Antibiotics

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 of poly(U) translation have been compared under a range (2.5-12 mM) of Mg2+ concentrations in a rat brain cell-free system . The effect of most of these agents was remarkably sensitive to the Mg2+ concentration under which the assay was made . Ethanol decreased the fidelity of translation, and the efficiency of ethanol was increased 3-10-fold by higher Mg2+ concentrations . The effect of paromomycin was identical with that of ethanol, despite its very different structure . Formamide, a "RNA denaturant", increased the accuracy of translation under all Mg2+ concentrations tested . Dimethyl sulfoxide, another type of RNA denaturant, decreased the accuracy of translation under all Mg2+ concentrations tested . Phenol increased the accuracy of translation at high Mg2+ concentrations but decreased it at low Mg2+ concentrations . D2O did not change to any appreciable extent the accuracy of translation, at all the Mg2+ concentrations used . There exists a cooperativity between the effects of Mg2+ and ethanol, Mg2+ and paromomycin, and Mg2+ and dimethyl sulfoxide on the fidelity of translation; no such cooperativity was detected between Mg2+ and formamide and between Mg2+ and D2O . The differential effects of dimethyl sulfoxide and formamide are interpreted in terms of their different dielectric constants . The dielectric constant of dimethyl sulfoxide is higher than that of water, while that of formamide is low er.

Med J Aust, 1984 Feb 4, 140(3), 140 - 2
Cryohypophysectomy for the relief of pain in malignant disease; Gonski A et al.; Fifty consecutive patients with metastatic carcinoma who underwent cryohypophysectomy were studied . Of these, 26 had breast cancer, 19 had prostatic cancer, one had malignant melanoma, one had cancer of the kidney, and three had metastatic adenocarcinoma from an unknown primary tumour . After cryohypophysectomy, excellent pain relief was obtained in 48% of patients, good or acceptable pain relief was obtained in 40%, and poor or no relief in 12% . Two patients died: one of aspiration pneumonia and one of an unknown cerebral cause . Sixteen patients developed diabetes insipidus, of whom three required therapy with vasopressin; eight patients developed a cerebrospinal fluid leak, two of whom required surgical repair; and four patients developed meningitis, which resolved in three after antibiotic therapy . Results are compared with those from other published reports . Pain relief from cryohypophysectomy is surmised to be due to the production of endorphins, but no proof of this is available.

Paraplegia, 1984 Feb, 22(1), 17 - 24
Osteomyelitis in the spinal cord injured: a review and a preliminary report on the use of hyperbaric oxygen therapy; Eltorai I et al.; Spinal Cord Injury patients are liable to develop osteomyelitis mostly by extension from pressure ulcers . In 2055 records reviewed in the Long Beach Spinal Cord Injury Service of the Veterans Administration Medical Center, the incidence was found to be 4.3 per cent . Of these osteomyelitis developed secondary to pressure ulcers in 88 per cent, the rest developed as a result of trauma and/or surgery . Forty-four patients manifesting chronic osteomyelitis were treated in a monoplace hyperbaric oxygen (HBO) chamber, in addition to receiving antibiotic and surgical treatment . HBO was found useful as an adjunct to help to resolve the bone infection and encourage wound healing . Two-thirds of the patients were cured, and the follow-up was from 6 months to 9 years . We believe that HBO is a useful adjunctive therapeutic measure in the management of chronic osteomyelitis in the spinal cord injured and in the prevention of its complications.

J Chir (Paris), 1984 Feb, 121(2), 101 - 4
{Early surgical treatment of acute cholecystitis}; Issa M et al.; Correlations between anatomic and clinical findings were absent in a series of 214 cases of acute cholecystitis, and there was a high percentage of severe forms (58 p . 100) . Early operation (between 48 and 72 hours) is therefore the most logical treatment and demonstrates comparable morbidity and mortality, if not lower figures, than with delayed surgery . Diagnosis can usually be made on clinical grounds and results of ultra-sound imaging and allows surgery to be performed after intensive care and preoperative antibiotic therapy . Total surgery with perioperative cholangiography is usually possible (95 p . 100 cases).

Arkh Anat Gistol Embriol, 1984 Feb, 86(2), 85 - 92
{Structural characteristics of the thymus in the antenatal and early postnatal periods of ontogeny in tetracycline exposure}; Petrova TB; Structural peculiarities of the thymus have been studied in Wistar rats during antenatal and early postnatal periods of ontogenesis under the effect of tetracycline hydrochlorid administered in therapeutic doses to the system mother--fetus during preimplantation period of the fetus development (the 1st - 6th days) . Histological, histochemical, electron microscopical and morphometrical methods have been used . Ultrastructural changes of epithelioreticulocytes and thymocytes, a delayed appearance of the subcapsular zone, a delayed division of the thymus lobules into the cortex and medullar substance, a decreasing content of all cellular forms of the lymphoid line during the intrauterine development have been revealed, as well as a decreased amount of small lymphocytes at all stages of the antenatal and early postnatal periods of ontogenesis . The data obtained are considered as a result of a toxic effect of the antibiotic.

J Antibiot (Tokyo), 1984 Feb, 37(2), 167 - 71
Influence of cefoperazone on ethanol and acetaldehyde metabolism in vitro; Greizerstein HB et al.; The effect of cefoperazone on ethanol and acetaldehyde metabolism was studied in rat liver homogenates and with a purified aldehyde dehydrogenase . Rat liver homogenates were incubated with ethanol (30 mM) alone or in combination with cefoperazone (15 or 150 micrograms/g liver) . Ethanol and acetaldehyde concentrations were determined at 6, 12, 18 and 24 minutes . Cefoperazone added to the incubation medium inhibited ethanol and acetaldehyde metabolism in a concentration-dependent manner . The addition of cefoperazone to rat liver homogenates incubated with acetaldehyde (300 microM), however, did not inhibit acetaldehyde disappearance for a period of 15 minutes . Purified aldehyde dehydrogenase was incubated with 300 microM acetaldehyde . When cefoperazone was added, acetaldehyde disappearance was significantly slower than without cefoperazone . The data indicate that cefoperazone inhibits ethanol metabolism in rat liver homogenates in a concentration-dependent manner . The effect of the antibiotic on acetaldehyde elimination in liver homogenate, however, depends on the concentration of acetaldehyde in the medium . The acetaldehyde dehydrogenase obtained from yeast is inhibited by cefoperazone.

J Antibiot (Tokyo), 1984 Feb, 37(2), 159 - 66
Demonstration of a metabolic grid at an early step in the streptonigrin biosynthetic pathway in Streptomyces flocculus; Speedie MK et al.; The enzyme activities which catalyze the conversion of tryptophan to beta-methyltryptophan by two different routes have been demonstrated in cell-free extracts of streptonigrin-producing Streptomyces flocculus . The first route involves direct methylation of tryptophan by a C-methyltransferase . The second involves transamination of tryptophan to indolepyruvate, methylation of indolepyruvate to beta-methylindolepyruvate, followed by a reverse transamination reaction to yield beta-methyltryptophan . The direct methylation route was confirmed by the fact that the methyltransferase activity is still present after the transaminase has been inactivated by hydroxylamine treatment . The L-tryptophan C-methyltransferase has been purified 30-fold by ammonium sulfate precipitation and a Sephadex G-150 column . The indolepyruvate C-methyltransferase activity copurified with the tryptophan C-methyltransferase activity, but the transaminase did not . These results show that a metabolic grid exists for the first antibiotic-committed step of the streptonigrin biosynthetic pathway.

HNO, 1984 Feb, 32(2), 81 - 3
{Topically induced ototoxicity}; Federspil P; Topically induced ototoxicity caused by applying substances into the middle ear is discussed in detail . The numerous ototoxic cases described in the recent literature and the high aminoglycoside antibiotic concentrations contained in ear drops are stressed . Methods for reducing the aminoglycoside antibiotic ototoxicity of these ear drops are given . These include safe and effective concentrations of 30 or 60 mg/l Gentamicin, Sisomicin or Tobramycin and their application by ointment . Different chapters deal with the ototoxicity of other antibiotics and solutions, particularly with the risk in sterilization of the middle ear space by surface disinfectants such as chlorhexidine or benzalkonium-chloride . The rare indications for topical ear drops in otitis media are described.

Med Radiol (Mosk), 1984 Feb, 29(2), 7 - 10
{Complex therapy of melanoma metastases in the lung}; Nivinskaia MM et al.; The authors present the therapeutic results of 25 patients with melanoma metastases of the lungs: 9 of them received radiotherapy only, 16 radiotherapy combined with i.v . injection of the antitumor antibiotic dactinomycin . The technique of large field irradiation of the lungs was employed as a single exposure (depending on tumor spread) of the entire volume of one or both lungs . The treatment resulted in a decrease of metastases by more than 50% of the initial value in 2 out of 6 patients in the 1st group; in the 2nd group in 16 patients metastases disappeared, in 2 patients they decreased by 50% . Pulmonites prevailed in the group of multiple modality treatment . The authors conclude that dactinomycin raises to a higher power the degree of radiation exposure of melanoma metastases as well as the normal lung tissue.

Arch Otolaryngol, 1984 Feb, 110(2), 130 - 1
Pyogenic otorhinologic infections in acquired immune deficiency syndrome; Poole MD et al.; A 25-year-old homosexual man with acquired immune deficiency syndrome had CNS toxoplasmosis, mucosal candidiasis, acute otitis media, and sinusitis . These problems persisted despite multiple courses of antibiotic therapy . Surgical drainage proved to be the only effective means of controlling his otorhinologic infections . We recommend early surgical intervention for this type of patient when standard antibiotic therapy for sinusitis and otitis media proves ineffective.

Am J Med, 1984 Feb, 76(2), 315 - 7
Fever on drug-free day of alternate-day steroid therapy; Semel JD; A patient is described who had high spiking fever following a changeover from daily to alternate-day prednisone therapy . No infectious cause was found, and antibiotic therapy did not affect the temperature graph . Previously, the patient, who had dermatomyositis, experienced minimal or no temperature elevation during observation in the hospital, first while receiving no therapy, and later while receiving daily prednisone therapy . Fever disappeared promptly when daily prednisone therapy was resumed . It is postulated that the 12- to 24-hour "drugless" period experienced by a patient during alternate-day prednisone therapy could lead to a withdrawal syndrome characterized by a tertian malaria-like temperature pattern . The importance of recognizing such a phenomenon and distinguishing it from infection is emphasized.

J Thorac Cardiovasc Surg, 1984 Feb, 87(2), 308 - 12
Percutaneous drainage of lung abscess; Weissberg D; Patients with primary lung abscess who do not respond to medical management are usually candidates for a lobectomy . Percutaneous tube drainage, used routinely and with good results before the antibiotic era, has nearly been forgotten . Seven patients with lung abscesses and severe sepsis were in critical condition, not permitting pulmonary resection . They were treated by tube drainage . Prompt clinical recovery occurred in all, with complete resolution of abscesses within 4 to 24 days . When medical therapy of lung abscess fails, tube drainage should be considered in preference to a lobectomy . It is safe and curative and avoids unnecessary loss of functioning lung parenchyma . Lobectomy should be considered in patients who have major life-threatening bleeding or massive pulmonary necrosis.

Arch Ophthalmol, 1984 Feb, 102(2), 207 - 10
Bacterial endophthalmitis after closed vitrectomy; Ho PC et al.; Four cases of bacterial endophthalmitis occurred after more than 2,800 closed vitrectomies . Despite vigorous antibiotic therapy, all four eyes were lost . The poor outcome seems to result from difficulties in diagnosing this condition in its early stages . Important clinical indications, such as orbital pain, corneal edema and infiltrate, excessive intraocular inflammatory reaction, hypopyon, and diminished fundus reflex, are often masked by the usual postoperative course . According to our study, the incidence of endophthalmitis after closed vitreous surgery is 0.14% . Three of the four patients with endophthalmitis were diabetic . Our clinical findings are compared with those in the four other cases reported in the literature.

AJR Am J Roentgenol, 1984 Feb, 142(2), 351 - 4
Percutaneous drainage of renal abscesses; Cronan JJ et al.; Percutaneous drainage combined with cross-sectional imaging is reported in five patients with intrarenal abscesses . No recurrences and no complications occurred . This nonsurgical approach avoids the risks inherent in surgical therapy . Combined with appropriate antibiotic coverage, percutaneous drainage is an effective nonsurgical therapy for unilocular intrarenal abscesses.

Emerg Med Clin North Am, 1984 Feb, 2(1), 77 - 86
The emergency management of caustic ingestions; Friedman EM et al.; In the emergency department, any patient who is suspected of having sustained a caustic ingestion must be handled in a serious manner . All patients should be initially stabilized with regard to airway and circulatory status . Initial questioning concerning the type and quantity of agent ingested will be most helpful . Signs and symptoms of shock, impending perforation, or airway distress take precedence over any further work-up . Patients who have a known history of ingestion require admission to the hospital . Complete physical examination should be carried out, bearing in mind that the lack of oropharyngeal involvement or other symptoms does not rule out the possibility of esophageal burns . One should avoid emesis and should begin early dilutional therapy . Water may be used initially to dislodge adherent solid particles, as well as to dilute the caustic ingestion . It is important not to be excessively aggressive with dilution, as this may cause nausea, vomiting, and possible aspiration . Early otolaryngologic evaluation will be most helpful . The role of early esophagoscopy has been demonstrated to aid greatly in determining the further management . This diagnostic procedure should be carried out within 48 hours after ingestion . Based on the information obtained with esophagoscopy, patients who have had moderate esophageal burns should receive 20 mg methylprednisone intravenously every eight hours if under the age of two and 40 mg intravenously every eight hours if over the age of two . When oral preparations can be used, 2 mg per kg of prednisone should be continued for three to four weeks . Antibiotic coverage should be reserved until the first sign of infection occurs.

Int J Oral Surg, 1984 Feb, 13(1), 65 - 8
Myospherulosis of the mandible . Report of a case and review of the literature; Ide F et al.; A case of myospherulosis in a 67-year-old female is reported . The lesion appeared as a submucosal mass firmly attached to the buccal periosteum of the right molar region of the mandible . Although the records of our case did not specify what medication was placed in the lesion, clinicopathologic features further supported the hypothesis that myospherulosis may be a unique instance of iatrogenic disease caused by petrolatum-based antibiotic ointments.

J Gen Microbiol, 1984 Feb, 130 ( Pt 2), 319 - 23
Aspergillic acids produced by mixed cultures of Aspergillus flavus and Aspergillus nidulans; Perry MJ et al.; A mixed culture of Aspergillus nidulans (GH79) and Aspergillus flavus (CMI 91019B) produced two antibiotics, designated VI and VII, which were not elaborated when either fungus was grown alone . Chemical and spectroscopic analysis of VI, the major component, indicated that this compound was identical to hydroxyaspergillic acid . The minor component, VII, was produced in too low a yield for its identity to be established . However, partial characterization suggests that this antibiotic also belongs to the aspergillic acid group of mycotoxins.

