in decision support . Although there are a variety of HIS and ICU PDMS systems available there are few that provide ICU decision support . The HELP system at the LDS Hospital is an example of a HIS which provides decision support on many different levels . In the ICU there are decision support tools for antibiotic therapy, nutritional management, and management of mechanical ventilation . Computer protocols for the management of mechanical ventilation (respiratory evaluation, ventilation, oxygenation, weaning and extubation) in patients with adult respiratory distress syndrome ((ARDS) have already been developed and clinically validated at the LDS Hospital . These protocols utilize the bedside intensive care unit (ICU) computer terminal to prompt the clinical care team with therapeutic and diagnostic suggestions . The protocols (in paper flow diagram and computerized form) have been used for over 40,000 hours in more than 125 adult respiratory distress syndrome (ARDS) patients . The protocols controlled care for 94% of the time . The remainder of the time patient care was not protocol controlled was a result of the patient being in states not covered by current protocol logic (e.g . hemodynamic instability, or transport for X-Ray studies) . 52 of these ARDS patients met extra corporal membrane oxygenation (ECMO) criteria . The survival of the ECMO criteria ARDS patients was 41%, four times that expected (9%) from historical data (p less than 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)

Biochim Biophys Acta, 1991 Jan 9, 1061(1), 65 - 77
A microscopic electrostatic model for the amphotericin B channel; Bonilla-Marin M et al.; A microscopic model of an amphotericin B channel is proposed . The structure of the pores is generated using the atomic coordinates of the molecule in the structure determined experimentally by X-ray diffraction . The net charges of the atoms are determined by Mulliken analysis . With these charges the electrostatic energy profiles are calculated for a monovalent ion passing through the channels formed by different number of antibiotic molecules having different radii . The water inside the channel was considered through a continuum medium using the dielectric constant of the bulk, and the membrane contribution was included using the virtual images of the pore in a dielectric slab of epsilon = 3 . The model satisfactorily explains the permeability and selectivity characteristics as well as other observations yet unexplained . The electrostatic profiles obtained reinforce the hypothesis of the existence of channels formed by a variable number of units.

Biochemistry, 1991 Jan 8, 30(1), 77 - 82
Potassium-selective amphotericin B channels are predominant in vesicles regardless of sidedness; Hartsel SC et al.; Amphotericin B (AmB) is a membrane-active antibiotic which has been shown to increase ion and small molecule permeability in a variety of model and biological membrane systems . A major mechanistic model, based on BLM systems, proposes that amphotericin forms barrellike pores with cholesterol which are cation selective when added to one side of the membrane and anion selective when added to both sides . We have tested this hypothesis on small and reverse-phase large unilamellar vesicles (SUV and REV) with and without cholesterol . The method used to measure K+, Cl-, and net ion currents is based on ion/H+ exchange detected by the entrapped pH probe pyranine . We find that AmB forms channels which have net selectivity for K+ over Cl- regardless of sidedness or sterol content in SUV . REV with 10% cholesterol also show net K+ selectivity with double-sided addition . Differences are noted between cholesterol- and non-sterol-containing vesicles consistent with at least two separate modes of action: (1) cholesterol-containing SUV form some larger diameter pores which allow the passage of larger ions especially when added to both sides; (2) SUV without sterol form pores which are still K+ over Cl- selective, but larger ions do not pass . The latter mode of action precludes a sterol/pore type of model but not necessarily a barrellike model consisting only of amphotericin molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene, 1991 Jan 2, 97(1), 143 - 6
Plasmid cloning vectors that integrate site-specifically in Streptomyces spp; Kuhstoss S et al.; Cloning vectors based on the Streptomyces ambofaciens plasmid pSAM2 and the streptomycete phage phi C31 were developed for use in Streptomyces spp . These vectors replicate in Escherichia coli but integrate by site-specific recombination in Streptomyces spp . Both pSAM2-based and phi C31-based vectors transformed a number of different Streptomyces spp; however, the phi C31-based vectors consistently transformed at higher frequencies than pSAM2-based vectors . Southern analysis indicated that the phi C31-based vectors integrated at a unique site in the S . ambofaciens chromosome, while the pSAM2-based vectors gave complex patterns which could indicate structural instability or use of multiple loci . Both types of vectors utilize the apramycin (Am)-resistance gene which can be selected in E . coli and Streptomyces spp . with either Am or the commercially available antibiotic Geneticin (G418).

Tex Heart Inst J, 1991, 18(4), 293 - 5
Management of infected vascular prostheses . The vascular homograft revisited; Julia P et al.; Treatment of infected aortic femoral grafts is difficult and controversial . We describe the case of a patient who presented for recurrent infections of an aorto-bifemoral prosthesis . An arterial homograft was used to replace the Dacron prosthesis . One year later, the patient is free of symptoms and is doing well . Although early experiences with long-term use of homografts showed late degeneration of the grafts, 2 points should now be raised in favor of homograft use: new techniques of fresh antibiotic storage of homografts appear to have improved durability; and if replacement of a homograft ever becomes necessary, implantation of a Dacron prosthesis could likely be performed in an aseptic environment . While the use of homografts may constitute a reasonable alternative for treating patients with infected vascular grafts, firm conclusions cannot be drawn until we have seen larger series of patients and longer follow-up periods than those few reported to date.

