Drug Metab Dispos, 1990 Sep-Oct, 18(5), 595 - 606 Cyclosporin A drug interactions . Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes; Pichard L et al.; In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA . We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it . In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to "reproduce" in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA . Our results were in close agreement with the clinical reports . Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 microM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media . Conversely, these cultures exhibited erythromycin concentration-dependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 microM erythromycin . In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 microM) as expected, this macrolide being a specific substrate of P-450IIIA . Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity . Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors . Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine . Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocriptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone . Finally, cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprim, amphotericin B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA. Biochim Biophys Acta, 1990 Aug 27, 1050(1-3), 197 - 202 The extension of polyphenylalanine and polylysine peptides on Escherichia coli ribosomes; Hardesty B et al.; Fluorescence techniques were used to examine aminoacyl-tRNA binding to Escherichia coli ribosomes and the subsequent extension of polyphenylalanine and polylysine nascent peptides . The results demonstrate that deacylated tRNA, an analogue of peptidyl-tRNA and puromycin (an analogue of aminoacyl-tRNA) can be bound simultaneously to the same ribosome . Moreover, the fluorescence properties of nascent polyphenylalanine and polylysine peptides with a fluorophore attached to their amino termini were determined and found to be quite different . This difference is reflected in the effects that erythromycin has in each case. Med Klin (Munich), 1990 Aug 15, 85(8), 481 - 4 {Therapy of bullous pemphigoid with erythromycin}; Mensing H et al.; Bullous pemphigoid is the most common autoimmune mediated bullous disease in men . Erythromycin combined with a low dose methylprednisolone was tested in eleven patients in a prospective study . A historical collective of the last 33 patients treated before this study was started served as the control group . The duration of hospitalization as an expression of therapeutic response, but also of lowered side effects dropped down from 43 to 33 days in the erythromycin treated group . The study further shows a responder rate of about two thirds of the patients, one third, however, required a high dose regimen of corticosteroids in order to ameliorate . From this could be concluded, that two different subtypes of bullous pemphigoid exist concerning their therapeutic response. Tidsskr Nor Laegeforen . 1990 Aug 10;110(18):2359. {Ergotamine induced ischemia}; Remme A et al.; Drugs containing ergotamine are commonly used in the treatment of migraine . Hypersensitivity to these drugs may be triggered off even with intake of recommended doses, inducing peripheral ischemia . Contributing factors to ergotism are concurrent fever, liver disease and drugs such as erythromycin or propranolol . We present a case history and different methods of treatment. Dtsch Med Wochenschr, 1990 Aug 3, 115(31-32), 1188 - 92 {Persisting alveolitis after Legionella pneumonia}; Hurter T et al.; Pneumonia was diagnosed radiologically in three patients (43, 54 and 58 years old, respectively), presenting with temperatures between 39 degrees and 40 degrees C, cough and weight loss . These signs persisted for 6, 7 and 13 weeks, respectively, but the pathogens could not be cultivated . Lung function analysis showed partial respiratory insufficiency with extensive restrictive impairment of ventilation . Samples of lung tissue were obtained in all three cases and histology revealed fibrosing alveolitis . In two patients serology yielded antibody titres of 1:512 and in one patient of 1:128, against Legionella pneumophila . Treatment with 1 g erythromycin three times daily was unsuccessful . Therefore, the patients were given prednisone at an initial dosage of 50-100 mg which was subsequently reduced . Lung function normalised during this treatment course, radiological findings and antibody titres receded . Hence, treatment with corticosteroids should be attempted if there is an urgent suspicion of fibrosing alveolitis caused by Legionella pneumophila, after having excluded a florid infectious pneumonia and after failure of erythromycin treatment. Mol Pharmacol, 1990 Aug, 38(2), 207 - 13 Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3); Wrighton SA et al.; The human P450III family has been shown to be composed of at least four members, P450IIIA3 (HLp), P450IIIA4 (P450NF), P450IIIA5 (HLp3), and P450IIIA6 (HLp2) . Due to the lack of probes that specifically recognize the individual members of this family, little is known about their relative expression . We prepared a form-specific antibody to P450IIIA5 by immunoabsorption of anti-P450IIIA5 IgG against Sepharose 4B upon which microsomes that did not contain P450IIIA5 or purified P450IIIA3 had been bound . Immunoblot analyses demonstrated that P450IIIA5 was expressed at detectable levels in only 19 of 66 (29%) human livers . The expression of P450IIIA5 was not influenced by the gender or medical history of the patients . When the expression of P450IIIA5 in different age groups was examined, it was observed that P450IIIA5 was detected in a statistically significantly higher percentage of children and adolescents (19 years old and under), as compared with the remaining population (8 of 17, 47%, versus 11 of 46, 24%, respectively) . Furthermore, P450IIIA5 was detected in 1 of 10 human fetal livers . Of the large number of compounds identified as substrates of P450III family members, P450IIIA5 was found to actively metabolize nifedipine, testosterone, estradiol, dehydroepiandrosterone 3-sulfate, and cortisol, whereas it metabolized poorly or did not metabolize erythromycin, quinidine, 17 alpha-ethynylestradiol, and aflatoxins . The acetylenic steroid gestodene was found to be an effective mechanism-based inhibitor of both P450IIIA4 and P450IIIA5 . Immunoblots of microsomes isolated from untreated and dexamethasone-, phenobarbital-, or 3-methylcholanthrene-treated HepG2 cells that were developed with an antibody that recognizes all the P450III family members demonstrated that no proteins in the P450III family were expressed by the HepG2 cells . In conclusion, our studies indicate that P450IIIA5 is polymorphically expressed at all stages of human development and is more limited in its metabolic capabilities than is P450IIIA4. Biochem Pharmacol, 1990 Aug 1, 40(3), 637 - 42 The in vivo induction of rat hepatic cytochrome P450-dependent enzyme activities and their maintenance in culture; Hammond AH et al.; Cytochrome P450-dependent enzyme activities were measured in hepatocytes from adult male rats, induced in vivo with phenobarbitone, beta-naphthoflavone, dexamethasone or isoniazid: the stability of the induced activities in culture was also determined . Each inducer produced a characteristically different pattern of enzyme activities with dexamethasone, isoniazid and beta-naphthoflavone selectively inducing erythromycin N-demethylase, p-nitrophenol hydroxylase and ethoxyresorufin O-dealkylase respectively . In general, the induced activities were maintained for 24 hr in culture . This indicates the feasibility of an in vivo induction-hepatocyte culture system for the study of metabolism-mediated toxicity. Antibiot Khimioter, 1990 Aug, 35(8), 14 - 6 {Pharmacological availability of erythromycin granules for children's use}; Korenev SV et al.; Pharmaceutical availability of erythromycin granules with polymeric coating of different composition+ was studied . With an account of the ++anatomo-physiological features of a child organism and the properties of the antibiotic, acetylphthalyl cellulose in combination with hydroxypropyl methylcellulose or methyl cellulose was used as a film forming agent . The coated granules were estimated by such parameters as the time of disintegration and the rate of dissolution in various media . The results of the study showed that coating of the erythromycin granules with the film composed of acetylphthalyl cellulose and hydroxypropyl methylcellulose in the ratio of 8 to 2 provided the required protection of the antibiotic in acid media and high pharmaceutical availability of the drug. Biochem Int, 1990 Aug, 21(5), 909 - 14 Co-operative binding of ribosomal proteins to an erythromycin affinity column; Pye DA et al.; The binding of the E . coli ribosomal proteins L4, L5 and L21 to an erythromycin affinity column has been found to be co-operative . Binding does not occur in the absence of other ribosomal proteins. Singapore Med J, 1990 Aug, 31(4), 378 - 80 The management of chronic non-gonococcal urethritis; Cheong WK; Non-gonococcal urethritis (NGU) is one of the most common sexually transmitted diseases today . Oral tetracyclines and erythromycin are well established choices of treatment . Despite adequate treatment, about 30-35% of NGU persist or recur . The cause of persistence or recurrence remains unknown . Prostate gland involvement has to be ruled out where indicated . A 4 to 6 week course of tetracyclines or erythromycin is suggested for persistent or recurrent NGU . Counselling to emphasize that chronic NGU is probably a self limited disorder would be of help. Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Aug, 28(8), 1066 - 71 {Effect of erythromycin on the generation of neutrophil chemiluminescence in vitro}; Hirata T et al.; In order to elucidate the therapeutic mechanisms of low dose-long term erythromycin (EM) therapy in patients with diffuse panbronchiolitis (DPB), the authors evaluated the effect of in vitro EM treatment on neutrophil (PMN) oxygen radicals production . EM has potent capacity to suppress PMN chemiluminescence (CL) induced by the N-formyl Met-leu-phe (FMLP), opsonized zymosan, and calcium ionophore A23187 stimulation . In marked contrast, phorbol myristate acetate (PMA)-induced PMN CL were much less affected by EM treatment . The suppressive activity of EM was dependent on the EM concentration and at a EM concentration of 25 micrograms/ml, FMLP-induced PMN CL were suppressed by 45.3 +/- 5.6% (n = 7), but PMA-induced CL were suppressed only marginally, 11.9 +/- 3.7% (n = 7) . The onset of inhibitory activity of EM is rapid and at 5 min., 60.1% of the maximum suppression at 60 min . was observed . This EM-induced suppression was found to be reversible and dependent on the EM-pretreatment temperature since the suppressive activity of EM were observed only at 37 degrees C but not at 0 degrees C . These results suggest that actively transported intracellular EM exerts its suppressive activity by inhibiting the process of Ca++ transfer or Ca++ utilization by cells . In addition, these results were consistent with the concept that EM might act as an anti-inflammatory agent in chronic bacterial airway infections such as bronchiectasis and DPB where the PMN appear to play an important role in the generation of airway destruction. J Am Acad Dermatol, 1990 Aug, 23(2 Pt 1), 269 - 79 Cutaneous surgery and the pregnant patient; Gormley DE; Cutaneous surgery in 34 pregnant women is described . The main indication for surgery was the diagnosis and/or treatment of malignancy . Surgery during the period of organogenesis (15 to 56 days) should be avoided when possible . Patients should be positioned on the left side during the procedure to avoid the supine hypotensive syndrome . Monitoring of the fetal heartbeat is desirable . Local anesthetics, penicillin, and erythromycin are safe if used carefully . Acetaminophen is the analgesic of choice . Exposure to the sun should be avoided during the perioperative period. Arch Dermatol, 1990 Aug, 126(8), 1064 - 7 Disseminated Mycobacterium chelonae subspecies chelonae infection with cutaneous and osseous manifestations; Drabick JJ et al.; A 75-year-old man who had been receiving corticosteroids for treatment of chronic obstructive pulmonary disease presented with nodulopustular skin lesions, bone pain, and constitutional symptoms . Evaluation revealed a disseminated infection with Mycobacterium chelonae subspecies chelonae, with cutaneous and osseous involvement documented by histopathologic studies and cultures . The bone involvement is a novel observation for this subspecies . The patient was successfully treated with a three-drug regimen of tobramycin sulfate, erythromycin stearate, and ciprofloxacin hydrochloride . We present a discussion of the case in the context of the literature. Clin Pharmacol Ther, 1990 Aug, 48(2), 120 - 9 The erythromycin breath test as a predictor of cyclosporine blood levels; Watkins PB et al.; The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients . Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine . Accordingly, the {14C-N-methyl} erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis . We found that a simple mathematical equation incorporating just the 14CO2 production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2 = 0.78) of the interpatient variability in cyclosporine blood levels we observed . Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient . We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing. Biochem Pharmacol, 1990 Jul 15, 40(2), 223 - 8 In vivo effects of erythromycin, oleandomycin and erythralosamine derivatives on hepatic cytochrome P-450; Delaforge M et al.; Rats have been treated with several derivatives of the erythromycin, erythralosamine or oleandomycin series, in order to compare their ability to induce cytochrome P-450 and to form stable 456 nm-absorbing cytochrome P-450 metabolite complexes . The data obtained confirm that the cytochromes P-450 induced in rats by various macrolides are similar to that induced by pregnenolone 16 alpha-carbonitrile: the cytochrome P-450 IIIA1 isozyme . It showed that: (i) formation of a stable inhibitory 456 nm-absorbing cytochrome P-450 complex is not a prerequisite for cytochrome P-450 induction but enhances induction by stabilization of the IIIA isozyme . Therefore, the best inducers lead also to the maximal in vivo amounts of cytochrome P-450 metabolite complex (except for 2'MBEM); (ii) affinity for cytochrome P-450 IIIA1 is not directly involved for induction; and (iii) hydrophobicity favors induction and formation of complexes . Structural factors are also involved. J Clin Pharmacol, 1990 Jul, 30(7), 621 - 31 Gastrointestinal behavior of orally administered radiolabeled erythromycin pellets in man as determined by gamma scintigraphy; Digenis GA et al.; The behavior of single 250-mg doses of a multiparticulate form of erythromycin base (ERYC(R)), each including five pellets radiolabeled with neutron-activated samarium-153, was observed by gamma scintigraphy in seven male subjects under fasting and nonfasting conditions . The residence time and locus of radiolabeled pellets within regions of the gastrointestinal tract were determined and were correlated with plasma concentrations of erythromycin at coincident time points . Administration of food 30 minutes postdosing reduced fasting plasma erythromycin Cmax and area under the plasma erythromycin versus time curve (AUC) values by 43% and 54%, respectively . Mean peak plasma concentration of erythromycin (Cmax) in the fasting state was 1.64 micrograms/mL versus 0.94 micrograms/mL in the nonfasting state . Total oral bioavailability, as determined by mean AUC (0-infinity) of the plasma erythromycin concentration versus time curve, was 7.6 hr/micrograms/mL in the fasted state, versus 3.5 hr/micrograms/mL in the nonfasting state . Mean time to peak plasma erythromycin concentration (tmax) in the fasting state was 3.3 hours, versus 2.3 hours in the nonfasting state . Plasma concentrations of erythromycin in both fasting and nonfasting states were within acceptable therapeutic ranges . Evidence provided by this study: 1) indicates that pellet erosion and absorption of active erythromycin base begins when the enteric-coated pellets reach the highly vascular mucosa of the jejunum and proximal ileum, and is essentially completed within the ileum, with a significant portion absorbed in the medial-to-distal ileum; 2) confirms that acceptable therapeutic plasma levels of erythromycin are attained in nonfasting subjects (Cmax = 0.94 microgram/mL) and that superior plasma erythromycin concentrations (Cmax = 1.64 micrograms/mL) are achieved by administration of the dose on an empty stomach 1 to 2 hours before or after meals; 3) corroborates other comparative studies reporting greater fasting bioavailability with this multiparticulate dosage form of erythromycin base than with reference single tablet or particle-in-tablet formulations; and 4) indicates that neutron activation of stable isotopes incorporated as a normal excipient in industrially-produced formulations provides an effective means for in vivo evaluation of dosage forms through gamma scintigraphy. Lijec Vjesn, 1990 Jul-Aug, 112(7-8), 216 - 21 {Clinical and epidemiologic features of acute respiratory infection caused by Mycoplasma pneumoniae}; Kuzman I et al.; The results of clinical and laboratory analysis and treatment, as well as epidemiological features of acute respiratory infections caused by Mycoplasma pneumoniae in 390 patients have been reported . The patients were treated at the University Hospital of Infectious Diseases "Dr . Fran Mihaljevic", Zagreb, between January 1, 1980, and December 31, 1985 . The diagnosis was established by the serologic method of complement fixation, on the grounds of fourfold increase or decrease of antibody titer in paired sera . Mycoplasma pneumoniae was the most frequently proved causative agent of acute respiratory infections in our admitted patients . There were 315 patients with pneumonia what makes 13.28% of all pneumonias, respectively 25.08% of nonbacterial pneumonias . Its participation in febrile respiratory catarrh syndrome was only 5.75% . Pneumonia occurred in schoolchildren most frequently, especially in those aged 10-14 years in whom 65.52% of nonbacterial pneumonias were connected with Mycoplasma pneumoniae . Men (230) were affected more frequently than women (160) . The main symptoms of pneumonia were temperature, headache and cough . Inflammatory infiltrates were mostly interstitial and located unilaterally in the lower lobes of the lungs . Pleural effusion was recorded in 24 patients (7.62%) . Doxycycline appeared to be the most effective antibiotic, but erythromycin and midecamycin yielded good results, as well. Rev Infect Dis, 1990 Jul-Aug, 12 Suppl 6, S580 - 9 Treatment of chancroid, 1989; Schmid GP; Since recommendations for the treatment of chancroid were made in 1985, in vitro and in vivo data indicate that the two drugs recommended, erythromycin (500 mg four times a day for 7 days) and ceftriaxone (250 mg intramuscularly in a single dose), remain effective . The alternative therapies of trimethoprim-sulfamethoxazole (160/800 mg twice a day for 7 days) and amoxicillin-clavulanic acid (500/125 mg three times a day for 7 days) also appear to be effective, although there has been little experience with these drugs in the United States . Single-dose trimethoprim-sulfamethoxazole (640/3,200 mg) now lacks the efficacy of other regimens . The experience with ciprofloxacin (500 mg twice a day for 3 days) has been favorable, and other quinolones may prove useful . Concurrent infection with human immunodeficiency virus appears to result in an increased rate of failure of treatment for chancroid, and such cases may require more prolonged therapy. J Fam Pract, 1990 Jul, 31(1), 62 - 4 Does patient education cause side effects? A controlled trial; Howland JS et al.; Ninety-eight adults treated with erythromycin for a variety of illnesses were randomized to two groups: the informed group received patient education about drug side effects, and the uninformed group were given no such information . Overall, 10% of the uniformed and 8% of the informed group felt the erythromycin bothered them in some way . There were no significant differences in the occurrence of various individual side effects . Compliance with therapy and the results of treatment were the same for both groups . In this study, informing patients about side effects of therapy did not have any detectable adverse effects. Pediatr Dent, 1990 Jul-Aug, 12(4), 246 - 9 Epidermolysis bullosa--dental management and anesthetic considerations: case report; Lanier PA et al.; Epidermolysis bullosa represents a group of hereditary skin disorders manifested by an exceptional tendency of the skin and mucosa to form bullae and vesicles as a result of trauma or friction . Comprehensive dental care for precooperative-age children with this disorder frequently is managed in the operating room under a general anesthetic . This case report describes an anesthetic protocol for dental management which was effective and resulted in minimal postoperative trauma . Eucerin cream, Gauztex bandages, and DuoDerm pads were used to lubricate and stabilize anesthetic armamentarium . Preoperative and postoperative erythromycin antibiotic therapy was instituted to prevent infection of the bullae present . Early diagnosis and institution of preventive measures can minimize the need for restorative and surgical management in these children . However, when anesthetic management is necessary, the use of appropriate consultants and adjuncts can provide valuable support. J Pediatr Gastroenterol Nutr, 1990 Jul, 11(1), 45 - 7 Intravenous erythromycin for postpyloric intubation; Di Lorenzo C et al.; Of 100 consecutive patients referred for antroduodenal manometry, we successfully intubated 89 with endoscopic and/or fluoroscopic guidance . In 8 of 8 patients who had failed with our usual techniques, we infused erythromycin 3 mg/kg i.v . over 1 h, and the tube moved through the pylorus and into the duodenum . Erythromycin, which stimulates propagation of 3 high amplitude antral contractions/min, appears to be a safe, noninvasive means to facilitate the postpyloric passage of tubes. J Bacteriol, 1990 Jul, 172(7), 4008 - 16 Streptomyces relC mutants with an altered ribosomal protein ST-L11 and genetic analysis of a Streptomyces griseus relC mutant; Ochi K; Several relaxed (rel) mutants have been obtained from Streptomyces species by selecting colonies resistant to thiopeptin, an analogue of thiostrepton . Using two-dimensional gel electrophoresis, I compared the ribosomal proteins from rel and rel+ pairs of S . antibioticus, S . lavendulae, S . griseoflavus, and S . griseus . It was found that all of the Streptomyces rel mutants thus examined had an altered or missing ribosomal protein, designated tentatively ST-L11 . These rel mutants therefore could be classified as relC mutants and were highly sensitive to erythromycin or high temperature . A relC mutant of S . griseus was defective in streptomycin production, but phenotypic reversion of this defect to normal productivity was found at high incidence among progeny of the relC mutant . This phenotypic reversion did not accompany a reappearance of ribosomal protein ST-L11, and furthermore the ability of accumulating ppGpp still remained at a low level, thus suggesting existence of a mutation (named sup) which suppresses the streptomycin deficiency phenotype exhibited by the relC mutant . Genetic analysis revealed that there is a correlation between the rel mutation and the inability to produce streptomycin or aerial mycelia . The sup mutation was found to lie at a chromosomal locus distinct from that of the relC mutation . It was therefore concluded that the dependence of streptomycin production on the normal function of the relC gene could be entirely bypassed by a mutation at the suppressor locus (sup) . The suppressing effect of the sup mutation on the relC mutation was blocked when the afs mutation (defective in A-factor synthesis) was introduced into a relC sup double mutant . It is proposed that the sup gene or its product can be direct or indirect target for ppGpp. Acta Gastroenterol Belg, 1990 Jul-Aug, 53(4), 446 - 57 The current status of gastric prokinetic drugs; Schapira M et al.; Several current gastrokinetic drugs (metoclopramide, domperidone, cisapride) are analysed in this review . After comparing the pharmacokinetics, the gastrointestinal prokinetic mechanisms and the side effects of each drug, their therapeutic uses are reviewed . All drugs improve symptoms of patients with gastro-oesophageal reflux disease, diabetic gastroparesis and idiopathic gastroparesis, but only cisapride seems capable to maintain a gastrokinetic effect under chronic administration . Erythromycin, which has a dramatic effect on hypomotility in diabetic gastroparesis, and opioid antagonists, may constitute new groups of efficient prokinetic drugs. JAMA, 1990 Jun 20, 263(23), 3160 - 3 Improved pregnancy outcome following successful treatment of chlamydial infection; Cohen I et al.; Pregnancy outcomes of 244 women, successfully treated with erythromycin ethylsuccinate for cervical chlamydial infection, were compared with those of 79 chlamydia-positive pregnant women, who failed to respond to treatment, and 244 chlamydia-free control women, who were not treated . The three groups were at high risk for infection with Chlamydia trachomatis . The frequencies of premature rupture of the membranes, premature contractions, and small-for-gestational-age infants were significantly lower in the successfully treated patients when compared with those of the chlamydia-positive patients, but were not significantly different when compared with those of the control patients . These data indicate that in a pregnant population at high risk for infection with C trachomatis, repeated prenatal chlamydial testing, plus successful erythromycin treatment, can significantly reduce certain adverse effects on