Eur J Respir Dis, 1984 Feb, 65(2), 114 - 24
Sputum sol-phase proteins and elastase activity in patients with cystic fibrosis; Jackson AH et al.; Sputum and serum samples were obtained from 38 patients with cystic fibrosis seen as out-patients at routine follow-up, or from patients admitted with acute pulmonary exacerbations of their disease . Elastolytic activity was measurable in the sputum of 13 of 16 out-patient samples and detectable in 21 of 22 patients admitted with pulmonary exacerbation . The enzyme activity was inhibited by soy bean trypsin inhibitor and alpha 1 antitrypsin, but not by ethylenediamine tetracetic acid, suggesting that it was predominantly a serine proteinase, probably leucocyte elastase . The mean sputum/serum albumin ratio was 2.53 X 10(-2) (SD +/- 2.4) for the out-patients and this was not significantly different from those of patients admitted with pulmonary exacerbation . However, those patients admitted with fever had increased sputum/serum albumin ratios (mean = 4.66 X 10(-2); SD +/- 3.19) compared with those admitted with a normal temperature (mean = 1.52 X 10(-2); SD +/- 0.41 . 2p less than 0.01) . The albumin ratios of the pyrexial group fell with antibiotic therapy . The sputum/serum alpha 1 antitrypsin ratios were generally greater than expected (by comparison with albumin) and evidence is presented suggesting that this is due to immunological over-estimation.

Thorax, 1984 Feb, 39(2), 121 - 4
Wound prophylaxis in thoracic surgery: a new approach; Walker WS et al.; A prospective double blind, randomised study was performed in 100 patients undergoing major elective thoracic surgery to assess a new method of prophylaxis of wound infection using one preincisional intraparietal infiltration of cefuroxime sodium along the line of proposed incision as the sole protection against wound infection . A significant (p less than 0.01) reduction in the incidence of wound infection occurred in the antibiotic treated group (2%) compared with the control group (20%), who received by the same route the same volume of saline only . The groups were comparable with respect to age, sex, pathological condition, and operative variables . The use of additional antibiotics was significantly greater in the control group (p less than 0.01), largely owing to a much greater incidence of postoperative pulmonary infection in the control group (60%) than in the antibiotic treated group (40%) . No morbidity was associated with this technique . The organisms found in oesophageal and bronchial operative luminal specimens did not correlate with postoperative wound or pulmonary infection or with organisms causing these infections . Reductions in wound and pulmonary infection rates equivalent to those produced by conventional multiple dose parenteral regimens were achieved by this technique.

Jpn J Antibiot, 1984 Feb, 37(2), 198 - 208
{Studies on the skin test of cefotiam and anti-cefotiam antibody}; Muranaka M et al.; Patients having previously not received cefotiam (CTM), a recently introduced cephem antibiotic, were subjected to skin tests with a 300 micrograms/ml solution of CTM in physiological saline before and after CTM therapy to detect sensitization with the drug . Anti-CTM antibody titration was carried out on sera from patients who showed a positive skin test and those who developed signs of hypersensitivity during CTM therapy . The results were as follows: Of 1,927 patients examined by skin test with CTM prior to initiation of CTM therapy, 31 patients (1.61%) showed positive reactions with formation of a wheal and erythema . There were 7 patients (0.36%) who proved negative in the skin test but developed mild symptoms of hypersensitivity in association with the skin test . The 847 patients negative on the CTM skin test were retested after a completion of CTM therapy, of whom 6 (0.71%) were found to have become positive showing formation of a wheal and erythema and 3 others (0.35%) showing a negative skin test developed mild adverse reactions associated with the skin test . Sixty-eight serum samples collected from the patients positive on the CTM skin test and those who developed manifestations of hypersensitivity following CTM therapy were examined for anti-CTM antibody by the Prausnitz-K ustner reaction, passive cutaneous anaphylaxis test and hemagglutination test . All proved negative in these tests . Of various background factors assessed, none was found to have causal relation to the skin reaction in any of the patients showing positive skin reactions to CTM.

J Biochem (Tokyo), 1984 Feb, 95(2), 431 - 42
Reconstruction of photosynthetic, cyclic electron transport system from photoreaction unit, ubiquinone-10 protein, cytochrome c2 and polar lipids purified from Rhodospirillum rubrum; Matsuda H et al.; It was previously reported that in chromatophores of Rhodospirillum rubrum, reaction center, which consists of three kinds of protein (Mm, about 78K), is a small fragment of a large protein complex (PRU; photoreaction unit), which contains six other kinds of protein including light-harvesting bacteriochlorophyll protein, has Mm of about 700K and is free of phospholipid {J . Biochem . 86, 1211-1224 (1979); 94, 1815-1826 (1983(} . In the present study, the photosynthetic, cyclic electron transport system sensitive to antimycin A was effectively reconstructed by incubating 60 nM PRU (which contained 1 mol of reaction center and 2 mol of ubiquinone-10 per mol) with 300 nM each of oxidized ubiquinone-10 protein, reduced cytochrome c2 and lipoamino acid (which were all purified from Rhodospirillum rubrum) in the presence of low concentrations of cholate and deoxycholate (pH 8.0) . In the light, the cytochrome was oxidized while the quinone was reduced . The oxidation and reduction each progressed rapidly at first, then slowly, reaching maxima (steady states) 1-2 min after the light had been turned on . At the steady states, 30% of the cytochrome was oxidized while 11% of the total quinone was reduced . When the light was turned off, the original oxidation-reduction states of the cytochrome and quinone were restored at rapid rates initially then at slow rates . Antimycin A stimulated the slow rates in the light-on state and depressed them in the light-off state, but did not influence the fast rates . Ubiquinone-10 protein was required for the antibiotic-sensitive, slow oxidation reactions . This indicates that the slow rates were due to cyclic electron transport . Cytochrome c2 was tightly bound to PRU at a molar ratio of 1:1 . This cytochrome as well as the quinone bound to PRU was responsible for the fast rates . PRU had other sites able to bind cytochrome c2 and ubiquinone-10 protein with Km of 0.4 and 0.1 microM, respectively . Of the polar lipids tested, lipoamino acid was the most effective for reconstruction, and its effect was maximal at 300 nM, which is far below its critical micelle concentration.

Behav Brain Res, 1984 Feb, 11(2), 109 - 16
Hormonal influence on the duration of short-term and intermediate stages of memory; Gibbs ME et al.; In day-old chicks trained on a single trial passive avoidance learning task, ACTH1-24 and corticosterone delayed the formation of long-term memory and the decay of the immediately preceding intermediate memory . This action of ACTH1-24 was attributed to its glucocorticoid activity since ACTH4-10 did not yield the same effect . ACTH1-24 and ACTH4-10, but not corticosterone, enhanced short-term memory retention levels . The effects of arginine vasopressin and arginine vasotocin were similar to those observed with ACTH1-24, but they also delayed the decay of short term memory and hence the formation of intermediate memory . These findings were discussed in the context of hormonal modulation of memory formation and counteraction of antibiotic-induced amnesia.

Sem Hop, 1984 Jan 26, 60(3), 202 - 4
{Diffuse diverticulosis of the small intestine and malabsorption syndrome . Apropos of a case}; Quilichini R et al.; A case of acquired jejuno-ileal malabsorption complicated by vitamin B12 malabsorption with macrocytic anemia and posterior column dysfunction is reported . Few such observations have been published in the medical literature . In the light of published studies and case-reports the authors review the pathogenic hypotheses concerning the formation of diverticula, the part played by bacterial infection in the mechanisms of malabsorption and the value of antibiotic therapy in the initial treatment of this condition.

Biochemistry, 1984 Jan 17, 23(2), 385 - 9
Inhibitory effect of duramycin on partial reactions catalyzed by (Na+,K+)-adenosinetriphosphatase from dog kidney; Nakamura S et al.; The polypeptide antibiotic duramycin inhibited the (Na+,K+)-adenosinetriphosphatase purified from dog kidney . An analysis of its mode of action revealed that the formation of phosphoenzyme from Pi but not from ATP was inhibited . The rate of dephosphorylation of the phosphoenzyme formed from ATP was markedly reduced . In contrast to quercetin, duramycin did not inhibit K+-dependent p-nitrophenylphosphatase activity . The effect of duramycin was completely reversed by phospholipids.

Biochem J, 1984 Jan 15, 217(2), 493 - 8
Influence of ubiquinone on the inhibitory effect of adriamycin on mitochondrial oxidative phosphorylation; Muhammed H et al.; The inhibition of succinate oxidation in both heart and liver mitochondria by the cardiotoxic anticancer antibiotic adriamycin in vitro was reversed to a large extent by exogenous ubiquinone-45 . Inhibition of the oxidation of NAD+-linked substrates in heart and liver mitochondria responded differently to ubiquinone, the inhibition being reversed only in liver organelles . Administration of adriamycin inhibited oxidative phosphorylation in rat heart, kidney and liver mitochondria, the inhibition being highest in the heart organelles (about 50% for both NAD+-linked substrates and succinate) . Exogenous addition of ubiquinone to mitochondria isolated from drug-treated animals did not reverse the inhibition . Administration of ubiquinone along with adriamycin did not change effectively the pattern of drug-mediated decrease in oxidative activity of the organelles, particularly in the heart.

Am J Nephrol, 1984, 4(3), 152 - 7
Peritoneal eosinophils during intermittent peritoneal dialysis; Piraino BM et al.; Peritoneal eosinophil counts were investigated in 61 intermittent dialysis patients over the course of 1 year . The peritoneal eosinophil percentage fell from 18 +/- 2% (mean +/- SEM) in the first 2 months of dialysis to 3 +/- 0.4% after 6 months of dialysis . Absolute eosinophils per cubic millimeter fell from 586 +/- 126 to 61 +/- 18 (p less than 0.01 for both percentage and absolute values) . There was a wide range in the mean eosinophil percentages per patient in the first 6 months of dialysis (0-84%) that narrowed to 0-9% after 6 months . The majority of the high initial eosinophil counts resolved after 2 months . Peripheral eosinophilia was seen in 8 of the 10 patients with the highest mean peritoneal eosinophil percentages during the first 2 months of dialysis . Patients who developed peritonitis had a significantly lower percentage of eosinophils in the first 1.5 months of dialysis than patients who did not develop peritonitis . At the time of diagnosis of peritonitis, the peritoneal eosinophil count was near zero . 4 cases of peritoneal eosinophilia which developed after antibiotic therapy are described.

Vet Med Nauki, 1984, 21(4), 35 - 41
{Tolerance for tetraolean i.m . and the blood levels in agricultural animals}; Dilov P et al.; Studied was a drug formula of tetraolean for i/m application, containing tetracycline hydrochloride and oleandomycin phosphate in a 2:1 ratio, produced by the Antibiotic Works, Razgrad, and released in flasks of 500 mg and 1.0 g . It was followed up with regard to its tolerable serum concentrations for rabbits, calves, pigs, and horses . It was found that in therapeutic amounts tetraolean was well tolerated and did not lead to local and general disturbances . In higher doses it was found to form transient oedema in the site of injection . Intramuscularly, tetraolean was well absorbed in the site of application, and, according to the animal species, it developed proper plasmal therapeutic concentrations at the following rates: calves--20 mg/kg body mass at 12-hour intervals; pigs--10 mg/kg at 6-hr intervals, or 20 mg/kg at 12-hr intervals; horses--10 mg/kg at 12-hr intervals or 20 mg/kg at 24-hr intervals.

Intensive Care Med, 1984, 10(3), 155 - 6
Primary pneumococcal pericarditis complicated by acute constriction; Laaban JP et al.; We report a case of a 31-year-old male with primary pneumococcal pericarditis . Severe acute constrictive pericarditis developed within a month of the onset of the illness in spite of adequate antibiotic therapy and pericardial drainage.

Am J Nephrol, 1984, 4(1), 38 - 42
Incomplete activation of intraperitoneal clindamycin phosphate during peritoneal dialysis; Golper TA et al.; Clindamycin phosphate (C-PO4) must be hydrolyzed to the active antibiotic, but whether this occurs within the peritoneal cavity during peritoneal dialysis is unknown . Therapeutic peritoneal levels are difficult to achieve after intravenous administration, so direct intraperitoneal instillation is preferred in treating dialysis-associated peritonitis . Therefore, the activation of C-PO4 in peritoneal dialysate was investigated . Fresh and 'uremic' peritoneal dialysates of 1.5 and 4.25% dextrose concentrations at pHs of 5.1 and 7.4 did not activate C-PO4 . Clindamycin hydrochloride in this same fluid was active, ruling out uremic deactivators . A patient with peritonitis was treated with intraperitoneal C-PO4, and therapeutic (greater than 5 micrograms/ml) serum and peritoneal levels were achieved . Infected (exudative) peritoneal dialysate drained from another patient with peritonitis activated C-PO4 in vitro . Commercial alkaline phosphatase added to uremic dialysate also activated C-PO4 in vitro . C-PO4 was instilled into the peritoneal cavities of 10 noninfected patients . Exposure to the peritoneal membrane at two concentrations resulted in a 3% activation of C-PO4 . From these observations it is clear that C-PO4 is only partially activated intraperitoneally . Uremia or uremic products in the dialysate do not deactivate the antibiotic . Exudative material (bacteria, white blood cells and proteins) in infected dialysate contribute to activation of C-PO4 . The peritoneal membrane further assists in activation . We recommend that C-PO4 be administered at a concentration of 167 mg/l of dialysate to ensure therapeutic peritoneal levels of the active antibiotic, especially after the exudative phase clears.

Zentralbl Allg Pathol, 1984, 129(2), 101 - 4
Histopathology of pseudomembranous colitis; Pesce CM et al.; Pseudomembranous colitis, an uncommon affection following surgery or antibiotic therapy, is characterized by whitish plaques ( pseudomembranes ) attached to the mucosa . Serial sectioning of these pseudomembranes disclosed that each of them was related to a lymphoid aggregate in the submucosa and the lamina propria . A group of glandular crypts overlying the aggregate were dilated by mucus, fibrin, leukocytes, and cellular debris . These contents jutted out of the mucosal surface into the lumen, constituting the stem of the pseudomembrane, and could spread over the surrounding mucosa . Accordingly, a morphologic unit was recognized in pseudomembranous colitis, including the lymphoid aggregate, the dilated glandular crypts, and the pseudomembrane stem.

Pediatr Radiol, 1984, 14(2), 91 - 3
Upper gastrointestinal and ultrasound examinations of gastric antral involvement in chronic granulomatous disease; Kopen PA et al.; Two brothers with chronic granulomatous disease of childhood are presented with circumferential gastric antral thickening demonstrated on sonography . Barium studies and sonography correlated well in one brother . The antral changes can resolve quickly without antibiotic therapy.

Mol Cell Biochem, 1984, 61(2), 183 - 91
Action of oligomycin on cultured mammalian cells . Permeabilization to translation inhibitors; Otero MJ et al.; Oligomycin, an inhibitor of ATP synthesis, has been used as a model to study the effects of ATP depletion on macromolecular synthesis and modification of membrane permeability . Protein synthesis is totally blocked by the antibiotic, whereas RNA and DNA synthesis are less inhibited . Different concentrations of monovalent and divalent cations do not revert the inhibition of protein synthesis . Measurement of cellular ATP and 86Rb+ content indicate that the blockade of translation depends on the ATP content . A significant decrease in cellular ATP does not lead to the reduction of monovalent ions in the cell, although hyperpolarization of the cell membrane does take place . An increased membrane permeability to some inhibitors develops when the cells are hyperpolarized by oligomycin.