Rev Fr Gynecol Obstet, 1991 Jan, 86(1), 53 - 5
{Use of sulprostone in the evacuation of molar pregnancies}; Pinet C et al.; The diagnosis of molar pregnancy is now easy based upon a triple clinical, laboratory and ultrasonographic approach . Histology provides final confirmation . However treatment is more difficult since uterine evacuation may be very hemorrhagic or traumatic . A clinical case forms the basis here for a review of the main features concerning the diagnosis and treatment of hydatidiform molePIP: Molar pregnancy, which results from an anomaly in the development of the trophoblastic tissue, is now easy to diagnose based on clinical evidence, beta hCG level, and sonography, although it must be histologically confirmed . Treatment remains difficult because of the danger of hemorrhage or trauma during uterine evacuation . Hydatidiform mole was diagnosed in the 1st pregnancy of a 27-year-old woman on the basis of a routine 1st trimester sonogram . Clinical examination revealed a voluminous uterus and a long, closed, very tonic cervix . Sulprostone was administered to aid cervical dilatation . An initial intramuscular injection of sulprostone caused uterine contractions without cervical modifications . 5 hours later an intravenous perfusion of sulprostone was started, during which significant contractions and cervical modifications were observed . An aspiration curettage was performed, in which numerous vesicles typical of the hydatidiform mole were evacuated . There was no need for further cervical dilatation and the curettage was rapid and nonhemorrhagic . The postoperative course was uneventful, and a test of beta hCG levels 6 weeks later was negative . The patient complained of pain during uterine contractions despite use of high doses of pethidine . The frequency of hydatidiform mole varies in different countries . It has been estimated at 1/85 in Indonesia and 1/2000 in the US . The clinical picture of hydatidiform mole includes vomiting often nonresponsive to treatment and metrorrhagia of varying volume, a large uterus for the gestational age, and often bilateral ovarian cysts . A vasculorenal syndrome may also begin at 13-16 weeks of amenorrhea . Beta hCG levels are high for the gestational age . Sonography reveals no embryonic structures . Biopsy shows a complete absence of embryo and amniotic sac . The karyotype is diploid and almost always XX . The mechanism is fertilization of an ovocyte whose nucleus is absent or inactive . The 2 chromosome sets are contributed by the father, a circumstance incompatible with embryonic development . Trophoblastic proliferation occurs without embryonic development . Hydatidiform moles may be transformed to invasive moles or chorioepithelioma . Treatment includes uterine evacuation by aspiration under sonographic control if possible . Many authors recommend oxytocin and antibiotic cover . The use of prostaglandin analogs to facilitate uterine evacuation is controversial, with some authors citing the increased risk of trophoblastic embolism . The mole should be histopathologically and cytogenetically studied, and postmolar follow-up is essential .

Fundam Clin Pharmacol, 1991, 5(1), 53 - 60
Ceftriaxone diffusion into cardiac fibrin vegetation . Qualitative and quantitative evaluation by autoradiography; Cremieux AC et al.; Heterogeneous diffusion of some antibiotics into fibrin rich infectious processes is one explanation of the difficulty to cure infections such as endocarditis . Ceftriaxone is a beta lactam antibiotic, potentially useful due to a broad spectrum of activity and its long elimination half-life . We investigated by means of autoradiography the diffusion of labelled ceftriaxone into large infected cardiac vegetations obtained in a rabbit model of endocarditis . Ten d after infection 250 microCi 14C ceftriaxone was injected over 30 min . Thirty min after the end of infusion (T30) vegetation/blood radioactivity ratio was 0.58 +/- 0.4 (n = 3) . At T200, radioactivity decreased approximatively 3-fold, in blood and in vegetations simultaneously . Autoradiography showed that at T30, ceftriaxone was 20-30 times more concentrated at the periphery of vegetation than in the core . Autoradiography obtained at T200 showed a progressive diffusion toward the core . The diffusion gradient may explain the fact that high local concentrations are necessary to sterilize vegetations . The pattern of diffusion of antibiotics in fibrin is an important pharmacokinetic parameter for predicting in vivo activity.

Fundam Clin Pharmacol, 1991, 5(1), 47 - 52
Effect of ponsinomycin on the pharmacokinetics of dihydroergotamine administered orally; Couet W et al.; Ponsinomycin is a new macrolide antibiotic . Its effect on DHE pharmacokinetics was investigated in this study . Twelve young healthy volunteers received a single 9 mg oral dose of DHE before and on the 8th day of treatment (800 mg twice daily) with ponsinomycin . DHE was assayed in plasma by RIA . Because of low plasma levels, only peak concentrations could be accurately compared for a ponsinomycin effect . We observed a 3-40-fold increase in maximum DHE plasma levels in the majority of cases and a much more important effect on one occasion, when DHE was administered in the presence of ponsinomycin . These data are consistent with an increase of DHE bioavailability in the presence of ponsinomycin, probably related to a reduction of its first-pass elimination . This pharmacokinetic interaction is likely to have clinical consequences and administration of ponsinomycin should be avoided in patients treated orally with DHE.

Gig Tr Prof Zabol, 1991, (1), 23 - 5
{Hygienic assessment of protective effects of overalls and individual protective devices used in the production of ampicillin trihydrate and its dosage form, ampicillin sodium salt}; Kaptsov VA et al.; The working clothes and individual protective devices recommended by the industrial Rules for the production of ampicillin trihydrate and its medicinal derivatives such as natrium salt ampicillin, do not provide adequate protection of the skin and respiratory mucous from antibiotic contamination . The use of the overalls in combination with the pressurized helmet (designed and produced at the 'Sintez' enterprise) which provided air supply for breathing and, partially, under the overalls, significantly decreased contamination of the body . At the stages of manual handling of the finished products, adequate protection was attained by using the protective paste produced at the 'Altaivitamine' enterprise.

J Int Med Res, 1991, 19 Suppl 1, 24A - 28A
Effect of ampicillin and sulbactam/ampicillin on the immune system; Gismondo MR et al.; An investigation was carried out into the possible effects of ampicillin and a sulbactam/ampicillin combination on the immune system of healthy subjects . The following immunological variables were compared before and after antibiotic therapy: proliferation response of peripheral mononuclear cells to phytohaemagglutinin; variation of T- and B-lymphocytes; dosage of interleukin-2; and production of immunoglobulin A . The data obtained did not demonstrate any immunodepressive activity by either ampicillin or the sulbactam/ampicillin combination.

