In Vitro, 1984 May, 20(5), 447 - 50 Selective elimination of fibroblasts from cultures of normal human melanocytes; Halaban R et al.; The main obstacle to establishing pure normal human melanocytes in vitro is contamination of the cultures by fibroblasts . The obstacle can be overcome by selective destruction of fibroblasts with geneticin ( G418 sulfate) . Treatment of mixed cultures with this drug at a concentration of 100 micrograms/ml for two days results in pure cultures of normal human melanocytes. Chem Biol Interact, 1984 May, 49(3), 311 - 28 DNA damage in HeLa s3 cells by an antitumor drug Ledakrin and other antitumor 1-nitro-9-aminoacridines; Woynarowski JM et al.; Ledakrin and seven other antitumor and cytotoxic derivatives of 1-nitro-9-aminoacridine were shown to induce DNA-single strand breaks in HeLa S3 cells as found by alkaline sucrose gradient centrifugation . The induced DNA damage is of non-random character . Some of Ledakrin -induced DNA breaks are probably generated by endonucleolytic cleavage in the course of repair processes as indicated by experiments with Novobiocin, an antibiotic preventing the incision step of DNA repair . Other Ledakrin -induced DNA breaks observed on alkaline sucrose gradients may arise from alkali-labile sites in DNA . Most of such sites seem to be converted to breaks after brief exposure to alkali . The extent of DNA damage by 1-nitro-9-aminoacridines was found to be correlated with cytotoxic activities of these compounds against HeLa S3 cells . Furthermore, Ledakrin and other derivatives seem to induce DNA-repair synthesis in HeLa S3 cells as judged by the stimulation of hydroxyurea (HU)-resistant incorporation of {3H} thymidine into DNA . The agents studied differ in their concentrations required to produce a considerable stimulation of DNA repair, whereas the maximal level of this effect is similar for all the derivatives assayed . The former values are correlated with cytotoxic activities of these compounds and seem to reflect the overall extent of DNA damage by 1-nitro-9-aminoacridines . Stimulation of DNA-repair synthesis is gradually shut off during prolonged incubation of the cells with Ledakrin or during postincubation of the cells in a drug-free medium . Such postincubation results also in the gradual accumulation of DNA-single strand breaks as observed by alkaline sucrose centrifugation . Hence, HeLa S3 cells are incapable of efficiently removing DNA damage by 1-nitro-9-aminoacridines, though the drug's action activates temporarily some repair mechanisms . The reported results suggest that overall DNA damage may contribute to the cytotoxic effects of 1-nitro-9-aminoacridines besides previously found ability of these agents to form interstrand DNA cross-links. Am J Gastroenterol, 1984 May, 79(5), 379 - 81 Pelvic-femoral osteomyelitis complicating Crohn's disease; Simpson MB Jr; Osteomyelitis of the pelvic bones arises in Crohn's disease when enteric fistulas from the ileocolonic region allow extention of the anaerobic intestinal flora to the psoas region of the right hemipelvis . Bone destruction is usually an unexpected finding during roentgenographic evaluation of abdominal symptoms in young men with severe ileocecal disease . Suppressive therapy and previous abdominal surgery do not appear to be significant predisposing factors . Therapy requires de-bridement, resection/saucerization, drainage, and appropriate antibiotic coverage. Urology, 1984 May, 23(5 Spec No), 93 - 7 Surgical treatment of impotence with Small-Carrion prosthesis . Preoperative, intraoperative, and postoperative considerations; Small MP; Since 1974, 900 patients with erectile dysfunction from various causes underwent implantation of a semi-flexible prosthesis, generally of the Small-Carrion type . The largest group had arteriosclerotic or hypertensive cardiovascular disease . The second largest group was composed of patients with diabetes mellitus . Those in the third group had undergone prostatectomy, cystectomy, or abdominal-perineal resection . For a large number of patients a diagnosis of psychogenic impotence was reached, mainly from the results of the history questionnaire and the Minnesota Multiphasic Personality Inventory . Complications were rare (8.1%) . Preoperative, intraoperative, and postoperative considerations include correct selection of prosthesis, rigorous antibiotic coverage, prevention or care of perforation, and possible need for reoperation . The results were almost uniformly successful . Psychogenic cases and instances of infertility related to the impotence are reviewed. J Allergy Clin Immunol, 1984 May, 73(5 Pt 2), 712 - 6 Sinusitis; Slavin RG; Sporting events may predispose the athlete to develop sinusitis . Similarly, sinusitis may adversely affect the athlete's performance . The physician caring for the athlete must be aware of a number of conditions that predispose to sinusitis and also of the subtle clinical presentation of sinusitis . Complications of sinusitis may be both local in terms of extension of infection and general, particularly bronchial asthma . Aggressive therapy with an appropriate antibiotic is necessary to ensure eradication of the infection . If there is no significant response to medical therapy, surgical intervention may be necessary. J Dermatol Surg Oncol, 1984 May, 10(5), 384 - 8 Vapor-permeable membrane therapy for ulcers of osteomyelitis; Angermeier MC et al.; Two patients with chronic ulcerations secondary to arterial insufficiency of the distal extremities were found to have concomitant osteomyelitis immediately beneath the ulcers . An adjunctive would care regimen is described in which local excision or debridement of the involved bone with subsequent systemic antibiotic therapy was the initial treatment . The resultant cutaneous defect was then covered with a vapor-permeable membrane and allowed to close by secondary intention . Rapid and complete healing occurred in both cases in spite of the compromised arterial supply to both areas . This technique is a useful adjunct to the treatment of ulcerations associated with chronic osteomyelitis. Cancer Res, 1984 May, 44(5), 1791 - 5 Imidazole-resistant phenotype and virus transformation in cultured rat cells; Ikezaki K et al.; Compared to an untransformed rat cell line, 3Y1, adenovirus 12-transformed cell lines of 3Y1 were highly sensitive to the cytotoxic action of an imidazole antibiotic, clotrimazole . In contrast, SV40-transformed rat cell lines derived from the 3Y1 cell line showed no appreciable difference in the response to clotrimazole when compared to 3Y1 cells . Clotrimazole-resistant clones, WCT-1 and WCT-2, which were spontaneously isolated from the adenovirus 12-transformed cell line W5, showed 5- to 10-fold higher resistance than did W5; the dose-response curves of clotrimazole-resistant clones were similar to those of the untransformed 3Y1 cells . The growth of 3Y1 cells was blocked in the presence of 1% serum, whereas those of W5, WCT-1, and WCT-2 cells were only slightly affected by the same dose of serum in the medium . The membrane fractions of 3Y1, W5, and WCT-1 cells were found to contain similar cholesterol:phospholipid ratios . The phospholipid composition in the membrane fraction of line WCT-1 was similar to that of line W5 but not to that of line 3Y1 . By contrast, the fatty acid composition was specifically altered in clotrimazole-resistant clones; cellular contents and some species of fatty acid such as 16:1, 18:2, and 20:4 in WCT-1 and WCT-2 cells were similar to those of 3Y1 but not to those of W5 cells . Differential sensitivities of various cell lines to clotrimazole are discussed in relation to the lipid composition. Arch Otolaryngol, 1984 May, 110(5), 337 - 8 Recurrent retropharyngeal abscess; Owens OT et al.; An infant had a case of recurrent retropharyngeal abscess . This clinical entity usually follows an upper respiratory tract infection with involvement of the retropharyngeal lymph nodes . Management includes incision and drainage as the patient's clinical status dictates and may require long-term intravenous antibiotic therapy . A biopsy of the abscess wall, assessment of the patient's immunocompetence, and a search for contributory anatomic defects may be useful . A computed tomographic scan is a valuable technique for diagnosis and follow-up. Arch Intern Med, 1984 May, 144(5), 945 - 8 Community-acquired bacteremic pneumococcal pneumonia . Effect of age on manifestations and outcome; Esposito AL; The cases of 38 hospitalized adults with community-acquired bacteremic pneumococcal pneumonia were evaluated prospectively to identify age-related differences in presenting features, clinical course, and outcome . Ten of 18 elderly patients (older than 65 years) were admitted from chronic care institutions v one of 20 younger adults . Coronary artery disease was more prevalent among the aged patients, and alcohol abuse and cigarette smoking were more common among the younger patients . All of the elderly persons and 90% of the younger had at least one serious underlying disorder . Older patients tended to report rigors and pleuritic chest pain less frequently than did the younger . Azotemia and roentgenographic evidence of multiple-lobe involvement were found more commonly in elderly persons . However, age-associated discrepancies were not observed in the duration of symptoms before admission, the prevalence of respiratory failure or metastatic infection, the interval between presentation and antibiotic administration, the duration of fever, the length of hospitalization, or the case fatality rates . Thus, the effects of advanced age on the manifestations and clinical course of community-acquired bacteremic pneumococcal pneumonia appear less pronounced than has been reported previously. Ann Intern Med, 1984 May, 100(5), 696 - 8 Doxycycline therapy for leptospirosis; McClain JB et al.; To study antibiotic efficacy, 29 patients with leptospirosis were treated in a randomized, double-blinded fashion with doxycycline, 100 mg orally twice a day, or placebo . Therapy was given for 7 days in a hospital, and patients were followed for 3 weeks afterwards . Duration of illness before therapy and severity of illness were the same in both groups . Doxycycline reduced the duration of illness by 2 days and favorably affected fever, malaise, headache, and myalgias . Treatment prevented leptospiruria and had no adverse effects . Doxycycline is effective in therapy for patients with leptospirosis. Clin Orthop, 1984 May, (185), 207 - 13 The role of arthroscopy in the management of low-velocity gunshot wounds of the knee joint; Parisien JS et al.; Eight patients with low-velocity civilian gunshot wounds of the knee were examined and evaluated by arthroscopy . Three of these patients were also treated by surgical arthroscopy and underwent limited arthrotomy for bullet removal . In two patients small arthrotomy incisions were made following arthroscopic exploration for removal of bullets . Two patients underwent diagnostic arthroscopy . One underwent internal fixation for a chondral fracture of the femoral condyle . The majority of patients sustained intra-articular damage and retained foreign materials (denim flecks and metallic shards) and osteochondral fragments . There were no postoperative infections after a minimum follow-up period of one year . Arthroscopy is highly effective in the diagnosis and surgical management of low-velocity gunshot wounds of the knee both alone and in combination with limited arthrotomy depending on the severity of the condylar damage . The length of the hospital stay is reduced (length of stay exceeded 3-4 days only as a result of intravenous antibiotic coverage) . Physical therapy requirements are minimal . Active mobility and a full range of motion are regained more rapidly with arthroscopy than with surgical exposure of multiple exploratory incisions or conventional standard arthrotomy. J Am Dent Assoc, 1984 May, 108(5), 851 - 2 Draining fistulas associated with an endodontically treated tooth; Craig RM et al.; A case of periapical actinomycosis is presented . Although apparently uncommon, actinomycosis should be considered when a chronic periapical lesion, often in the maxilla, is associated with an endodontically treated tooth or a previous history of trauma . Histologic examination of the tissue or the presence of "sulfur granules" in the exudate will usually establish the diagnosis . Treatment consists of local curettage and antibiotic therapy. J Antibiot (Tokyo), 1984 May, 37(5), 602 - 9 Isolation, drug sensitivity, and some biochemical and genetical properties of macromomycin-resistant mouse lymphoblastoma L5178Y cells; Suzuki H et al.; A macromomycin (MCR)-resistant subline of mouse lymphoblastoma L5178Y cells was isolated after successive treatment of tumor-bearing mice with the antibiotic for 7 transplant generations, followed by cloning in culture in MCR-containing soft agar medium . The resistant cell line was about 17 times more resistant to MCR than was the parental cell line and exhibited cross-resistance to neocarzinostatin, mitomycin C and adriamycin in a similar degree to MCR . No significant cross-resistance was observed with aclarubicin, bleomycin and neothramycin . Alkaline phosphodiesterase activity in the plasma membrane of resistant cells was higher than that of parental cells . Uptake and efflux studies with {3H}adriamycin suggested that the resistance is due to decreased uptake and increased efflux of the antibiotic in resistant cells . Hybridization studies with MCR-sensitive and -resistant cells showed that the MCR resistance is a codominant trait in somatic cell hybrids. Pathol Biol (Paris), 1984 May, 32(5), 443 - 5 {Action of pristinamycin on Chlamydia}; Orfila J et al.; In vitro study on C . psittaci and C . trachomatis demonstrates that pristinamycin