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, whi