Cytobios, 1991, 65(260), 31 - 7
Effect of ichthyomycin on the ultrastructure of tissues of Culex pipiens; Zizka Z et al.; A new antibiotic ichthyomycin produced by Streptomyces sp . strain 1107 was tested for its toxicity and effect on the ultrastructure of tissues of larvae of Culex pipiens autogenicus . Concentrations used were 5 x 10(-7), 2.5 x 10(-7), 1.5 x 10(-7) and 1 x 10(-7) g ml-1 . The mortality of larvae after 24 h exposure was 90, 30, 0 and 0%, and after 48 h was 100, 100, 87 and 0%, respectively . The effect of the antibiotic was most evident on mitochondria . They distended and ruptured with subsequent dissolution of their cristae . The microvilli of the brush border of the midgut cells and cell membranes were unchanged, and the peritrophic membrane remained coherent . Cisternae of the rough endoplasmic reticulum and microbodies filled the cytoplasm . Chromatin of the nuclei was aggregated into amorphous masses on the wall, but the nucleolus remained intact . Some cells showed large vacuoles in their cytoplasm from destroyed mitochondria . In muscle cells the mitochondria were in the process of dissolving and the sarcoplasmic reticulum formed elongate cisternae.

Antibiot Khimioter, 1991 Jan, 36(1), 43 - 5
{Pneumocystis carinii infection in a pediatric tuberculosis hospital}; Kovaleva EP et al.; An outbreak of pneumocytosis in a children's tuberculosis hospital was analyzed . The infection was characterized by few signs and favourable progress . Antibiotic therapy failed . To eliminate the outbreak of pneumocystosis in the hospital it was necessary to detect all the children with pneumocystosis and carriers of pneumocysts among the patients and medical staff, to use furazolidone for etiotropic treatment of the patients with pneumocystosis and to perform one-stage sanation of the carriers with antiparasitic agents.

Antibiot Khimioter, 1991 Jan, 36(1), 32 - 4
{Pharmacokinetics of gentamicin after its regional endolymphatic and lymphotropic administration to dogs}; Buianov VM et al.; It was shown that intralymphatic+ inguinal administration of gentamicin provided its high concentrations in central lymph, blood and ++para-aortic lymph nodes and increased the antibiotic levels in the abdominal organs 2.33 to 6.66 times as compared with its intramuscular administration while lymphotropic retroperitoneal administration of gentamicin provided more prolonged maintenance of the antibiotic therapeutic concentrations in lymph of the thoracic lymphatic duct, central blood, ++para-aortic lymph nodes and the abdominal organs in comparison to its intramuscular administration . Intralymphatic+ inguinal administration of drugs providing the highest concentrations in all the organs of the abdominal cavity and the ways of the infection penetration is useful in therapy of severe inflammatory diseases of the abdominal organs inclined to generalization and lymphotropic retroperitoneal administration of drugs is useful in therapy of less severe purulent inflammatory processes in the abdominal cavity.

Antibiot Khimioter, 1991 Jan, 36(1), 22 - 6
{Chemotherapeutic effectiveness of doxycycline in experimental Q fever}; Nikitin AV et al.; Comparative chemotherapeutic efficacy of doxycycline administered orally or parenterally was studied on a model of experimental Q fever in guinea pigs and albino mice . The advantage of the parenteral use of the antibiotic was observed only in the treatment of the albino mice . Optimization of the doses and time of doxycycline use providing the maximum therapeutic effect and the required levels of the complement binding antibodies was achieved with employing the multifactorial analysis.

An Otorrinolaringol Ibero Am, 1991, 18(2), 169 - 76
{Ludwig's angina, its evolution and treatment}; Tormo MA et al.; An anaerobic neck infection located in the submandibular layer is described in this paper . We report a case of satisfactory evolution and make a bibliographic review of this problem . All the AA . agree that the key to successful management of such infections is early diagnosis, prompt surgery and associated antibiotic therapy.

Perit Dial Int, 1991, 11(1), 59 - 63
Single-dose pefloxacin pharmacokinetics and metabolism in patients undergoing continuous ambulatory peritoneal dialysis (CAPD); Nikolaidis P et al.; Seven adult patients on continuous ambulatory peritoneal dialysis (CAPD) received one dose of pefloxacin, a novel quinolone antibiotic, orally and intravenously on two separate occasions to characterize the pharmacokinetics and metabolism of the drug . Concentrations of both pefloxacin and its active metabolite N-desmethyl-pefloxacin (norfloxacin) were measured in serum and dialysate by HPLC . Half-life, total body clearance and peritoneal clearance were determined . The overall elimination half-life was 19.9h . Relative to the IV dose the bioavailability following oral administration of pefloxacin was 76% . The mean serum and dialysate concentrations were similar up to 24 h after the oral or IV dose . After a 6-h dwell time the dialysate concentration of pefloxacin was 2.24 mg/L which is above the MIC90 for most bacteria responsible for peritonitis in CAPD patients . The peritoneal clearance of pefloxacin averaged 2.5 mL/min . Serum concentrations of the metabolite norfloxacin were less than 0.5 mg/L during the 24 h study period . We conclude that pefloxacin might be equally effective in the treatment of peritonitis of CAPD after oral or IV administration . Since the peritoneal clearance contributes insignificantly to the elimination of pefloxacin during CAPD, the proposed maintenance regimen of an oral or IV 400 mg dose/day seems to be a reasonable therapy for infections in CAPD patients.