pregnancy outcome. Biochem J, 1990 Jun 15, 268(3), 765 - 9 Induction of cytochrome P450III and P450IV family proteins in streptozotocin-induced diabetes; Barnett CR et al.; The effect of insulin-dependent diabetes on the hepatic microsomal activity of cytochrome P450III and P450IV family proteins was investigated in rats pretreated with streptozotocin . In order to discern between the effects of the diabetogen per se and those of the ensuing diabetes, streptozotocin-treated rats received in addition either nicotinamide to prevent the onset of diabetes or daily treatment with insulin to antagonize the effects of diabetes . Streptozotocin-treated rats displayed higher ethylmorphine and erythromycin N-demethylase activities and lauric acid hydroxylase activity . Increases were also detected immunologically by using monospecific polyclonal antibodies against the P450III and P450IV families . All effects were prevented by nicotinamide and effectively antagonized by insulin . In order to evaluate the role of the ketone bodies in the diabetes-induced increases in the above activities, rats were rendered hyperketonaemic by dietary administration of medium-chain triacylglycerols . These hyperketonaemic animals displayed high laurate hydroxylase activity and P450IV apoprotein levels, similar to those seen in the diabetic animals . Hyperketonaemia induced by dietary means caused a modest increase in the demethylation of erythromycin and had no significant effect on the N-demethylation of ethylmorphine . Furthermore, no marked increases were evident in the P450III apoprotein levels in the hyperketonaemic animals . It is concluded that insulin-dependent diabetes induces proteins of the P450III and P450IV families, and that the hyperketonaemia that accompanies diabetes is largely responsible for the changes in the latter family. Ir Med J, 1990 Jun, 83(2), 70 - 1 Management of tonsillitis by the general practitioner; Timon CI et al.; Seventy-eight of 107 general practitioners completed a questionnaire to assess the management of recurrent acute tonsillitis by the primary care physician . Penicillin was the antibiotic of choice in acute tonsillitis, used by 74 (95%) respondents . Of these, 45% recommended ampicillin/amoxycillin . In the case of penicillin allergy, 67 (86%) chose erythromycin . For the treatment of tonsillitis unresponsive to initial therapy, a wide variety of agents were quoted; the most common being erythromycin (27 cases, 35%) and co-trimoxazole (16 cases, 20%) . There were 17 separate indications for surgical referral given, the most common being recurrent tonsillitis (68 cases, 87%) . Two or more reasons for surgical referral were stated by 55 (71%) GPs . These findings are discussed with particular reference to recent reports of penicillinase producing bacteria in association with recurrent acute tonsillitis. Pneumologie, 1990 Jun, 44(6), 826 - 8 {Ciprofloxacin in the treatment of Legionnaires' disease}; Zabel L et al.; Case report on a granulocytopenic patient suffering from acute myeloid leukaemia and legionnaire's disease as a complication . Under therapy with ciprofloxacin (2 x 200 mg/die) the symptoms decreased within five days; hence, ciprofloxacin seems to be a good alternative to erythromycin and rifampicin in the therapy of legionnaire's disease in immunodeficient patients. Clin Pharmacol Ther, 1990 Jun, 47(6), 694 - 7 Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine; Nelson MV et al.; A study was performed to determine if the pharmacokinetics of bromocriptine is altered by factors that have been shown to interact with other ergot compounds . The effects on bromocriptine plasma concentrations by bromocriptine coadministration with caffeine and erythromycin were evaluated in five male volunteers . Serial blood samples were obtained during a 12-hour period after a single 5 mg oral dose of bromocriptine (alone and after 4-day treatments of either erythromycin estolate, 250 mg four times/day, or caffeine, 200 mg four times/day) . There were no significant alterations of bromocriptine pharmacokinetic parameters after caffeine, although statistical power was very low . With the use of erythromycin, the bromocriptine area under the concentration-time curve standardized to body weight increased significantly by 268%, whereas peak bromocriptine plasma concentration (Cmax) increased to 4.6 times the Cmax from bromocriptine alone . Time to achieve Cmax was not altered by erythromycin . We conclude that erythromycin can markedly increase the systemic bioavailability of bromocriptine, which can lead to increased therapeutic or adverse effects, whereas the effects of caffeine require further study. Ann Otol Rhinol Laryngol, 1990 Jun, 99(6 Pt 1), 445 - 50 Otolaryngologic management of posttransplant lymphoproliferative disease in children; Sculerati N et al.; Twelve of 14 children (86%) given a pathologic diagnosis of posttransplantation lymphoproliferative disease (PTLD) at the Children's Hospital of Pittsburgh presented with head and neck symptoms, and are included in this retrospective analysis . Upper airway obstruction was the most common symptom, evident in nine children (75%) . Ten children (83%) had febrile illnesses with dysphagia, odynophagia, and evidence of hypertrophy of components of Waldeyer's ring . Associated findings included cervical adenopathy, sinusitis, and otitis media . The two remaining children had an intratracheal and paratracheal mass, respectively . Excision of obstructing lymphoid tissue with proper handling of the specimen is advocated for diagnosis and relief of airway obstruction . Systemic therapy is necessary for treatment of PTLD and includes reduction of immunosuppression . Erythromycin causes elevation in cyclosporine levels and should be avoided in patients taking this drug. Acta Paediatr Jpn, 1990 Jun, 32(3), 315 - 8 Intrauterine Chlamydia trachomatis infection in a premature infant; Niwa A et al.; Intrauterine Chlamydia trachomatis infection was strongly suspected in a premature infant born in the 32nd week of gestation . The membranes were artificially ruptured at the time of delivery . This infant showed a high titer of specific IgM antibody to Chlamydia trachomatis at one hour after birth . He showed mild respiratory distress and was treated with oral erythromycin for three weeks . He was discharged home at the age of 46 days. J Antimicrob Chemother, 1990 Jun, 25(6), 975 - 84 Comparative efficacy and tolerance of erythromycin and josamycin in the prevention of bacteraemia following dental extraction; Sefton AM et al.; The tolerance and pharmacokinetics of erythromycin stearate and josamycin base were compared in healthy dental students . The efficacy and tolerance of the two antibiotics were compared in the prevention of bacteraemia following dental extraction . Erythromycin achieved higher serum levels at the time of extraction in dental patients than did josamycin . Erythromycin was rapidly and better absorbed than josamycin in the student volunteers, but josamycin caused less gastrointestinal side effects than erythromycin . Both antibiotics were only marginally more effective than placebo in preventing bacteraemia following dental extraction. J Infect Dis, 1990 Jun, 161(6), 1296 - 8 Pertussis in an adult man infected with the human immunodeficiency virus; Doebbeling BN et al.; A 25-year-old man infected with the human immunodeficiency virus (HIV) presented with paroxysmal cough and dyspnea of 4-months duration . An extensive evaluation including bronchoscopy was negative . A nasopharyngeal swab was positive by direct fluorescent antigen detection and culture for Bordetella pertussis . Respiratory isolation, treatment with erythromycin, and prophylaxis of household contacts was used to eradicate the organism and prevent transmission . Pertussis should be considered as a cause of prolonged cough and dyspnea in patients with HIV infection . The course of this patient was consistent with the concept that cell-mediated immunity is necessary for elimination of B . pertussis. Arzneimittelforschung, 1990 Jun, 40(6), 686 - 9 Mechanism of azithromycin uptake in human polymorphonuclear leucocytes; Laufen H et al.; The new antibiotic azithromycin (CP-62.993) is enriched in human polymorphonuclear leucocytes by up to 300-fold the extra-cellular concentrations . To approach an understanding of the underlying mechanism of this unique behavior of azithromycin, some characteristics of the uptake process were investigated in vitro . The speed of the uptake in human polymorphonuclear leucocytes was found to be independent of the extracellular starting concentrations of azithromycin . There was no indication of saturation up to extracellular concentrations of 100 micrograms/ml . The uptake was largely determined by incubation temperatures . At 4 degrees C no penetration into the cells could be observed . The activation energy of azithromycin uptake came to 144 kJ mol-1, twice the value of erythromycin uptake . The presence of various inhibitors of cell metabolism did not change the intracellular accumulation compared to control, nor did the presence of some agents which interfere with certain transport channels . These findings suggest that passive diffusion is an essential mechanism of azithromycin transport through the phagocyte membrane, while active transport is less important . The high cellular enrichment of azithromycin and the relatively high activation energy of the uptake process could be explained by accumulation of the drug in phagocytic lysosomes and this would also be in keeping with pH partition considerations. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1056 - 60 Intracellular accumulation of azithromycin by cultured human fibroblasts; Gladue RP et al.; Azithromycin was shown to achieve high concentrations in human skin fibroblasts . Intracellular penetration occurred rapidly (10 micrograms/mg of cellular protein after 3 h) and then increased progressively over a 3-day period; azithromycin accumulated up to 21 times more than erythromycin (61.1 versus 2.9 micrograms/mg of protein) . Uptake was dependent on the extracellular concentration, was inhibited at 4 degrees C, did not occur in nonviable cells, and was reduced by a low pH . Intracellular accumulation was not affected by the metabolic inhibitor 2,4-dinitrophenol or sodium fluoride or by the nucleoside transport inhibitor 2-chloradenosine . Once concentrated in cells, azithromycin remained intracellular and was released slowly in the absence of extracellular drug, compared with erythromycin (17 versus 78% released after 1 h) . After 48 h of incubation in drug-free medium, 27% of the initial amount of azithromycin remained cell associated . The release of azithromycin was not affected by various monokines reported to stimulate fibroblasts (interleukin-1 or tumor necrosis factor) or by exposure to bacteria . Incubation of azithromycin-loaded fibroblasts with human polymorphonuclear leukocytes resulted in a higher intracellular accumulation of azithromycin in polymorphonuclear leukocytes than in cells incubated with free nonintracellular azithromycin for the same time (8.3 versus 2.2 micrograms/ml after 2 h), suggesting a more efficient or rapid uptake through cell-to-cell interaction . The widespread distribution of fibroblasts in tissues suggests a potential for these cells, and possibly other lysosome-containing tissue cells, to serve as a reservoir for azithromycin, slowly releasing it for activity against extracellular organisms at sites of infection and passing it to phagocytes for activity against intracellular pathogens and potential transport to sites of infection. Control Clin Trials, 1990 Jun, 11(3), 187 - 98 Value of a run-in period in a drug trial during pregnancy; Blackwelder WC et al.; The Vaginal Infections and Prematurity (VIP) Study included a clinical trial of the efficacy of erythromycin in preventing adverse pregnancy outcomes . A prerandomization run-in period was part of the trial design . During this period, women were given 1 week's supply of placebo pills to test their compliance . Those who met certain criteria for compliance, were otherwise still eligible, and agreed to participate were then randomized to receive erythromycin or placebo for a maximum of 10 weeks . During 2 years of the VIP Study, 1476 (71%) of 2071 women who began the run-in period were randomized . Women at least 30 years of age, those not smoking during pregnancy or shortly before pregnancy, and those still working outside the home at the time of enrollment were more likely than other women to be randomized after the run-in . Calculations of relative efficiency, based on a standard sample-size formula, suggest that the VIP run-in procedure not only eliminated potentially noncompliant women before randomization but also increased the power of the trial . Similar calculations which incorporated costs suggest that the run-in also resulted in lower costs, compared to a trial with equivalent power but no run-in period. Ann Otol Rhinol Laryngol Suppl, 1990 Jun, 148, 39 - 41 Clinical perspectives on ototoxic drugs; Matz GJ; Ototoxic