Jpn J Antibiot, 1984 Jan, 37(1), 145 - 51
{Fundamental and clinical studies on cefpiramide in the field of obstetrics and gynecology}; Yamamoto T et al.; Fundamental and clinical studies were performed on cefpiramide (CPM), a new cephem antibiotic, with following results . Following a single intravenous administration of 1.0 g dose of CPM, the average serum level of CPM was 129.5 micrograms/ml after 1 hour and the half-life in beta-phase was about 5.0 hours . The transfer of CPM to the internal genital organs was found to be good . the transfer of CPM to retroperitoneal fluid was moderate . In clinical trial, CPM was given to 9 patients with obstetrical and gynecological infection . Efficacy was excellent in 1 case and good in 6 cases (effectiveness rate: 77.8%) . No side effects were observed . In laboratory findings, a mild elevation of S-GOT was noted in 1 case.

Clin Ther, 1984, 6(3), 344 - 53
A multicenter clinical study of cefoperazone; Alix M et al.; Thirty-five adult and 11 pediatric patients in nine Philippine hospitals were treated with cefoperazone for various moderate to severe infections . Adults received 1 to 8 gm/day and children received 0.450 to 4 gm/day in two divided doses, for a mean period of eight to nine days (ranges, 5 to 11 days for children and 5 to 30 days for adults) . The efficacy rate (cured and improved) was 90.90% for pediatric patients and 85.72% for adult patients . In a group of patients shifted from other antibiotic regimens, efficacy rates were 100% for pediatric patients and 85% for adult patients treated with cefoperazone . No follow-up cultures were obtained from patients from whom 26 pathogens were isolated, but correlations between the isolates and clinical efficacy showed that cefoperazone had an efficacy rate of 92.3%.

Z Naturforsch {C}, 1984 Jan-Feb, 39(1-2), 126 - 35
Cell cycle kinetics and metabolism of Ehrlich ascites tumor cells in the presence of chloramphenicol as inhibitor of mitochondrial protein synthesis; Kroll W et al.; In the presence of 150 micrograms/ml of chloramphenicol, viability (dye exclusion test) of Ehrlich ascites tumor cells is not severely affected within 48 h; however the number of dead cells increases above this concentration; more than 10 mg/ml render all of the cells dye-positive within a culture period of 24 h . With the highest concentration tested (25 mg/ml) cells begin to lose viability 8 h after beginning of treatment . In the first passage in the presence of the antibiotic, proliferation of the cells is reduced by about 50%; in the second passage cell growth was about 65% that of controls . As is shown by flow cytometric analysis and BrdU-H33258 technique of flow cytometry, the reduction of proliferation in the second passage is caused by retardation of cell cycle progression of about 8 h; in the third passage the cell cycle is delayed by further 8 h as compared to controls . On recultivation in the third passage in the absence of the inhibitor an increase of cell number of about 75% of controls was observed . Lactate production and glucose uptake of the cells were stimulated by the inhibitor by about 20%; oxygen consumption was 60% that of controls after 24 h; however the ATP/ADP ratio of chloramphenicol treated cells was in the range of controls . Over a time period of 24 h the incorporation of {2-14C}thymidine is reduced to 34 +/- 3%, incorporation of {2-14C}uridine was 88 +/- 4% that of controls, incorporation of {U-14C}lysine was not significantly affected by 150 micrograms/ml of chloramphenicol; the same was found for the uptake of {2-14C}-alpha-aminoisobutyric acid . Electron micrographs of chloramphenicol treated cells reveal a high amplitude of swelling of all mitochondria with a translucent appearance of the inner compartment . The mitochondrial membranes remain largely intact but the number of cristae is drastically reduced.

Med Microbiol Immunol (Berl), 1984, 172(4), 197 - 205
Rifampicin-induced suppression of antitumor immunity; Roszkowski W et al.; The effect of rifampicin on transplantable tumor growth and antitumor immunity was studied . The growth of transplantable lung sarcoma was significantly enhanced in mice when rifampicin was given for 7 days or longer . Also, the antitumor effects of preimmunization of the animals with killed tumor cells were abrogated by this antibiotic . In vitro studies showed that spleen cells from tumor-bearing animals expressed significantly lower specific cytotoxicity toward syngeneic tumor cells, when the animals had been previously treated with rifampicin . Also, natural killer activity in healthy animals was diminished in mice receiving the antibiotic.

Arch Orthop Trauma Surg, 1984, 102(4), 238 - 41
Local penetration of gentamicin into the femoral cortex of rats; Mirovsky Y et al.; To investigate the extent of local penetration of antibiotic into the bone, a single dose of 10 mg/kg gentamicin sulphate was injected over the midshaft of the left femur in 12 young and 14 old rats . In some of the rats the injected gentamicin was dissolved in saline while in the others it was dissolved in dimethylsulphoxide (DMSO) . Up to 120 minutes after the injection gentamicin concentrations were measured by the fluoroimmunoassay method in the serum, cortex and spongiosa of both femurs . In young rats gentamicin was shown to have penetrated directly into the bone and its presence was limited to the femoral cortex . In the old rats, on the other hand hematogenic was found to be the antibiotic spread in the femurs . No significant difference was observed between DMSO and saline as solvents in facilitating gentamicin penetration into the bone or capillaries in either age group.

Eur J Respir Dis, 1984 Jan, 65(1), 35 - 44
Dosing regimen of budesonide and occurrence of oropharyngeal complications; Toogood JH et al.; The influence of the dosing regimen on the occurrence of oropharyngeal complications during a trial of the anti-asthmatic aerosol steroid budesonide was assessed by systematically varying the daily dose (400, 800, 1,600 micrograms), dose frequency (b.i.d . vs . q.i.d.), and dosing schedule (AM vs . AM/PM) . Dysphonia was infrequent and was not affected by any features of the treatment regimen . ;Its incidence was unrelated to that of candidiasis . The amount of oropharyngeal candidiasis on the other hand correlated strongly with the daily dose of budesonide and dosing frequency . B.i.d . treatment abolished the effect of increasing budesonide dose on candidiasis, and virtually eliminated any need for nystatin . A 24 h interval between doses (using an AM schedule), or two intervals of about 12 h were both effective in conserving antifungal host defences in the oropharynx . Temporary conversion to b.i.d . dosing can facilitate the control or prevention of thrush, especially when the risk is increased by concomitant antibiotic therapy, as was shown to be the case in these patients . A small, but statistically significant, deterioration in peak expiratory flow occurred during b.i.d . dosing . Thus, despite its ability to virtually eliminate the problem of recurring thrush, b.i.d . dosing should not be continued indefinitely . These considerations probably apply to other topically active steroids currently used to treat asthma.

Antimicrob Agents Chemother, 1984 Jan, 25(1), 113 - 7
Synthesis and biological activities of 4"-deoxy-4"-sulfonamido-oleandomycin derivatives; Bright GM et al.; Chemical modification of the macrolide antibiotic oleandomycin (C-1) is described . Reductive amination of 11-acetyl-4"-deoxy-4"-oxo-oleandomycin (C-6) with ammonium acetate provides amino-oleandomycin derivative C-7 in which the 4"-amine is oriented in the axial configuration . The structure-activity relationship of a series of 4"-sulfonamide analogs prepared from amino-oleandomycin derivative C-7 is discussed . Noteworthy is the significant in vitro potency enhancement of the para-chlorobenzenesulfonamide analog C-12 over that of the parent oleandomycin . The absolute configuration of the 4"-amino-oleandomycin derivative C-7 was established through X-ray analysis of the para-iodobenzenesulfonamide analog C-14.

Acta Chir Scand, 1984, 150(1), 45 - 9
Intra-operative irrigation of the peritoneal cavity with ampicillin in experimental posttraumatic peritonitis; Nystrom PO et al.; Penetrating abdominal wounds with injury to the intestines were inflicted on 24 anaesthetized pigs . The injured gut was resected . During this operation the peritoneal cavity in 9 pigs was irrigated with 3 litres of antibiotic solution (ampicillin 2 g/l) . In 15 pigs the irrigation was done with 3 litres of saline solution only . During the postoperative observation period the animals were in continuous anaesthesia . Absorption of ampicillin, reduction of the peritoneal bacterial flora and emergence of resistant strains were evaluated . Ampicillin was rapidly absorbed to the systemic circulation, with an average peak concentration of 42.4 +/- 1.7 mg/l . The average half-life of the drug in serum was 54 +/- 4 min . The average density of the total aerobic flora decreased during the operation from 10(4.74) CFU/ml peritoneal exudate fo 10(1.20) CFU/ml, but increased to 10(5.16) CFU/ml during the posttraumatic observation period . Total anaerobic counts changed to similar extent . The results were not significantly different from the values in the saline-irrigation group . Ampicillin irrigation led to a significant increase of resistant strains, from 25% before irrigation to 97% at the end of the observation period.

Eur Urol, 1984, 10(1), 40 - 2
Urolithiasis in pregnancy; O'Regan S et al.; A retrospective analysis of pregnancies complicated by urolithiasis in a major referral center for high-risk pregnancies indicated an incidence of 1:2,534 . In contrast to previous series, the majority of patients were primiparas . The judicious use of hydration, analgesics and antibiotic therapy resulted in a high rate of spontaneous passage of stones initially localized below the renal pelvis and a favorable outcome for all pregnancies.

Chemotherapy, 1984, 30(2), 119 - 24
Combination of anticancer agents with folic acid in the treatment of murine leukaemia P388; Parchure M et al.; Folic acid (FA) was combined with anticancer agents such as (i) antimetabolites like methotrexate (MTX), 5-fluorouracil (5-FU), arabinosyl cytosine (Ara-C) and 6-mercaptopurine (6-MP); (ii) plant-derived mitotic inhibitor, vincristine (VCR), and (iii) an antibiotic, mitomycin C (Mit-C) . This combination modality was used for the treatment of P388 lymphocytic leukaemia . Large doses of FA were administered to the tumour-bearing mice either prior to or simultaneously with different anticancer agents . Pre-treatment with FA significantly improved the therapeutic efficacy of 5-FU, Ara-C and Mit-C; while MTX was more effective when given simultaneously with FA . The efficacy of 6-MP and VCR was not enhanced by FA when tested similarly . Large doses of FA can potentiate the activity of certain anticancer agents when administered to P388-bearing mice at critical times that vary according to the particular drug used.

Am J Ophthalmol, 1984 Jan, 97(1), 7 - 10
Oestrus ovis ophthalmomyiasis externa; Reingold WJ et al.; Oestrus ovis, the sheep nasal botfly, is the most common cause of ophthalmomyiasis externa in North America . In the United States, most cases occur on Catalina Island . The symptoms of acute infestation with this organism resemble those of catarrhal conjunctivitis and the condition is considered to be self-limiting . Treatment consists of careful removal of the organisms and topical administration of corticosteroid and antibiotic drugs to relieve the symptoms and prevent bacterial contamination . We recently examined a 17-year-old woman who had visited Catalina Island and later developed acute O . ovis ophthalmomyiasis externa . To determine the incidence of chronic complications, we performed ophthalmic examinations on 15 Catalina Island residents who had had documented O . ovis ophthalmomyiasis externa before 1981 . We found no evidence of persistent infestation or intraocular penetration by these organisms.

Hum Genet, 1984, 65(4), 377 - 84
The use of distamycin A in human lymphocyte cultures; Schmid M et al.; The effect of the oligopeptide antibiotic distamycin A on human lymphocyte cultures was examined . Distamycin A specifically inhibits the condensation of the Y heterochromatin and induces a fragile site in the chromosome 16 (band q22) in some individuals . The optimal culture conditions under which an undercondensation of the Y heterochromatin and an induction of the fragile site in 16q22 can be achieved by in vitro treatment of lymphocytes were determined . This also permits the use of distamycin A in routine diagnostics of human chromosomes . The use of this technique in the analysis of translocations involving the Y chromosome is presented . The distamycin A-DNA interaction and the different possible explanations for the distamycin A-induced undercondensations of the Y heterochromatin and fragile sites 16q22 are discussed.

Dev Biol, 1984 Jan, 101(1), 212 - 20
Epithelial sheet movement: effects of tunicamycin on migration and glycoprotein synthesis; Gipson IK et al.; Corneas with central epithelial wounds, 3 mm in diameter, were organ cultured in the presence of tunicamycin (TM) (1 microgram/ml), an antibiotic that inhibits glycosylation of asparagine-linked glycoproteins . Compared with control corneas, which healed in 22 hr, corneas cultured in the presence of TM for the entire culture time or for only the first 6 hr displayed a progressively slower epithelial healing rate that essentially dropped to zero by 24 hr of culture time . At 24 hr, approximately 75% of the wound was covered . After repeated washings with TM-free culture media (6X, 10 min each), this effect could consistently be reversed in corneas exposed to TM for 6 hr . Incorporation of {3H}glucosamine into trichloroacetic acid-precipitable proteins of migrating epithelial sheets was reduced to 14% that of controls after 12 hr of culture with TM, whereas {14C}leucine incorporation was not significantly affected . The decreased glycosylation was reflected on the cell surface after 12 and 20 hr culture in the presence of TM: apical cell membranes of the first six cells of the leading edge of the migrating sheet bound significantly fewer ferritin-concanavalin A particles per micrometer of membrane than did controls . These results indicate that synthesis of asparagine-linked glycoproteins is required for continued migration of corneal epithelial sheets . The asparagine-linked glycoproteins that are required for migration probably include cell-surface glycoproteins.

Am Surg, 1984 Jan, 50(1), 40 - 2
Valve replacement for native valve endocarditis; Weaver JP et al.; Over a 10-year period (1972-1981) 40 valves were replaced in 35 patients with native valve endocarditis . Hospital mortality was 17 per cent (6/35) . Long-term follow-up is current in 27 of 29 survivors . Twenty-three of these patients are alive with a mean follow-up of 44.7 months (11-91 months) and an overall survival of 70 per cent . Eighty-seven per cent of the long-term survivors are New York Heart Association (NYHA) Class I or II . In our series, anular or myocardial abscess was an ominous finding; only 25 per cent (2/8) of these patients were alive at long-term follow-up . When abscess was not present, early operation (less than 4 weeks of preoperative antibiotic therapy) was associated with better long-term survival (91%) than was late operation (greater than 4 weeks of preoperative antibiotic therapy, 79%).

Urology, 1984 Jan, 23(1), 84 - 6
Perinephric abscess masquerading as renal tumor in an adolescent; Lo RK et al.; A perinephric abscess in an adolescent, initially mistaken for a renal tumor, was managed conservatively with antibiotic therapy alone . Computed tomography revealed that resolution was complete, eliminating the need for surgical drainage . The case suggests the wisdom of altering traditional diagnostic and therapeutic approaches to lesions in the perinephric area.