Parasitol Res, 1991, 77(3), 224 - 9
Ultrastructural studies of the effects of the ionophore lasalocid on Eimeria tenella in chickens; Daszak P et al.; The ultrastructural development of Eimeria tenella was studied in experimentally infected chicks fed 90 ppm lasalocid, an ionophorous anticoccidial antibiotic . Drug treatment was timed to target-specific endogenous stages . At 6 h after infection, many sporozoites within the epithelium showed degradation as a result of drug action . Only a few intact sporozoites were seen . The drug caused outer-membrane blistering, large surface swellings and enlarged mitochondria in both first- and second-generation merozoites . No effect on the gamonts was discerned.

Pharmacotherapy, 1991, 11(2 ( Pt 2)), 84S - 89S
Diagnosis and management of pneumonia; Kemper CA et al.; The management of patients with pneumonia, the fifth leading cause of death in the United States, remains frequently problematical . Because a precise etiologic diagnosis is often not possible when the patient is first examined, initial antibiotic therapy is often empiric . Problems in early diagnosis include the frequent lack of access to true respiratory secretions, necessary delays in identification of organisms in culture, and contamination of expectorated sputum with oropharyngeal bacteria . Early management must therefore depend on epidemiologic and clinical clues as well as examination of available respiratory secretions . It is generally helpful in the selection of initial antibiotic therapy to consider the disease in two broad epidemiologic categories, community- and nosocomially acquired . As new laboratory and clinical information become available, the appropriateness of the antibiotic therapy must be continually reevaluated.

Jpn J Antibiot, 1991 Jan, 44(1), 22 - 34
{A clinical study on pulmonary tissue uptake of flomoxef}; Imaizumi M et al.; Based on the results of a study on pulmonary tissue uptake of flomoxef (FMOX), a new antibiotic agent, in 45 patients undergoing thoracotomy, the following conclusions were drawn: 1 . Immediately preoperative 1 hour-drug infusion of 1 g FMOX led to maximum serum concentration (averaging 42.4 micrograms/ml) 1 hour later, with a half-life of its beta phase of 1.26 hours . 2 . Normal lung (alveolar) tissue concentration was Cmax 17.98 micrograms/g with its ratios to serum peak value being 31.8, 27.1, 22.2, 9.4, 5.9 and 5.0% at 1, 2, 3, 4, 5 and 6 hours later, respectively . 3 . Bronchiolar tissue concentration was Cmax 31.91 micrograms/g, with its ratios to serum peak value being 27.8, 19.3 and 10.1% at 2, 3 and 4 hours later, respectively, indicating its good bronchiolar intra-tissue transition . The above results suggested the usefulness of FMOX for both the treatment of respiratory infections and the prevention of postoperative infections.

Am J Physiol Imaging, 1991, 6(1), 26 - 8
Bone scans in sternal osteomyelitis complicating hemodialysis blood access; Eisenberg B et al.; Sternal osteomyelitis complicating infection of vascular access for hemodialysis is exceedingly rare and presents serious diagnostic and therapeutic difficulties . Two hemodialysis patients with sternal osteomyelitis following vascular access infection are reported . Factors favoring sternal location of the infection included previous chest trauma in the first patient and difficult insertion of a dialysis subclavian catheter in the second patient . Indium oxine, gallium, and three-way bone scans were instrumental in establishing diagnosis and in documenting cure by prolonged antibiotic courses . Sternal scans should be performed in dialysis patients with vascular access infections and signs of sternal disease.

Z Naturforsch {C}, 1991 Jan-Feb, 46(1-2), 133 - 8
X-ray studies on phospholipid bilayers . X . Interactions with chlortetracycline hydrochloride; Suwalsky M et al.; This study deals with the structural perturbations that the antibiotic chlortetracycline hydrochloride (CTC) can produce on phospholipid bilayers . Two multibilayer systems, one built-up of dimyristoylphosphatidylethanolamine (DMPE) and the other of dimyristoylphosphatidylcholine (DMPC) were allowed to interact with different concentrations of CTC in the absence and presence of water . The study was carried out by X-ray diffraction methods and all experiments were done below the phospholipid main transition temperatures . The results showed that CTC produced significant perturbations on DMPC even in the absence of water, whereas they were much milder in DMPE.

Annu Rev Med, 1991, 42, 471 - 89
Sinusitis; Friedman RA et al.; Paranasal sinusitis is one of the most common diseases treated in outpatient centers across the United States . Improved bacterial culture techniques have revealed the variety of pathogens involved in acute and chronic sinusitis . The growing numbers of antibiotic-resistant bacterial strains and of immunocompromised patients have changed the clinical face of sinusitis . New diagnostic modalities, including magnetic resonance imaging, are facilitating more rapid and accurate disease detection.

Neurosurg Rev, 1991, 14(1), 65 - 7
Cervical destructive spondylodiscitis: a report on three cases; Brenner A et al.; Three patients suffering from hematogenous destructive spondylodiscitis were treated with one-session spondylectomy, bone graft-fusion and halo-device stabilization . A stable osseous fusion was achieved after three months with additional antibiotic therapy.

Enferm Infecc Microbiol Clin, 1991 Jan, 9(1), 30 - 2
{Fungal peritonitis during continuous ambulatory peritoneal dialysis (CAPD)}; Garcia-Martos P et al.; We report three cases of fungal peritonitis in patients undergoing CAPD, representing 1.3% of 228 episodes recorded during an 8 year period . The three patients, who had been catheterized for a long time, had previous episodes of bacterial peritonitis and had received antibiotic therapy . The culture was decisive to make the diagnosis . The change of the catheter and the treatment with antifungal agents contributed to cure the infection, although the three patients died from other causes . One case of peritonitis was caused by Candida lusitaniae.