is active in a very small dose . With 5 g/l, inclusions are rare . To study pristinamycin activity in vivo, we used mice infected IP with C . psittaci . Mortality in the control group was 70% . Three groups of mice received 25 mg/kg, 50 mg/kg and 100 mg/kg pristinamycin respectively . The antibiotic was active in the 100 mg/kg dosage which is the therapeutic dosage . Due to its action on Gonococcus, it would be of interest to study pristinamycin in patients with sexually transmitted disease. Clin Pharm, 1984 May-Jun, 3(3), 264 - 72 Drug therapy and nutritional management of patients with gastrointestinal fistulas; Dombrowski SR et al.; The drug therapy and nutritional management of patients with gastrointestinal fistulas are reviewed . The goal of therapy is to compensate for loss of electrolytes, nutrients, and water in the fistula drainage and to monitor the acid-base status of the patient . Positive nitrogen balance is essential for anabolism and closure of the fistula . Usually it is not feasible to analyze the fistula drainage for nitrogen content, and nitrogen requirements must be estimated . To prevent folic acid deficiencies, patients should receive daily doses of folic acid 1 mg orally or 0.5 mg in parenteral nutrient solutions . Positive zinc balance usually can be established with the addition to parenteral nutrient solutions of zinc 3-12 mg/day . It is not clear whether the parenteral or enteral route of nutrient administration is preferable . Drug therapy may be needed to treat diarrhea, infection, and any underlying disease . Reductions in the acidity and the volume of fluid lost may allow spontaneous closure and healing; antacids and anticholinergic drugs are not recommended for these purposes . The use of cimetidine has been effective in decreasing the acid content and volume of output from fistulas in the upper gastrointestinal tract and has allowed spontaneous healing to occur . Drainage of any intra-abdominal abscesses is essential; this should be combined with systemic antibiotic therapy . The management of patients with gastrointestinal fistulas is complex because of disturbances in fluid, electrolyte, and acid-base balance and because of difficulties in determining nutritional requirements. Infect Control, 1984 May, 5(5), 226 - 30 Assessment of catheter-associated infection risk with the Hickman right atrial catheter; Fuchs PC et al.; One hundred fifty Hickman right atrial catheters were inserted into 143 patients and were followed prospectively until removal . Primary indications for their use were: cancer chemotherapy (45), parenteral nutrition (35), antibiotic therapy (63), and miscellaneous (7) . The overall catheter-associated infection rate was 12.0% . Since the mean duration of catheterization was 125 days, the infection/duration rate was 1.0/1,000 days of use . The risk of infection differed significantly according to the primary indication for catheterization: parenteral nutrition greater than antibiotic therapy greater than cancer chemotherapy . The increased risk of catheter-associated infection attributable to duration of catheterization was additive, and the per day risk of such infections remained constant regardless of duration . Nearly two-thirds of patients were discharged home with catheters in place, without adversely affecting infection risk. Antibiotiki, 1984 May, 29(5), 332 - 6 {Various aspects of regulation of the biosynthesis of novobiocin and exoproteases in cultures of Streptomyces spheroides 35}; Egorov NS et al.; Streptomyces spheroides 35, a novobiocin-producing organism, was used in the study . In addition to the antibiotic the culture produces proteases capable of splitting fibrin . Depending on the medium composition and component ratio different amounts of novobiocin and proteases were formed . To show various aspects of the biological interaction of the synthesis of proteolytic enzymes and novobiocin, the studies were performed with chloramphenicol . It was found that the main quantity of free amino acids accumulated in the culture liquid phase, while in the mycelial phase only traces of the amino acids were detected . The regularities of the free amino acid accumulation in the media with novobiocin and chloramphenicol were identical as compared to the control . The excess of novobiocin during the second phase of the culture development was shown to influence the synthesis of nucleic acids, whereas inhibition of protein synthesis was secondary. Behring Inst Mitt, 1984 May, (74), 239 - 49 Immunosuppression by cytostatic drugs? Ulrichs K, Yu MY, Duncker D, Muller-Ruchholtz W. In the present study, an attempt was made to characterize the immunomodulating abilities of the cytostatic drugs cyclophosphamide, ifosfamide, vinblastine, vincristine, procarbazine, dacarbazine, 6-mercaptopurine, methotrexate, 5-fluorouracil and adriamycin in a defined experimental model . Varying combinations of drug plus transplantation alloantigen, (C3H-lymphocytes) were injected into Balb/c mice at different time intervals in vivo . The resulting T-effector cell reactivity was determined in vitro with the microcytotoxicity assay on day +5 for primary (1 degree) and day +7 for secondary (2 degrees) sensitized mice . According to the type of drug (alkylating agent vs . vinca alkaloid vs . antimetabolite vs . cytostatic antibiotic), the dosage (20% LD50 vs . 60% LD50), the state of sensitization (1 degree vs . 2 degrees sensitized recipients), and the time of drug application in relation to the antigen treatment on day 0 (in varying steps from day -6 to day +4), so-called "pharmacon-antigen-variation-effects" (PAVE) were established for each of the investigated drugs in form of reaction profiles . The results were as follows: For almost all substances, characteristic reaction profiles involving immunostimulation and/or immunosuppression could be established . Similarities in the profiles of different substances made it possible to classify the drugs according to different reaction types . The reaction type however is not definitely correlated to the biochemical mechanism of drug action . The PAVE are decisively influenced by some of the biological parameters, such as the time of drug application in relation to the antigen treatment and the state of sensitization but relatively little by the dosage of the drug . Considering the different processes occurring during primary and secondary immune responses, the PAVE may give hints for a distinct manipulation of the immunoregulation and thus information on the immunobiological mechanism of drug action. Antibiotiki, 1984 May, 29(5), 344 - 9 {Virus-inhibiting properties of the carbonyl-conjugated pentaene roseofungin}; Shneider MA et al.; The antiinfluenza activity of roseofungin, a polyenic macrolide antibiotic was studied in vitro on surviving fragments of the chick embryo chorionallantoic membranes and in ovo on growing chick embryos . It was shown that the antibiotic activity against influenza A and B viruses was sufficiently high . The activity of roseofungin against influenza A virus did not differ from that of remantadin, the most active inhibitor of influenza virus reproduction . However, the activity of roseofungin against influenza B virus was an advantage of this antibiotic over remantadin, which had practically no effect on this virus type . A statistically significant protective effect of roseofungin (p less than 0.05) was shown on the animals with experimental influenza . The study on the antiviral activity of roseofungin against the DNA-containing variolovaccine virus revealed that it markedly inhibited the plague reduction . Roseofungin had a pronounced inhibitory effect on cell neoplastic transformation induced by the RNA-containing oncogenic virus of Rous sarcoma. J Antimicrob Chemother, 1984 May, 13(5), 479 - 85 The pharmacokinetics of ceftriaxone in serum, skin blister and thread fluid; Kalager T et al.; Following 4 g of ceftriaxone, given intravenously, to eight volunteers, the antibiotic concentration in serum, suction skin blister fluid and fluid from subcutaneously implanted threads was followed for 28 h . High and sustained levels were found in both serum and extravascular fluids; the mean maximum serum concentration was 448 mg/l, and the mean peak concentrations in blister and thread fluid were 94 mg/l and 63 mg/l, respectively . The terminal, half-lives were: serum 7.2 h, blister fluid 10.3 h and thread fluid 11.3 h . The total area under the concentration versus time curves for serum was 1636 mg X h/l . For blister and thread fluid the areas were 1573 mg X h/l and 808 mg X h/l . The results suggest a twice daily dosage regimen. Behring Inst Mitt, 1984 May, (74), 250 - 7 Immunosuppression as a desired pharmacological effect; Dickneite G et al.; The immunosuppressive efficacy of the antineoplastic antibiotic Aclacinomycin A (ACM) was assayed in several test models for humoral and cellular immune response . Humoral immune response, measured as splenic plaque forming cells (PFC) in vitro and in vivo was markedly inhibited by ACM . Suppression of PFC in vivo could be observed when ACM was administered together with the antigen, or three days later . Concomitantly a decrease of circulating antibodies to SRBC was obtained . No effect on T-cell mediated immune response - DTH reaction and allogeneic cytotoxic lymphocytes - or on skin transplantation or a T-cell mediated autoimmune disease, EAE, was observed . ACM beneficially influenced the course of the disease in two GvH-models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B-cell mediated autoimmune disease with fatal outcome . It was concluded that the therapeutic effect of ACM on GvH-disease is mediated via its suppression of the B-cell response. J Cell Biol, 1984 May, 98(5), 1720 - 9 Glucose removal from N-linked oligosaccharides is required for efficient maturation of certain secretory glycoproteins from the rough endoplasmic reticulum to the Golgi complex; Lodish HF et al.; 1- Deoxynojirimycin is a specific inhibitor of glucosidases I and II, the first enzymes that process N-linked oligosaccharides after their transfer to polypeptides in the rough endoplasmic reticulum . In a pulse-chase experiment, 1- deoxynojirimycin greatly reduced the rate of secretion of alpha 1-antitrypsin and alpha 1-antichymotrypsin by human hepatoma HepG2 cells, but had marginal effects on secretion of the glycoproteins C3 and transferrin, or of albumin . As judged by equilibrium gradient centrifugation, 1- deoxynojirimycin caused alpha 1-antitrypsin and alpha 1-antichymotrypsin to accumulate in the rough endoplasmic reticulum . The oligosaccharides on cell-associated alpha 1-antitrypsin and alpha 1-antichymotrypsin synthesized in the presence of 1- deoxynojirimycin , remained sensitive to Endoglycosidase H and most likely had the structure Glu1- 3Man9GlcNAc2 . Tunicamycin, an antibiotic that inhibits addition of N-linked oligosaccharide units to glycoproteins, had a similar differential effect on secretion of these proteins . Swainsonine , an inhibitor of the Golgi enzyme alpha-mannosidase II, had no effect on the rates of protein secretion, although the proteins were in this case secreted with an abnormal N-linked, partially complex, oligosaccharide . We conclude that the movement of alpha 1-antitrypsin and alpha 1-antichymotrypsin from the rough endoplasmic reticulum to the Golgi requires that the N-linked oligosaccharides be processed to at least the Man9GlcNAc2 form; possibly this oligosaccharide forms part of the recognition site of a transport receptor for certain secretory proteins. Antibiotiki, 1984 May, 29(5), 353 - 7 {Acidity and solubility of gramicidin S in water}; Fomicheva GK et al.; The acid-base transformations of the gramicidin S molecule in water were studied . The protonization constants of the antibiotic amino group were calculated by the data of the potentiometric titration and the antibiotic distribution in the system of chloroform-water: K1 1.55 X 10(10), K2 1.38 X 10(6), the logarithm of the distribution coefficient of gramicidin S in the system of chloroform-water (1:1) lg alpha G 4.10 . By the same data the constants of water solubility of gramicidin S base (1.02 X 10(7) mol/l), gramicidin S monohydrate (1.06 X 10(-4) mol/l) and gramicidin S dihydrochloride (2.08 X 10(-4) mol/l) were calculated. J Foot Surg, 1984 May-Jun, 23(3), 203 - 6 Gunshot wound to the foot: early management and pathophysiology of projectile wounds; Newman P et al.; The authors present a case study of gunshot wound and discuss the rationale for therapy after hemostasis is established . Treatment consists of debridement of necrotic tissue, immobilization to prevent further movement of the bullet, and immediate antibiotic therapy to prevent bacterial invasion . They emphasize the necessity of understanding the pathomechanics and pathophysiology of ballistic injuries and advocate removal of the bullet, when possible, to relieve discomfort, to prevent anemia and renal failure, and to avoid the danger of lead intoxication. Can J Surg, 1984 May, 27(3), 283 - 5, 288 Subdural empyema: a retrospective study of 15 patients; Khan M et al.; Subdural empyema is a surgical emergency, which, if not recognized and managed promptly, is rapidly fatal . The clinical features, diagnosis, infecting organisms, treatment and results in 15 patients with subdural empyema admitted to the University and Saskatoon City hospitals between 1956 and 1982 are evaluated . There were 11 males and 4 females; 80% were under 50 years of age . Paranasal sinusitis in six patients was the most common cause of the condition . The most frequent presenting features were fever, headache, vomiting, seizures and motor deficit . Preoperative diagnostic methods included skull roentgenography, cerebrospinal fluid studies, electroencephalography, cerebral angiography and