J Clin Invest, 1984 Jan, 73(1), 134 - 47
Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity; Humes HD et al.; The divalent cations, Ca++ and Mg++, are known to competitively inhibit a large number of aminoglycoside-membrane interactions, so that Ca++ prevents both the neurotoxic and ototoxic effects of these antibiotics acutely in vitro . Since gentamicin-induced plasma and subcellular membrane damage appear to be critical pathogenetic events in gentamicin nephrotoxicity, Ca++ may play a similar protective role in gentamicin-induced acute renal failure . To test this possibility in vivo, rats (group 2) were given a 4% calcium (in the form of CaCO3) supplemented diet to increase delivery of Ca++ to the kidney and administered single daily subcutaneous injections of gentamicin, 100 mg/kg, for 10 d . Compared with a simultaneously studied group (group 1) of rats receiving identical gentamicin dosages and normal diets, Ca++ supplementation ameliorated gentamicin-induced acute renal failure . After 10 doses of gentamicin, blood-urea nitrogen values in group 1 averaged 213 +/- 15 (SE) and 25 +/- 3 (P less than 0.001) in group 2 . The progressive decline in renal excretory function, as measured by BUN, in group 1 animals was accompanied by simultaneous declines in renal cortical mitochondrial function and elevations in renal cortex and mitochondrial Ca++ content, quantitative indices of the degree of renal tubular cell injury . Oral Ca++ loading markedly attenuated these gentamicin-induced derangements . After eight and 10 doses of gentamicin, mitochondria isolated from the renal cortex of group 2 rats had significantly higher rates of respiration supported by pyruvate-malate, succinate and N,N,N',N'-tetramethyl-p-phenyldiamine-ascorbate, higher rates of dinitrophenol-uncoupled respiration and greater acceptor control ratios than those measured in mitochondria isolated from the renal cortex of group 1 animals . Similarly, after 8 and 10 doses, renal cortex and renal cortical mitochondrial Ca++ content of group 2 was significantly lower than values observed in group 1 . Thus, dietary calcium supplementation significantly protected against gentamicin-induced renal tubular cell injury and, consequently, gentamicin-induced acute renal failure . The mechanism for this protective effect of Ca++ may relate to the manner in which this polycationic antibiotic interacts with anionic sites, primarily the acidic phospholipids of renal membranes . In this regard, Ca++ was found to be a competitive inhibitor both of 125I-gentamicin binding to renal brush border membranes, the initial site of interaction between gentamicin and renal proximal tubule cells, with a composite inhibition constant (Ki) of 12 mM and of 125I-gentamicin binding to phosphatidic acid, an important membrane acidic phosph

Cancer Chemother Pharmacol, 1984, 12(2), 87 - 9
Disturbance of 6-mercaptopurine metabolism by cotrimoxazole in childhood lymphoblastic leukaemia; Rees CA et al.; The effect of cotrimoxazole on the utilization of 6-mercaptopurine (6MP) was studied in a group of children receiving remission maintenance treatment for lymphoblastic leukaemia (ALL) . This was done by measuring the level of an active metabolite of 6MP, 6-thioguanine nucleotide (6TGN), and comparing it both with the drug dose and with subsequent neutropenia in the presence or absence of concurrent cotrimoxazole . In children who were not taken cotrimoxazole, the concentration of 6TGN showed a significant positive correlation with the dose and a significant negative correlation with the absolute neutrophil count 2 weeks later . In those who were taking the antibiotic both these relationships were lost . This suggests that cotrimoxazole can interfere with both the absorption and the cytotoxicity of 6MP and may, in turn, alter its antileukaemic effect.

Basic Life Sci, 1984, 29 Pt B, 885 - 93
Sister chromatid exchange frequency and cell cycle kinetics in cancer patients treated with cytostatic drugs; Singh NP et al.; The ability of various cytostatic drugs to induce sister chromatid exchanges (SCE) and to alter the progression of cells through mitosis was analyzed in lymphocytes cultured from cancer patients following various in vivo chemotherapy treatments . Control individuals exhibited 4.87 +/- 0.08 SCEs per metaphase . Patients being treated with cyclophosphamide (CP), mitomycin C (MMC), and/or cisplatinum (CPT) in combination with other drugs exhibited 3- to 5-fold greater levels of SCEs . Other cytostatic drugs: the plant alkaloids; vincristine (VCR); and homoharringtonine (HHT); the antibiotic, adriamycin (ADM); the folic acid antagonist, methotrexate (MTX); and the nucleotide analogue, dihydroazacytidine (HAC) did not appear to induce SCE levels significantly above controls . Most of the cytostatic drugs used in cancer patients appeared to delay the progression of cells through mitosis . All the drug protocols which included a known DNA-damaging agent induced SCE . There was no relationship between SCE and cell cycle kinetics . Thus, SCE appears to be a sensitive assay for monitoring the in vivo exposure of individuals to genotoxic agents.

Acta Otolaryngol Suppl, 1984, 411, 45 - 52
Implant material tolerance; Josset P et al.; After surgical and antibiotic destruction of guinea pig cochleas non specific lesions appear which seem more due to this destruction than to the electrode implantation or chronic stimulation . Moreover, despite these lesions, the electrical threshold level value necessary to elicit brain stem evoked responses in these implanted animals does not vary in time . The electrical chronic stimulation of the newborn deafened guinea pigs cochlea prevents the cochlear nucleus atrophy observed in the non stimulated animals . In man the implanted material tolerance is perfect provided this material is covered by a Silastic or teflon sheet and is located far from the skin incision . Degradation of isolating material occurred only in case of chronic movements . For this reason device and electrodes must be placed above and behind the ear . The waterproofness of the implanted receptor is indispensable to avoid physiological liquid penetration inside the electronic device . High level voltage stimulation may involve bubble formation responsible for temporary system failure; this drawback is suppressed by enlarging the electrode tip surface allowing low level stimulation . The threshold level and the frequency discrimination of the implanted electrodes did not change for more than 6 years . Post-operative infection occurred especially in case of pre-operative chronic otitis; it may be due also to the large use of "Histoacryl" . However, these infections, which never affected the threshold level voltage of the implanted electrodes, are no longer encountered since we use "Tissucol", exclude the middle ear closing the Eustachian tube, and employ our electrode bearer.

Arch Toxicol Suppl, 1984, 7, 455 - 8
A 2'guanidyl derivative of gentamicin (S86451) with reduced nephrotoxicity studies at low and medium dose levels in the rat; Maldague P et al.; The nephrotoxic potential of S86451 (2'guanidyl, 2'deamino gentamicin C1) has been investigated in Sprague-Dawley rats at 10 and 25 mg/kg, in comparison with gentamicin at 4 and 10 mg/kg . The criteria were (i) the severity of the lysosomal phospholipidosis, as assessed by both biochemical and morphological investigations; (ii) the degree of tubular regeneration, a consequence of the aminoglycoside-induced focal necrosis measured by 3H-thymidine incorporation into kidney cortex DNA . S86451 was found at least 2-5 times less toxic than gentamicin . Thus, this compound should be a safer antibiotic than gentamicin in combating organisms with a similar sensitivity to either drug.

Arch Otorhinolaryngol, 1984, 240(2), 103 - 6
Permeability of the round window membrane; Okuno T et al.; Cefmetazole sodium, a cephamycin antibiotic, was shown to pass through the round window membrane into the inner ear of the guinea pig . The concentration of the drug in the inner ear fluid indicated that a larger amount of the drug reached the inner ear through the round window membrane than when administered intraperitoneally.

Somat Cell Mol Genet, 1984 Jan, 10(1), 85 - 91
Retention of both parental mitochondrial DNA species in mouse-Chinese hamster somatic cell hybrids; Zuckerman SH et al.; Interspecific somatic cell hybrids were isolated following the fusion of an oligomycin-resistant derivative of LM (TK-) mouse cells to a chloramphenicol-resistant derivative of AK412 Chinese hamsters cells . Hybrids were selected in either HAT medium, HAT plus chloramphenicol (CAP), HAT plus oligomycin (OLI), or HAT plus chloramphenicol and oligomycin . Cytogenetic analysis of the hybrids indicated that their karyotype reflected the sum of the parents . Hybrids selected in HAT medium alone or HAT plus OLI retained primarily mouse mitochondrial DNA while those selected in HAT plus CAP, or HAT plus CAP plus OLI retained both species of mitochondrial DNA . There was no evidence for mitochondrial DNA recombination, despite the continued growth of these hybrids in CAP plus OLI . Hybrids that were removed from dual antibiotic selection for over three months retained both species of mitochondrial DNA in approximately equal amounts with no detectable loss or rearrangement.

Antibiotiki, 1984 Jan, 29(1), 56 - 9
{Treatment results in osteogenic sarcoma in children and adolescents with the use of karminomycin}; Bizer VA et al.; Carminomycin, a new antibiotic made in the USSR, was used in the treatment of 21 patients aged 5 to 15 years with extended osteogenic sarcoma . As a result of the treatment the number of the patients with lifetime prolonged for 1-2 years increased from 7.6 to 46 per cent . It was shown that the drug might be used for the prophylaxis of the localized forms of the disease in children.

Infect Control, 1984 Jan, 5(1), 32 - 5
Practical aspects for cost reduction in hospital infection control; Daschner FD; Nosocomial infections consume a significant amount of the total hospital budget . This article describes some practical aspects for cost reduction in hospital infection control . Within one year total savings of 91.000 DM could be achieved by discontinuing unnecessary disinfection procedures . Within six years 2,27 million DM could be saved by discontinuing unnecessary infection control procedures or employing cheaper methods . Of the total antibiotic costs 25% can be reduced by certain measures.

Cancer Chemother Pharmacol, 1984, 13(3), 171 - 5
Studies on the biochemical mechanism of the novel antitumor agent, CI-920; Fry DW et al.; Biochemical studies on a new antitumor antibiotic, CI-920, have been directed toward understanding its mode of action . The most striking effect brought on by CI-920 was a marked inhibition of macromolecular synthesis . L1210 leukemia cells exposed to 10 microM CI-920 exhibited a decreased rate of DNA, RNA, and protein synthesis within 45 min, and maximal inhibition occurred within 60 min . The reduction in nucleic acid synthesis was not due to precursor depletion, since ribonucleoside and deoxyribonucleoside triphosphate levels in cells exposed to 10 microM CI-920 for 2 h either remained unchanged relative to control cells or were elevated, suggesting a block more directly at the level of nucleotide incorporation . Nevertheless, CI-920 (50 microM) had no effect on DNA or RNA polymerase activity as assessed in permeabilized L1210 cells . However, if viable cells were exposed to 20 microM CI-920 for 1 h prior to permeabilization and then the polymerases assayed in the absence of drug, there was a 60% depression in enzyme activity . The inhibition of RNA polymerase appears to result from an effect on the enzyme rather than the template, since inhibition of RNA polymerase activity in cell-free systems from drug-treated cells could not be restored by addition of excess DNA template . DNA polymerase, however, was at least partially restored by addition of template and therefore was inconclusive in this respect . The data, then, suggest that CI-920 inhibits nucleic acid synthesis directly at the level of nucleotide incorporation, either by direct inhibition of DNA or RNA polymerase or by inactivation of an essential component of these enzyme systems . Since the drug in its parent form did not inhibit nucleic acid synthesis in cell-free systems the effects may possibly be mediated through conversion of this agent to another chemical form within viable cells.

Neurotoxicology, 1984 Summer, 5(2), 101 - 12
Behavioral analysis of kanamycin administration to mice; Perdue VP et al.; The present series of experiments investigated behavioral changes in HET mice following administration of kanamycin, one of the aminoglycoside antibiotics . After drug treatment, HET mice showed changes in complex behaviors, including male agonistic behavior, female postpartum aggression, and tactile discrimination performance . Specifically, the temporal distribution of agonistic behavior appears to be affected by kanamycin treatment in both males and females, and kanamycin administration seems to alter reversal performance on a tactile discrimination task . These findings suggest the need for more careful examination of behaviors which may prove to be sensitive indices of antibiotic toxicity.

Arzneimittelforschung, 1984, 34(1), 39 - 43
{Effect of cefaclor and tobramycin on the phagocytic activity of peritoneal macrophages in mice}; Holl G et al.; The influence of Cefaclor and of Tobramycin on phagocytosis of sheep erythrocytes by murine peritoneal macrophages was investigated . The antibiotics in various concentrations were either added to the cells directly during the phagocytosis period or injected i.v . into cell donor mice at different times before cell harvest and the cells subsequently assayed for phagocytic activity in vitro . When antibiotic was added during the phagocytosis a dose-dependent inhibition of phagocytosis was observed which, however, became significant only at extremely high concentrations of the antibiotic . In all other experimental set-ups, phagocytosis was not influenced by antibiotics . Restrictive usage of either antibiotic in clinical situation does not appear mandatory on the basis of the reported observations.

Antimicrob Agents Chemother, 1984 Jan, 25(1), 93 - 7
Immunology of the monobactam aztreonam; Adkinson NF Jr et al.; To assess the immunological cross-reactivity of the monobactam antibiotic aztreonam (AZ), rabbits were immunized with protein conjugates of benzylpenicillin, cephalothin (CEPH), and AZ . The resulting antibenzylpenicilloyl (BPO) and anti-CEPH rabbit antibodies showed negligible cross-reactivity with AZ conjugated to human serum albumin (AZ-HSA), whereas anti-AZ showed negligible cross-reactivity with BPO-HSA and CEPH-HSA . Unlike benzylpenicillin and CEPH, unconjugated AZ was as effective as AZ conjugated to epsilon aminocaproic acid (AZ-EACA) in inhibiting the binding of homologous antibody . Studies with various analogs of AZ confirmed that immunoglobulin G (IgG) anti-AZ was entirely side-chain specific . The inhibition of the binding of human IgE anti-penicilloyl to BPO-HSA was studied in the presence of AZ-EACA, BPO-formyl lysine, and CEPH-EACA . Whereas CEPH-EACA displayed 3% cross-reactivity with BPO-lysine, AZ-EACA showed little or no cross-reactivity (much less than 0.9%) . To assess the immunogenicity of AZ in humans, IgE and IgG antibodies were measured in sera from 36 healthy male volunteers receiving 0.5 or 1 g intravenously or intramuscularly every 8 h for 7 days . None of the subjects had detectable preexisting IgE reactive with AZ or demonstrated an IgE response to antibiotic administration . Four subjects gave evidence for naturally occurring IgG cross-reactive with AZ, but only one subject demonstrated a rise in IgG levels after exposure to AZ . This anti-AZ IgG did not cross-react with BPO or CEPH conjugates of bovine thyroglobulin and was completely side-chain specific . These studies suggest that AZ displays very low immunological cross-reactivity with other beta-lactam antibiotics and may be only weakly immunogenic in humans.

Tierarztl Prax, 1984, 12(4), 455 - 67
{Occurrence and control of psittacosis/ornithosis in West Germany}; Wachendorfer G; Avian chlamydiosis remains to be an important, in birds widely spread zoonosis . In the past 15 years in the Federal Republic of Germany 6133 cases in birds or aviaries officially were recorded, 88% in aviaries consisting of psittacines, 9% in pigeons and 3% in other bird species . Among all bird species psittacines are of greatest importance for human health . Therefore, public health control measures must concentrate on these species . For this purpose the longterm-treatment with tetracyclines in feed or by intramuscular injection has proved effective since chlamydial agents perfectly can be eliminated . But control of psittacosis by medication in the hands of laymen is problematical . Effectivity of medication depends on proper and careful performance . Therefore, if treatment is necessary due to state regulations, strict surveillance, including measuring of antibiotic levels in blood, by experienced veterinary public health personnel is mandatory.

Clin Ther, 1984, 7(1), 60 - 8
Evaluation of cefoperazone in the treatment of bacterial infections in patients with hematological diseases; Ichimaru M et al.; This study was conducted as a multicenter trial in 12 institutions in the Kyushu region of Japan . The clinical effects of cefoperazone were evaluated in 101 patients with 112 infections complicated by hematological disease . In about half of the patients, the baseline neutrophil count was below 1,000/mm3 . Results were excellent in 23 of 101 cases and good in 48, with an efficacy rate of 70.3% . Cefoperazone alone or in combination with other antibiotics was effective in 60.7% of patients who had not responded to previous antibiotic therapy . No serious side effects attributable to cefoperazone were noted . The results indicate that cefoperazone is a useful antibiotic for the treatment of severe infections in patients with hematological diseases.