Pharmacotherapy, 1991, 11(1), 88 - 9
Rifampin and ansamycin interactions with cyclosporine after renal transplantation; Vandevelde C et al.; Cyclosporine whole blood concentrations are routinely monitored to help ensure optimal therapy . Several drugs have been shown to alter cyclosporine disposition by altering hepatic metabolism . Rifampin, a potent enzyme inducer, has been demonstrated to increase cyclosporine clearance . The effects of ansamycin, a chemically related investigational antibiotic, on cyclosporine disposition, have not been previously published . We report a renal transplant patient receiving cyclosporine and consecutive therapy with rifampin and ansamycin . When compared to rifampin, ansamycin's effect on cyclosporine disposition appeared to be delayed and of less magnitude . Further characterization of this interaction is required . Until this issue is resolved, we would advise careful monitoring of cyclosporine blood levels in patients receiving either rifampin or ansamycin in concert with cyclosporine.

Cornea, 1991 Jan, 10(1), 21 - 4
Moraxella keratitis; Marioneaux SJ et al.; Moraxella corneal ulcers are uncommon but may be complicated by marked inflammation and corneal perforation . In a series of eight cases treated over a period of 6 years, despite appropriate antibiotic therapy, descemetoceles and/or perforations developed in four cases, resulting in loss of the eye in two cases . In our series, the final visual acuity was count fingers or less in most patients (six of eight; 75%) . Ulcers not only occurred in patients with systemic diseases, including alcoholism and malnutrition, but also in patients with various pre-existing ocular surface diseases . It is important to be aware of the potential of Moraxella ulcers to result in loss of vision and the eye.

Aust Vet J, 1991 Jan, 68(1), 17 - 20
Monensin controlled-release intraruminal capsule for control of bloat in pastured dairy cows; Lowe LB et al.; Monensin, a polyether ionophore antibiotic, is potentially an important agent for bloat relief in dairy cows grazing temperate legume-based pasture . A series of studies was undertaken to determine the effect of monensin, when delivered continuously in the rumen of lactating dairy cows by means of controlled-release capsules (monensin CRC) . Such devices release approximately 300 mg/head/day for 100 d . A short-term pilot study made at Ruakura, New Zealand, tested monensin CRC in cows selected for high susceptibility to bloat and grazing lucerne (Medicago sativa) or red clover (Trifolium pratense) . Treatment significantly reduced the incidence of bloat, while milk yield and protein yield were increased . There was no effect on fat yield . Following the pilot study, 6 large-scale field experiments involving a total of 368 lactating dairy cows, were made in Australia and New Zealand to confirm the effectiveness of monensin CRC for bloat control and to measure the effect of such treatment on milk production and composition . A severe bloat problem occurred in 2 experiments, mild bloat occurred in 2 others, while no visual signs of bloat were observed in the remaining 2 experiments . Bloat was significantly (P less than 0.05) reduced by monensin CRC treatment when data was pooled over the 4 experiments in which bloat occurred . Daily milk yield was increased in all experiments from a mean of 17.7 in untreated groups to 18.8 kg/head/day (P less than 0.05) in monensin CRC-treated cows . Protein percentage was not affected by treatment, while there was a decrease from 4.29 to 4.10% fat, although total fat yield was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aust Vet J, 1991 Jan, 68(1), 1 - 2
Chloramphenicol 1 . Hazards of use and the current regulatory environment; Page SW; Chloramphenicol is a broad-spectrum antibiotic which has enjoyed extensive use in both medical and veterinary practice . Shortly after its introduction in the late 1940s, the use of chloramphenicol was associated with the induction of an idiosyncratic form of aplastic anaemia in man . This rare and unpredictable adverse effect has since been associated not only with systemic use but with topical applications, as well as occupational exposure . Recognition of the small risk of a potentially fatal adverse reaction, together with the risk of selection of chloramphenicol-resistant pathogens, has led to restrictions on the veterinary uses of chloramphenicol . In Australia at present, the use of chloramphenicol is only permitted in small animals . Its use is specifically prohibited in food-producing animals, including horses.

Ann Chir, 1991, 45(2), 96 - 9
{Endocarditis after Bentall's operation . Apropos of 3 reoperated cases}; Soyer R et al.; The authors report three cases of endocarditis after replacement of the aortic valve and the ascending aorta by Bentall's method . This complication, rare in published series, is a serious possible complication during medium and long term follow-up . Its treatment consist of early complete removal of prosthetic material under suitable antibiotic therapy.

Arch Orthop Trauma Surg, 1991, 110(2), 78 - 82
Indications for and results of operative treatment of spondylitis and spondylodiscitis; Krodel A et al.; We present a retrospective follow-up study of 24 patients with spondylitis or spondylodiscitis whose treatment included surgical intervention . Tuberculous spondylitis was diagnosed in 14 patients and 10 suffered from non-specific spondylitis . The average age of the patients was 50.2 years and average follow-up was 3 years . All patients were asymptomatic at the time of examination and showed radiographic evidence of solid fusion . We recommend radical debridement and spinal fusion through a ventral approach in patients with destruction of the ventral vertebral body, progressive neurological impairment, septicaemia and antibiotic-resistant, symptomatic infections of the spine . In the elderly patient, even in reduced states of health, early surgical intervention can be particularly valuable . Although surgical intervention should be reserved for specific indications, we were able to document favourable results in all 24 patients treated with debridement and spinal fusion.