computerized tomography . Cultures of the pus were positive for bacteria in 13 of the 15 patients . Drainage of the empyema was accomplished through multiple burr holes, craniotomy and craniectomy . Follow-up ranged from 1 month to 15 years . Eleven patients recovered with minimal or no neurologic deficit, 2 patients had permanent major deficits and 2 died . Successful management of subdural empyema depends on early diagnosis, prompt evacuation of the pus and appropriate antibiotic therapy. Calcif Tissue Int, 1984 May, 36(3), 279 - 84 Adriamycin inhibits PTH-mediated but not PGE2-mediated stimulation of cyclic AMP formation in isolated bone cells; Kohler G et al.; We have examined the effect of adriamycin, an anthracycline antibiotic which modifies plasma membrane functions, on the cyclic AMP response to PTH and PGE2 in isolated osteoblastlike cells . Adriamycin blunted the increment in bone cell cyclic AMP caused by exposure to PTH . This effect appeared rapidly (within 3 min after bone cells were exposed to adriamycin) and disappeared soon after exposure of adriamycin-treated cells to adriamycin-free incubation medium . Inhibition was evident over the entire time course of PTH action, at low as well as high PTH concentrations, and was one-half maximal at 31 microM adriamycin . It could not be attributed to alterations in cyclic AMP exodus, degradation or interference with the cyclic AMP assay, nor to impaired cell viability . Adriamycin also reduced the stimulatory effect of PTH on adenylate cyclase activity in a crude plasma membrane preparation . By contrast, adriamycin failed to modify the effects of PGE2 on cyclic AMP generation in intact bone cells, and on adenylate cyclase activity in broken cells . Moreover, concentrations of adriamycin that blunted the effect of PTH on adenylate cyclase activity did not inhibit the stimulatory effects of sodium fluoride or of GppNHp . These results suggest that adriamycin selectively alters the interaction between PTH and its receptor or impairs the transmission of information from hormone-receptor complex to adenylate cyclase (or both), perhaps by binding to specific lipid domains in the plasma membrane . Structural analogues of adriamycin, which vary in their lipophilic properties, also varied in their capacity to perturb the cyclic AMP response.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Obstet Gynecol, 1984 Apr 15, 148(8), 1088 - 91 Comparative pharmacokinetics of cefoxitin in postpartum normotensive and pregnancy-induced hypertensive patients; Gonik B et al.; Limited pharmacokinetic data exist on cefoxitin, a semisynthetic cephamycin antibiotic, in the obstetric patient . Thirteen normotensive and five subjects with severe pregnancy-induced hypertension were identified within the first two postpartum days after cesarean section . After a 2 gm intravenous infusion, serial samples of blood were obtained and analyzed for cefoxitin by high-pressure liquid chromatography . Peak cefoxitin concentrations after infusion were 53.3 +/- 18.6 and 50.8 +/- 25.2 micrograms/ml for the normotensive and pregnancy-induced hypertensive groups, respectively . The only significant difference in pharmacokinetic parameters between these groups was a higher serum trough concentration of cefoxitin in the patients with pregnancy-induced hypertension as compared to the normotensive group . Because of diminished trough levels in our study patients, attention may need to be given to the adjustment of dosages in postpartum women with serious infections. Cancer, 1984 Apr 15, 53(8), 1777 - 82 Jaw involvement in American Burkitt's Lymphoma; Sariban E et al.; A total of 100 patients with American Burkitt's lymphoma (AMBL) (mean age, 15 years; M:F ratio 3:1; 3% black) have been treated at the National Cancer Institute since 1964 . Eighteen of these had jaw involvement, 16 at presentation and 2 at relapse (mean age, 16 years; M:F ratio 1.6:1) . None of these 18 patients was black . Of the 16 patients presenting initially with jaw tumors, 14 were first evaluated by their dentist; 8 were 16 years of age or older (adults) and 6 were younger than 16 years of age (children) . Toothache and perioral numbness were the most frequent findings in adults, whereas toothache, loose teeth, intra-oral and extra-oral swelling were the most common complaints in children . Ten patients were treated with antibiotic therapy and/or dental extractions for presumed tooth infection . The distribution of jaw lesions was: unilateral mandibular (7), unilateral maxillary (4), bilateral mandibular (5), and four quadrants (2) . Radiologic evaluation was abnormal in all 17 cases evaluated . Only three patients (all children) had disease limited to the jaw . Four of eight children and 3 of 10 adults are long-term survivors with a median follow-up of seven years (range, 2-15 years) . American Burkitt's lymphoma with jaw involvement differs from African Burkitt's lymphoma (AFBL) with jaw involvement in a number of ways: (1) the incidence of jaw tumors in adults is similar to that in children; (2) the incidence of jaw tumors is not greater in males; (3) tumor is considerably more limited in extent with a single quadrant mandibular lesion being the most common presentation; and (4) clinical presentation also differs, with toothache and perioral numbness, uncommon in AFBL, being the most frequent complaints . These marked differences in the frequency and clinical characteristics of jaw tumor of AMBL and AFBL are consistent with other findings indicating that these diseases may differ phenotypically. J Biol Chem, 1984 Apr 10, 259(7), 4353 - 8 Neplanocin A . A potent inhibitor of S-adenosylhomocysteine hydrolase and of vaccinia virus multiplication in mouse L929 cells; Borchardt RT et al.; Neplanocin A, a novel cyclopentenyl analog of adenosine, is a naturally occurring antibiotic which exhibits significant antitumor activity against L1210 leukemia in mice (Yaginuma, S., Muto, N., Tsujino, M., Sudate, Y., Hayashi, M., and Otani, M . (1981) J . Antibiot . 34, 359-366) . In the present study we demonstrate that neplanocin A is also a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) having a Ki of 8.39 nM for the purified bovine liver enzyme . Analysis of the apparent irreversible inactivation of AdoHcy hydrolase by neplanocin A indicates that the drug is a tight binding inhibitor, exhibiting a stoichiometry of one molecule of inhibitor to one molecule (tetramer) of enzyme . In addition, we show that neplanocin A is a potent inhibitor of vaccinia virus (WR) multiplication in monolayer cultures of mouse L-cells . Concentrations of the drug as low as 0.5 and 1.0 microM in the culture medium produce 84 and 95% inhibition of plaque formation, respectively, while exhibiting little toxicity to the host cells . The inhibition of virus multiplication by neplanocin A coincides with a rapid inhibition of AdoHcy hydrolase activity in the infected cells and a subsequent 10-fold increase in the intracellular AdoHcy/S-adenosylmethionine ratio . These findings suggest that the antiviral actions of this compound may be related to an inhibition of S-adenosylmethionine-dependent macromolecular methylation reactions which are essential to the production of new virus particles (e.g . viral messenger RNA). J Biol Chem, 1984 Apr 10, 259(7), 4437 - 40 Structure of cupric bleomycin . Nitrogen and proton couplings from EPR and electron nuclear double resonance spectroscopy; Antholine WE et al.; Low frequency (S-band) EPR and electron nuclear double resonance (ENDOR) data have been used to provide a detailed description of the magnetic environment of the cupric complex of the antitumor antibiotic, bleomycin . S-band EPR spectra show well resolved nitrogen hyperfine structure in both gl and g regions . Computer simulation of these spectra are consistent with binding to four donor nitrogen atoms, three with AN = 10 gauss and one with AN = 15 G . ENDOR data confirm the presence of at least two inequivalent nitrogens with AN approximately 11 and 15 G . In addition, at least six proton couplings were evident in the ENDOR spectrum although these could not be unambiguously assigned . Diminution of the matrix ENDOR signal in D2O relative to that in H2O was found; this demonstrates the accessibility of H2O to the metal site. Behav Brain Res, 1984 Apr, 12(1), 21 - 7 Dual action of cycloheximide on memory formation in day-old chicks; Gibbs ME et al.; Amnesia for a single trial discriminated passive avoidance learning task in day-old chicks, resulting from the antibiotic cycloheximide, is shown to begin after 30 min following learning when cycloheximide is given immediately after or before learning . However, amnesia does not begin until after 50 min following learning when cycloheximide is given 5 min or later after learning . The results are interpreted in the context of a 3 stage model of memory formation . It is suggested that the second or intermediate stage involves two phases: phase A which lasts up to 30 min following learning, is energy dependent, and is susceptible to inhibition by 2,4-dinitrophenol; phase B which occurs after phase A, lasts up to 50 min following learning, is energy independent, and is not susceptible to inhibition by 2,4-dinitrophenol . It is concluded that cycloheximide given immediately after or before learning inhibits expression of phase B of intermediate memory as well as formation of long-term memory, while cycloheximide given 5 min or later after learning only inhibits formation of long-term memory . Another antibiotic, anisomycin, is shown to have no effect on intermediate memory, independent of time of administration. Z Kinderchir, 1984 Apr, 39(2), 102 - 5 A plea for conservative treatment of large, unruptured omphaloceles; Bax NM et al.; Forty-six babies with an unruptured omphalocele were admitted over a 10-year period . The conservative treatment consisted of the application of mercurochrome or an antibiotic powder, while the primary surgical treatment consisted of either full-layer closure or silastic sac insertion . Liver containing omphaloceles were considered large . Of the 25 babies without associated life-threatening congenital anomalies, all 9 with a small omphalocele survived, irrespective of the method of treatment . Sixteen babies had a large omphalocele of which all 8 conservatively treated babies survived against only 4 of the 7 who underwent surgery . The remaining baby, weighting 960 g, died prior to treatment, due to respiratory distress . Eighteen of the 21 babies with associated life-threatening congenital anomalies died, irrespective the extent of the defect . Although the conservative treatment of the large defects did not result in an improved survival rate, therapy-related complications did not occur . From this study it appears that large unruptured omphaloceles should be treated conservatively . Babies not doing well with a small omphalocele or a large one treated conservatively, will have one or more major associated anomalies, necessitating urgent diagnosis and treatment. J Clin Microbiol, 1984 Apr, 19(4), 538 - 40 Septic arthritis involving Capnocytophaga ochracea; Winn RE et al.; Septic arthritis of the knee developed in a 21-month-old child . The causative organism, isolated from two separate arthrocenteses, was identified as Capnocytophaga ochracea morphologically and by biochemical reactions . Previous human infections (bacteremias) have occurred in granulocytopenic hosts with concomitant oral pathology including periodontitis and gingivitis . No abnormalities of oral hygiene were present in this patient, and granulocyte numbers were normal or elevated . Eradication of the infection was accomplished with 8 weeks of antibiotic therapy combined with surgical drainage . Septic arthritis expands the spectrum of infections reported to be caused by Capnocytophaga spp. Am J Med, 1984 Apr, 76(4), 597 - 603 Utility of naproxen in the differential diagnosis of fever of undetermined origin in patients with cancer; Chang JC et al.; The clinical utility of naproxen as an antipyretic agent was examined in the differential diagnosis of fever of undetermined origin in patients with cancer . Twenty-two patients with cancer and fever of undetermined origin for more than seven days were treated with naproxen to control fever when there was no evidence of infection after a careful initial evaluation, and in most cases, after failure of antibiotic therapy . In final analysis, none of five patients with infectious fever had responses to naproxen . In contrast, 14 of 15 patients with neoplastic fever showed a prompt, complete, and sustained lysis of fever within 24 hours after the initiation of naproxen treatment, and the patients also showed symptomatic improvement . One patient with neoplastic fever who did not have a response to naproxen had lysis of fever after the removal of necrotic tumor tissue . Two patients with fever from connective tissue disease had a partial lysis of fever in response to naproxen . These data suggest that naproxen specifically produces the lysis of neoplastic fever and, therefore, is a useful agent in assisting in the differential diagnosis of infectious fever and neoplastic fever in patients with cancer and fever of undetermined origin. Invest Ophthalmol Vis Sci, 1984 Apr, 25(4), 486 - 90 Pharmacokinetics of subconjunctival liposome-encapsulated gentamicin in normal rabbit eyes; Barza M et al.; Subconjunctival injections of antibiotics produce very high corneal levels of drug that fall rapidly as the drug is dissipated . The authors studied the effects of liposome-encapsulation as a means of slowing release from the subconjunctival depot . Liposomes (0.1-1.0 micron) were made of phosphatidic acid, phosphatidylcholine, and alpha-tocopherol . The final suspension contained gentamicin 10 mg/ml with 60-70% encapsulated . Rabbits