Acta Obstet Gynecol Scand, 1984, 63(7), 591 - 5
Induced abortion by the suction method . An analysis of complication rates; Nesheim BI; PIP: Complication rates among all 3036 patients who had pregnancies terminated by suction techniques, under general anesthesia, at Akershus Central Hospital in Norway between 1977-80 were analyzed . Abortions performed in conjuction with sterilizations were not included in the study . Almost all of the abortions were performed during the 1st trimester . A few early 2nd trimester suction abortions were included . Information for the analysis was obtained from medical records . Registered complication variables included prolonged hospital readmissions, perforations, cervical laceratios, blood transfusions, laparotomies, repeat curettages, temperature rises of 38 degrees celsius or more, antibiotic treatments, and infections with or without a palpable pelvic mass . 29.3% of the patients had outpatient sterilizations, and 70.7% had inpatient sterilizations . The only criteria used to select inpatients were age and parity . Outpatient sterilizations were performed by the same medical teams and in the same operating theater as the inpatient sterilizations . Complications were registered for 7.1% of the patients . Complication rates varied by parity, outpatient and inpatient status, and gestational length . The complication rate was 9.2% for nulliparous women, and 5.3% for parous women . The difference was significant (p0.001) . Nulliparous women has a higher number of registered temperature rises, antibotic treatments, and infections without palpable pelvic masses than parous women . When only hospitalized nulliparous and parous women were compared the difference in complication rates was smaller, but still significant (p0.03) . Hospitalized patients had higher complication rates for minor complications than inpatients, and similar rates for major complications . Only parous patients were compared in regard to inpatient and outpatient differences since there were very few nulliparous outpatients . The complication rate for the 798 parous outpatients was 3.6%, and for the 872 parous inpatients the rate was 6.9% . The difference was significant (p0.001) . Even when the length of gestation was controlled, the parous inpatients still had a significantly higher rate of complications than the parous outpatients . Perhaps hospitalized patients were more likely to seek medical attention for minor complaints than outpatients, or perhaps hospitalized patients were more likely to acquire infections than oupatients . In regard to gestation length, the lowest complication rates were observed for abortions performed during the 7th to 10th gestation weeks . After 10 weeks gestation, complication rates tended to increase and the highest rates were observed during the 14 gestation week . Rates at 6 week gestation were also high, especially among nulliparous women . The rate of retained tissue was higher during the 6th week of gestation than during any other week .

Circ Shock, 1984, 14(3), 203 - 8
Methylprednisolone plus ibuprofen increases mortality in septic rats; Elinger JH et al.; Steroids and cyclooxygenase inhibitors have been advocated as adjunctive treatment for sepsis . We studied the influences of these treatments on the survival of 98 male Sprague-Dawley rats in which sepsis was induced by cecal ligation and puncture . Rats received one of four treatments: sodium chloride (NaCl); methylprednisolone, 30 mg/kg (MP); ibuprofen, 12.5 mg/kg (I); methylprednisolone, 30 mg/kg, plus ibuprofen, 12.5 mg/kg (MP + I) . Cumulative survival statistics were determined daily for 14 days thereafter . Survival was not altered by either MP or I when compared to animals receiving NaCl only . However, the combination of MP + I increased mortality from day 2 through day 14 . The authors conclude that (1) MP administration alone does not increase mortality in septic rats; therefore, the results do not support the contention that steroid treatment in the absence of antibiotic therapy may be detrimental; (2) the cyclooxygenase inhibitor I does not improve survival in septic rats; and (3) the combined administration of MP and I increases mortality in septic rats and the possibility that this combination might be harmful in septic patients should be considered also.

Zentralbl Gynakol, 1984, 106(18), 1281 - 7
{Actinomycotic tubo-ovarian abscess in the presence of an intrauterine device}; Lunow E et al.; Two cases of women with actinomycotic tubo-ovarian abscesses are reported . Both of the patients were users of intrauterine contraceptive devices . They were successfully treated by abdominal hysterectomy with salpingooophorectomy--in one cases appendectomy in addition--and pelvic drainage combined with antibiotic therapy . Aspects of nature, diagnosis, mode of infection and therapy of actinomycosis are discussed.

Zentralbl Gynakol, 1984, 106(18), 1274 - 80
{Substitution of immunoglobulins in severe infections}; Briese V et al.; In cases of severe infections substitution therapy of immunoglobulins shall improve the course of the disease . At example of a case report the possibility of the immunosubstitution is demonstrated . 31 days after the radical vulvectomy a bacteriantoxic phlegmone of the cutis and the subcutis in the abdominal, genital and thigh regions has been occurred . The acute medical care consists of shock therapy, large incisions of the cutis and the subcutis and high level antibiotic therapy . In the following course the immunoglobulins (Gamma-Venin) were substituted . The serum concentrations of IgG, M and A were estimated . The dosage of Gamma-Venin amounted to 1,5 grams per day . This dosage is lower compared with the amounts reported from other authors.

Ther Drug Monit, 1984, 6(3), 298 - 301
Gentamicin penetration into diseased appendix tissue; Gill MA et al.; Gentamicin concentrations in appendix tissue, serum, and peritoneal fluid were obtained in suspected cases of gangrenous or perforated appendicitis . Despite widely ranging gentamicin concentrations, no infectious complications developed . Correlations were made between the pathologic state of the tissue and the tissue gentamicin concentrations . Correlations were also made with tissue gentamicin concentrations and the time after the antibiotic dose to the time of sampling.

J Neurosci Res, 1984, 12(2-3), 161 - 78
Ganglioside biosynthesis in Golgi apparatus: new perspectives on its mechanism; Yusuf HK et al.; The synthesis of gangliosides GM1 and GM2 in intact rat liver Golgi vesicles is stimulated by phosphatidylglycerol as much as or even more than by detergents (Triton X-100 and octyglucoside, respectively) . The antibiotic tunicamycin, known as an inhibitor of the N-glycosylation of proteins, strongly inhibits the synthesis of the above gangliosides, in the presence as well as in the absence of the phospholipid . Both phosphatidylglycerol dependence and tunicamycin inhibition disappear when the Golgi vesicles are solubilized by addition of detergents or disrupted by ultrasonication or pretreated with pronase . Transport studies with UDP-{3H}Gal show that tunicamycin blocks the penetration of the sugar nucleotide into the Golgi vesicles in a concentration-dependent manner up to 80% . The results show that tunicamycin inhibits ganglioside biosynthesis by blocking the transport of the nucleotide sugar and not by inhibiting the transferase directly . Studies on glycoprotein-galactosyltransferase with ovalbumin as exogenous acceptor showed that phosphatidylglycerol does not destroy the integrity of the Golgi vesicles . So this phospholipid is an excellent tool for studying ganglioside biosynthesis at optimal transferase activities without solubilizing the Golgi membranes.

Gastrointest Radiol, 1984, 9(4), 283 - 6
Candidiasis-induced esophageal strictures; Agha FP; Candidiasis of the esophagus progressing to hard fibrosed strictures of the esophagus in 2 patients is reported . Both patients had deficient immunologic systems and received extended courses of broad-spectrum antibiotic therapy for control of sepsis . The strictures were progressive despite adequate antifungal therapy and several attempts at dilatations and necessitated visceral esophageal substitution as definitive surgical therapy.

Eksp Onkol, 1984, 6(4), 33 - 5
{Effect of levorin on RNA synthesis in Ehrlich ascites carcinoma cells}; Gorozhankina IS et al.; The polyene antibiotic levorin had no effect on the incorporation of 14C-uracil into the pool of intracellular free nucleotides in Ehrlich ascites tumour cells . RNA synthesis was inhibited by the antibiotic only at the late stages of incubation, evidently, due to earlier disturbances of the protein synthesis and in cell energetics.

Eksp Onkol, 1984, 6(1), 57 - 61
{Changes in various biochemical indices and ultrastructure of ascites tumors after combined administration of cyclophosphamide and levorin}; Oksman AIa et al.; The fractional composition of chromatin proteins and an electron-microscopic pattern of cell ultrastructure of the Ehrlich ascite tumours and ascite lymphoma NK/Ly were studied when suppressing their growth by a combined action of cyclophosphane and polyene antibiotic . Changes in the fractional composition of chromatin proteins were found under the effect of levorin . A sharp increase in this effect and summation of heterogeneous morphological changes provoked by each of the preparation occur under a combined application of the preparations.

Pediatr Pharmacol (New York), 1984, 4(3), 193 - 7
Pharmacokinetics of cefoperazone in newborn infants; Philips JB 3rd et al.; We studied the disposition of two 100 mg/kg doses of cefoperazone given intravenously 12 hr apart in ten newborn infants . Peak levels were a mean 352 +/- SD 75 and 371 +/- 68 micrograms/ml immediately after the first and second dose, respectively, with corresponding troughs of 60 +/- 10 and 76 +/- 28 mcg/ml 12 hr later . Mean half-life was 6.5 +/- 0.9 hr and decreased with increasing gestational age and birthweight . Steady-state volume of distribution averaged 410 +/- 40 ml/kg and total clearance 0.78 +/- 0.13 ml/min X kg and neither varied with gestational age nor birthweight . No untoward physical or laboratory effects were noted . Additional studies including postnatal age effects on kinetics, efficacy, and cerebrospinal fluid penetrance are necessary prior to widespread use of this potentially valuable antibiotic in newborn infants.

Acta Otorhinolaryngol Belg, 1984, 38(2), 133 - 9
{Emergencies in orbital complications of sinusitis}; Skenazi JJ et al.; Sixty to 80% of orbital infections are secondary to sinusitis . That sinusitis can be everwhelming . Some symptoms must incite us to a quick response: the general state of the patient, his temperature, chemosis, cornean anaesthesia, mydriasis, ocular motor palsy, exophthalmia . We believe that ocular motor palsy and exophtalmia are imperative symptoms . In such cases, it is not only necessary to drain the sinuses, but also to explore the orbit by an external approach with an antibiotic cover.

Prog Clin Biol Res, 1984, 161, 265 - 88
Modification in the antibody-dependent cellular cytotoxicity as influenced by chemicals; Lawman MJ et al.; With the increased use of chemicals in health related sciences, there is a need for a better understanding as to how these chemicals interact with the immune system . The purpose of this review was to bring together published information on the effects chemicals have on antibody-dependent cellular cytotoxicity (ADCC) . This immunoeffector mechanism requires the interaction of both the humoral (antibody) and cellular components (expressing Fc receptors on the plasma membrane) with the specificity being determined by the antibody . Most of the chemicals tested and mentioned in this review are those that are currently used in chemotherapy, antibiotic and drug regimes and in the maintenance of anesthesia . The major point that emerges from this review is that while a great deal of information has been obtained, there is also a good deal of conflicting information . Furthermore, the mechanisms of action are not fully understood or are unknown in many cases . Further work, therefore, is needed to ascertain the importance and relevance of these chemicals in interfering with the ADCC phenomenon and the mode of action of these chemicals within the ADCC mechanism.

Histochemistry, 1984, 80(6), 563 - 7
Localization of filipin-sterol complexes in cell membranes of eosinophils; Pimenta PF et al.; The polyene antibiotic filipin was used as a probe for the detection of cholesterol in the cell membranes of eosinophils isolated from the peritoneal exudate of rats . A homogenous distribution of filipin-sterol complexes was observed, both in thin sections and freeze-fracture replicas throughout the whole plasma membrane but not in the membrane of pynocytic vesicles, Golgi complex, endoplasmic reticulum, mitochondria and the nucleus . Few complexes were seen in freeze-fracture replicas showing the membrane of the specific granules . Treatment of living cells with filipin induced aggregation of filipin-sterol complexes at some points of the plasma membrane.

Scand Audiol Suppl, 1984, 23, 1 - 40
Accumulation of drugs on inner ear melanin . Therapeutic and ototoxic mechanisms; Wasterstrom SA; The aim of this study was to obtain more information about the possible role of melanin in the hearing process and to investigate the ototoxic and therapeutic effects of certain drugs with known affinity to this pigment . In order to obtain hearing threshold curves, young albino and pigmented guinea pigs were tested by N1-electrocochleography . There were no significant differences between the curves for the two strains, indicating that melanin has no major influence on the hearing process in young guinea pigs under normal conditions at thresholds . The acute and long-term ototoxic effect of kanamycin, an aminoglycoside antibiotic capable of accumulating on melanin in vitro, was studied in albino and pigmented guinea pigs by electrophysiological and morphological methods . In the highest dose used, 200 mg/kg/day, kanamycin caused significantly more damage in the pigmented guinea pigs than in the albino ones . To elucidate the possible role of melanin affinity in pharmacological treatment of tinnitus and the site of action of lidocaine and tocainide, nine patients with disabling tinnitus were treated with lidocaine, QX-572 (a quaternary derivative of lidocaine which does not readily penetrate the blood-brain barrier) and tocainide (an amine analogue of lidocaine which can be taken orally) . In six patients all three substances had a beneficial effect, but in the remaining three patients none of them produced any response . Autoradiographic studies in rats, both in vivo and in vitro, showed that all three substances accumulated on inner ear melanin . Auditory brainstem-evoked responses (ABRs) were measured in 10 healthy male subjects after single-dose injections of the respective drugs, in doses normally reducing tinnitus in sensitive patients . Neither drug produced any significant change in ABR . The results of these studies support a hypothesis that accumulation of drugs on inner ear melanin can constitute both an ototoxic and a therapeutic mechanism.

Am J Emerg Med, 1984 Jan, 2(1), 28 - 37
The potential role of thromboxane and prostacyclin in endotoxic and septic shock; Cook JA et al.; The potential role of thromboxane (TxA2), a platelet aggregator and vasoconstrictor, and prostacyclin (PGI2) a platelet anti-aggregator and vasodilator, in endotoxic and septic shock was investigated . Early endotoxic shock in the rat is associated with marked elevations of plasma TxB2 (the stable metabolite of TxA2) and lesser increases in plasma 6-keto-PGF1 alpha (the stable metabolite of PGI2) . Selective inhibition of TxA2 synthesis by several different chemical classes of Tx synthetase inhibitors was beneficial in endotoxic shock . In contrast, shock induced by acute intra-abdominal sepsis in the rat was characterized by high levels of plasma 6-keto-PGF1 alpha, which exceeded plasma TxA2 six- to eight fold at most time intervals studied . Tx synthetase inhibitors were not protective in this model of acute sepsis, but treatment with fatty acid cyclo-oxygenase inhibitors, an antibiotic (gentamicin), or reduction in arachidonic acid metabolism by essential fatty acid (EFA) deficiency significantly prolonged survival time . An important aspect of the latter study is that decreased arachidonic acid metabolism was an effective adjunct to antibiotic therapy . Conjoint administration of gentamicin in EFA-deficient rats or with indomethacin synergistically improved long-term survival, a result that was not evident with single treatment interventions . In addition to experimental studies, plasma TxB2 levels were measured during clinical sepsis . These studies demonstrated that plasma TxB2 levels were elevated tenfold in patients dying of septic shock compared with septic survivors or nonseptic controls . These composite experimental and clinical observations suggest that arachidonic acid metabolites play a role in the pathogenesis of endotoxic and septic shock.