Vet Clin North Am Small Anim Pract, 1991 Jan, 21(1), 51 - 64
Canine Lyme borreliosis; Greene RT; Lyme borreliosis is now the most commonly reported tick-transmitted disease in humans and is an important disease in dogs . Case reports of canine Lyme borreliosis have appeared in the literature during the last 6 years, but a complete description of the disease still is not available . Until an accurate diagnostic scheme is developed, the disease will remain incompletely understood . A nonlocalizing polyarthropathy is the most commonly described clinical manifestation of canine Lyme borreliosis, but other syndromes probably also exist . The difficulty in making a diagnosis is a result of the fact that dogs do not develop a characteristic skin lesion to mark the beginning of their disease, and many dogs become seropositive but never develop clinical manifestations . Also, Borrelia burgdorferi has been isolated from the blood of healthy dogs, which suggests that detecting a spirochetemia may not have diagnostic significance . Newer diagnostic tests are being evaluated, but at present the diagnosis of canine Lyme borreliosis should be one of exclusion . After other common illnesses are ruled out, serology and response to antibiotic therapy help suggest a diagnosis . Once the disease is accurately diagnosed, efficient therapeutic schemes will be developed based on randomized therapeutic trials . In addition, vaccines are being developed . Currently, without the ability to diagnose the disease accurately, their efficiency can not be demonstrated adequately . Future findings surely will change our understanding of this disease.

Pharm Res, 1991 Jan, 8(1), 84 - 7
Relationship between drug absorption enhancing activity and membrane perturbing effects of acylcarnitines; LeCluyse EL et al.; Acylcarnitines with chain lengths of 2 to 18 carbon atoms were tested for their effects on rat intestinal brush border membrane order (S) by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) . These results were compared to the previously reported effectiveness of the acylcarnitines as absorption enhancers of the poorly absorbed antibiotic cefoxitin . Acylcarnitines with fatty acids less than 12 carbon units in length were ineffective in increasing drug absorption and perturbing brush border membrane order . Long-chain acylcarnitines (12-18 carbons) significantly increased the bioavailability of cefoxitin and decreased the lipid order of brush border membranes . The results suggest that, in order to promote drug absorption, the acylcarnitines must surpass a critical chain length (10 carbon units) to partition effectively into the membrane and, in addition, must perturb the lipid order beyond a threshold value (15-20%) . Membrane perturbing capacity may serve as an indicator of the absorption enhancing potential of other aliphatic-type compounds.

Infection, 1991 Jan-Feb, 19(1), 46 - 8
Pneumonia caused by Bordetella bronchiseptica in a patient with a thoracic trauma; Reina J et al.; We report a case of pneumonia, caused by Bordetella bronchiseptica, in a previously healthy, immunocompetent 37-year-old male patient who had suffered chest injury in a car accident . The patient was admitted to the Intensive Care Unit where endotracheal intubation was performed . Seventy-two hours later he presented with fever associated with pulmonary affection which was diagnosed as right lobar pneumonia . Abundant colonies of B . bronchiseptica were isolated from the pharyngeal exudate and respiratory secretions, suggesting prior oropharyngeal colonization by B . bronchiseptica, as a result of repeated contact with his dog, with subsequent infection of the lower respiratory tract assisted by the process of intubation . We review different human infections produced by B.bronchiseptica as well as the antibiotic susceptibility studies performed.

Infection, 1991, 19 Suppl 1, S9 - 12
{Documentation and assessment of adverse drug effects with ofloxacin as an example}; Esch B et al.; A systematical and comprehensive evaluation of all reports on adverse drug reactions ascribed to ofloxacin since this antibiotic was launched (1985) until October 1988 shows that rare and severe adverse drug reactions are more often reported spontaneously than in the course of clinical trials . In particular, severe reductions of white blood cell counts, shock and shock fragments, and impairment of sensory organs and renal functions have for the first time been detected by spontaneous case reports . The results demonstrate exemplarily the potency of the spontaneous reporting system as superior to that of clinical trials in providing information on rare adverse drug reactions.

Cancer Immunol Immunother, 1991, 32(6), 342 - 52
Retrovirus-mediated gene transfer into CD4+ and CD8+ human T cell subsets derived from tumor-infiltrating lymphocytes and peripheral blood mononuclear cells; Morecki S et al.; Studies were undertaken to test the susceptibility of individual T cell subpopulations to retroviral-mediated gene transduction . Gene transfer into human tumor-infiltrating lymphocytes (TIL) or peripheral blood mononuclear cells (PBMC) was carried out by transduction with an amphotropic murine retroviral vector (LNL6 or N2) containing the bacterial neoR gene . The presence of the neoR gene in the TIL population was demonstrated by Southern blot analysis, detection of the enzymatic activity of the gene product and by the ability of transduced TIL to proliferate in high concentrations of G418, a neomycin analog that is toxic to eukaryotic cells . The presence of the neoR gene in TIL did not alter their proliferation or interleukin-2 dependence compared to nontransduced TIL . The differential susceptibility of CD4+ and CD8+ lymphoid cells to the retro-virus-mediated gene transfer was then tested . Transduction of heterogeneous TIL cultures containing both CD4+ and CD8+ cells resulted in gene insertion into both T cell subsets with no preferential transduction frequency into either CD4+ or CD8+ cells . In other experiments highly purified CD4+ and CD8+ T cell subpopulations from either TIL or PBMC could be successfully transduced with the neoR gene as demonstrated by Southern blot analysis and detection of the gene product neophosphotransferase activity . No such activity of vector DNA could be detected in controls of nontransduced cells . In these highly purified cell subsets the distinctive T cell phenotypic markers were continually expressed after transduction, G418 selection and long-term growth . Clinical trials have begun in patients with advanced cancer using heterogeneous populations of CD4+ and CD8+ gene-modified TIL.

Indian J Gastroenterol, 1991 Jan, 10(1), 20 - 2
Medication induced esophageal injury; Mohandas KM et al.; Five patients of medication-induced esophageal injury are reported . A history of ingestion of medications preceding the onset of dysphagia was obtained in all patients . Endoscopy revealed localised mucosal ulceration with surrounding edematous mucosa at the level of the aortic arch in four, and in the retro-cardiac esophagus in one patient . The medications involved were sustained release potassium chloride, doxycycline, ibuprofen, and an unidentified antibiotic and antihypertensive (one each) . Healing of the esophageal ulcers was confirmed in all the patients by endoscopy.