drugs such as salicylates, the aminoglycoside antibiotics, loop diuretics, cisplatin, erythromycin, and vancomycin are widely used in clinical practice . The most commonly used are aspirin and the aminoglycoside antibiotics . This chapter briefly discusses the pharmacology of the commonly prescribed ototoxic drugs and the doses that may result in ototoxicity . An outline for the monitoring of ototoxic drugs is presented . The role of topical ear drops as a possible cause of ototoxicity is reviewed. Gene, 1990 May 31, 90(1), 21 - 9 Cloning of genes involved in erythromycin biosynthesis from Saccharopolyspora erythraea using a novel actinomycete-Escherichia coli cosmid; Tuan JS et al.; Two plasmids were constructed that replicate in Saccharopolyspora (Sac.) erythraea, Escherichia coli and Streptomyces (S.) lividans, and used for the cloning of a locus involved in the synthesis of the macrolide antibiotic erythromycin (Er) . Plasmid pAL7002 contains the thiostrepton-resistance gene (tsr), a replicon-containing fragment from pJVI and pUC9 . Plasmid pNJI contains the lambda cos site but is otherwise similar to pAL7002 . A library of total DNA from Sac . erythraea was constructed in pNJI and probed in colony hybridizations with a DNA fragment containing ermE, the Sac . erythraea ErR-encoding gene . Plasmids obtained were subsequently introduced into EryA mutants of Sac . erythraea blocked in synthesis of Er (Ery-) and transformants were screened for restoration of Er production (Ery+) . Several plasmids were found to convert two mutants to Ery+, but a third EryA strain could not be restored to Ery+ by any of the plasmids employed . A 5-kb segment, designated eryAI, responsible for restoring the Ery+ phenotype in the EryA strains, was identified and mapped in the segment 12 to 17 kb downstream from ermE . Gene disruption experiments indicated that the 5-kb length of eryAI is fully internal to an eryAI-containing transcript . In Southern blots it was shown that one of the EryA strains carried a small deletion in eryAI and that, in at least some of the transformants restored to Ery+, the deletion had been replaced by the wild-type eryAI allele.(ABSTRACT TRUNCATED AT 250 WORDS) J Biol Chem, 1990 May 15, 265(14), 7894 - 9 Identification of a rRNA/chloramphenicol interaction site within the peptidyltransferase center of the 50 S subunit of the Escherichia coli ribosome; Marconi RT et al.; We have used oligodeoxyribonucleotide probes to investigate possible interactions between chloramphenicol and portions of the rRNA contained within the peptidyltransferase center of the Escherichia coli ribosome . Oligodeoxyribonucleotide probes complementary to bases 2448-2454, 2468-2482, and 2497-2505 of 23 S rRNA were hybridized to 50 S subunits in situ . Probe binding was qualitatively assessed by sucrose gradient centrifugation . Each probe was shown to bind specifically with its intended binding site through digestion of the rRNA within the RNA/DNA hetero-duplexes with RNase H and analysis of the digestion fragments using gel electrophoresis . Competitive binding experiments were conducted between each probe and the antibiotics chloramphenicol and erythromycin . The binding of a probe complementary to bases 2497-2505 was attenuated by 70% upon the binding of chloramphenicol . A probe complementary to bases 2468-2482 showed an increase in binding of 14% while binding of a probe complementary to bases 2448-2454 was not affected by chloramphenicol binding . Erythromycin did not affect the binding of any of these probes to 50 S subunits . These results suggest that bases within the 2497-2505 region of 23 S rRNA in E . coli may be involved in a chloramphenicol/rRNA interaction. Peptides, 1990 May-Jun, 11(3), 515 - 9 The erythromycin derivative EM-523 is a potent motilin agonist in man and in rabbit; Depoortere I et al.; Erythromycin may stimulate gastrointestinal motor activity via its effect upon motilin receptors . We have studied the ability of the derivative EM-523 {de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal} to induce contractions in duodenal smooth muscle strips and to displace labeled motilin bound to antral smooth muscle, in man and in rabbit . In both species EM-523 approached the potency of motilin for inducing contractions . Thus pED50 values were 7.84 +/- 0.11 and 8.69 +/- 0.12 for motilin in, respectively, man and rabbit, against 6.08 +/- 0.13 and 8.19 +/- 0.10 for EM-523 . In rabbit the efficacy of both compounds decreased in parallel aborally, the responses to EM-523 could not be blocked by atropine (10(-7) M) or TTX (10(-7) M), and both compounds were unable to further enhance the maximum effect to the other compound . In binding studies the order of potency was the same as in the contraction studies . The pIC50 values were: motilin (8.84 +/- 0.31, 9.17 +/- 0.20) greater than EM-523 (7.89 +/- 0.1, 8.40 +/- 0.10) . A Schild plot revealed that EM-523 was a competitive inhibitor of motilin receptor binding in man and in rabbit . We conclude that EM-523 is a potent motilin agonist. J Toxicol Environ Health, 1990 May, 30(1), 33 - 52 Comparison of polychlorinated dibenzodioxin levels with hepatic mixed-function oxidase induction in great blue herons; Bellward GD et al.; As part of the Canadian Wildlife Service monitoring of great blue herons in British Columbia, eggs were collected from three colonies with low, intermediate, and high levels of PCDD and PCDF contamination: Nicomekl, Vancouver, and Crofton, respectively . One egg from each nest was used for chemical analysis by GC-MS; the others were hatched . Liver microsomes were prepared from the heron chicks and used for determination of cytochrome P-450-dependent activities . No erythromycin N-demethylase activity was found in any sample . Ethoxyresorufin O-dealkylase activity in the Nicomekl group was similar to that in pigeons, a control altricial species . The ethoxyresorufin activity in the herons from the Crofton colony was 2.6-fold higher than in the Nicomekl group . The Vancouver colony was intermediate . No difference among the three heron colonies was found in pentoxyresorufin O-dealkylase activity, although levels were 20-33 times that in the pigeon . Chemical analysis was carried out on paired heron eggs . Vancouver and Crofton eggs contained 13.5 and 21 times the levels of 2,3,7,8-TCDD compared to the Nicomekl group . The Crofton eggs contained higher levels of several other contaminants also . A highly significant correlation (p less than .001) was found between ethoxyresorufin O-dealkylase and 2,3,7,8-TCDD concentrations . The correlation coefficient did not change when ethoxyresorufin O-dealkylase was compared to total chemical contamination using several toxic equivalency factors . Multiple regression analysis resulted in only one predictor variable for ethoxyresorufin O-dealkylase: 2,3,7,8-TCDD. J Infect, 1990 May, 20(3), 227 - 9 Legionnaires' disease due to Legionella anisa; Fallon RJ et al.; The first case of Legionnaires' disease due to Legionella anisa is described . The patient, a 31-year-old man, made a rapid and complete recovery when treated with erythromycin. Obstet Gynecol, 1990 May, 75(5), 752 - 6 Amoxicillin therapy for Chlamydia trachomatis in pregnancy; Crombleholme WR et al.; For treating Chlamydia trachomatis cervical infection in pregnancy, the Centers for Disease Control guidelines recommend either erythromycin base or erythromycin ethylsuccinate . There is no alternate therapy . Because of compliance problems with erythromycin regimens due to gastrointestinal side effects, such an alternative is needed . For this reason, we compared, in an open trial, the efficacy and patient compliance of amoxicillin (500 mg three times a day for 7 days) with those of erythromycin base (500 mg four times a day for 7 days) in treating C trachomatis cervical infections during pregnancy . In the amoxicillin group, 63 of 64 women (98.4%) had negative cervical cultures after treatment, compared with 55 of 58 women (94.8%) treated with erythromycin base . Vertical transmission to the infants was assessed by culture and/or persistent or rising immunoglobulin G antichlamydial antibody . In the amoxicillin group, 37 of 39 infants (94.9%) had no evidence of chlamydial infection, compared with 32 of 36 infants (88.8%) in the erythromycin group . These differences were not significant . The frequency of side effects was higher with erythromycin base than with amoxicillin (15 versus 8%), although not significantly so . However, the frequency of stopping medication because of side effects was significantly higher with erythromycin base than with amoxicillin (13 versus 2%; P less than .006) . These results suggest that amoxicillin may be an acceptable alternative treatment for chlamydial infections in pregnancy. Oral Surg Oral Med Oral Pathol, 1990 May, 69(5), 619 - 30 A comparison of erythromycin and cefadroxil in the prevention of flare-ups from asymptomatic teeth with pulpal necrosis and associated periapical pathosis; Morse DR et al.; In a previous study by our group with patients having asymptomatic teeth with pulpal necrosis and an associated periapical radiolucent lesion (PN/PL), it was shown that prophylactic administration of penicillin V or erythromycin (high-dose, 1-day regimen) resulted in a low incidence of flare-up (mean = 2.2%) and a low incidence of swelling and pain not associated with flare-up . No hypersensitivity responses occurred, and gastrointestinal side effects were found primarily with the erythromycins . To ascertain whether a single-dose administration of a long-acting 1-gm tablet of the cephalosporin antibiotic cefadroxil would result in a similar outcome, the present study was undertaken with 200 patients having quiescent PN/PL . The patients were randomly given either cefadroxil or erythromycin (base or stearate) . Evaluations of flare-up were done 1 day, 1 week, and 2 months after endodontic treatment . A 2.0% flare-up incidence was found, with no statistically significant differences for cefadroxil (1.0%), stearate (2.0%), or base (4.0%) . No hypersensitivity responses occurred . Gastrointestinal side effects were found primarily with the erythromycins (19.0%) . The results showed that a 1-gm, single-dose regimen of cefadroxil was as effective as erythromycin and penicillin in preventing flare-ups and serious sequelae . A comparative analysis of the data from our first study (no peritreatment antibiotics) and the pooled data from our last three investigations (including the current trial) showed that peritreatment antibiotic coverage significantly reduced flare-ups and serious sequelae after endodontic treatment of asymptomatic PN/PL (p less than 0.001). J Bacteriol, 1990 May, 172(5), 2541 - 6 Mutation and cloning of eryG, the structural gene for erythromycin O-methyltransferase from Saccharopolyspora erythraea, and expression of eryG in Escherichia coli; Paulus TJ et al.; A mutant strain derived by chemical mutagenesis of Saccharopolyspora erythraea (formerly known as Streptomyces erythreus) was isolated that accumulated erythromycin C and, to a lesser extent, its precursor, erythromycin D, with little or no production of erythromycin A or erythromycin B (the 3"-O-methylation products of erythromycin C and D, respectively) . This mutant lacked detectable erythromycin O-methyltransferase activity with erythromycin C, erythromycin D, or the analogs 2-norerythromycin C and 2-norerythromycin D as substrates . A 4.5-kilobase DNA fragment from S . erythraea originating approximately 5 kilobases from the erythromycin resistance gene ermE was identified that regenerated the parental phenotype and restored erythromycin O-methyltransferase activity when transformed into the erythromycin O-methyltransferase-negative mutant . Erythromycin O-methyltransferase activity was detected when the 4.5-kilobase fragment was fused to the lacZ promoter and introduced into Escherichia coli . The activity was dependent on the orientation of the DNA relative to lacZ . We have designated this genotype eryG in agreement with Weber et al . (J.M . Weber, B . Schoner, and R . Losick, Gene 75:235-241, 1989) . It thus appears that a single enzyme catalyzes all of the 3"-O-methylation reactions of the erythromycin biosynthetic pathway in S . erythraea and that eryG codes for the structural gene of this enzyme. J Bacteriol, 1990 May, 172(5), 2372 - 83 Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea; Weber JM et al.; We used a series of gene disruptions and gene replacements to mutagenically characterize 30 kilobases of DNA in the erythromycin resistance gene (ermE) region of the Saccharopolyspora erythraea chromosome . Five previously undiscovered loci involved in the biosynthesis of erythromycin were found, eryBI, eryBII, eryCI, eryCII, and eryH; and three known loci, eryAI, eryG, and ermE, were further characterized . The new Ery phenotype, EryH, was marked by (i) the accumulation of the intermediate 6-deoxyerythronolide B (DEB), suggesting a defect in the operation of the C-6 hydroxylase system, and (ii) a block in the synthesis or addition reactions for the first sugar group . Analyses of ermE mutants indicated that ermE is the only gene required for resistance to erythromycin, and that it is not required for production of the intermediate erythronolide B (EB) or for conversion of the intermediate 3-alpha-mycarosyl erythronolide B (MEB) to erythromycin . Mutations in the eryB and eryC loci were similar to previously reported chemically induced eryB and eryC mutations blocking synthesis or attachment of the two erythromycin sugar groups . Insertion mutations in eryAI, the macrolactone synthetase, defined the largest (at least 9-kilobase) transcription unit of the cluster . These mutants help to define the physical organization of the erythromycin gene cluster, and the eryH mutants provide a source for the production of the intermediate DEB. Enferm Infecc Microbiol Clin, 1990 May, 8(5), 278 - 81 {Childhood legionellosis}; Ferrer A et al.; Four cases of hospital acquired pneumonia are reported in children aged from 10 days to 7 years, in whom L . pneumophila serogroup 6 was isolated . All patients were sporadic cases occurring during a two year period (1987-1988) in the Pediatric Hospital of our institution . L . pneumophila was isolated in samples of pleural fluid, lung biopsy, tracheal aspirate, bronchial brushing and bronchoalveolar lavage . All our patients were immunologically depressed and three died . Only in two cases of erythromycin therapy was administered, as the etiology of their pneumonia was not suspected . The literature on other reported cases of infantile legionellosis is discussed. N Engl J Med, 1990 Apr 12, 322(15), 1028 - 31 Improvement of gastric emptying in diabetic gastroparesis by erythromycin . Preliminary studies; Janssens J et al.; Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist . Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis . To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis . We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design . Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal . For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects . The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively . Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day) . These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis. Rinsho Ketsueki, 1990 Apr, 31(4), 502 - 5 {Long-term surviving child with acute lymphoblastic leukemia complicated with legionellosis}; Tanabe N et al.; An 11 year-old girl was diagnosed as acute lymphoblastic leukemia (ALL) on November 26th 1979 and was induced into complete remission with vincristine and prednisolon . After consolidation therapy with daunomycin, vincristine and prednisolone, she developed pneumonia on January 21st 1980 . No cause of pneumonia was found by sputum culture or serologic tests . Treatment with cefmetazol (CMZ), sulbenicillin (SBPC) and minocycline (MINO) was not effective but 9 g/day of LCM made a remarkable effect . Indirect immunofluorescence assay of antibody showed x 512 titers on January 22nd and in her recovery period, the titers showed eight times increased up to x 4,000 . The diagnosis of Legionellosis was made on CDC's criteria . She recovered completely with sequential lincomycin (LCM) and erythromycin (EM) therapy . On October 1989, she is still in the first complete remission of ALL for more than 8 years. Antimicrob Agents Chemother, 1990 Apr, 34(4), 594 - 9 In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes; Sarkar M et al.; Some quinolone antibiotics cause increases in levels of theophylline in plasma that lead to serious adverse effects . We investigated the mechanism of this interaction by developing an in vitro system of human liver microsomes . Theophylline (1,3-dimethylxanthine) was incubated with human liver microsomes in the presence of enoxacin, ciprofloxacin, norfloxacin, or ofloxacin . Theophylline, its demethylated metabolites (3-methylxanthine and 1-methylxanthine), and its hydroxylated metabolite (1,3-dimethyluric acid) were measured by high-pressure liquid chromatography, and Km and Vmax values were estimated . Enoxacin and ciprofloxacin selectively blocked the two N demethylations; they significantly inhibited the hydroxylation only at high concentrations . Norfloxacin and ofloxacin caused little or no inhibition of the three metabolites at comparable concentrations . The extent of inhibition was reproducible in five different human livers . Inhibition enzyme kinetics revealed that enoxacin caused competitive and mixed competitive types of inhibition . The oxo metabolite of enoxacin caused little inhibition of theophylline metabolism and was much less potent than the parent compound . Nonspecific inhibition of cytochrome P-450 was ruled out since erythromycin N demethylation (cytochrome P-450 mediated) was unaffected in the presence of enoxacin . These in vitro data correlate with the clinical interaction described for these quinolones and theophylline . We conclude that some quinolones are potent and selective inhibitors of specific isozymes of human cytochrome P-450 that are responsible for theophylline metabolism . This in vitro system may be useful as a model to screen similar compounds for early identification of potential drug interactions. J Pharmacol Exp Ther, 1990 Apr, 253(1), 387 - 94 Cytochrome P 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues; de Waziers I et al.; The organ distribution of microsomal cytochrome P 450 isoenzymes (P 450), microsomal epoxide hydrolase (EH) and cytosolic glutathione-S-transferases was investigated by immunoblotting and enzyme measurements in rats and humans . In rats, P 450 IA1 was detected only in the duodenum, and P 450 IA2 and IIC11 were detected only in the liver . The highest concentrations of P 450 IIB1/B2 were found in the lung and in the duodenum; pentoxyresorufin-O-dealkylase activity was closely correlated with the amounts of P 450 IIB1/B2 in the different organs . P 450 IIE1 was present in liver, kidney and lung, whereas EH was found in liver, intestine and kidney . In humans, P 450 IIIA4 was detected in all tissues investigated; the highest concentrations were found in liver and intestine . The P 450 IIIA4 level was closely correlated with that of erythromycin demethylase and pentoxyresorufin-O-dealkylase activities . P 450 IIC8-10, IIE1 and IID6 were expressed in liver and intestine, P 450 9 in liver and kidney and P 450 IA2 in liver . EH was identified only in liver, intestine and kidney . In both species, concentrations and total amounts of P 450 isoenzymes and EH were much lower in all extrahepatic tissues than in the liver . Conversely, glutathione-S-transferase-pi was abundant in human intestine and colon compared to liver . Glutathione-S-transferase-mu polymorphism was confirmed in all tissues investigated . This extensive study showed that the pattern of (iso) enzymes was different in all tissues studied; consequently, xenobiotic metabolism would appear to be very different in each type of tissue. J Reprod Med, 1990 Apr, 35(4), 362 - 7 Treatment of Chlamydia trachomatis identified with Chlamydiazyme during pregnancy . Impact on perinatal complications and infants; Black-Payne C et al.; A rapid enzyme immunoassay antigen detection system (Chlamydiazyme) was used to screen 199 asymptomatic, third-trimester women . Fifty-two (26%) were Chlamydiazyme positive; they were mostly primiparous, single, young and black . Infected women were offered erythromycin therapy, counseling and posttherapy retesting . Sexual partners were treated likewise . Erythromycin compliance, determined by a questionnaire, was high (92%), and side effects (16%) were tolerable . Pregnancy outcome and infant illnesses were monitored to determine the effectiveness of therapy . There were no significant differences in pregnancy outcome in the Chlamydiazyme-negative and treated, Chlamydiazyme-positive women . Prospective evaluation of infants born to 48 negative and 50 treated, Chlamydiazyme-positive women revealed no significant differences in the incidence of respiratory tract illnesses or conjunctivitis . Chlamydiazyme can be used in a screening program to identify and treat third-trimester women infected with C trachomatis . As previously reported, erythromycin therapy for colonized women interrupted the expected transmission of C trachomatis to their infants. Genitourin Med, 1990 Apr, 66(2), 105 - 7 Sulphaphenazole, streptomycin and sulphaphenazole combination, trimethoprim, and erythromycin in the treatment of chancroid; Kumar B et al.; One hundred and thirty six patients with chancroid were treated with four different treatment regimens; (A) Sulphaphenazole 1 g 12 hourly by mouth x 10 days (B) Inj streptomycin 1 g intramuscularly daily with sulphaphenazole 1 g 12 hourly orally x 10 days; (C) trimethoprim 200 mg 12 hourly by mouth x 7-10 days, and (D) erythromycin 500 mg 6 hourly orally x 7-10 days . Cure rates of 9% with sulphaphenazole alone, 48% with streptomycin and sulphaphenazole combination, 93% with trimethoprim and 100% with erythromycin were obtained . Sulphaphenazole alone or in combination with streptomycin were thus inferior in the treatment of chancroid . There is need for modification of treatment regimens recommended for chancroid in the textbooks of dermatology and venereology . Trimethoprim can be recommended as first line of treatment for chancroid in developing countries like India where resistance to trimethoprim is uncommon and erythromycin is suggested as a second line of therapy because by that time syphilis can be easily ruled out. J Infect Dis, 1990 Apr, 161(4), 618 - 25 A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR; Grayston JT et al.; Chlamydia pneumoniae strain TWAR, the new third species of Chlamydia, is a common cause of pneumonia and other acute respiratory tract infections . About 10% of hospitalized and outpatient pneumonia cases have been associated with TWAR infection . TWAR is among the four or five most commonly identified causes of all pneumonia . Most TWAR infections are mild or asymptomatic, but occasionally severe pneumonia with death has been observed . Laboratory diagnosis is not generally available . Vigorous treatment with tetracycline or erythromycin is recommended . Both epidemic and endemic infections have been described in North America and the Nordic Countries . Population prevalence antibody studies suggest that TWAR infection is wide-spread throughout the world, that nearly everyone is infected and reinfected during their life-time, and that infection is common in all ages except those less than 5 years in temperate zone countries . The infection is transmitted from person to person, apparently with a long incubation period. Acta Virol, 1990 Apr, 34(2), 171 - 7 Properties in culture and persistence in cotton rats of the Rickettsia prowazekii vaccine strain E and its mutants; Ignatovich VF et al.; Cultural properties and the capacity for persistence were studied in spontaneous erythromycin-resistant (E errSM), in induced erythromycin-resistant (E errI) mutants and in a virulent revertant (E Vir) of the vaccine strain E, as compared with parent vaccine strain E and standard virulent strain Breinl of Rickettsia prowazekii . Cultural properties of the strains were found to differ in passages in chick embryos (CE) and cultures of FL cells . Multiplication indices in CE of mutant E errI were significantly lower than those of other strains (E, E errSM, E Vir, Breinl) . The multiplication rate in FL cells was found to be high in strains E errSM, Breinl, E Vir, being much lower in strains E errI and E . The capacity of the virulent revertant E Vir to persist in cotton rat (CR) was higher as compared with that of standard strain Breinl and significantly higher than that of the parent strain E . Low level carrier state of rickettsia was registered in CR infected with the mutant E errI. J Laryngol Otol, 1990 Mar, 104(3), 200 - 2 Otitis media with effusion: can erythromycin reduce the need for ventilating tubes? Moller P, Dingsor G. Otitis media with effusion (OME) is a common condition among children and is characterized by nonpurulent fluid in the middle ear and fluctuating conductive hearing loss . Most children will spontaneously regain normal air-filled middle ears, but a certain number will have persistent problems . In our department we will treat annually about 500 children on an outpatient basis, with the insertion of ventilating tubes in the eardrum . The reason for this study was to evaluate the effect of erythromycin, instead of inserting a ventilation tube, in children with bilateral OME of longer duration than three months (double blind/placebo) . The study comprises 147 children, 1-15 years of age, 83 boys and 64 girls, all with OME for more than three months . All the patients were candidates for tube insertion . In the group treated with erythromycin, 12 patients out of 69 had bilaterally air-filled middle ears after one month, as compared to 19 out of 72 in the group treated with the placebo . No difference was noted due to sex or age . The results support our indication and timing for ventilation tube insertion. Klin Padiatr, 