Clin Exp Neurol, 1984, 20, 153 - 60
Neurological complications of Mycoplasma pneumoniae infection; Hely MA et al.; This study documents five patients with neurological disease associated with evidence of recent Mycoplasma pneumoniae infection . Four patients had encephalitis associated with coma . Two of these had hemiparesis (one with dysphasia), one had seizures, and one had cerebellar and brainstem involvement . Two also had evidence of a radiculopathy and peripheral neuropathy . One patient had aseptic meningitis with later transverse myelitis . Three patients had multiple sites of neurological involvement . Respiratory infections preceded the neurological syndromes in four cases . Antibiotic therapy did not appear to alter the course of the disease . All patients had a favourable outcome.

C R Acad Sci III, 1984, 299(3), 49 - 51
{Photochemical affinity labeling of the macrolide binding site on the 70S E . coli ribosome}; Siegrist S et al.; Photoactivation of the alpha, beta-unsaturated ketone-epoxide system of {3H} dihydrorosaramycin at a wavelength above 300 nm allows the covalent attachment of the antibiotic to its receptor site . The radioactivity is mainly associated to proteins L1, L5, L6, S1; as a consequence, the binding site of this type of drug could be located at the peptidyltransferase center and in between both subunits.

Dev Biol Stand, 1984, 56, 593 - 5
Brucellosis in a farming community in Saudi Arabia; Talukder MA et al.; This communication describes a study of the prevalence of brucellosis in a farming community of Saudi Arabia . Standard agglutination tests of sera from 21 patients were tested for Brucella abortus and Brucella melitensis . The results show that 8 (38%) were positive with titres of 160 or over 20 480 and with titre of complement fixation tests ranging from 8 to 64 . Agglutination titres of 20 to 40 were present in only 3 cases . Those patients with positive agglutination titre of 160 or higher admitted histories of consumption of raw milk . All 8 patients presented typical symptoms of brucellosis and responded to appropriate antibiotic therapy . This study suggests that farm workers and those who drink raw milk are more likely to contract brucellosis than are the general population.

Epidemiol Rev, 1984, 6, 1 - 30
Epidemiology of gonorrhea: current perspectives; Barnes RC et al.; Once considered a public nuisance of the developed countries, gonorrhea is now established as a leading worldwide public health problem . The rapid increase in reported disease in many developed countries noted in the 1960s and 1970s has been followed by stable or declining disease rates . This may reflect improved gonorrhea control programs or changes in sexual behavior . The assault on the developed countries by imported antibiotic-resistant strains of N . gonorrhoeae has increased, however, indicating the need for intensive control programs . New methods of identifying strains of gonococci have allowed investigation of the distribution and patterns of transmission of gonorrhea . Future studies using these methods will provide valuable knowledge of the ecology and epidemiology of gonorrhea . Within the developing countries, gonorrhea caused by resistant strains of N . gonorrhoeae has become hyperendemic . The current decreases of gonorrhea incidence in the developed countries may not be maintained unless some success is attained in the control of gonorrhea in developing countries.

EMBO J, 1984 Jan, 3(1), 121 - 6
The binding of 6-demethylchlortetracycline to 70S, 50S and 30S ribosomal particles: a quantitative study by fluorescence anisotropy; Epe B et al.; The binding of demeclocycline (6-demethylchlortetracycline) to ribosomes and ribosomal subunits from Escherichia coli was investigated by using the fluorescence anisotropy of the antibiotic to determine the extent of binding . Binding data obtained from 70S and 30S particles differed fundamentally from those obtained from 50S subunits: the first two showed a strong, specific interaction while the third did not . In addition, all three particles possessed weak, unspecific binding sites . Computer-aided least-squares analysis of the data yielded the following numbers of sites and equilibrium constants: for 30S, n1 = 1, K1 = 2.2 X 10(6) M-1, n2 K2 = 0.029 X 10(6) M-1; for 50S, n1 = 0, n2 K2 = 0.035 X 10(6) M-1; for 70S, n1 = 1, K1 = 3.2 X 10(6) M-1, n2 K2 = 0.082 X 10(6) M-1 . These data resolve current disagreement in the literature and are a prerequisite for quantitative studies of the mechanism of inhibition by tetracycline of protein biosynthesis.

Clin Chem, 1984 Jan, 30(1), 87 - 92
Use of monoclonal antibodies in an enzyme immunoassay for factor VIII-related antigen; Bradley LA et al.; Two monoclonal antibodies (MAb 53, MAb D7) were produced, each having specificity for Factor VIII-related antigen (FVIIIR:Ag), but exhibiting no inhibitory effect on either procoagulant activity or the ability of von Willebrand factor to agglutinate platelets in the presence of the antibiotic ristocetin . For quantification of FVIIIR:Ag, we used the antibodies in a competitive enzyme-linked immunosorbent assay (ELISA) . Binding of either of the MAb's to solid-phase antigen was inhibited by free FVIIIR:Ag in the test sample . Dose-response curves for the reference standards were consistently linear (r2 greater than 0.990) and reproducible . The normal range of FVIIIR:Ag detected in plasma (normal defined as 1000 units/L) was similar to that reported for polyclonal heterologous antibodies in similar ELISA or immunoradiometric (IRMA) systems, and the assay was sensitive to 10 units of FVIIIR:Ag per liter . Inter- and intra-assay precision was good, coefficients of variation being less than 11% . Studies on patients showed good correlations between values measured by MAb ELISAS and IRMA (polyclonal rabbit antibody) over FVIIIR:Ag concentrations ranging from less than 10 to 2700 units/L (r = 0.971, p less than 0.001 for MAb 53; r = 0.938, p less than 0.001 for MAb D7) . Both ELISAS could be used to quantify FVIIIR:Ag in other mammalian species . The assay is inexpensive and simple, and all reagents required for it are commercially available.

Radiat Med, 1984 Jan-Mar, 2(1), 24 - 6
Opportunistic esophagitis caused by Aspergillus fumigatus; Murata K et al.; The authors report on a 59-year-old man with opportunistic esophagitis caused by Aspergillus fumigatus . Although the patient had no underlying disease, esophagitis occurred after a short course of antibiotic therapy . A double contrast esophagogram showed multiple nodular or vertical plaque-like projections . Endoscopy provided pathological conformation of Aspergillus infection.

Scand J Infect Dis Suppl, 1984, 43, 67 - 70
Early reclosure versus conventional secondary suture of severe wound abscesses following laparotomy; Lykkegaard-Nielsen M et al.; The study comprised 81 consecutive cases of severe incisional abscesses following laparotomy during a 28-month period . Severe incisional abscess was defined as wound infection necessitating opening of the entire wound down to the fascia . During the first 12 months of the study period, 30 patients had conventional secondary suture with a median time of 12 days from drainage of wound abscesses until closure of clean and granulating wounds . During the last 16 months, 51 patients had early closure of contaminated wounds 4 days after drainage under systemic antibiotic cover with clindamycin . The surgical technique used in early closure allowed complete occlusion of the wound cavity without sutures in the wound itself . Recurrent incisional infection occurred in 3 of 30 patients having secondary suture and in 1 of 51 having early reclosure . It is concluded that early reclosure under systemic antibiotic cover is a safe procedure, which reduces hospitalization and convalescence.

Mol Gen Genet, 1984, 198(1), 100 - 4
Streptomycin preferentially perturbs ribosomal proofreading; Ruusala T et al.; We have studied the influence of streptomycin (Sm) on the kinetics and accuracy of translation by wild-type as well as Ram-mutant ribosomes in an in vitro system that mimics the performance characteristics of ribosomes in bacteria . It can be shown in this system that the accuracy of translation is made up of an initial selection step and one or more proofreading steps . The data show that the antibiotic has only a small influence on the initial selectivity step of wild-type or mutant ribosomes . Streptomycin stimulates the missense rate primarily by suppressing the proofreading of the ribosomes . The kinetic effects of Sm and of Ram alteration are not additive, but seem to be overlapping if not identical.

J Toxicol Environ Health, 1984, 14(5-6), 763 - 71
Paraquat and nitrofurantoin inhibit growth of Escherichia coli by inducing stringency; Seither RL et al.; The herbicide paraquat and the antibiotic nitrofurantoin (redox-active compounds that can transfer electrons singly to oxygen) induced intracellular accumulation of the regulatory inhibitor guanosine tetraphosphate (stringency) in Escherichia coli . This mechanism is sufficient to account for the rapid bacteristasis produced in minimal medium by these agents . The growth inhibition and stringency induction were prevented by inclusion of specific amino acids in the medium . Stringency was first reported to result from amino acid starvation, with unloaded transfer ribonucleic acids (tRNAs) acting as the trigger . Previously, inhibition of growth of E . coli by paraquat and hyperbaric oxygen were shown to be prevented by inclusion in the medium of a nearly identical profile of specific amino acids, including branched-chain amino acids, which were required because of poisoning of their biosynthesis at the dihydroxyacid dehydratase site, and stringency has been induced by hyperbaric oxygen poisoning . Thus, stringency induction via a common poisoned site in branched-chain amino acid biosynthesis appears to be a shared mechanism of toxicity for these agents and hyperbaric oxygen, which also share the propensity for one-electron-transfer, free-radical reactions in cells.

Yale J Biol Med, 1984 Jan-Feb, 57(1), 83 - 95
Management of acute neurologic syndromes in infants and children; Shaywitz BA; Neurological problems in the pediatric intensive care unit all too frequently seem to be among the most mysterious of disorders . This review provides a framework to diagnose and treat four frequently observed neurological syndromes: coma, status epilepticus, central nervous system infections, and post-infectious polyneuropathy (Guillain-Barre syndrome) . An emphasis is placed on the diagnosis of coma due to metabolic disorders, the most common cause of coma, and coma as a result of supratentorial lesions . This differentiation can be effected by an easily performed assessment (Glasgow Scale) supplemented by a limited number of tests of brain stem function (pupillary responses, oculocephalic, and oculovestibular responses) . Preserved pupillary responses are characteristic of the metabolic coma while an orderly rostral-caudal deterioration, termed the central syndrome, is characteristic of coma resulting from an enlarging supratentorial mass . If confusion exists, the CT scan may be helpful . The approach to emergency management emphasizes the establishment and maintenance of airway and circulation . Management of status epilepticus emphasizes the role of pharmacotherapy, particularly the use of diazepam and phenytoin in combination . The management of infections details antibiotic therapy of bacterial infections and new antiviral therapy for herpesvirus infections . The section on Guillain-Barre syndrome emphasizes good supportive care.

Mol Gen Genet, 1984, 194(1-2), 195 - 9
Multiple effects of kanamycin on translational accuracy; Jelenc PC et al.; We have studied the effects of kanamycin on the accuracy of translation in vitro by wild-type and mutant ribosomes from Escherichia coli . Kanamycin stimulates the leucine missense error of poly(U) translation by wild-type, Ram, and streptomycin-resistant ribosomes in characteristic ways; in particular, the streptomycin-resistant ribosomes are significantly less error-prone than wild-type or Ram ribosomes at all concentrations of the antibiotic . Kinetic analysis of the effects of kanamycin on the translational accuracy of wild-type ribosomes reveals a different concentration dependence for the perturbation of the initial selectivity of streptomycin-resistant ribosomes is not affected by kanamycin; the drug enhances only the error of proofreading by this mutant ribosome . We suggest that the multiple effects of kanamycin on the errors of translation are due to separate effects at different ribosomal sites.

Mol Gen Genet, 1984, 194(1-2), 166 - 72
Genetic studies on the beta subunit of Escherichia coli RNA polymerase . IV . Structure-function correlates; Nene V et al.; We have isolated a set of strains that synthesise 331 potential variants of E . coli DNA-dependent RNA polymerase making use of nonsense suppression of amber mutations in the beta structural gene; rpoB . Translational mapping, together with the effect of known amino acid substitutions, has allowed us to locate sites on the beta polypeptide involved in transcription termination, stringent response and resistance to the antibiotic rifampicin . In general, the C-terminal quarter appears to be less affected by such single amino acid exchanges than the rest of beta . These studies permit for the first time structure-function correlates for the beta subunit of RNA polymerase.

Jpn J Antibiot, 1984 Jan, 37(1), 23 - 7
{Fundamental and clinical studies on ceftazidime in the field of obstetrics and gynecology}; Yamamoto T et al.; Fundamental and clinical studies were performed on ceftazidime ( CAZ ), a new cephem antibiotic . Following a single intravenous administration of 1 g dose of CAZ , the transfer of CAZ to the internal genital organs was good . The transfer of CAZ to retroperitoneal fluid was excellent . In a clinical trial, CAZ was given to 6 patients with obstetrical and gynecological infections . The efficacy was evaluated as excellent in 3 cases and good in the other 3 cases . No adverse effects were observed in any of the patients treated with CAZ .

Jpn J Antibiot, 1984 Jan, 37(1), 1 - 5
{Clinical efficacy of ceftazidime in inflammatory diseases in the field of gynecology}; Okamura K et al.; Ceftazidime ( CAZ ) was evaluated for its clinical efficacy in a total of 12 cases, namely 3 cases of endometritis, 3 cases of intrapelvic infections, 4 cases of adnexitis and 2 cases of external genital infections . In all the cases, CAZ was administered by intravenous drip infusion, and the duration of the treatment ranged from 3 to 22 days . Daily dose was 2 g in 10 cases, and in the remaining 2 cases, daily doses were changed during the course of treatment in the range from 2 to 4 g . The clinical results of CAZ by disease were as follows; excellent in 1 case and good in 2 cases of endometritis, good in all the 3 cases of intrapelvic infections and the 4 cases of adnexitis, and excellent in 1 case and good in 1 case of external genital infections . The overall efficacy rate was 100%, namely, excellent in 2 cases and good in 10 cases of the total of 12 cases . Neither side effects nor abnormal laboratory findings attributable to CAZ were observed in any of the case . From these results, we may conclude that CAZ is a safe antibiotic with satisfactory clinical effects on gynecological infections.

Z Allg Mikrobiol, 1984, 24(2), 125 - 7
Use of nystatin for random spore selection in the yeast Saccharomycopsis lipolytica; Barth G et al.; Nystatin was used to develop a new method to select spores of the yeast Saccharomycopsis lipolytica . At low concentrations nystatin killed preferently growing cells of this yeast . At high concentrations nongrowing cells were affected as well . In contrast, spores were not sensitive to nystatin action . This differential response to the antibiotic suggested its use to select spores from sporulated yeast cultures.

J Clin Pathol, 1984 Jan, 37(1), 74 - 7
Disseminated toxoplasmosis in cardiac transplantation; McGregor CG et al.; The first case of disseminated toxoplasmosis following cardiac transplantation in the UK is described, with details of Toxoplasma antibody tests made on other cardiac transplant patients . Sixteen of 40 (39%) of recipients had Toxoplasma antibody before operation . Eleven of 30 (37%) of donors had Toxoplasma antibody . The were four occasions when a negative recipient received a heart from a positive donor . Three survived the immediate postoperative period and two became infected with toxoplasmosis . The implications of this are discussed . Disseminated toxoplasmosis appears much more often when heart muscle from a dye test positive donor is given to a dye test negative recipient . Antibiotic therapy is limited by the fact that the antitoxoplasma drugs available are static in their effect, and need to be given for prolonged periods postoperatively.