Spine, 1991 Jan, 16(1), 52 - 3
Postoperative cerebrospinal fluid leakage after lumbar spine operations . Conservative treatment; Waisman M et al.; Cerebrospinal fluid (CSF) leakage from a postoperative wound after lumbar spine operation is an uncommon complication . It may result from excessive traction of the nerve roots, direct trauma, or laceration at the time of operation, causing the dura to be inadvertently opened . Other reasons for this complication are postlaminectomy residual bone spikes, traumatic myelography puncture, and improper suture of dura defects . Eight patients who had postoperative CSF leakage as the only complication after lumbosacral spine operations were examined . They were all treated conservatively with bed rest in the Trendelenburg position, antibiotic coverage, watertight skin suturing, and daily subcutaneous punctures . No patient was operated on for the same type of complication.

J Ophthalmic Nurs Technol, 1991 Jan-Feb, 10(1), 15 - 7
Postoperative instillation of mitomycin eye drops in the treatment of primary pterygium; Spires R; 1 . Pterygia, triangular sheets of fibrovascular tissue that invade the cornea, have recurrence rates of 30% to 50% with currently available surgical procedures . 2 . Mitomycin, an antimetabolite-antibiotic agent, has been reported to be effective in preventing recurrences of surgically excised pterygia when used adjunctively as eye drops . 3 . Because mitomycin-C is an antineoplastic agent, appropriate policies and proper patient education are important.

Arch Otolaryngol Head Neck Surg, 1991 Jan, 117(1), 83 - 6
Drug response of head and neck tumors in native-state histoculture; Robbins KT et al.; We describe a chemosensitivity testing of head and neck tumors, in which a native-state histoculture, ie, a three-dimensional culture system that maintains important in vivo properties, including tissue architecture, was used . Fifteen specimens of head and neck tumors were evaluated for sensitivity to the following drugs: cisplatin (DDP) at concentrations of 1.5, 15, and 37.5 micrograms/mL; fluorouracil at concentrations of 4.0, 40, and 100 micrograms/mL; and combinations of cisplatin and fluorouracil in corresponding doses . Growth and measurement of drug responses were successfully completed in 10 specimens (five others were contaminated, four of them prior to instituting rigorous antibiotic washes) . The results indicated cisplatin sensitivity in five of 10 patients; fluorouracil sensitivity in four of 10 patients; and fluorouracil-cisplatin sensitivity in seven of eight patients . Our preliminary results indicate that the native-state histoculture technique is feasible to test chemosensitivity of head and neck tumors.

Am J Nephrol, 1991, 11(3), 257 - 9
Acute renal failure due to acute pyelonephritis; Jones BF et al.; We report a case of biopsy-proved acute pyelonephritis which caused acute renal failure . Despite appropriate antibiotic therapy, recovery of renal function was slow and incomplete . Renal papillary necrosis was an apparent complication, which the patient may have been predisposed to by alcoholism . Although rare, acute pyelonephritis is an important consideration in the differential diagnosis of acute renal failure because of the need for specific therapy.

J Fr Ophtalmol, 1991, 14(4), 260 - 4
{Diffusion of pefloxacin in the aqueous humor and crystalline lens after repeated oral administration in man}; Salvanet-Bouccara A et al.; The intraocular penetration of pefloxacin was evaluated in 38 patients undergoing extracapsular cataract extraction . Patients were treated for three days with 400 mg of pefloxacin every twelve hours (the first dose being 800 mg) . The mean maximum concentration of pefloxacin reached six hours after the last dose in the aqueous humor was 7.69 +/- 3.50 mg/l and reached twelve hours after the last dose in the lens was 4.59 +/- 3.15 micrograms/g . Antibiotic levels were measured by high performance liquid chromatography . Several doses until plasma steady state were effective in obtaining a higher level than a single dose of 400 mg . The ratio between aqueous humor and serum concentrations ranged between 0.50 and 0.89 (mean 68%) . These concentrations in aqueous humor were higher than the MIC90 of pefloxacin for most bacterial pathogens involved in endophthalmitis 24 hours after the last dose.

Scand J Infect Dis Suppl, 1991, 77, 81 - 4
Lyme carditis: clinical characteristics of 105 cases; van der Linde MR; 105 North American and European cases of Lyme carditis, being documented and in part published in the period 1977-1990, are reviewed and compared . The male: female ratio was 3:1, as well in Europe as in the USA . Transient atrioventricular block is the most frequent manifestation of Lyme carditis, with a remarkable similarity in the frequency of complete AV block and attending neurological illness in Europe and the USA . The distribution of (maximal observed) atrioventricular block in all patients existed of 49% third degree, 16% second degree and 12% first degree . Data of electrophysiological studies show that affection of the cardiac conduction system can be local or very diffuse . Other manifestations like rhythm disturbances, (myo)pericarditis and heart failure were less striking and have a less similar frequency in the European and American cases . Medicational therapy seems not to be an unconditional requirement for recovery of Lyme carditis itself, but cannot be withheld because of the proven beneficial effects of antibiotic therapy in other manifestations of Lyme borreliosis . Temporary pacemakers are frequently inserted, but pacemaker implantation is rarely needed . The overall prognosis of Lyme carditis seems to be good, although delayed recovery has been described and possible late manifestations have been suggested.