1990 Mar-Apr, 202(2), 120 - 3 Dientamoeba fragilis infection, a cause of gastrointestinal symptoms in childhood; Preiss U et al.; Clinical and laboratory findings of 123 paediatric patients with infections due to intestinal protozoa were analysed . Dientamoeba fragilis (D.f.) was found in 102 cases . The other patients had infections with Giardia lamblia or mixed infections with several other protozoa . Acute and recurrent diarrhoea were the most common findings (56 cases), whereas abdominal pain was more common in children with chronic symptoms . Peripheral eosinophilia was present in 32% of the children with dientamoebiasis . Metronidazole, oxytetracycline, doxycycline, and erythromycin were the most effective drugs in the treatment of D.f . infections . The therapy led coincidentally to the sanitation of stools and elimination of abdominal complaints . The investigations underline the pathogenic role of D.f . in those children with gastrointestinal symptoms . Mixed infections of D.f . and Enterobius vermicularis suggest a vector bound transmission of D.f. Biochem Pharmacol, 1990 Mar 1, 39(5), 901 - 9 Purification of a sheep liver cytochrome P-450 from the P450IIIA gene subfamily . Its contribution to the N-dealkylation of veterinary drugs; Pineau T et al.; Oral administration of troleandomycin at a dose of 100 mg/kg/day for 6 days to three adult male Lacaune sheep produced a 1.6-fold increase in specific content of liver microsomal cytochrome P-450 . In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, microsomal preparations from treated animals exhibited a strong band in the zone of electrophoretic mobility of cytochromes P-450 . This band corresponded to a cytochrome P-450 which cross-reacted with rabbit P450IIIA6 antibodies, as demonstrated by immunoblotting . The ovine isozyme was purified to electrophoretic homogeneity by means of successive DEAE cellulose, CM cellulose and hydroxylapatite chromatographic separations . This hemoprotein had an apparent molecular weight of 52 kD as determined by calibrated sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was characterized in terms of spectral data, NH2-terminal amino acid sequence, immunologic and catalytic properties . This study revealed some interspecies differences with the orthologous rabbit isozyme . The contribution of this form to the N-demethylation of erythromycin and of three veterinary drugs: chlorpromazine, chlorpheniramine and bromhexine was demonstrated from inhibition by TAO, from immunoinhibition studies, using polyclonal antibodies raised in rabbit and from the existence of significant correlations between its microsomal level and these N-demethylase activities . In contrast, the results suggest that ovine P450IIIA could not be predominantly involved in the N-dealkylation of benzphetamine, ephedrine, ivermectine or spiramycin. Laryngoscope, 1990 Mar, 100(3), 231 - 6 Head and neck sequelae of cardiac transplantation; Teixido M et al.; Cardiac transplantation has become the treatment of choice for end-stage cardiomyopathies . In 1987, nearly 2000 cardiac transplants were performed in the United States . Otolaryngologists will be asked with increasing frequency to evaluate and treat these patients . The otolaryngology service at Loyola University Medical Center has been involved in the follow-up and treatment of head and neck complications in 100 transplant patients . Sixty percent of these patients manifest head and neck sequelae . The results of this review are presented . The otolaryngologist should be aware of the special features of this patient population that require modification of the treatment approach, such as 1 . the need to avoid the drugs erythromycin, trimethoprim/sulfamethoxazole, and ketoconazole, 2 . the need to preserve the right internal jugular vein, and 3 . the high risk of silent myocardial infarction . A discussion of these treatment modifications is provided . All patients should be treated in close communication with the medical transplant treatment team. Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Mar, 28(3), 410 - 6 {Chronic bronchitis and related disorders}; Izumi T; Chronic bronchitis was a disease which attracted much attention in the U.K . in the 1950's . It was classified into three forms known as simple chronic bronchitis, recurrent or mucopurulent bronchitis, and chronic obstructive bronchitis and it was thought that the disease progressed from one form to the next in accordance with their order as listed here . Later, however, it was realized that the disease did not progress according to this order and that chronic bronchitis actually included three kinds of the disease . Furthermore, in the U.K., with the prohibition of the use of coal and the reduction of air pollution and with the decline of infectious disease in child age, recurrent or mucopurulent bronchitis underwent an extreme reduction . Chronic obstructive bronchitis is known to be caused by smoking and is now called chronic bronchitis and emphysema or COPD . Simple chronic bronchitis may in fact be only a simple physical response to smoking . Now in Japan the disease called chronic bronchitis is often recognized when written on receipts for health insurance, but patients of chronic bronchitis as were seen in the U.K . in the 1950's are extremely rare . Diffuse panbronchiolitis is seen in Japan but is a disease not found in the West . Diffuse bronchiectasis and its differentiation become the point of question for this disease . With the effectiveness of erythromycin, we can expect a decline in the number of patients and an improvement in prognosis. An Esp Pediatr, 1990 Mar, 32(3), 225 - 7 {Rheumatic fever: clinical and therapeutic aspects}; Cadenas Gallego M et al.; From 1974 to 1987 we have diagnosed thirty three patients with rheumatic fever . The age of onset ranged from three to sixteen years with a mean age of nine years and six months . Carditis was the most frequent major criteria (27/33) followed by arthritis (14/33) and Sydenham's chorea (6/33) . All the patients with carditis had the mitral valve affected . The usual treatment in the acute phase was penicillin and aspirin . The prophylaxis recommended to the patients was penicillin G benzatine every 21 days if they had carditis and every 28 days if they didn't . Two patients allergic to penicillin are receiving erythromycin . We have observed that the incidence of rheumatic fever has remained unchanged that the age of onset increased and that the antiinflammatory drug of choice in most patients with carditis is aspirin. Semin Respir Infect, 1990 Mar, 5(1), 30 - 7 Legionella infection in transplant patients; Ampel NM et al.; Since the discovery of Legionella pneumophila in the late 1970s, this organism and other Legionella sp have been an important cause of pneumonia in solid organ transplant recipients . Legionella sp are obligate aerobes that require a source of amino acids, iron, and L-cystine . Growth is enhanced in a 5% CO2 atmosphere at 37 degrees C in the presence of charcoal . Legionella sp reside in water supplies and hospital outbreaks associated with contaminated water have been described . Transplant recipients are particularly susceptible to Legionella infection . Legionella pneumonia tends to occur within several weeks after transplantation and frequently coincides with episodes of rejection . A prodrome of influenza-like symptoms is followed by a sometimes "explosive" pneumonia with patchy lobular or interstitial infiltrates on chest radiograph . High fever, abdominal pain, and mental status changes are sometimes seen . Diagnosis is made by examination of respiratory secretions by the direct fluorescent antibody technique or culture of the organism . Intravenous erythromycin is the treatment of choice . Rifampin is added if there is a lack of response . Both erythromycin and rifampin have important and opposite effects on cyclosporine metabolism, which may result, respectively, in increased cyclosporine toxicity or graft loss . Patients who must continue cyclosporine will, therefore, require frequent monitoring of cyclosporine levels. Prim Care, 1990 Mar, 17(1), 85 - 93 Chlamydial infections; Graham JM et al.; Chlamydia causes many human infections and should be treated aggressively . Tetracycline or doxycycline are the drugs of choice, but erythromycin can be used if a drug allergy is present or if tetracyclines are contraindicated . In the pregnant woman, aggressive treatment can improve neonatal outcome . In the United States, each year 155,000 infants are exposed to Chlamydia trachomatis during the birth process, and more than 100,000 will be infected . Of these, 75,000 will get conjunctivitis, and 30,000 will get pneumonia . In pregnancy, erythromycin is the drug of choice, with treatment recommended after initial culture and at term if repeat cultures are positive . If erythromycin is not tolerated, or the patient has an allergy to it, ampicillin or clindamycin may be effective alternatives. J Am Acad Dermatol, 1990 Mar, 22(3), 489 - 95 A clinical trial comparing the safety and efficacy of a topical erythromycin-zinc formulation with a topical clindamycin formulation; Schachner L et al.; One hundred three patients with acne vulgaris were randomly designated to receive either a topical formulation of erythromycin plus zinc or a topical solution of 1% clindamycin phosphate (Cleocin-T) . The patients treated themselves twice daily and were examined at 3, 6, 9, and 12 weeks after the start of therapy . By week 6 the overall severity grade was consistently lower and the percent reduction of severity, papules, pustules, and total comedones was higher in the erythromycin-zinc-treated group than in the clindamycin-treated group . In the 92 patients who completed this study (48 receiving erythromycin-zinc and 44 receiving clindamycin), no serious topical or systemic side effects were reported . Two patients, one from each treatment group, suffered mild irritation . One patient was withdrawn from the erythromycin-zinc-treated group . Results of patch tests were negative . The superiority of the erythromycin-zinc formulation may be due to the increased (4%) erythromycin concentration and/or the ability of 1.2% zinc acetate to enhance the product's activity. Arch Biochem Biophys, 1990 Feb 15, 277(1), 166 - 80 Reconstitution of testosterone oxidation by purified rat cytochrome P450p (IIIA1); Halvorson M et al.; Cytochrome P450p (IIIA1) has been purified from rat liver microsomes by several investigators, but in all cases the purified protein, in contrast to other P450 enzymes, has not been catalytically active when reconstituted with NADPH-cytochrome P450 reductase and dilauroylphosphatidylcholine . We now report the successful reconstitution of testosterone oxidation by cytochrome P450p, which was purified from liver microsomes from troleandomycin-treated rats . The rate of testosterone oxidation was greatest when purified cytochrome P450p (50 pmol/ml) was reconstituted with a fivefold molar excess of NADPH-cytochrome P450 reductase, an equimolar amount of cytochrome b5, 200 micrograms/ml of a chloroform/methanol extract of microsomal lipid (which could not be substituted with dilauroylphosphatidylcholine), and the nonionic detergent, Emulgen 911 (50 micrograms/ml) . Testosterone oxidation by cytochrome P450p was optimal at 200 mM potassium phosphate, pH 7.25 . In addition to their final concentration, the order of addition of these components was found to influence the catalytic activity of cytochrome P450p . Under these experimental conditions, purified cytochrome P450p converted testosterone to four major and four minor metabolites at an overall rate of 18 nmol/nmol P450p/min (which is comparable to the rate of testosterone oxidation catalyzed by other purified forms of rat liver cytochrome P450) . The four major metabolites were 6 beta-hydroxytestosterone (51%), 2 beta-hydroxytestosterone (18%), 15 beta-hydroxytestosterone (11%) and 6-dehydrotestosterone (10%) . The four minor metabolites were 18-hydroxytestosterone (3%), 1 beta-hydroxytestosterone (3%), 16 beta-hydroxytestosterone (2%), and androstenedione (2%) . With the exception of 16 beta-hydroxytestosterone and androstenedione, the conversion of testosterone to each of these metabolites was inhibited greater than 85% when liver microsomes from various sources were incubated with rabbit polyclonal antibody against cytochrome P450p . This antibody, which recognized two electrophoretically distinct proteins in liver microsomes from troleandomycin-treated rats, did not inhibit testosterone oxidation by cytochromes P450a, P450b, P450h, or P450m . The catalytic turnover of microsomal cytochrome P450p was estimated from the increase in testosterone oxidation and the apparent increase in cytochrome P450 concentration following treatment of liver microsomes from troleandomycin- or erythromycin-induced rats with potassium ferricyanide (which dissociates the cytochrome P450p-inducer complex) . Based on this estimate, the catalytic turnover values for purified, reconstituted cytochrome P450p were 4.2 to 4.6 times greater than the