Toxicol Pathol, 1984, 12(4), 361 - 8
Short- and long-term studies on chemical carcinogenesis in BALB/Mo mice; Chieco-Bianchi L et al.; To study the interactions between chemical carcinogens and oncogenic retroviruses, BALB/Mo mice which carry the Moloney murine leukemia virus (M-MuLV) as an endogenous virus, and conventional (M-MuLV-free) BALB/c mice, as well as their Bc1 (M-MuLV+ or M-MuLV-) hybrids were injected neonatally with a single dose of urethane . BALB/Mo and V+ Bc1 mice showed accelerated lymphoma development; similar results were obtained in BALB/Mo mice receiving one or two doses of urethane transplacentally . Lung adenomas developed with shorter latency and higher incidence in BALB/Mo mice given urethane at birth; however, significant differences in the incidence of lung adenomas in BALB/Mo mice were found only in two experiments . Additional short-term experiments were carried out to investigate the mechanism of the higher susceptibility to sister chromatid exchange induction observed in BALB/Mo lymphocytes . It was found that BALB/Mo spleen lymphocytes incubated with cordycepin, an antiviral antibiotic, with or without mitomycin C treatment, showed reduction in both M-MuLV synthesis and sister chromatid exchange frequency, and the latter values were similar to those seen in control cultures . These data suggest that the integration of M-MuLV proviral DNA into the host genome is per se not sufficient to increase the susceptibility to carcinogenic stimuli, but that other events, such as viral gene expression and amplification, are most likely required for the chemical-viral synergistic effect to occur.

Acta Cardiol, 1984, 39(4), 293 - 9
Pacemaker endocarditis: contribution of two-dimensional echocardiography; Daelemans R et al.; A case of pacemaker endocarditis is presented . Electrode vegetations could be diagnosed by two-dimensional echocardiography . Prolonged antibiotic therapy failed . Only when the entire pacing system had been removed by cardiotomy with cardiopulmonary bypass, the infection cleared.

Z Allg Mikrobiol, 1984, 24(4), 239 - 45
ATP levels in phosphate-deregulated and arsenate-resistant mutants of Streptomyces noursei; Hanel F et al.; Mycelial levels of ATP and glucose-6-phosphate were investigated in mutants of streptothricin-producing S . noursei JA 3880b differing from the wild-type strain in antibiotic formation, in the control by inorganic phosphate of the secondary metabolism, and in the resistance to growth inhibition by toxic arsenate ions . As compared with the ancestral strain, mutants exhibited a lower content of ATP in the mycelium while addition of 0.1 M arsenate to growing cultures provoked only moderate changes in the level of this high-energy metabolite . The results suggest that there exists a correlation between growth resistance to arsenate and insensitivity to phosphate inhibition of the secondary metabolism, on the one hand, and the capacity to produce streptothricin-type antibiotics, on the other.

Histochemistry, 1984, 80(4), 327 - 31
Freeze-fracture cytochemistry with polymyxin B . A study on the plasma membrane of uterine epithelial cells; Murphy CR et al.; The peptide antibiotic polymyxin B, has been used as a label in a freeze-fracture cytochemical study of anionic phospholipids in the plasma membrane of uterine epithelial cells . The reagent produces mainly circular lesions visible on both P and E faces of fractured membranes . IMPs are found to be associated with lesions and we consider the possible association of integral membrane proteins with anionic phospholipids as well as the mechanisms of lesion formation.

Jpn J Antibiot, 1984 Jan, 37(1), 136 - 44
{Therapeutic effectiveness of ceftizoxime on severe infections associated with hematologic disorders}; Kanamaru A et al.; One hundred patients with severe infections associated with hematologic disorders, including leukemia and lymphoma, were treated with ceftizoxime (CZX) in daily doses of 4 approximately 9 g for an average of 8.9 days . In the 84 patients who completed the trial, response was excellent in 27 (32.1%) and moderate in 25 (29.8%) . The rate of effectiveness was 61.9% . The only side effect seen during the treatment was skin rash in 3 patients . Hepatic disorders were observed in 5 patients . The relation between CZX and these abnormal findings was not established . These results indicate that CZX is a therapeutically effective and safe antibiotic for the treatment of severe infections in patients with underlying hematologic disorders.

Z Allg Mikrobiol, 1984, 24(1), 13 - 9
Isolation and biological properties of arsenate-resistant strains of Streptomyces noursei; Friedrich W et al.; Arsenate-resistant (AsR) clones were obtained with high frequency from colony populations of streptothricin-producing strains of Streptomyces noursei by the paper strip method . Whereas in the AsR-strains obtained from both wild type and mutant NG 13 the antibiotic production was reduced to approx . 60% of the parental level, the AsR clones isolated from colony populations of mutant UV 12 displayed increased productivity (less than or equal to 150%) . However, their improved capacity to produce streptothricins was lost rapidly after repeated cell propagation in submerged cultures, suggesting that unstable genetic elements were involved in enabling S . noursei to grow in the presence of toxic concentrations of arsenate.

Pharmacopsychiatry, 1984 Jan, 17(1), 9 - 15
Adenylate cyclase and the search for new compounds with the clinical profile of lithium; Belmaker RH; It is possible to evaluate the beta-adrenergic receptor-adenylate cyclase complex in the human periphery by measuring the plasma cyclic AMP rise after adrenergic agonists . A clinical trial of the beta 2 adrenergic agonist salbutamol in depression provided an opportunity to test whether adrenergic receptor subsensitivity does occur during clinical antidepressant treatment . After 1 and 3 weeks of oral salbutamol treatment, depression scores declined significantly in 11 depressed patients, while the plasma cyclic AMP response to i.v . salbutamol declined over 60% . The results support the concept that receptor sensitivity changes occur during human antidepressant therapy . Data are presented that Li, too, markedly reduces activity of beta-adrenergic adenylate cyclase in humans . The effect was evaluated by studying the effect of Li at therapeutic serum concentrations on the plasma cyclic AMP response to subcutaneous epinephrine . The Li effect is specific, since the plasma cyclic AMP response to glucagon is not inhibited . In rat cortical slices Li inhibition of noradrenaline-induced cyclic AMP accumulation is clearly demonstrable only at concentrations close to 2 mM Li . However, fresh human brain slices from edges of surgically-removed tumors show Li inhibition at 1 mM Li concentrations . These results imply that in brain as well as periphery, human noradrenergic adenylate cyclase is inhibited by therapeutic concentrations of Li . Demeclocyclin, a tetracycline-derived antibiotic, was found to inhibit noradrenaline-sensitive adenylate cyclase in rat cortical slices and to inhibit amphetamine-induced hyperactivity in rats in an open field . Clinical trials should search for new compounds with the clinical profile of Li.

EMBO J, 1984 Jan, 3(1), 113 - 20
Specific alterations of the EF-Tu polypeptide chain considered in the light of its three-dimensional structure; Duisterwinkel FJ et al.; Specific alterations of the elongation factor Tu (EF-Tu) polypeptide chain have been identified in a number of mutant species of this elongation factor . In two species, Ala-375, located on domain II, was found by amino acid analysis to be replaced by Thr and Val, respectively . These replacements substantially lower the affinity of EF-Tu.GDP for the antibiotic kirromycin . Since kirromycin can be cross-linked to Lys-357, also located on domain II but structurally very far from Ala-375, these data suggest that the replacements alter the relative position of domains I and II . The Ala-375 replacements also lower the dissociation rates of the binary complexes EF-Tu.GTP and the binding constants for EF-Tu.GTP and Phe-tRNA . It is conceivable that these effects are also mediated by movements of domains I and II relative to each other . Replacement of Gly-222 by Asp has been found in another mutant by DNA sequence analysis of the cloned tufB gene, coding for this mutant EF-Tu . Gly-222 is part of a structural domain, characteristic for a variety of nucleotide binding enzymes . Its replacement by Asp does not abolish the ability of EF-Tu to sustain protein synthesis . It increases the dissociation rate of EF-Tu.GTP by approximately 30% . In the presence of kirromycin this mutant species of EF-Tu.GDP does not bind to the ribosome, in contrast to its wild-type counterpart . A possible explanation is now open for experimental verification.

Antimicrob Agents Chemother, 1984 Jan, 25(1), 58 - 61
Effect of protein binding on simulated intravascular and extravascular kinetics of cefotaxime in an in vitro model; Peterson LR et al.; The simulated intravascular and extravascular kinetics of cefotaxime were studied in an in vitro model to evaluate the effect of antibiotic protein binding in the "intravascular" and "extravascular" space . Intravascular fluid consisted of either phosphate-buffered saline, which has no cefotaxime binding, or 3% bovine albumin, which has 63% cefotaxime binding . Extravascular spaces were filled with phosphate-buffered saline, 1.5% bovine albumin (46.6% cefotaxime binding), or 3% bovine albumin . Cefotaxime (80 mg per dose) was infused every 3 h for eight doses, and intravascular and extravascular drug concentrations were measured after doses one and eight . The corresponding intravascular and extravascular spaces were at (phosphate-buffered saline) or approaching (3% bovine albumin) equilibrium by dose eight . There were marked differences in drug concentrations achieved in the various extravascular spaces, but all could be explained on the basis of differing amounts of albumin present and the resultant differences in cefotaxime binding.

Int J Cardiol, 1984 Jan, 5(1), 83 - 7
Prosthetic valve endocarditis caused by Trichosporon cutaneum; Thomas D et al.; We report, to our knowledge, the first case of Trichosporon cutaneum endocarditis which developed in a 58-year-old woman 14 months after mitral valve replacement . The patient had not had antibiotic therapy . She was treated with an oral antifungal agent, ketoconazol, and prosthetic valve replacement . The initial outcome was favorable, but she died 5 months later of aortic valve endocarditis . Fungal infection was documented by isolation of the fungus from blood cultures, by anatomical and pathological examination and by the changes in serology.

Rev Chir Orthop Reparatrice Appar Mot, 1984, 70(5), 383 - 8
{Arthritis of the hip in paraplegic patients . Apropos of 8 cases}; Lortat-Jacob A et al.; Eight instances of septic arthritis of the hip were treated in 6 paraplegics . On each occasion the hip had been infected through a nearby ulcer . In 2 cases the diagnosis was only made at operation because signs of a severe infection are not obvious in paraplegics . The radiographs were often misleading, the joint space being either normal or narrowed even before the onset of sepsis . The treatment combined antibiotic therapy with resection of the head and neck stabilized by external fixation for 45 days . The procedure was only successful in 5 cases out of 8 as far as infection was concerned . The resection did not impair ability to sit in this type of patient.

Childs Brain, 1984, 11(3), 183 - 7
Shunt nephritis: a report on five children; Zamora I et al.; Of 5 children with glomerulonephritis with infected ventriculoatrial shunt, 3 had improved renal function after antibiotic therapy and removal of the infected shunt . 1 patient with endoextracapillary proliferative glomerulonephritis with 70% glomerular crescents developed a rapidly progressive renal insufficiency . Renal failure was successfully managed by hemodialysis and kidney transplantation . 1 patient died from extrarenal causes in the course of a septic episode.

CRC Crit Rev Biochem, 1984, 16(1), 21 - 49
Inhibitors of the biosynthesis and processing of N-linked oligosaccharides; Elbein AD; A number of glycoproteins have oligosaccharides linked to protein in a GlcNAc----asparagine bond . These oligosaccharides may be either of the complex, the high-mannose or the hybrid structure . Each type of oligosaccharides is initially biosynthesized via lipid-linked oligosaccharides to form a Glc3Man9GlcNAc2-pyrophosphoryl-dolichol and transfer of this oligosaccharide to protein . The oligosaccharide portion is then processed, first of all by removal of all three glucose residues to give a Man9GlcNAc2-protein . This structure may be the immediate precursor to the high-mannose structure or it may be further processed by the removal of a number of mannose residues . Initially four alpha 1,2-linked mannoses are removed to give a Man5 - GlcNAc2 -protein which is then lengthened by the addition of a GlcNAc residue . This new structure, the GlcNAc- Man5 - GlcNAc2 -protein, is the substrate for mannosidase II which removes the alpha 1,3- and alpha 1,6-linked mannoses . Then the other sugars, GlcNAc, galactose, and sialic acid, are added sequentially to give the complex types of glycoproteins . A number of inhibitors have been identified that interfere with glycoprotein biosynthesis, processing, or transport . Some of these inhibitors have been valuable tools to study the reaction pathways while others have been extremely useful for examining the role of carbohydrate in glycoprotein function . For example, tunicamycin and its analogs prevent protein glycosylation by inhibiting the first step in the lipid-linked pathway, i.e., the formation of Glc NAc-pyrophosphoryl-dolichol . These antibiotics have been widely used in a number of functional studies . Another antibiotic that inhibits the lipid-linked saccharide pathway is amphomycin, which blocks the formation of dolichyl-phosphoryl-mannose . In vitro, this antibiotic gives rise to a Man5GlcNAc2 -pyrophosphoryl-dolichol from GDP-{14C}mannose, indicating that the first five mannose residues come directly from GDP-mannose rather than from dolichyl-phosphoryl-mannose . Other antibodies that have been shown to act at the lipid-level are diumycin , tsushimycin , tridecaptin, and flavomycin . In addition to these types of compounds, a number of sugar analogs such as 2-deoxyglucose, fluoroglucose , glucosamine, etc . have been utilized in some interesting experiments . Several compounds have been shown to inhibit glycoprotein processing . One of these, the alkaloid swainsonine , inhibits mannosidase II that removes alpha-1,3 and alpha-1,6 mannose residues from the GlcNAc- Man5GlcNAc2 -peptide . Thus, in cultured cells or in enveloped viruses, swainsonine causes the formation of a hybrid structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Eksp Onkol, 1984, 6(4), 73 - 4
{Effect of bleomycetin on the proliferative activity of bone marrow and lymph node cells in SJL/J mice}; Markochev AB et al.; Dynamics of dose and time dependence of bleomycin action on bone marrow and lymph node cells of SJL/J mice has shown that 6 h after administration of 25 micrograms of bleomycin the proliferative activity is 1.5 times reduced . The antibiotic influences the interphase cells and delays a cellular cycle . A durable and persistent decrease of the proliferative activity (up to 10 days) of bone marrow and lymph node cells shows a prolonged action of the bleomycin single dose and a pronounced cytostatic effect of the antibiotic on cellular elements of SJL/J mice . Bleomycetin is established to produce action both on lymph node and bone marrow tumour cells of SJL/J mice.

Cytogenet Cell Genet, 1984, 38(2), 152 - 4
Bleomycin-induced chromosome breakage in G2 lymphocytes of retinoblastoma patients; Chaum E et al.; Retinoblastoma (Rb) cells may be more sensitive to X-irradiation than normal cells when assayed for clonogenic survival, suggesting that such sensitivity can be used as a trait for detecting RB1 gene carriers . We studied induction of chromosome damage in lymphocytes from patients with Rb by the radiomimetic antineoplastic antibiotic, bleomycin (BL) . Lymphocytes were treated in G2 for 4 h at four concentrations of the drug (0.0, 0.3, 0.9, and 2.7 micrograms/ml), and chromosome damage was evaluated . No difference in levels of spontaneous or induced damage was detected among hereditary Rb, non-hereditary Rb, and normal lymphocytes . The role of X-ray treatment in the induction of second tumors in Rb patients is discussed.