were given a single subconjunctival injection of liposome-encapsulated gentamicin, gentamicin with "empty" liposomes, or gentamicin alone . In each instance the dose of antibiotic was 5 mg . Gentamicin levels in the sclera and cornea, measured 3,9, and 24 hr after injection, were generally markedly higher with the liposome-encapsulated drug than with the other two preparations . The differences were 5- to 20-fold in the cornea at 24 hr and were statistically significant for temporal cornea . Liposome-encapsulation may be a useful means of extending the effects of a subconjunctival injection of antibiotic. Clin Orthop, 1984 Apr, (184), 193 - 203 Infections simulating bone tumors . A review of subacute osteomyelitis; Lindenbaum S et al.; The problem of differentiating primary bone tumors from subacute osteomyelitis was reviewed in 15 typical cases . Presenting symptoms, duration of illness, admitting laboratory data, and location of the pathologic condition were of little assistance in diagnosis . Preoperative diagnoses included benign and malignant neoplasms as well as osteomyelitis . In all cases the final diagnosis of subacute osteomyelitis was made only after open biopsy . Surgical curettage combined with appropriate antibiotic therapy was deemed essential for adequate treatment of this infectious process . Drug therapy included three to six weeks of parenteral antibiotics followed by three to six weeks of oral antibiotics . The protocol for duration of antibiotic therapy was based on the type of bacteria, the antibiotic serum levels achievable via the oral route, and patient compliance. Cancer Res, 1984 Apr, 44(4), 1712 - 7 Relationship of the growth of leukemic cells in vitro to the outcome of therapy for acute nonlymphocytic leukemia; Preisler HD et al.; Bone marrow cells obtained from 166 patients with acute nonlymphocytic leukemia were cloned in vitro . The number and size of clones produced differed among patients and was unrelated to French-American-British type of leukemia, to patient age, to whether the patient was studied at the time of initial diagnosis or at relapse, or to the cytogenetic (normal or abnormal metaphases) or cell cycle characteristics of the leukemic bone marrow cells . The ability of leukemic cells to clone in vitro was associated with poor response to therapy in vivo, with the remission rate being inversely related to cloning efficiency of the leukemic cells, and with remission durations being inversely correlated with the size of the cluster/colonies formed in vitro . Only an occasional patient whose marrow cells produced clonal growth in vitro and in whom cytogenetic abnormalities were detected entered complete remission with conventional remission induction therapy . Measurement of the clonogenic potential in vitro of leukemic marrow cells together with their cytogenetic type may help to distinguish between patients who should and should not receive cytosine arabinoside/anthracycline antibiotic remission induction therapy and patients who do and do not require intensive remission consolidation chemotherapy. J Antibiot (Tokyo), 1984 Apr, 37(4), 344 - 53 The structure of decilorubicin; Ishii K et al.; The structure of a new anthracycline antibiotic, decilorubicin was determined by a combination of chemical conversion, degradation and spectral interpretation, and the studies of this structure are reported in detail. Cancer, 1984 Apr 1, 53(7), 1456 - 60 High-dose cyclophosphamide . An effective treatment for advanced refractory multiple myeloma; Lenhard RE Jr et al.; The Eastern Cooperative Oncology Group evaluated cyclophosphamide 600 mg/m2 intravenously daily X 4 (total dose each cycle 2400 mg/m2) as an aggressive approach to the treatment of patients with advanced multiple myeloma . The overall objective response rate is 43% . This includes a 38% response rate for all previously treated patients and a 29% response rate for patients refractory to prior therapy with cyclophosphamide . The objective response duration was 3 months and the survival of responding patients 9 months . A subjective response rate of 63% was observed, characterized by effective pain relief and improved performance . Sixty-nine percent of patients experienced leukocyte cell nadirs less than 500/mm2 with a mean time to marrow recovery of 17 days . Thrombocytopenia was less severe but required platelet transfusion in 43% of patients . Bone marrow toxicity was encountered in all patients, and death in aplasia is a significant risk . Strict adherence to entry criteria, and a systematic plan for hospitalization for antibiotic and blood component support is required for treatment with this regimen. Metabolism, 1984 Apr, 33(4), 309 - 16 Tunicamycin blocks the emergence and maintenance of insulin receptors on mitogen-activated human T lymphocytes; Ercolani L et al.; Treatment of phytohemagglutinin (PHA) activated human T lymphocytes with tunicamycin, an antibiotic that specifically inhibits asparagine-linked N-glycosylation of proteins, totally blocked the normal emergence of insulin receptors on these lymphocytes and their cellular proliferation during culture in a dose-dependent manner . Carbohydrate incorporation into protein was inhibited 82% by 0.5 microgram/mL while leucine incorporation was unaffected . Tunicamycin exposure of activated T lymphocytes, which had acquired insulin receptors during culture, reduced cellular insulin binding by 35% to 84% and reduced PHA binding to 40% of control levels within 24 hours . Scatchard analysis revealed decreases in insulin binding capacity but not affinity . Similar treatment with cycloheximide only decreased insulin binding by 12% . These findings suggest N-glycosylation of proteins is a necessary biochemical event (1) for the emergence and maintenance of insulin receptors on mitogen activated T lymphocytes, and (2) for mitogen activated T lymphocytes to undergo cell division. Microbiologica, 1984 Apr, 7(2), 121 - 32 Effect of coumermycin on influenza A virus replicative cycle; Portincasa P et al.; Coumermycin A1, a Novobiocin related antibiotic, has been tested in vivo and in vitro for its activity on Influenza A viruses . In a range of concentrations between 3 and 5 micrograms/ml virus production was drastically reduced . The drug was able to inhibit virus release into culture medium also if added up to the sixth hour following infection and its action was reversible within this time . The synthesis of virus induced polypeptides was generally depressed but production of the HA was more deeply inhibited . Viral transcriptase activity in vitro was also affected by the presence of Coumermycin A1 but at doses which seem to high to consider this event as a phenomenon likely to play a role in vivo . It is suggested that the antiviral activity of the drug is mediated by the inhibition of the host cell metabolism. Ann Thorac Surg, 1984 Apr, 37(4), 314 - 8 Mycotic aortic aneurysms in children; Bergsland J et al.; Mycotic aneurysms of the aorta are uncommon in babies and children . Prior to the development of antibiotics, most mycotic aneurysms were seen secondary to bacterial endocarditis, but this is now uncommon . Instead, more cases have been reported as complications of umbilical artery catheters in newborns . We have seen five cases of mycotic aneurysms in children, two of them secondary to umbilical artery catheters . One patient had coarctation of the aorta, and the other patients had different sources of infection . Three patients were treated surgically by us with good results after antibiotic therapy . One patient died of sepsis before the aneurysm was diagnosed . The fifth patient was treated elsewhere and now has a recurrent aneurysm . We think a combination of aggressive medical and early surgical therapy may save a high percentage of these patients. J Radiol, 1984 Apr, 65(4), 289 - 91 {Posttraumatic esophagopericardial fistula}; Strohl D et al.; The outcome in a case of esophagopericardiac fistula due to a closed chest injury was spontaneously favorable, the absence of infective complications probably resulting from adequate antibiotic therapy. Lab Anim, 1984 Apr, 18(2), 115 - 8 Canine tooth root infection as a cause of facial abscess in the common marmoset (Callithrix jacchus); Baskerville M; Facial abscesses in a colony of common marmosets were found to be caused by abscessation of an upper canine tooth root . Trauma to the upper canine, resulting in exposure of the pulp cavity, was thought to be the mode of infection . Radiography was the most useful diagnostic aid in establishing the nature and extent of the lesion . Antibiotic therapy alone was inadequate, and provision of drainage by extracting the tooth, in conjunction with antibiotics, proved the most effective treatment. Am J Med, 1984 Apr, 76(4), 678 - 84 Symposium on infectious complications of neoplastic disease (Part II) . Current status of prophylaxis of infection with protected environments; Bodey GP; Protected environments and prophylactic antibiotics have been evaluated as a method for reducing the risk of infection in patients undergoing cancer chemotherapy . Initial studies were conducted in patients with acute leukemia, and most of them demonstrated that patients in the protected environment/prophylactic antibiotic program had fewer infections and infectious deaths than control patients . In two studies, remission rates were significantly higher for the group in the protected environment/prophylactic antibiotic program . Subsequently, studies were conducted in patients with lymphoma, sarcoma, and breast carcinoma . The protected environment/prophylactic antibiotic program reduced the risk of infection and permitted the administration of higher doses of chemotherapy . However, the more intensive chemotherapy only minimally improved response rates or durations of response . Further studies should be directed toward identifying those patients most likely to benefit from this prophylactic program. Antimicrob Agents Chemother, 1984 Apr, 25(4), 446 - 9 Energetics of tetracycline transport into Escherichia coli; Smith MC et al.; The nature of energy coupling for the active transport of tetracycline into Escherichia coli was examined under conditions in which antibiotic uptake was directly compared with transport of proline (proton motive force dependent) and glutamine (phosphate bond dependent) . Tetracycline transport was partially inhibited by osmotic shock and by exposure of bacteria to arsenate, two procedures which substantially reduced glutamine transport . Tetracycline transport was also partially inhibited in an uncB mutant (AN283) exposed to the uncoupler carbonyl cyanide-m-chlorophenyl hydrazone (CCCP) under conditions that inhibited proline transport . Taken together, these data indicate involvement of both phosphate bond hydrolysis and the proton motive force for the active transport of tetracycline into E . coli. Acta Med Okayama, 1984 Apr, 38(2), 117 - 24 Production of a macromomycin (MCR)-monoclonal antibody conjugate and its biological activity; Manabe Y et al.; Macromomycin (MCR), an unique membrane-reactive anticancer antibiotic, was incubated with murine monoclonal anti-HLA IgG1 antibody (H-1) in the presence of carbodiimide . The resulting mixture was fractionated with a Sephadex G-200 column . The first and second fractions were shown to contain MCR-(H-1) conjugate by the elution profile, as well as by the Sarcina lutea growth inhibition assay and Ouchterlony double-diffusion method . A membrane immunofluorescence test with anti-MCR and anti-mouse IgG antibodies demonstrated specific localization of MCR-(H-1) on the surface of HLA-bearing NALL -1 cells . MCR-(H-1) inhibited the growth of HLA-lacking NS-1 cells statistically less effectively than MCR alone (p less than 0.01) . On the other hand, the conjugate and free MCR equally inhibited the growth and 3H-TdR incorporation of HLA-bearing NALL -1 cells . These results indicate that the antibody-bound MCR retained both MCR and antibody activities, and thus exerted antibody-targeting MCR cytotoxicity in vitro. J Antimicrob Chemother, 1984 Apr, 13(4), 361 - 7 Interaction of subminimal inhibitory concentrations of clindamycin and Escherichia coli: effects on adhesion and polymorphonuclear leukocyte function; Bassaris HP et al.; Subinhibitory concentrations (sub-MICs) of clindamycin interfere with the adhesion of Escherichia coli to buccal epithelial cells and promote phagocytosis and killing of this organism by human polymorphonuclear leukocytes (PMNLs) . Adherence of E . coli grown in the presence of clindamycin, at concentrations of 2-32 mg/l, varied from 21.1 +/- 7.4 to 25.8 +/- 7.8 bacteria per epithelial cell (EC) (mean +/- S.D.) as compared with 58.3 +/- 10.3 per EC when the organism was cultured in the absence of the antibiotic (P less than 0.01) . The number of phagocytosed bacteria per 200 PMNLs increased from 166.1 +/- 36.6 when E . coli was grown in medium 199 containing no antibiotic, to 289.3 +/- 56.4 (P less than 0.01) when the organism was preincubated with 4 mg/l of clindamycin . The same concentration of clindamycin also increased the percentage of phagocytosed bacteria killed by the PMNLs from 42.0 +/- 9.0% to 63.7 +/- 11.2% (P less than 0.01) . The results of this study indicate that sub-MICs of clindamycin enhance host-defence mechanisms against E . coli. Br J Clin Pharmacol, 1984 Apr, 17(4), 477 - 80 Pharmacokinetics of phosphomycin during haemofiltration; Fernandez Lastra C et al.; The pharmacokinetics of phosphomycin were studied in 10 adult patients with terminal renal impairment during a 4 h haemofiltration session . A single i.v . dose of 30 mg/kg of the antibiotic was administered to each patient at the beginning of the haemofiltration session . The half-life of the slow disposition phase (t 1/ 2z ) showed an average value of 4.05 +/- 1.77 