Scand J Infect Dis Suppl, 1991, 77, 64 - 73
Neurological manifestations of Lyme borreliosis: clinical definition and differential diagnosis; Kristoferitsch W; Neurological manifestations occur in early disseminated Lyme Borreliosis and in the chronic late stage . Two of them, Bannwarth's syndrome and acrodermatitis chronica atraphicans-associated neuropathy, were known as well defined clinical entities many years prior to the detection of their causative agent . Soon after B . burgdorferi was identified and serologic tests became available, many reports were published which attributed to a large variety of different neurological disorders to Lyme borreliosis . In many cases the diagnosis was primarily based on serodiagnostic results . Yet some scepticism is indicated since 10-30% of the population in endemic areas have been found to be seropositive . While prior to 1983 and before the availability of serodiagnostic tests neurological manifestations of Lyme borreliosis were recognized by a minority of neurologists, they now seem to be overdiagnosed . Therefore clear diagnostic criteria have to be set up . They include the clinical picture, other preceding or concomitant diseases of the Lyme borreliosis complex, serodiagnostic results, cerebrospinal fluid findings, demonstration of intrathecal specific antibody synthesis, results of nerve biopsies, response to adequate antibiotic therapy and exclusion of other diseases . The significance of each of these criteria depends on the clinical involvement and on the stage of Lyme borreliosis.

Klin Khir, 1991, (6), 4 - 7
{Modern aspects of reduction of mortality in acute appendicitis in children under three years of age}; Sitkovskii NB et al.; The experience with treatment of 216 young children with acute appendicitis is summarized . All the patients were operated on after the complex preoperative preparation . Median laparotomy was performed in 17 patients, 199 were operated on with local approach . Sanation of the abdominal cavity, intestinal decompression were performed . At the postoperative period, the correction of metabolic disorders, hemosorption, lymphosorption, endolymphatic antibiotic therapy, intravascular laser and ultra-violet irradiation of the blood were performed . One patient, who was admitted 10 days after the onset of the disease died . There are the following reserves for reduction of lethality: timely taking medical advice, early diagnosis of the disease, effective preoperative preparation, adequate operative intervention and postoperative management of a patient, timely detection and elimination of complications.

J Orthop Trauma, 1991, 5(3), 341 - 8
Unilateral external fixation until healing with the dynamic axial fixator for severe open tibial fractures; Marsh JL et al.; One hundred one cases of open tibia fractures were treated until healing with a unilateral external fixation device that permits fracture site compression with weight bearing . There were 38 type II and 63 type III (24 IIIA, 33 IIIB, six IIIC) open fractures . A standard protocol was followed including irrigation and debridement and, when necessary, flap coverage (19 cases) and bone grafting (31 cases) . Fixators were applied at the first debridement and removed when the fracture was healed . All patients were permitted early partial weight bearing and progressed to full weight bearing with fixator dynamization . Ninety-six cases healed in the fixator (12-50 weeks; average, 24.6) . Three of the five failures were associated with screw complications . Five patients required screw changes and 29 required oral antibiotic therapy for screw complications . Ninety-five percent of healed cases had angulation of less than 10 degrees (in any plane) . There were only six fracture site infections during the course of treatment . Dynamic axial fixation may be applied at the first debridement and be used until healing in severe open tibia fractures . Change of the fixator to another treatment method is not required.

J Nucl Biol Med, 1991 Jan-Mar, 35(1), 10 - 3
Reversibility of complete unperfusion in a patient with recurrent hemoptysis; Baldi S et al.; We present a case of a 68-year-old woman with a history of mild smoking and chronic bronchitis who showed recurrent hemoptysis . She presented with a nearly normal chest roentgenogram, a non-diagnostic fiberoptic bronchoscopy and a computed tomography and lung scanning both of which were highly suggestive for malignancy . In fact, the former showed obstruction of the main left bronchus, of the superior bronchus for the left upper lobe and of the apical bronchus for the left lower lobe, the latter showed a total cessation of blood flow through the left lung . Pulmonary angiography, however, was normal and aortography showed dilatated and twisted left bronchial arteries . Computed tomography and lung scanning came back to normal after bronchoscopic aspiration of endobronchial clots and a nonspecific antibiotic therapy were carried out . Although very infrequent, bronchial stenosis on CT and complete monolateral unperfusion on lung scintigraphy may occur in patients with hemoptysis of benign origin . We recommend the use of pulmonary arteriography in patients with the above pattern when diagnostic doubt remains after bronchoscopy.

Br J Clin Pract, 1991 Spring, 45(1), 31 - 2
Why flush peripheral intravenous cannulae used for intermittent intravenous injection?
Walsh DA, Toeg D, Mellor JA.
We aimed to investigate whether regular flushing of peripheral intravenous cannulae used for intermittent injections with heparin-saline, in a unit for acute medicine for the elderly, reduced the incidence of complications necessitating cannula removal . We wanted to see if this could also prolong the time that cannulae may remain functional in situ . In a prospective, open study, 50 consecutively inserted cannulae were flushed regularly and a subsequent 50 consecutive cannulae were not flushed . The incidence of complications necessitating removal was not significantly different between the two groups (18% flushed, 22% unflushed) . Overall, only 5% of cannulae were removed because of blockage . Heparin-saline flushes did not significantly increase the time that cannulae remained in situ . Antibiotic use was found to be associated with an increased rate of complications necessitating cannula removal . We found no significant advantage in heparin-saline flushing of peripheral intravenous cannulae used for intermittent administration of medications.

Eur Arch Otorhinolaryngol, 1991, 248(6), 342 - 4
Experimental investigations on the influence of anemia on gentamicin ototoxicity; Delb W et al.; The purpose of this study was to determine whether or not anemic patients have a higher risk of gentamicin ototoxicity . Using the laboratory rat as an animal model with auditory brain-stem response measurements and surface preparations of the organ of Corti, it could be shown that cochlear damage in anemic rats treated with gentamicin was significantly higher (P less than 0.05) than in the nonanemic ones treated with the same dosages of antibiotic . Doses of gentamicin used were 50 mg/kg for 30 days and 40 mg/kg for another 75 days.






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