rate catalyzed by microsomal cytochrome P450p. J Am Acad Dermatol, 1990 Feb, 22(2 Pt 1), 253 - 60 Topical erythromycin and zinc therapy for acne; Schachner L et al.; A double-blind, 12-week study was undertaken to determine the safety and efficacy of a formulation of 4% erythromycin plus 1.2% zinc acetate compared with its vehicle . The study was continued for 40 weeks after the 12-week double-blind phase by switching vehicle-treated patients to active treatment and continuing to give patients treated with active drug the same treatment . Seventy-three female patients started the study; 39 completed 1 full year of study . In the first 12 weeks statistically significant differences were noted in the efficacy of the erythromycin-zinc compared with vehicle for acne severity grades (global assessment) and for papule, pustule, and comedo counts . After crossover, the vehicle-treated group receiving active therapy duplicated the improvement of the group initially treated with erythromycin-zinc . No clinical problems with superinfection or secondary infection occurred during 1 year of treatment in 39 patients. Monatsschr Kinderheilkd, 1990 Feb, 138(2), 85 - 7 {Vitamin K deficiency with erythromycin . Observation of a boy treated with valproate}; Cordes I et al.; A nine year old boy had been treated with valproic acid during one and a half years because of a grand mal epilepsy . Under an additional medication with erythromycin succinate syrup this patient developed a deficiency of prothrombin-complex, which was reversible immediately after oral intake of vitamin K . In this case it is assumed that the simultaneous application of both valproic acid and erythromycin succinate seems to suppress the vitamin K producing intestinal tract bacteria, which has not been reported in the literature so far. Pol Tyg Lek, 1990 Jan 22-29, 45(4-5), 82 - 4 {Occupational allergy in the production of drugs}; Rembadel P et al.; Quinazoline oxide--an intermediate in chlordiazepoxide synthesis--is the most potent contact allergen in the pharmaceutical industry . Penicillins proved to be potent allergens . Conditions of the technological process favor development of hypersensitivity to tetracyclines . No single case of allergy to erythromycin was noted . In case of employees hypersensitive to disulfiram and aminophylline cross reactions with compounds of similar structure were observed . The authors discuss also some problems concerning contact allergy in all persons occupationally dealing with various medicines. Clin Ter, 1990 Jan 15, 132(1), 41 - 4 {Medical treatment of pelvic inflammatory disease . A clinical study on the therapeutic effectiveness of piperacillin + erythromycin and of piperacillin + clindamycin + gentamycin}; Sesti F et al.; The aim of the present clinical study was to evaluate the therapeutic effectiveness of two different antibiotic combinations (piperacillin + erythromycin and piperacillin + clindamycin + gentamycin) in the medical treatment of patients with pelvic inflammatory disease, respectively at the II and III stage . The findings confirm the therapeutic value and the low toxicity of both pharmacological regimens. Cas Lek Cesk, 1990 Jan 12, 129(2), 56 - 7 {Acute ischemia of the extremities in the puerperal period}; Petr P et al.; The development of pharmacotherapy implies great advantages for patients, at the same time it is, however, also the source of more frequent side-effects of drugs, which may result also from mutual interactions of commonly used drugs . The authors describe a case of ergotism which developed as a result of drug interaction between the ergot uterotonic Cornutamine and the marcolid antibiotic Erythromycin . This interaction could have seriously damaged the health of the young woman . At the same time the authors remind of the clinical picture of ergotism and the possible way of its treatment . In the Czechoslovak literature no report on this interaction was published during the past three years. Lancet, 1990 Jan 6, 335(8680), 11 - 5 Cyclosporin toxicity at therapeutic blood levels and cytochrome P-450 IIIA; Lucey MR et al.; A 40-year-old male liver allograft recipient had neurological dysfunction and renal failure while his cyclosporin blood levels were in the therapeutic range; these features recurred on rechallenge . The hypothesis that this toxic effect might have resulted from abnormal metabolism of cyclosporin by liver cytochrome P-450 IIIA was investigated with the {14C}erythromycin breath test, which is a measure of this enzyme's activity . P-450 IIIA activity was decreased compared with that in controls, including other liver transplant recipients . Pretreatment with rifampicin, an inducer of P-450 IIIA, increased enzyme activity . After treatment with rifampicin the patient could be rechallenged with cyclosporin at a dose almost twice that which had previously been toxic . The patient died during a second transplantation and the microsomal content of P-450 IIIA was found to be low in the first transplant. Sex Transm Dis, 1990 Jan-Mar, 17(1), 48 - 50 Comparison of chlamydial culture with Chlamydiazyme assay during erythromycin PCE treatment of Chlamydia genital infections; Havlichek DH Jr et al.; We compared chlamydial culture with the chlamydial antigen detection enzyme immunoassay system (Chlamydiazyme, Abbott Diagnostic Products; Abbott Park, IL) during treatment of Chlamydia genital infections . Participants received 333 mg of erythromycin PCE (Abbott Laboratories; Abbott Park, IL) 3 times per day for 7 days . On days 0, 3, 7, and 14, chlamydial cultures were positive in 30/30 (100%), 5/29 (17.2%), 0/27, and 0/25 participants, respectively . Concurrent Chlamydiazyme assays were positive in 30/30 (100%), 11/30 (37%), 1/28 (4%), and 0/25 participants . Twenty-eight of 28 persons who received erythromycin PCE for at least 3 days had negative test results for both chlamydial culture and Chlamydiazyme at their last clinic visit . Chlamydiazyme assay tended to remain positive longer than chlamydial culture during treatment, but 7 days after therapy was completed, no Chlamydia trachomatis antigens were detectable by this assay . Erythromycin PCE was well tolerated and rapidly eliminated Chlamydia genital infections in 83% of persons showing negative cultures by the third day of therapy. Mol Pharmacol, 1990 Jan, 37(1), 130 - 6 Effects of 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine on hepatic cytochrome P-450 heme, apoproteins, and catalytic activities following in vivo administration to rats; Riddick DS et al.; Various 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) cause mechanism-based inactivation of cytochrome P-450 (P-450) via heme destruction . We have examined the time course of effects of DDC analogues on the catalytic activities and apoproteins of the major beta-naphthoflavone-, dexamethasone-, and phenobarbital-inducible isozymes of rat liver P-450 following in vivo administration . In beta-naphthoflavone-treated rats, all DDC analogues examined caused loss of the P-450 chromophore and dramatic loss of 7-ethoxyresorufin O-deethylase activity, a catalytic marker for P-450c . The isopropyl, hexyl, and isobutyl analogues caused the most pronounced loss/alteration of P-450c apoprotein levels, as revealed by two monoclonal antibodies (MAbs), 1-31-2 and 1-7-1 . The apoprotein of P-450d was not altered . In dexamethasone-treated rats, all analogues except 4-hexyl-DDC caused loss of the P-450 chromophore and erythromycin N-demethylase activity, a catalytic marker for P-450p-related isozymes . Only 4-isopropyl-DDC caused significant loss/alteration of the apoprotein of P-450p-related forms, as revealed by MAb 2-13-1 . In phenobarbital-treated rats, all analogues reduced the level of the P-450 chromophore, whereas only 4-hexyl-DDC and 4-isopropyl-DDC lowered 7-pentoxyresorufin O-dealkylase activity, a catalytic marker for P-450b . MAbs 2-66-3 and 2-8-1 revealed no change in the level of phenobarbital-inducible apoproteins recognized by these probes . In agreement with our previous in vitro studies {Mol . Pharmacol . 35;626-634 (1989)}, P-450 c and p are targets for mechanism-based inactivation by DDC analogues . However, unlike the situation in vitro, loss of enzyme activity in vivo is, at least in some instances, accompanied by loss/alteration of the corresponding P-450 apoprotein. Am Rev Respir Dis, 1990 Jan, 141(1), 72 - 8 Erythromycin inhibits respiratory glycoconjugate secretion from human airways in vitro; Goswami SK et al.; Erythromycin and other antibiotics have been used empirically in the treatment of patients with chronic obstructive pulmonary disease (COPD) . We studied whether this empirical role of antibiotics might not be related to a possible direct effect on respiratory glycoconjugate (RGC) secretion . The effect of erythromycin on RGC secretion and hypersecretion was studied in an in vitro preparation of human airways that were secreting {3H}glucosamine respiratory glycoconjugate (RGC), and on a human endometrial adenocarcinoma cell line secreting a glycoconjugate (tumor glycoconjugate = TGC) chemically similar to the RGC secreted by the airways . Erythromycin at 10(-5) M reduced RGC secretion by 35 +/- 4% (n = 9, p less than 0.001) in both human airways and the adenocarcinoma cells, and was increasingly active in the pharmacologic range of 10(-7) to 10(-4) M . The inhibitory effect of erythromycin was maximal within 16 h and was still evident 34 h after incubation . Erythromycin was noted to reduce both spontaneous (baseline) and stimulated RGC secretion (by histamine and methacholine) from airways in culture . The blocking effect appeared to be more selective for histamine than methacholine . These effects were not associated with any toxicity to the tissues and were not associated with the inhibition of protein synthesis . Dexamethasone also inhibited RGC release in both assay systems and exhibited dose-related effects in the physiologic ranges (10(-9) to 10(-5) M) . When administered together, erythromycin and dexamethasone had an additive inhibitory effect on RGC secretion (68.0 +/- 3.0%, n = 7, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) Rev Esp Anestesiol Reanim, 1990 Jan-Feb, 37(1), 28 - 31 {Severe heart arrhythmia secondary to magnesium depletion . Torsade de pointes}; Papaceit J et al.; We report a case of torsade de pointe ventricular tachycardia in a patient with chronic magnesium depletion . The etiological aspects implicated this unusual cardiac arrhythmia are: the congenital long QT syndrome; bradycardia, either sinusal or due to atrioventricular block; ionic depletions: hypokalemia, hypocalcemia and hypomagnesemia; treatment with antiarrhythmic class AI drugs (quinidine-like agents), tricyclic antidepressants, phenothiazines and erythromycin; organophosphate poisoning . After ruling out other factors, we concluded that it was caused by hypomagnesemia on the basis of laboratory findings and the good response to replacement therapy . We then discuss the several types of therapy proposed for this arrhythmia; finally, we emphasize the major role of magnesium in myocardial repolarization. Pharmacol Toxicol, 1990 Jan, 66(1), 49 - 52 Cyclosporin metabolism in human liver microsomes and its inhibition by other drugs; Henricsson S et al.; The metabolism of cyclosporin was studied in human liver microsomes . There was no metabolism in the presence of cytochrome C or carbon monoxide or in the absence of cofactors, suggesting metabolism by cytochrome P-450 enzymes . The metabolism was inhibited by ketoconazole and erythromycin, by the steroids methylprednisolone and oestradiol, and by the calcium antagonists diltiazem, nifedipine, prenylamine and verapamil . These in vitro findings correlate well with previously published clinical reports suggesting that these drugs may inhibit the metabolism of cyclosporin in vivo . Our observations suggest that metabolic interactions between cyclosporin and other drugs in vivo may be predicted in vitro under proper experimental conditions. J Clin Pharmacol, 1990 Jan, 30(1), 39 - 44 Effect of concurrent sucralfate administration on the absorption of erythromycin; Miller LG et al.; To determine the influence of sucralfate on the absorption of erythromycin, prior to evaluating its efficacy in decreasing erythromycin-associated gastrointestinal (GI) intolerance, we assessed pharmacokinetic parameters in six healthy adult volunteers . Erythromycin ethylsuccinate administered alone or with sucralfate as a single dose was compared . Sucralfate did not significantly alter the elimination rate constant, half-life, or area under the curve for erythromycin ethylsuccinate . It is therefore unlikely that efficacy of erythromycin ethylsuccinate will be altered when sucralfate is coadministered. Arch Intern Med, 1990 Jan, 150(1), 215 - 6 Fulminant hepatic failure associated with intravenous erythromycin lactobionate; Gholson CF et al.; Fatal fulminant hepatic failure accompanied by brisk hemolysis developed in an elderly man after intravenous administration of erythromycin lactobionate for a lower respiratory infection . To our