h, much lower than that established in patients who did not undergo any purification techniques . Serum phosphomycin concentrations at the input and the output of the haemofilter at the end of the session were, respectively, 26.65 and 19.13 micrograms/ml . During haemofiltration, 64.90% of the original dose was eliminated . In this kind of patient we recommend a dose of 30 mg/kg at the beginning and at the end of each haemofiltration session for interfiltration periods of 48 h. Clin Obstet Gynaecol, 1984 Apr, 11(1), 209 - 26 A reappraisal of the endometrium in infertility; Robertson WB; It will be obvious to the reader that the author has gone to considerable lengths to exculpate the endometrium from playing a significant role in the aetiology and pathogenesis of infertility . No apology is necessary for this approach as it is known to obstetricians and gynaecologists engaged in the management and treatment of the infertile couple that most causes of infertility have little to do directly with endometrial abnormalities . This does not mean, however, that an endometrial biopsy or curettage specimen has no place in the investigation of the infertile woman . It can be used as an adjunct to the monitoring of the efficacy of treatment for ovulatory failure and in the confirmation and typing of endometrial hyperplasia in the woman with persistent anovulatory cycles . It is virtually indispensable for the diagnosis of genital tuberculosis and as a means of culturing the mycobacterium for antibiotic sensitivity testing so that appropriate therapy can be given . While there are better methods now available, such as laparoscopy, for the diagnosis of pelvic inflammatory disease, the finding of unsuspected endometritis in the infertile woman can be used as an indicator of low-grade chronic genital tract infection that may not be otherwise apparent . There would seem to be no need for routine investigation of the endometrium in women afflicted with endometriosis or tubal disorders . The most controversial use of endometrial biopsy as an investigational technique is in the diagnosis of luteal deficiency and related disorders . If it is to be used in this circumstance, then it is essential that there should be the closest possible consultation between the clinician and the pathologist . It is too early yet to declare the endometrium always blameless in reproductive failure but there is little hope that purely morphological studies, even at the ultrastructural level, will supply answers to the unresolved questions . The investigation of the complex biochemistry and biology of the endometrium is still very much in the developmental stage . Pathologists interested in reproductive biology must be prepared to adapt and to devise new techniques based on biochemical discoveries to supplement their traditional morphological assessment of this important and fascinating tissue. J Microencapsul, 1984 Apr-Jun, 1(2), 137 - 55 Preparation and biopharmaceutical evaluation of microcapsules of amoxicillin; Goto S et al.; Two methods of microencapsulation of amoxicillin, an orally administered antibiotic, were studied . One is based on dispersion of gelatin-amoxicillin mixture in liquid paraffin followed by drying and hardening with formalin-isopropanol treatment; the other is based on dispersion of ethylcellulose-amoxicillin mixture in purified water containing sodium lauryl benzene sulphonate . The microcapsules were recovered as discrete, free-flowing fine granules with a particle diameter of about 250-1000 microns . Dissolution of amoxicillin from ethylcellulose microcapsules was suppressed considerably with a zero-order dissolution pattern in solutions of various pH . Gastric-emptying-controlled rabbits were used for the in vivo evaluation of gelatin and ethylcellulose microcapsules . The ethylcellulose microcapsule containing 25 per cent amoxicillin showed a significantly sustained release pattern of amoxicillin . To establish a suitable design and for the evaluation of the sustained release microcapsules, a nomogram was made using pharmacokinetic parameters obtained after administration of a conventional formulation . It is advantageous for the preparation of sustained release microcapsules to chose pharmaceuticals having over about 2 as the ratio of the elimination rate constant, k10, to the release/absorption rate constant, kr, in the rabbit. Am J Med, 1984 Apr, 76(4), 631 - 6 Symposium on infectious complications of neoplastic disease (Part II) . Granulocyte transfusions; Clift RA et al.; Laboratory and clinical studies have demonstrated beyond question that granulocyte transfusions can have a beneficial effect on the incidence and course of bacterial infection . The increment of improved survival produced by granulocyte transfusions depends on the effectiveness of the alternative (primarily antibiotic) therapy alone, and this varies with the pattern of bacterial predominance and sensitivity, which is notoriously changeable . The absolute effectiveness of granulocyte transfusion therapy is influenced by the quality of the transfusions and the immune status of both the recipient and the granulocyte donor . The indiscriminate transfusion of inadequate quantities of granulocytes from random donors into sensitized recipients should be discouraged . Severely neutropenic patients with established infection unresponsive to antibiotic therapy are appropriate recipients of granulocyte transfusions . Well-designed programs of prophylactic granulocyte transfusions can reduce the occurrence of bacterial infection in neutropenic patients, but there are few clinical situations in which their use is justified . The use of cytomegalovirus-seropositive granulocyte donors for cytomegalovirus-seronegative recipients should be avoided . There is a need for technical advances that will increase the ease and efficiency of granulocyte procurement. Cell, 1984 Apr, 36(4), 943 - 9 Amplification and excision of integrated polyoma DNA sequences require a functional origin of replication; Pellegrini S et al.; Cells transformed by Polyoma virus (Py) can undergo a high rate of excision or amplification of integrated viral DNA sequences, and these phenomena require the presence of homology (i.e., repeats) within the viral insertion as well as a functional viral large T antigen (T-Ag) . To determine whether the main role of large T-Ag in excision and amplification was replicative or recombination-promoting, we studied transformed rat cell lines containing tandem insertions of a ts-a Py molecule (encoding a thermolabile large T-Ag) with a deletion of the origin of viral DNA replication . Culturing of these cells at the temperature permissive for large T-Ag function did not result in any detectable excision or amplification of integrated Py sequences . We then introduced into origin-defective lines a recombinant plasmid containing the viral origin of replication and the gene coding for resistance to the antibiotic G418 . All G418-resistant clones analyzed readily amplified the integrated plasmid molecules when grown under conditions permissive for large T-Ag function, showing that these cells produced viral large T-Ag capable of promoting amplification in trans of DNA sequences containing the Py origin . These observations strongly suggest that Polyoma large T antigen promotes excision or amplification of viral DNA by initiating replication at the integrated origin, providing a favorable substrate for subsequent recombination. Arch Biochem Biophys, 1984 Apr, 230(1), 61 - 8 Amine fluorescamine compounds inhibit oxidative phosphorylation in rat liver mitochondria; Ramirez F et al.; The reaction of fluorescamine with ammonia, benzylamine, o,p-dimethylbenzylamine, 2-phenylethylamine, p-aminobenzoic acid, and the mycosamine-containing macrolide antibiotic, amphotericin B, yield compounds which induce significant effects on mitochondrial activities . From their effects on energy-yielding processes which lead to transmembranous proton movements, the compounds may be divided into three classes . While all modifiers significantly inhibit proton movement induced by both ATP hydrolysis and electron transfer in mitochondria, their influence on the primary energy yielding steps are quite different . Class I modifiers, e.g., the compound made from amphotericin B, inhibit electron transfer but have no effect on the Pi release associated with ATP hydrolysis . Class II modifiers, e.g., the compound made from benzylamine, inhibit respiration but stimulate Pi release . Class III modifiers, e.g., the compound made from p-aminobenzoic acid, on the other hand, only slightly increase Pi release but have no effect on redox reactions . These and other effects of the modifiers are taken to mean that the proton movements and their associated energy-yielding processes are only linked indirectly . The effects of the modifiers on State 3 mitochondrial activities were also investigated . Although all the modifiers decrease the rates of both State 3 respiration and its coupled ATP synthesis, the efficiency of energy conversion measured by the P/O ratio remains unaltered. Antibiotiki, 1984 Apr, 29(4), 282 - 5 {Pharmacokinetics of dihydrostreptomycin, after intravenous administration as a liposomal preparation, in the blood serum and tissues of intact mice and those with generalized tuberculosis}; Vladimirskii MA et al.; Distribution of 3H-dihydrostreptomycin ( DHS ) in the blood serum and organs of intact mice and mice with generalized tuberculosis was studied . The antibiotic was administered in the form of a liposomal preparation and solution . It was shown that the distribution pattern of DHS administered in the form of a liposomal preparation corresponded to that of liposomes, which were the drug carriers . The serum levels of DHS injected intravenously in the form of a liposomal drug in a dose of 1 mg per mouse in the intact animals were 19 and 17 times higher 1 and 3 hours after injection, respectively as compared to those provided by the solution . In animals with generalized tuberculosis, the respective figures were 5 and 1.9 times . The levels of DHS in the liver provided by the liposomes were 4-6 times higher at all the time intervals in both the groups of animals . The antibiotic levels in the spleen of intact and infected animals were 2.5-3 and 8-12 times higher, respectively . In the lungs of intact animals, the antibiotic levels were 2 times higher 1 hour after administration . In infected animals, the levels of the antibiotic in the lung tissue were 3 times higher in 1 and 3 hours . The DHS levels in the kidneys of infected and intact animals were similar after drug administration in the form of a solution and liposomal preparation . The extremely high difference in the DHS levels in the spleen tissues of the mice with generalized tuberculosis after drug administration in the form of a solution and liposomal preparation may be of a significant importance for sanation of the organ lymphoid system affected with tuberculosis. Thorac Cardiovasc Surg, 1984 Apr, 32(2), 92 - 5 Orthotopic transplantation of aortic valve allografts . Early hemodynamic results; Yankah AC et al.; The aortic root as a functional unit includes the sinuses of valsalva, valve ring, the leaflets and the commissures . This unit is impaired by the insertion of a bioprosthetic three-leaflet valve . Moreover, bioprostheses fail because of fatigue and flexion stresses . Consequently a program was started for free-handed orthotopic transplantation of allogeneous aortic valves at the Department of Cardiovascular Surgery, University Kiel . A series of 16 consecutive antibiotic, sterilized aortic valve allografts were transplanted in the last 12 months without death . There were 4 females and 12 males between 18 and 63 years old (mean 47.9) . The dominant lesion was aortic regurgitation (in 9), stenosis (in 3) and mixed (in 4) . Out of the 13 patients who maintained their allografts, 10 (77%) were in class III and 3 (23%) in class IV of the NYHA functional classification . Four patients improved from class III to class I, and 9 from class III and IV to class II of the NYHA functional classification after surgery . All patients except one had postoperative recatheterization including videodensitometry to quantitate the regurgitation, expressed as a regurgitant fraction ( RGF ) in percent of the total stroke volume of the left ventricle, and pressure measurements to determine systolic gradients across the aortic valve allograft, 3 to 6 days and 9 months after surgery . Eleven (68.75%) patients had no regurgitation, 2 (12.5%) patients had trivial aortic regurgitation with RGF of 7% and 10%, respectively . Three (18.75%) patients had severe aortic valve regurgitation with RGF between 40% and 60% due to technical errors and their allografts had to be replaced.(ABSTRACT TRUNCATED AT 250 WORDS) Gastroenterology, 1984 Apr, 86(4), 753 - 6 Hepatic granulomas in Whipple's disease; Saint-Marc Girardin MF et al.; Hepatic epithelioid cell granulomas that were negative for periodic acid-Schiff stain after diastase digestion were found in a 32-yr-old man who presented with painless hepatomegaly and slight fever . The patient never complained of intestinal symptoms, which in part explains why the diagnosis of Whipple's disease was made only 3 mo later, at a time when severe neurologic manifestations had appeared . The definitive diagnosis was made on the basis of the characteristic histologic findings in biopsy material obtained from jejunum and abdominal lymph nodes at laparotomy . The patient's condition, especially neurologic manifestations, rapidly improved after antibiotic therapy . It is noteworthy that Whipple's disease is generally not included among the causes of hepatic epithelioid cell granulomas . It is suggested that its possibility should be considered in patients with hepatic granulomas without obvious etiology, even in the absence of intestinal symptoms. Cancer Res, 1984 Apr, 44(4), 1364 - 7 Stimulation of glycolysis by placental polypeptides and inhibition by duramycin; Racker E et al.; Placental polypeptides present in crude preparations of transforming growth factors stimulate glycolysis when added to quiescent 3T3 cells, normal rat kidney, and chick embryo fibroblasts . The stimulation was apparent over a time period of at least 90 min and was seen at glucose concentrations ranging from 1 to 30 mM . Duramycin, an antibiotic isolated from Streptomyces cinnamomeus, inhibits the polypeptide-stimulated and nonstimulated glycolysis of intact cells, since it permeabilizes cells to Pi and nucleotides . However, duramycin also inhibits the Na+-K+-ATPase as well as the ouabain-insensitive Mg2+-ATPase of plasma membranes . Duramycin has no effect on glycolysis catalyzed by cell-free extracts of Ehrlich ascites tumor cells in the presence of mitochondrial ATPase but partially inhibits glycolysis when ADP and Pi are generated by ATPases of plasma membrane preparations. Minerva Med, 1984 Mar 31, 75(13), 757 - 60 {A case of lymph node aspergillosis}; Piaserico PL; Lymph node aspergillosis in an otherwise healthy patient receiving neither antibiotic corticosteroid or immunodepressive drug treatment is an uncommon event . In addition the case reported revealed no deficiency in humoral or cellular immunity . The possibility that aspergillosis may occur in cases without identifiable immunodeficiency is therefore put forward. Lancet, 1984 Mar 31, 1(8379), 721 - 3 Aetiology and pathogenesis of postinfective tropical malabsorption (tropical sprue); Cook GC; Postinfective tropical malabsorption (TM; tropical sprue) starts with an acute intestinal infection (bacterial, viral, or parasitic) which can affect predominantly the small or the large intestine . Miscellaneous invasive pathogens cause subsequent enterocyte damage affecting the entire small intestine and, to a lesser extent, the colon . Enteroglucagon, a tropic hormone, is then liberated and reaches a high plasma concentration . Small-intestinal stasis results . Further bacterial colonisation (in the lumen and also at the enterocyte surface) is encouraged . Continuing enterocyte damage is worsened by coexistent folate depletion, which is initiated at the onset of disease; body stores of folate reach a low concentration by 3 or 4 months . The cycle continues until the bacterial overgrowth is eliminated with an antibiotic (eg, tetracycline), or mucosal integrity recovers (hastened by oral folic-acid supplements), or both. Biochemistry, 1984 Mar 27, 23(7), 1479 - 84 4-Methyl-3-hydroxyanthranilic acid activating enzyme from actinomycin-producing Streptomyces chrysomallus; Keller U et al.; A 4-methyl-3-hydroxyanthranilic acid (4-MHA) activating enzyme was purified 24-fold from a crude protein extract of Streptomyces chrysomallus . The enzyme catalyzes both 4-MHA-dependent ATP/PPi exchange and the formation of the corresponding adenylate . No AMP was formed during the reaction, indicating that no covalent binding of 4-MHA takes place . Besides 4-MHA, the enzyme also catalyzes the formation of adenylates from 3-hydroxyanthranilic acid (3-HA), anthranilic acid (AA), benzoic acid (BA), 3-hydroxybenzoic acid (3-HB), 4-methyl-3-hydroxybenzoic acid (4-MHB), 4-methyl-3-methoxybenzoic acid (4- MMB ), and 4-aminobenzoic acid (4-AB) . No such adenylates were formed from 2-aminophenol (2-AP), 2-hydroxybenzoic acid (2-HB), 3-hydroxykynurenine (3-HK), and tryptophan (Trp) . 3-HA, 4-MHB, and 4-AB were among the structural analogues of 4-MHA that were the most effective for adenylate synthesis . In the case of 3-HA, considerable AMP release was observed, most probably due to nonenzymatic hydrolysis of the corresponding adenylate . A molecular weight between 53 000 and 57 000 was estimated . The specific activity of the enzyme was correlated with the titer of antibiotic in the cultures, and feeding experiments with whole mycelium of S . chrysomallus showed that 4-MHB was a strong inhibitor of actinomycin synthesis in vivo . The data strongly suggest that the enzyme is involved in the biosynthesis of actinomycin. Minerva Med, 1984 Mar 17, 75(11), 577 - 8 {Surgical therapy of tuberculosis}; Paletto AE et al.; Authors report the indications of surgical treatment of tuberculosis . At present undoubtedly these indications so diminished that now they are only the following: rare stabilized results; adenobronchial syndromes with their complications; indications of rescue in drug-resistant lesions; operations in subjects with results of treatments made in pre-antibiotic time; presence of rigid cavities . The surgery of tuberculosis has become more and more unusual, but in spite of that this surgery is complicated for the surgeon operates an inflammatory tissue with solid adhesions on the blood-vessels and on the near structures. Biochem Biophys Res Commun, 1984 Mar 15, 119(2), 779 - 85 Microcin 7: purification and properties; Garcia-Bustos JF et al.; Microcin 7 is an antibiotic peptide, produced and excreted to the culture medium by E . coli strains harboring the plasmid pRYC7 . This peptide was extracted from the culture media by adsorbing it on octadecyl silica . It was purified by gel filtration on Sephadex G-25 and reverse phase high performance liquid chromatography . Its amino acid composition is the following: Ala (0.8), Arg (1.9), Asx (1.9), Gly (1.5), Met (0.8) and Thr (0.9) . The purified peptide dose not react with ninhydrin and it is resistant to carboxypeptidase degradation, indicating that the molecule may be a cyclic or end-blocked oligopeptide. J Biol Chem, 1984 Mar 10, 259(5), 2701 - 3 Inhibition of clathrin-coated vesicle acidification by duramycin; Stone DK et al.; Clathrin-coated vesicles contain a proton translocating ATPase which operates in parallel with a chloride transporter (Xie, X.-S., Stone, D.K., and Racker, E . (1983) J . Biol . Chem . 258, 14834-14838) . The polypeptide antibiotic, duramycin, has a dual inhibitory effect on clathrin-coated vesicle acidification . Low amounts of duramycin (5 micrograms/100 micrograms of protein) inhibit by 50% the proton translocation facilitated by chloride translocation . Under these conditions duramycin inhibits also 36Cl uptake when driven by either the electrogenic proton pump or by inward directed K+ movement in the presence of valinomycin . Higher amounts of duramycin (20 micrograms/100 micrograms of protein) are needed to inhibit by 50% the proton pump itself, as evidenced by reduced proton translocation facilitated by an outward potassium movement in the presence of valinomycin . In addition, the amount of duramycin needed to inhibit the proton pump corresponded well with the amount needed to inhibit the ouabain-insensitive, N-ethylmaleimide-sensitive ATPase activity of clathrin-coated vesicles. Vet Rec, 1984 Mar 3, 114(9), 212 - 3 Infectious (septic) arthritis of the distal intertarsal and tarsometatarsal joint in cattle; Merkens HW et al.; The results of treatment of infectious (septic) bone spavin in cattle admitted to the department of large animal surgery, Utrecht University, between 1961 and 1982 are reviewed . Treatment comprised either antibiotic administration, radiation or surgery, of which the latter two methods appeared to produce better results . However, radiation of the affected area was both time consuming and expensive . Therefore, surgical treatment is advocated. Jpn J Antibiot, 1984 Mar, 37(3), 318 - 28 {Clinical results of cefaclor treatment of infections of oral regions}; Yoshida Y et al.; Cefaclor (CCL) is a cephem antibiotic for oral use . Thirty cases of infection of oral regions, in the First Department of Oral and Maxillofacial Surgery, School of Dentistry, the University of Tokushima, were treated with CCL at 750 mg/day . The results were as follows: The efficacy rate for all kinds of diseases was 80.0% in 3 days and 96.7% in 5 days and 86.7% as an overall assessment by the patients' doctors . With regard to the degree of symptoms, the efficacy rate for cases with moderate symptoms was less than that for mild cases in 3 days and according to the assessment by the patients' doctors . Some moderate cases required increased medication because no beneficial effect was observed . In sensitivity tests, CCL was shown to be effective on all 27 isolated clones of bacteria tested . CCL caused no detectable changes in laboratory data . No side effects were observed in any case . From these results, it is concluded that CCL is a highly effective antibiotic for use on infections of the oral regions. Antibiotiki, 1984 Mar, 29(3), 208 - 14 {Interaction of rubomycin and its aglycone with DNA studied by fluorescent methods}; Baranov EP et al.; The fluorescent characteristics of rubomycin as dependent on the environmental conditions (different solvents, acidity of the medium, ionic strength) were studied . A model explaining suppression of the rubomycin fluorescence on the antibiotic interaction with DNA is described . The model confirmed intercalation and preferable binding with purines as compared to pyrimidines . The constants of rubomycin and aglycone interaction with DNA were determined . The use of the antibiotic concentrations less than 10(-6) M allowed the determination of a higher constant characterizing "strong binding" . The nonlinearity of the curve of DNA titration with the antibiotic plotted on the Scatchard coordinates indicates the heterogeneity of the binding sites . The constant of the aglycone binding to DNA was approximately 2 orders lower at the same number of the binding sites in one molecule . The decrease in the constant of rubomycin interaction with DNA of an increased ionic strength and the low constant of the aglycone interaction with DNA as compared to that of the antibiotic itself confirmed the suggestion that there formed a bond between the amino sugar and the phosphate groups. Antibiotiki, 1984 Mar, 29(3), 166 - 70 {Kinetics of ampicillin breakdown in the solid state}; Ovcharova GD et al.; The degradation kinetics of solid sodium ampicillin, ampicillin trihydrate and anhydrous ampicillin was studied in relation to the disintegration level of the powder before and after its screening by the particle size . It was shown that the effect of the powder disintegration level on the degradation rate constant proceeded by the spherical model and the reaction of the antibiotic degradation proceeded according to the equation of the first order reaction . The degradation rate constants of the total fractions and the fractions with the particle size of 60, 80 and 100 micron at elevated and room temperatures and their half-lives were evaluated . Different mechanisms of degradation of three ampicillin forms were shown on the basis of the dependence of the degradation rate constant on the temperature and the data of thin-layer chromatography . Higher stability levels of ampicillin powder with the particle size of 100 micron and anhydrous ampicillin in comparison with sodium ampicillin and ampicillin trihydrate were observed . This allows recommending anhydrous ampicillin for preparation of oral dosage forms. Pediatr Infect Dis, 1984 Mar-Apr, 3(2), 114 - 6 Postoperative wound infections in a children's hospital; Davis SD et al.; A prospective study was made of postoperative wound infections at Milwaukee Children's Hospital for 1 year . Essentially all procedures requiring a skin incision were included . The clean surgical wound infection rate was 3.1% (26 infections in 849 cases) . There were no significant differences in clean wound infection rates among the individual surgeons or among the four busiest surgical services . The occurrence of postoperative wound infections was associated with administration of prophylactic antibiotics, longer duration of surgical procedures and longer hospital stay before and after surgery . About 50% of patients having a clean surgical procedure were given prophylactic antibiotics . Prophylactic antibiotic were given for 4 days or more in about half the cases. J Antibiot (Tokyo), 1984 Mar, 37(3), 285 - 92 Effect of infusion time on the pharmacokinetics of dibekacin in rabbits; Navarro AS et al.; A study was made of the serum levels and of the pharmacokinetic parameters of dibekacin after administration by intravenous infusion at a dose of 2 mg/kg of the drug to rabbits using different infusion times . The peak serum level (Cmax) was seen to decrease progressively on increasing infusion time . The maximum value of Cmax was obtained after administration of the antibiotic by single bolus injection with an average value of 18.297 +/- 9.694 micrograms/ml, while the minimum value was obtained after intravenous infusion over 1 hour, with an average value of 6.597 +/- 1.250 micrograms/ml . A series of linear relationships was established between different pharmacokinetic parameters and the infusion time and a decrease was observed in the pharmacokinetic parameters alpha, K12, K21 and K13 when the infusion time was increased . Changes were also observed in the distribution kinetics of dibekacin in the rabbit on varying the infusion conditions, suggesting alterations in the access and permanence of the antibiotic in tissues. J Antibiot (Tokyo), 1984 Mar, 37(3), 253 - 9 Inhibition of chitin metabolism by avermectin in susceptible organisms; Calcott PH et al.; Avermectin inhibits Mucor miehei and Artemia salina chitin synthesis and to a degree DNA synthesis in the former . The antibiotic interferes with chitin turnover in brine shrimp and inhibits Streptomyces antibioticus chitinase activity in vitro . In light of the proposed mode of action of avermectin and the anomolies in the literature, it is proposed that avermectin can kill susceptible organisms not only by a neurotoxic mechanism