knowledge, this is the first case of fatal hepatotoxicity associated with intravenous erythromycin therapy . Erythromycin should be added to the list of drugs that can cause fulminant hepatic failure. Mikrobiyol Bul, 1990 Jan, 24(1), 41 - 7 {Prevention of wound infection in elective colon surgery by the use of systemic ceftriaxone and ornidazole}; Alhan E et al.; In this study prophylactic effects of ceftriaxone and ornidazole on the patients undergoing elective colon surgery was studied in the surgical clinics, Medical Faculty of Karadeniz Technical University . Colon cleaning with Nichol's method was performed in all cases . But kanamycin and metronidazole were given instead of erythromycin and metronidazole . One hour before the operation ceftriaxone 1 gr . and ornidazole 500 mg . (IV, IM) were administered . Those antibiotics were followed by ceftriaxone 2 gr . daily and ornidazole 1 gr . daily (IV, IM) three days after operation . The wound infection were observed in the postoperative period (5%) . The average hospitalization time of the cases were 12 days . This period was 18 days and 21 days in the cases having infection . Side effects related the drugs were not observed and there were no significant laboratory changes. Food Addit Contam, 1990, 7 Suppl 1, S127 - 30 Cytoprotective effects of Gypsophila saponins towards isolated rat hepatocytes; Braut-Boucher F et al.; Saponins are glycosides widely distributed in the plant kingdom and are found in many foods . The hepatoprotective potential of glucuronogypsogenin (GG) and gypsoside (GY) towards isolated rat hepatocytes treated by three toxic models used at sub-lethal doses: galactosamine (5 x 10(-3) M), CCl4 (5 x 10(-4) M) and erythromycin (5 x 10(-4) M) was investigated . Two schedules were carried out corresponding to curative or preventive treatment . No protection was observed on hepatocytes treated with GY before or after addition of the toxicants . In contrast, a protective action was detected when hepatocytes were pretreated with GG (5 x 10(-5) M) as probe, by the normalisation of LDH leakage and ATP content . It depends on the toxicant: the cytoprotective spectrum is 5 x 10(-5) to 5 x 10(-7) M with galactosamine; 5 x 10(-5) to 5 x 10(-6) M with CCl4; and around 5 x 10(-5) M with erythromycin . Taking into account the importance of LDH as an indicator of membrane damages, GG was assumed to interact with membrane hepatocyte. Eur J Clin Pharmacol, 1990, 39(2), 161 - 4 Effect of age on single- and multiple-dose pharmacokinetics of erythromycin; Miglioli PA et al.; The effect of age on the pharmacokinetics of erythromycin was investigated by comparing its kinetic behaviour in eight young healthy adults and eight healthy elderly subjects after single and repeated oral doses of erythromycin stearate 1 g b.d . for 7 doses . The peak serum concentration and area under the serum concentration-time curve (AUC) were significantly greater in the elderly subjects than in the young controls after single and multiple doses . Accordingly, the apparent oral clearance was lower in the elderly subjects (0.31 vs 0.64 and 0.22 vs 0.69 l.h-1.kg-1 after the first and seventh administration, respectively) . The mean elimination half-life was significantly longer in the elderly group only after multiple dosing (4.8 vs 2.3 h) . No age-related difference was observed in the time to peak serum concentration and apparent volume of distribution . The multiple-dose regimen resulted in an almost two-fold accumulation of erythromycin in the older individuals and no accumulation in the young adults . Mean drug accumulation in elderly subjects at steady state was 43% greater than was predicted from the AUC after the first dose, suggesting a time-dependent reduction in both systemic and presystemic clearance . The results indicate that the metabolic elimination processes for erythromycin are impaired in normal elderly subjects and suggest that caution is required on administering a high dose of it to aged people. Padiatr Grenzgeb, 1990, 29(4), 291 - 4 {Chlamydia-induced pneumonia in children}; Drak D et al.; Three cases of pneumonia caused by Chlamydia were observed . The disease ran a protracted course and was refractory to treatment . Erythromycin was given initially intravenously and then orally, with improvement of the general condition of children and regression of inflammatory changes in the lungs . Such cases are worth of reporting in view of only isolated reports on respiratory infections caused by these organisms. J Antimicrob Chemother, 1990 Jan, 25 Suppl A, 91 - 9 Efficacy of azithromycin for therapy of active syphilis in the rabbit model; Lukehart SA et al.; Azithromycin was shown to be as effective as standard benzathine penicillin and erythromycin in the therapy of active syphilis in the rabbit model . Following production of primary chancres by intradermal inoculation of 10(6) Treponema pallidum, groups of six rabbits were treated with benzathine penicillin (200,000 units im weekly for two weeks), erythromycin base (30 mg/kg/day orally four times daily for 15 days) or azithromycin (30 mg/kg/day given orally once or twice daily for 15 days); one group was untreated . Daily darkfield (DF) microscopic examinations of chancre aspirates were conducted to identify motile organisms . Although all treated animals became DF negative prior to completion of therapy, the median time to DF negativity was longer in animals given azithromycin once daily, compared with animals receiving benzathine penicillin (P less than 0.01); no difference was seen in comparison with animals receiving erythromycin . Untreated animals remained DF positive for greater than 15 days . The mean maximum lesion diameters for all treated animals were similar and were significantly smaller than in untreated rabbits; fewer lesions ulcerated in treated than in untreated animals . Subsequent dose-ranging studies indicated that administration of lower doses of azithromycin (15 mg/kg/day given orally either once or twice daily, or 7.5 mg/kg/day given once daily) was as effective as benzathine penicillin for therapy of active syphilis in this model, though the median time to darkfield negativity was significantly longer in the azithromycin-treated animals (P less than 0.01) . Persistent infection was demonstrable in lymph nodes of untreated animals, but no evidence of virulent T . pallidum was found three months following transfer of tissue from any animal treated with penicillin, erythromycin, or azithromycin. J Antimicrob Chemother, 1990 Jan, 25 Suppl A, 123 - 6 Comparison of azithromycin and erythromycin in the treatment of atypical pneumonias; Schonwald S et al.; An open, randomized, multicentre study compared the efficacy and safety of the prototype, azalide, azithromycin, and erythromycin in the treatment of atypical pneumonias . Azithromycin was administered for five days at a dosage of 250 mg bd on day 1 and 250 mg once daily on days 2 to 5 . Erythromycin was given for ten days at 500 mg qid . Causative pathogens were identified by serological methods . Of 57 patients treated with azithromycin, Mycoplasma pneumoniae and Chlamydia psittaci were identified in 31 and eight patients, respectively . Of 44 patients treated with erythromycin, M . pneumoniae and C . psittaci were identified in 24 and eight patients, respectively . There were no therapeutic failures in either treatment group . Side effects were observed in one of 57 patients on azithromycin and in six of 44 patients on erythromycin . Azithromycin appears to be as effective as erythromycin in the treatment of atypical pneumonias and better tolerated. J Antimicrob Chemother, 1990 Jan, 25 Suppl A, 101 - 8 Efficacy of azithromycin in the treatment of guinea pigs infected with Legionella pneumophila by aerosol; Fitzgeorge RB et al.; Azithromycin and erythromycin were compared for efficacy in guinea pigs infected with an aerosol containing Legionella pneumophila . When administered intraperitoneally, azithromycin was very effective in the treatment of experimental Legionnaires' disease . Even at the low dose of 3.6 mg/kg/day it gave 100% survival and eliminated lung infectivity two days following infection . In contrast, erythromycin at a much higher dose (96 mg/kg/day) gave only 83.3% survival and failed to eliminate organisms from the lung six days after infection . The histological findings confirmed the superiority of azithromycin . A single dose of azithromycin given intraperitoneally at 3.6 or 14.4 mg/kg gave survival rates of 83.3 and 100%, respectively . Azithromycin was also found to be superior to erythromycin in eliminating lung infectivity and reducing mortality, when administered orally . However, oral administration of azithromycin was not as effective as intraperitoneal when assessed by lung histopathology, although it was still superior to oral erythromycin treatment. Przegl Dermatol, 1990 Jan-Feb, 77(1), 56 - 60 {Akne-Mycyna in the local treatment of acne}; Rubisz-Brzezinska J et al.; Akne-Mycyna, a new preparation for external treatment of acne containing 1% erythromycin, was used in 30 cases of acne: 12 cases of papulo-pustolous acne, 13 with pustulous acne, 5 with acne conglobata . The age of the patients ranged from 16 to 27 years, the mean duration of acne was 3.5 years . Selected lesions were smeared with Akne-Mycyna twice daily, mostly on one side of the face; symmetrical lesions were treated by conventional external methods . In the light of the study it is concluded that Akne-Mycyna is a very effective preparation for external treatment of papulo-pustulous acne and in milder cases of pustulous acne, with the duration of treatment at least 3 weeks . In deep forms of acne, particularly acne conglobata, Akne-Mycyna may be a valuable supplementation of systemic treatment. Rev Elev Med Vet Pays Trop, 1990, 43(4), 453 - 5 {In vitro antibiosensitivity of different strains of Mycoplasma capricolum}; Benkirane A et al.; The in vitro sensitivity of 20 wild strains of M . capricolum and that of the reference strain (California kid) against 14 antibiotics was investigated by means of a micromethod . The technique is based on the determination of the inhibitory minimum concentration (IMC) in a liquid medium as revealed by the inhibition of glucose metabolism . The following results were obtained: all strains were sensitive to five antibiotics (tylosin, oxytetracyclin, gentamycin, neomycin, nalidixic acid) with an IMC varying from 0.06 to 8 meq/ml . The variation in the IMC values from 8 to 32 meq/ml for spiramycin and erythromycin indicated that some of these strains were sensitive and other resistant to these two drugs . All strains were resistant to seven antibiotics (streptomycin, bacitracin, polymyxin, chloramphenicol, lincomycine, rifampicine and novobiocine), sometimes at a concentration exceeding 128 meg/ml. Boll Ist Sieroter Milan, 1990, 69(1), 319 - 31 {Validity limits of data on secretory IgA}; Rosaschino F et al.; Secretory IgA (sIgA) in saliva, and sometimes in expectoration, have been titrated in various groups of persons, both in pediatric age and in adults, by means of radial immunodiffusion technic . The aim was to find differences among sIgA levels in the course of respiratory tract infections, both acute and chronic, in consequence of treatment with Erythromycin (in children and in adults) in consequence of surgical intervention (in adults) . Adjunctive aim was to establish if it was possible to recognize hereditary of the character that remark the predisposition to produce high sIgA quantities . The very high variability of the data collected in the various occasions and situations allowed serious doubts about the possibility of use of the parameter sIgA in saliva for the evaluations that were assumed as aim of the research . The said high variability was confirmed in a single surely healthy boy, in which sIgA were performed on saliva specimens collected for ten consecutive days, morning and evening, always at the same time (8 a.m . and p.m.) . In the attempt to clarify the reason of such a variability, the intervention of psychical solicitation and emotional conditions were ipotized to modify production, mobilization and secretion of IgA generally considered and sIgA particularly. Ann N Y Acad Sci, 1990, 590, 168 - 86 Interferon-alpha/beta and Rickettsia prowazekii: induction and sensitivity; Turco J et al.; Rickettsia prowazekii Madrid E established persistent infections in cultures of growing L-929 cells . Although some L-929 cells died, the cultures survived, remained infected with rickettsiae, and continued to grow . R . prowazekii Madrid E also induced interferon in L-929 cell cultures, and this interferon modulated rickettsial growth . Production of interferon (anti-viral activity) by cultures of R . prowazekii-infected L-929 cells was directly related to the initial rickettsial infection and was blocked by erythromycin . The media collected from R . prowazekii-infected L-929 cells suppressed not only the replication of vesicular stomatitis virus but also the growth of R . prowazekii in fresh L-929 cells . Both anti-viral and anti-ricketts