but also by inhibiting chitin turnover and synthesis at low concentration and thus the molting/ecdysis process. Mol Biol (Mosk), 1984 Mar-Apr, 18(2), 332 - 42 {Interactions between distamycin A analogs bound to DNA}; Nechipurenko IuD et al.; The experimental binding isotherms of the distamycin A analog to 8 natural and synthetic DNAs were analyzed . The shapes of binding isotherms suggest that the bound ligand molecule induces transitions of DNA (B-form) into two perturbated conformation states . These transitions are responsible for the existence of positive and negative cooperative effects on binding of distamycin analogs to DNA . At low levels of binding positive cooperative effects play a dominating role whereas at high levels of binding negative cooperative effects are observed . These cooperative effects can be described by the aid of a potential of pairwise interactions between nearest neighbour bound antibiotic molecules . A detailed analysis of experimental binding isotherms shows that characteristic distances over which these interactions are extended depend on the AT content of DNA . The energetical and structural parameters characterising the allosteric transitions of DNA to the perturbated states are obtained. J Hand Surg {Am}, 1984 Mar, 9(2), 245 - 7 Infected mucous cyst of the finger; Rangarathnam CS et al.; The potentially serious complication of septic arthritis of the distal interphalangeal joint of the finger secondary to an infected mucous cyst is documented with a report of four cases seen within the past 6 years . Debridement, open packing, and antibiotic therapy resulted in satisfactory control of the infection in these cases . This report provides additional basis for prophylactic extirpation of mucous cyst of the the finger. Pharmacol Biochem Behav, 1984 Mar, 20(3), 405 - 13 Investigation of the reported protective effect of cycloheximide on memory; Davis HP et al.; Many findings support the hypothesis that formation of long-term memory requires synthesis of proteins in the nervous system close to the time of learning . This hypothesis has been challenged recently by reports that the protein synthesis inhibitor cycloheximide (CYC) injected 2 hr prior to passive avoidance training in mice or rats attenuated the memory impairment induced by a usually amnestic dose of CYC administered 30 min pretraining . To investigate the reports of a "protective" effect of the prior injection, we attempted to replicate them and test their generality . For replication we administered either paired injections of CYC--120 mg/kg 2 hr prior to training and 30 mg/kg 30 min prior to training--or single injections of CYC (either 120 mg/kg or 30 mg/kg) 30 min pretraining and tested for retention of the passive avoidance habit either 1 or 7 days later . No attenuation of amnesia was observed at 1 day tests . Attenuation of amnesia following the double injection of CYC was observed at 7 day tests . When another protein synthesis inhibitor, anisomycin, was used in the same experimental design, there was no "protective" effect; two injections of anisomycin produced greater memory impairment for the passive avoidance habit than did the single low dose . Also, for active avoidance training, two successive injections of CYC caused significantly greater amnesia than did a single dose; this is the opposite of a "protective" effect . We suggest that the reported "protective" effect of CYC on memory is an as yet unexplained phenomenon that does not generalize to other antibiotic drugs and is specific to the passive avoidance task. Am J Surg, 1984 Mar, 147(3), 322 - 4 Bacterial presence in aortic thrombus at elective aneurysm resection: is it clinically significant? McAuley CE, Steed DL, Webster MW. Infected thrombus in an abdominal aortic aneurysm represents a potential source of subsequent aortic graft sepsis . Previous reports have documented a 10 to 15 percent incidence of positive results of culture of the contents of an abdominal aortic aneurysm and have recommended prolonged postoperative organism-specific antibiotic therapy when a positive culture is encountered . In our study, we cultured the intraluminal thrombus during elective aneurysm repair in 64 patients with abdominal aortic aneurysms and found bacterial growth in 9 (14 percent of all patients) . Eight of the nine patients received no antibiotic therapy other than the routine prophylaxis regimen, and no evidence of either early or late prosthetic graft sepsis occurred (mean follow-up 25 months) . We conclude that a positive result of culture may not imply clinical infection at the time of operation and that prolonged postoperative organism-specific antibiotic therapy does not appear necessary in the patient with an asymptomatic aneurysm and no overt evidence of infection of the aneurysm at the time of operation. South Med J, 1984 Mar, 77(3), 347 - 50 Compound frontobasal skull fractures: surgical management of the acute phase; Rosenwasser RH et al.; The management of frontobasal skull fractures must be dealt with in a multidisciplinary manner . The advent of computed tomography has simplified the emergency radiologic investigation and expedited immediate surgical intervention . The major problem to be dealt with is closure of the frontobasal dura, which we accomplish by using an autogenous fascial graft packed under the frontal lobes and secured basally with autogenous adipose implants . In such contaminated injuries, the use of a triple antibiotic regimen should be considered based on the chance of eliminating resistant organisms. Laryngoscope, 1984 Mar, 94(3), 363 - 6 Radiographic findings in progressive necrotizing "malignant" external otitis; Gold S et al.; Twenty-three cases of progressive necrotizing (malignant) external otitis were reviewed . Radiographic evaluation was correlated with clinical disease . CT scanning accurately demonstrated subtle foci of involvement in the skull base which may be clinically unsuspected or go undetected with other studies . Central skull base erosion indicates advanced disease and selects those patients requiring extended antibiotic therapy . Soft tissue thickening of the parapharyngeal space and roof of the nasopharynx also implies advanced disease requiring prolonged therapy . Soft tissue improvement can be visualized on CT . While CT scanning demonstrates the progression of bony disease, it cannot be used to follow resolution of central skull base osteomyelitis . Radionuclide scans provide information regarding the overall extent of the inflammatory process. J Pediatr Orthop, 1984 Mar, 4(2), 170 - 4 Fever, C-reactive protein, and erythrocyte sedimentation rate in monitoring recovery from septic arthritis: a preliminary study; Peltola H et al.; Body temperature, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured sequentially in nine children less than 11 years old during their recovery from culture-positive septic arthritis (SA) . The measurements were compared with those of two other children who recovered without antibiotic therapy . A clinical investigation carried out several months after discharge suggested permanent recovery in all cases, including the spontaneously recovered patients . Defervescence and normalization of the primarily elevated CRP and ESR values occurred in a similar manner in both groups . On average, fever lasted 5 days, CRP level decreased below 20 mg/L in 7 days, and ESR reached a value of less than or equal to 20-25 mm/h in 22 days . The normalization time of ESR differed highly significantly (p less than 0.001) both from the duration of fever and from the normalization time of CRP level . Because CRP behaved in a similar manner in both the medicated and the nonmedicated groups, its normalization suggests true extinction of the active inflammatory process . If so, CRP level may be of benefit in monitoring the duration of antibiotic therapy for SA, but the hypothesis has to be confirmed in a larger clinical trial. Br Heart J, 1984 Mar, 51(3), 339 - 45 The bowel, the genitourinary tract, and infective endocarditis; Bayliss R et al.; Of 582 episodes of infective endocarditis 75 were attributable to organisms normally resident in the bowel and 12 others were associated with alimentary tract operations, investigations, or disease . The mean age of the 87 patients in this particular group was higher (59.7 years) than that of all the patients with infective endocarditis (51.4 years) . As far as could be ascertained 41% had no pre-existing cardiac abnormality, and in a little under a half no predisposing event to initiate the illness was apparent . Where the portal of entry of the organism to the blood stream was evident it was slightly more often in the genitourinary than the alimentary tract . Bowel organisms are no less important than those associated with the teeth in causing infective endocarditis . It is suggested that in all those patients with known cardiac abnormalities and possibly in those over the age of 60 with normal hearts antibiotic cover should be considered when they undergo genitourinary or alimentary tract surgery or instrumentation. Mikrobiologiia, 1984 Mar-Apr, 53(2), 290 - 5 {Intergeneric hydridization of the actinomycetes Streptoverticillium mycoheptinicum and Streptomyces coelicolor}; Lapina IK et al.; Intergeneric crossing of the actinomycetes Streptoverticillium mycoheptinicum and Streptomyces coelicolor yielded recombinants which were mostly nonviable and unstable despite a relatively high frequency (10(-2)-10(-4)) at which their colonies appeared . The rare viable and stable recombinants were prototrophs . The structure of antibiotics in the hybrid cell may be modified as follows from the differences in the antibiotic activity of the LIA-973 hybrid and the parent strains. Br J Haematol, 1984 Mar, 56(3), 399 - 407 Relationship between the per cent of marrow cells in S phase and the outcome of remission-induction therapy for acute nonlymphocytic leukaemia; Preisler HD et al.; The relationship between the pretherapy cell cycle characteristics of leukaemic marrow cells and the outcome of remission-induction therapy for acute nonlymphocytic leukaemia was studied in newly diagnosed and relapsed patients who were then treated with either combination chemotherapy consisting of cytosine arabinoside/anthracycline antibiotic +/- 6 thioguanine or with single agent high-dose cytosine arabinoside therapy . The outcome of high-dose cytosine arabinoside therapy was highly dependent upon the per cent of pretherapy cells in S phase with no remissions occurring in patients in whom the 3H-TdR labelling index was less than 6% . In contrast, the outcome of cytosine arabinoside/anthracycline antibiotic therapy was independent of the pretherapy cell cycle characteristics of the leukaemic cells. Am J Otolaryngol, 1984 Mar-Apr, 5(2), 118 - 26 Total deafness from aminoglycoside overdosage: histopathologic case study; Johnsson LG et al.; A 57-year-old patient became totally deaf two days after receiving excessive doses of the aminoglycosidic antibiotic lividomycin parenterally for 14 days; she died four and a half months later . Her temporal bones were examined by microdissection, surface preparation, and serial sectioning of the modiolus . Loss of inner and outer cochlear hair cells was virtually complete . Refractile concretions were scattered along the atrophic stria vascularis, especially in the middle turn . The distal half of the radial cochlear nerve fibers in the osseous spiral lamina had degenerated, but closer to the modiolus they appeared to be intact . The spiral ganglion in the basal turn showed partial loss of neurons . Scanning electron microscopy revealed hair cell loss from the vestibular end-organs, more severe in the ampullar cristae than in the utricular macula . The dark cells of the utricular wall appeared to be altered. Eur J Cancer Clin Oncol, 1984 Mar, 20(3), 421 - 5 Comparison of antitumor effects of daunorubicin covalently linked to poly-L-amino acid carriers; Zunino F et al.; Daunorubicin was covalently linked to poly-L-aspartic and poly-L-lysine of different molecular weights via the methylketone side-chain of the drug by the use of a method that employs the 14-bromo derivative of the antibiotic . During reaction ester and C-N linkages were formed with poly-L-aspartic acid and poly-L-lysine respectively . Whereas a reduction of drug toxicity was observed with both types of conjugate, only the linking to the anionic polymer produced an enhancement of drug activity . In contrast, when drug was covalently attached to poly-L-lysine, cytotoxic activity and in vivo potency and efficacy were markedly reduced . The different therapeutic properties of these conjugates can be explained in terms of the different nature and stability of chemical bonds formed between the drug and the amino groups and carboxyl functions of the polyamino acid carrier. Clin Rheumatol, 1984 Mar, 3(1), 71 - 3 Septic arthritis and thigh abscess after dilatation and curettage; Struthers GR et al.; A previously fit 57-year old housewife who developed a septic arthritis of the right knee and abscess in the right thigh after dilatation and curettage is described . This is the first report of joint and soft tissue complications occurring together after this procedure . Despite antibiotic therapy which eradicated the joint infection, the abscess required surgical intervention . This illustrates the potential morbidity of septic complications after a minor surgical procedure. Gene, 1984 Mar, 27(3), 289 - 99 Length of foreign DNA in chimeric plasmids determines the efficiency of its integration into the chromosome of the cyanobacterium Synechococcus R2; Kolowsky KS et al.; The photosynthetic cyanobacterium Synechococcus R2 is efficiently transformed by DNA molecules that contain antibiotic genes from Escherichia coli linked to a segment of Synechococcus R2 chromosomal DNA . Antibiotic-resistant transformants result from integration of donor DNA into the cyanobacterial chromosome by homologous recombination . Foreign DNA interrupting the cyanobacterial sequence in the donor molecule integrates by replacement of homologous recipient DNA with donor DNA containing the foreign insert . Foreign DNA linked to the ends of the cyanobacterial fragment in a circular donor molecule integrates by a reciprocal cross-over between donor and recipient sequences . Using donor molecules that contain different lengths of foreign DNA in both of the above positions, we have determined that the probability of integration decreases by half for each increase of 2 to 3 kb in length of a foreign segment, regardless of its position in the donor molecule . The length of one of the two foreign segments has no effect on the integration of the other . Foreign DNA 20 kb in length is completely stable when it has integrated by the replacement mechanism . The ability to stably introduce large pieces of foreign DNA makes Synechococcus R2 an attractive organism in which to study and modify both native and heterologous genes involved in oxygenic photosynthesis. Jpn J Antibiot, 1984 Mar, 37(3), 338 - 43 {Clinical experience with ceftazidime in the infectious disease of children}; Nagamatsu I et al.; Thirteen patients mainly with lower respiratory tract infections were treated with ceftazidime (CAZ) . The drug was given intravenously in a dose of 11 approximately 34 mg per 1 kg of body weight 2 approximately 3 times per day . The clinical response to treatment was satisfactory in 10 patients (76.9%) . There was no side effects . CAZ appears to be an safe and effective antibiotic for the treatment of children with bacterial infections. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Mar, 256(3), 305 - 13 Effect of salinomycin-Na on malaria parasites (Plasmodium falciparum and P . berghei); Mehlhorn H et al.; In vitro exposure of Plasmodium falciparum and P . berghei to salinomycin-Na showed that 10 min incubation in RPMI 1640 medium containing 100 micrograms/ml of the polyether antibiotic led to complete destruction of most parasites; in media containing 10 or 1 microgram/ml salinomycin-Na some young developmental stages seemed to survive, apparently due to the protection of the mostly intact host cell . In vitro treatment of rats infected with P . berghei revealed that a single subcutaneous (oral) dose of 20 mg/kg (80 mg/kg salinomycin-Na caused complete destruction of parasites . Incipient degeneration of the parasites could be already observed 1 h after treatment . After 22 h parasites had disappeared from blood smears . Repeated subcutaneous doses of the polyether as low as 5 mg/kg (X3) completely destroyed the asexual stages of P . berghei . During the ultrastructural investigation of the action of salinomycin-Na it was found that initially the inner lacunes (such as endoplasmic reticulum and perinuclear space) and the mitochondrion were markedly swollen . This was followed by mitochondrial disruption with rupture of the parasites' pellicle . Since the infected host cells also ruptured, mainly extracellular parasites were seen in blood smears beginning 6 h after treatment . Salinomycin-Na seems to act similarly on the malarial parasites and on the free merozoites of chicken intestinal coccidia. Jpn J Clin Oncol, 1984 Mar, 14(1), 21 - 30 Controlled study of therapeutic granulocyte transfusions in granulocytopenic patients with severe infections; Matsue K et al.; The effectiveness of therapeutic granulocyte transfusions was studied in a controlled trial involving 75 granulocytopenic patients with severe infections . Patients who had granulocyte counts of less than 200/mm3 and no response to antibiotic therapy were assigned to receive antibiotic therapy alone or granulocyte transfusions plus antibiotic therapy . Granulocytes were collected by filtration leukapheresis (FL), intermittent flow centrifuge leukapheresis (IFCL) or continuous flow centrifuge leukapheresis (CFCL) . Therapeutic effects of granulocyte transfusions were evaluated on the basis of 20-day survival after entry into the study . The patients were divided into three groups: 1) 22 patients received antibiotic therapy alone for 29 infectious episodes (control group); 2) 27 patients received 131 transfusions of granulocytes collected by FL for 31 infectious episodes (FL group); 3) 26 patients received 139 transfusions of granulocytes collected by IFCL and CFCL for 27 infectious episodes (IFCL & CFCL group) . The overall survival of the transfused patients was not significantly different from that of the untransfused patients . Similarly, there was no significant difference in survival between the transfused and untransfused patients when the data concerning septicemia were analyzed . When patients showed bone-marrow recovery, which was indicated by recovery of granulocytes to 500/mm3 or more during the study, 20-day survival was observed in 13 of 14 untransfused patients and in all of 26 transfused patients . In contrast, the survival rate for the patients without bone-marrow recovery was 13% (2/15) in the control group, 39% (7/18) in the FL group and 57% (8/14) in the IFCL & CFCL group respectively . Thus, the survival rate was significantly higher for the transfused than for the untransfused patients . These observations suggest that therapeutic granulocyte transfusions may be of limited value in improving the outcome of severe infections in persistently granulocytopenic patients . Since bone-marrow recovery is a critical factor for the prognosis of severe infections, therapeutic granulocyte transfusions do not provide any beneficial effects in granulocytopenic patients whose bone-marrow function will recover. HNO, 1984 Mar, 32(3), 91 - 8 {Operative treatment of paranasal sinus diseases in childhood}; Hellmich S; An exact knowledge of the developing anatomy and physiology, and very conservative operative technique are the prerequisites for surgical therapy of the nose and the paranasal sinuses in children . These requirements are fulfilled by uncapping of the ethmoidal cells in chronic and especially acute ethmoid sinusitis . Intranasal antrostomy allows diagnosis to be made and limited local treatment to be given in acute and chronic maxillary sinusitis . More radical surgical procedures are not indicated in children, except in those cases, where severe orbital or endocranial complications have already developed . Uncapping of the ethmoidal cells and/or intranasal antrostomy combined with the elimination of mechanical obstruction of the upper respiratory tract are necessary, when conservative treatment of acute or chronic sinusitis is unsuccessful . Continuation of conservative therapy is then no longer indicated . The uncapping of the ethmoidal cells under antibiotic cover usually leads to a complete disappearance of the symptoms within a few days, even when orbital or periorbital complications of an acute ethmoiditis have already set in . Even after unsuccessful long-term treatment of a chronic maxillary sinusitis, intranasal antrostomy is successful in 75-90 per cent of cases . Complications did not occur in a personal series of 1,349 intranasal antrostomies in children in a period of 5 years. Am J Dis Child, 1984 Mar, 138(3), 287 - 92 Cefaclor v amoxicillin in treatment of acute otitis media; Giebink GS et al.; A randomized clinical trial compared cefaclor and amoxicillin for the treatment of acute otitis media (AOM) . Twenty-four (77%) of the 31 examined patients treated with cefaclor and 25 (83%) of the 30 examined patients treated with amoxicillin had resolution of signs and symptoms after completing a ten- to 14-day course of the antibiotic . Patients who had bilateral AOM, serous or mucoid middle ear effusion, Hemophilus influenzae cultured from effusion, or more than five previous otitis media episodes, or who were 3 years of age or younger were more likely to fail treatment . Hemophilus influenzae isolated from effusion were significantly less susceptible to cefaclor than amoxicillin, but none of the 12 treatment failures were caused by antibiotic-resistant infections . Eight (36%) of the 22 patients who recovered after treatment and were reexamined one to three weeks later experienced recurrent AOM . Ear-specific, as well as patient-specific, analyses showed no significant differences between cefaclor and amoxicillin. Somat Cell Mol Genet, 1984 Mar, 10(2), 123 - 7 Somatic cell hybrid selection with a transfectable dominant marker; Riera FC et al.; A recombinant plasmid vector, pSV2-neo, coding for resistance to neomycin and the related antibiotic G-418, was transfected into the mouse myeloma line X63-Ag8.653 by a modification of the protoplast fusion technique . The time interval required to obtain 10(6) G-418 resistant cells was 20 days and the efficiency was 10(-4)-10(-5), which represents a significant advantage over classical methods of selecting mutant cells bearing a dominant selection marker . To investigate the efficiency of this marker in somatic cell hybrid selection, these cells were fused to the human myeloma line U-266 and the hybrids were selected either in HAT + G-418 or HAT + ouabain . The pSV2-neo vector was as efficient as ouabain as a dominant marker with respect to the number of viable hybrid colonies selected and their levels of immunoglobulin secretion . The reciprocal experiment was also performed: HAT-sensitive, mutant U-266 cells were transfected with pSV2-neo, clones selected in G-418 and fused with X63-Ag8.653 cells, and hybrids selected in ouabain plus G-418, yielding HAT-sensitive hybrid "heteromyelomas" that were effective fusion partners with human B lymphocytes. Antibiotiki, 1984 Mar, 29(3), 163 - 6 {Production of liposomal preparations of streptomycin and dihydrostreptomycin}; Vladimirskii MA et al.; The effect of the conditions of the formation of liposomal preparations of streptomycin and dihydrostreptomycin on incorporation of the antibiotics into the liposomes was studied . The liposomes were obtained with the detergent (cholate) method modified by the authors . The modification implies preliminary application of a 20 per cent antibiotic buffer solution on columns for gel filtration of a mixed mycellar antibiotic solution (20 per cent) . The volume ratio of the preliminary applied buffer solution and the mixed mycellar solution is higher than 4:1 . The new procedure is simple, readily reproduced, providing formation of the liposomal preparations characterized by high levels of the antibiotic incorporation (about 300 micrograms per 1 mg of lecithin) . The preparations are stable with regard to the antibiotic release . The liposomes do not aggregate on storage for a long period (more than 6 months) . The liposomal preparations thus formed may be useful as intravenous dosage forms of the antibiotics. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Mar, 256(3), 300 - 4 Effects of bleomycin on kinetoplast DNA and nuclear DNA in Trypanosoma gambiense using in situ microfluorometry technique; Inoki S et al.; The effect of Bleomycin, an anti-tumour antibiotic, on either kinetoplast DNA(K-DNA) or nuclear DNA(N-DNA) in a single Trypanosoma gambiense cell was measured successfully utilizing the in situ microfluorometry technique . This microfluorometric assay clearly revealed that the relative fluorescence intensity (RFI) of K-DNA and N-DNA was greatly reduced by bleomycin, suggesting the occurrence of the single strand breaks in these DNAs . The present results have shown that bleomycin acts on N-DNA stronger than K-DNA at least in Trypanosoma gambiense . Microfluorometry technique can be employed valuably for studying the DNA damages of several anti-protozoan drugs. Drug Metab Dispos, 1984 Mar-Apr, 12(2), 209 - 16 The murine metabolism and disposition of marcellomycin; Dodion P et al.; The metabolism and disposition of marcellomycin (MCM), a new anthracycline antitumor antibiotic, were studied after iv administration to mice . In plasma, total drug fluroescence decreased according to first order kinetics and was mainly comprised of parent drug . In addition to MCM, five compounds (M2, P1, P2, G1, G2) were seen . M2 reflected the presence of a contaminant in the parent drug . P1 and P2 represented polar conjugates of MCM and M2, respectively; and G1 and G2 proved to be aglycones . P1 and G1 were observed during the first hours after injection, and G2 was more persistent and represented 35-50% of total drug fluorescence by 8 hr after injection . MCM was distributed widely to organs, except the brain . High MCM concentrations were measured in the lungs initially but they decreased quickly and, by 60 min, reached values similar to those present in the liver and kidneys . Low MCM concentrations were observed in heart and muscles . The splenic concentration of fluorescence rose progressively and, by 16 hr, was higher than that in all other organs . The concentrations of MCM metabolites were small in all tissues except in the liver, where an aglycone identified as 7-deoxypyrromycinone, was seen during the first 4 hr after injection . Our results indicate that the metabolism of MCM in the mouse is qualitatively similar to that in man, but that important quantitative differences exist . The significance of this observation as a possible explanation of the differences in observed toxicities between the two species remains to be established. Biochemistry, 1984 Feb 14, 23(4), 753 - 8 Effect of ethanol, phenol, formamide, dimethyl sulfoxide, paromomycin, and deuterium oxide on the fidelity of translation in a brain cell-free system; Laughrea M et al.; The effects of six different agents (ethanol, phenol, formamide, dimethyl sulfoxide, heavy water, and a misreading-inducing antibiotic, paromomycin) on the activity and the accuracy