Biochem Pharmacol, 1984 Jan 1, 33(1), 147 - 54
Nature of toxicity for chick embryo fibroblast cells of coumermycin A1 and its physico-chemical interactions with protein and nucleic acid; Palu G et al.; The results reported in this paper describe the effects produced by the antibiotic Coumermycin A1 (CA1) on survival and metabolism of chick embryo fibroblast cells (CEF), and give a clue to the understanding of its toxicity . The drug acts primarily at the level of DNA and RNA synthetic enzymes; no effect on DNA superstructure is detectable at doses at which cytotoxicity is pronounced . A spectroscopic approach produced evidence that CA1 binds to DNA, RNA, chromatin components such as histones and to a structurally unrelated protein such as bovine serum albumin . Furthermore, CA1 behaves like a pure non-competitive inhibitor of lactic dehydrogenase, a ubiquitous enzyme not involved in nucleic acid metabolism . The interaction of CA1 with a wide range of macromolecules playing different biological roles is certainly relevant to its activity and adds a new insight into the mechanism of action of this antibiotic . These observations are also discussed in the light of the alleged role of CA1 as a specific inhibitor of DNA topoisomerase in eukaryotic cells.

Oncology, 1984, 41(1), 43 - 8
Inhibitory effect of gramicidin S on the growth of murine tumor cells in vitro and in vivo; Okamoto K et al.; The Effect of gramicidin S (GS), a polypeptide antibiotic, on the growth of murine tumor cells such as allotransplantable sarcoma 180 (S180) and Ehrlich ascites carcinoma (EAC) and Meth A fibrosarcoma (Meth A) was studied . GS inhibited the proliferation of EAC cells in culture and its effect on cell viability was dependent on the concentration of GS . On exposure to GS at concentrations ranging from 1 to 100 micrograms/ml for 10 min, EAC cells lost their transplantability in ddY mice depending on the concentration of GS . In particular, the transplantability of EAC cells was completely missing on exposure to GS at a concentration of 100 micrograms/ml . In the in vivo experiments, a daily intraperitoneal injection of GS exhibited a high inhibitory effect not only on the growth of subcutaneously implanted S180 in ICR mice but on the growth of subcutaneously implanted syngeneic Meth A in BALB/c mice . In the studies using radioactively labeled DNA, RNA and protein precursors, GS at high concentrations inhibited the incorporation of all the precursors into EAC cells.

Cytometry, 1984 Jan, 5(1), 42 - 54
Filipin as a flow microfluorometry probe for cellular cholesterol; Muller CP et al.; The polyene antibiotic filipin, which forms specific complexes with 3 beta-hydroxysterols, displays spectral properties compatible with its use in flow microfluorometry (FMF) . The purpose of this study was to test the suitability of filipin as an FMF probe for unesterified cellular cholesterol . The following experimental conditions appeared optimal for cells with an average unesterified cholesterol content of less than 3 nmol per 10(6) cells: 2 X 10(6) fixed cells (1-4% p-formaldehyde, 30 min, 21 degrees C) stained for 2-4 h with 100 micrograms/ml filipin and excited at 350.7/356.7 nm . Fluorescence emission (Em) was measured above 510 nm . Less suitable conditions involved excitation at 488 nm or using cells which had not been fixed . Fixation preserved the live-dead cell discrimination provided by forward light scatter measurements, so that dead cells could be excluded from the FMF analysis of cellular cholesterol . Under the above conditions FMF analysis of a variety of murine cell types showed that in all cases the fluorescence intensity of filipin-stained cells was clearly increased above autofluorescence levels of the unstained control cells . The increase in fluorescence signal in different filipin stained cell types correlated (P less than or equal to .001) with the cellular content of unesterified cholesterol determined by an independent enzymatic assay . The sensitivity of the FMF assay was in the femtomole (10(-15) ) range . Mixing experiments with cells of different cholesterol levels showed that the technique distinguishes cell populations with distinctive levels of unesterified cholesterol . We therefore concluded that filipin is a useful FMF probe for determining relative levels of unesterified cholesterol in cells.

Comp Biochem Physiol C, 1984, 79(1), 31 - 3
Effect of tetracycline hydrochloride on the physical and chemical properties of Heliothis virescens larvae; Thompson AC et al.; The effects of various levels of tetracycline hydrochloride on the feeding habits, larval growth, and the metabolism of lipids, carbohydrates and proteins of Heliothis virescens were studied . Regression analysis showed that larval weight, fatty acids and glycogen decreased exponentially with increasing concentration of antibiotic, whereas protein showed a linear decrease . Larval feeding was initially decreased when antibiotics were added to the diet but there was no difference after 24 hr.

Intervirology, 1984, 22(4), 227 - 31
Replication of Junin virus in the presence of tunicamycin; Padula PJ et al.; In the presence of tunicamycin (TM), an antibiotic which inhibits glycosylation, Junin virus-infected cells released 70% as much virus as control cultures, as measured by {35S}-methionine appearing in a sucrose gradient virus particle fraction . In this same fraction, the incorporation of {14C}-glucosamine was inhibited 85% by TM, accompanied by a dramatic decrease in the envelope glycoprotein, Gp38, and a marked decrease in virus infectivity . These results indicate that the presence of Gp38 on the viral surface is essential for viral infectivity . In contrast, maturation and release of virus particles do not seem to be affected by the absence of Gp38 from the viral envelope.

Cancer Immunol Immunother, 1984, 18(3), 164 - 8
Effects of cefotaxime, clindamycin, mezlocillin, and piperacillin on mouse sarcoma L-1 tumor; Roszkowski K et al.; For the study described in the paper, the effects of 10 days' chemotherapy with cefotaxime, clindamycin, mezlocillin, and piperacillin on local tumor growth and on spontaneous or artificial metastatic spread into the lungs were studied . For the animal tumor model Balb/c mice and the mouse sarcoma L-1 tumor were used . Chemotherapy was administered before, immediately after, or some time after the injection of tumor cells . The antibiotic dosage given to mice was calculated on a body weight basis from the doses recommended for humans . Cefotaxime and clindamycin did not influence the animal tumor model, whereas mezlocillin and piperacillin showed positive or negative effects depending on the chemotherapy schedule . In vitro none of the four antibiotics caused cytotoxic activity in cell cultures of mouse sarcoma L-1, human lung cancer E-14, or human malignant melanoma MEW.

Arzneimittelforschung, 1984, 34(7), 798 - 800
Influence of experimentally induced cholestasis on the pharmacokinetics of cefotiam; Alonso IG et al.; The pharmacokinetics of (7 beta-{2-(2-amino-thiazol-4-yl) acetamido}-3-{{1-(2-dimethylaminoethyl)-1H-tetrazol- 5-yl}thio)methyl)-ceph-3-em-4-carboxylic acid (cefotiam) was studied in rabbits with normal and experimentally decreased or annulled biliary excretion . The latter two states were induced by administration of 17 beta-estradiol and by tying of the choledochus, respectively . All animals included in the study received a single i.v . bolus type injection of 40 mg/kg of the antibiotic . The average values of the pharmacokinetic parameters obtained after such administration to the control rabbits, with normal biliary excretion, expressed in accordance with a two-compartment open kinetic model were: alpha = 15.598 h-1; beta = 2.717 h-1; K12 = 5.247 h-1; K21 = 7.093 h-1 and K13 = 5.975 h-1 . Cholestasis modifies the parameters defining the distribution and elimination of cefotiam to a considerable extent . The serum half-life of the slow elimination phase had an average value of 0.116 h in the control group and 0.207 h in the group with mechanically induced cholestasis . Chemically induced cholestasis caused a lesser increase in the serum half-life.

J Fr Ophtalmol, 1984, 7(2), 137 - 41
{Intraocular penetration of ceftriaxone in man . Comparison with other beta-lactamins}; Adenis JP et al.; The intraocular penetration of a new antibiotic, ceftriaxon, was studied in 30 patients . Serum samples in 29 patients showed an average level of 42 micrograms/ml . Penetration into the aqueous humour flow studied in 28 patients under general anesthesia at one, two, three, four and six hours after the injection . An average level of 0,53 micrograms/ml was found which is 1,25% of average serum level . In 23 patients the dry level in tears averaged 5,75 micrograms/ml (13% of the serum level) . In one case of retinal detachment the level in the subretinal fluid was 1,56 micrograms/ml . The kinetics drug secretion in tears was studied in 3 patients without anesthesia every 2 hours until the 16 th to 22 nd hours . Lower levels than those obtained under general anesthesia were obtained . This study shows that ceftriaxon has an intraocular penetration at levels above the minimal inhibitory concentrations for most commun intraocular infection.

Experientia, 1983 Dec 15, 39(12), 1402 - 4
High resolution of heterochromatin of Drosophila melanogaster by distamycin A; Faccio Dolfini S et al.; A DNA-binding AT-specific antibiotic, distamycin A, was used as inhibitor of the condensation process of the heterochromatic regions in Drosophila melanogaster embryonic cells . By this treatment the structural organization of heterochromatin at interphase is preserved until metaphase . The different patterns observed are interpreted as chronological steps in the condensation process.

J Biol Chem, 1983 Dec 10, 258(23), 14490 - 5
Post-translational modification of the fourth component of complement . Effect of tunicamycin and amino acid analogs on the formation of the internal thiol ester and disulfide bonds; Karp DR; The appearance of a functional thiol ester within murine pro-C4 (the intracellular precursor of C4) has been studied . This was assessed by testing the ability of pro-C4 molecules to undergo denaturation-dependent autolytic cleavage . In pulse-chase experiments, {35S}methionine-labeled pro-C4 does not autolyze until approximately 20 min after synthesis by peritoneal macrophages . When intact (not autolyzed) pro-C4 was examined by nonreducing gel electrophoresis, an increase in its apparent Mr was seen, with a time course similar to that for autolysis . Both the capacity to undergo autolytic cleavage and the Mr increase were inhibited by cell culture in the presence of the antibiotic tunicamycin or the threonine analog beta-hydroxynorvaline, both of which inhibit glycosylation . Upon isolation from tunicamycin- or hydroxynorvaline-treated cells, pro-C4 associates with other cell constituents, probably via disulfide bonds . This phenomenon is not seen with the mature (high Mr) form of pro-C4 in control cultures, and can be prevented if the cells are lysed in the presence of a sulfhydryl reagent such as iodoacetamide . These data suggest that the post-translational modification of pro-C4 includes the acquisition of a disulfide-stabilized conformation with a greater apparent Mr . This conformation, along with an intact thiol ester, is necessary for autolytic cleavage to occur.

Presse Med, 1983 Dec 10, 12(45), 2869 - 72
{Role of Chlamydia trachomatis in the etiology of acute salpingitis . Value of the determination of IgG in 2 blood samples collected at 6 week intervals}; Henry-Suchet J et al.; Cultures of specimens from the abdominal cavity (14) or the lower genital tract (11) were positive for Chlamydia trachomatis in 25 (22.7%) of 110 patients with a laparoscopic diagnosis of acute salpingitis . Microimmunofluorescence serodiagnosis showed positive IgG levels (greater than or equal to 1/64) in 35 patients (32%) . Of the 34 patients in whom a second serodiagnosis was performed after 6 weeks, 20 (58%) had positive IgG levels (greater than or equal to 1/64) and 12 (35%) had a fourfold or more change in dilution . Thus, culture and serodiagnosis provided evidence of Chlamydia infection in 46% of the patient population . Forty-six patients were followed up for several months to evaluate the response to antibiotic therapy . Among tetracyclines, lymecycline was effective in 19/25 cases, doxycycline in 15/19 cases and minocycline in 2/4 cases . Switching to another tetracycline after failure of the first one usually gave satisfactory results.

Tex Heart Inst J, 1983 Dec, 10(4), 337 - 41
Surgical Considerations in Aortitis : Part III: Syphilitic and Other Forms of Aortitis; Duncan JM et al.; The majority of cases involving clinically significant aortitis result from Takayasu's disease, syphilis, and mycotic aneurysms, although aortitis may occur as a part of the clinical manifestation in other diseases of known and unknown etiology . Syphilitic aortitis can be treated successfully if an accurate diagnosis is made early and if appropriate antibiotic therapy is instituted . Untreated or treated inadequately, late cardiovascular complications can occur, namely, aortic aneurysm, aortic valvular insufficiency and coronary osteal stenosis . Surgical treatment should be considered when any of these late complications become manifest . Aortitis can occur with rheumatic fever and, occasionally, in rheumatoid arthritis . Giant-cell arteritis is a disease that can affect large, medium or small arteries, and usually occurs in patients over 50 years of age, chiefly women . The entire aorta may be affected . It is the only form of aortitis commonly associated with dissecting aneurysm of the aorta . Corticosteroids are effective in treating the active form of the disease and can usually prevent the development of later severe complications . Surgery is indicated when a dissecting aneurysm develops.

Tex Heart Inst J, 1983 Dec, 10(4), 329 - 35
Surgical Considerations in Aortitis : Part II: Mycotic Aneurysms; Duncan JM et al.; Mycotic aneurysms were first described as the result of nonsyphilitic bacterial infection of the arterial wall . They were often caused by septic emboli from bacterial endocarditis and were much more common prior to the era of antibiotics . Although the aorta is most often affected, such aneurysms may arise in any artery . Classified according to their etiology as primary, secondary, and cryptic mycotic aneurysms, it is imperative that immediate treatment be instituted once the diagnosis is confirmed by angiography . The patient should be placed on high doses of antibiotics appropriate for the offending pathogens . The goal of surgical treatment is the complete removal of the infected aneurysm and preservation of the distal circulation . Alternate methods of treating these lesions include the use of bypass grafts and interposition grafts . The virulence of the offending pathogen and the sensitivity to antibiotic therapy play a significant role in the success of these procedures.

Am J Clin Pathol, 1983 Dec, 80(6), 844 - 9
How sensitive is the Papanicolaou smear in the diagnosis of infections with Chlamydia trachomatis?
Giampaolo C, Murphy J, Benes S, McCormack WM.
Fifty-three patients who presented to the sexually transmitted disease clinic at Boston City Hospital had simultaneous cervicovaginal Papanicolaou smears and cultures for Chlamydia trachomatis taken prior to the initiation of antibiotic therapy . Eleven of the chlamydial cultures had positive results . None of the Papanicolaou smears satisfied the morphologic criteria for the diagnosis of chlamydial infection . This suggests that the Papanicolaou smear is an insensitive technic for the diagnosis of chlamydial infection of the cervix.

J Anim Sci, 1983 Dec, 57(6), 1474 - 8
Tiamulin feed medication for the maintenance of weight gains in the presence of mycoplasmal pneumonia in swine; Hsu FS et al.; Tiamulin, a semisynthetic antibiotic, was fed to growing pigs and its value in maintaining weight gain and feed efficiency in the face of mycoplasmal pneumonia was determined . Four treatments divided among 64 growing pigs from a conventional pig farm were used to test the effects of tiamulin administered in feed at levels of 10, 20 and 30 ppm . All pigs were artificially infected with Mycoplasma hyopneumoniae . Medication was started on the 14th day after infection (d 0) and continued for 28 d (d 0 to 28) . Pigs were continued on test for an additional 14-d period for further observation (d 28 to 42) after the medicated feed was withdrawn . Tiamulin fed at 10, 20 and 30 ppm for 28 d did not cure the mycoplasmal pneumonia . The effect of tiamulin on growth performance was not the same for all periods . During the medication period (d 0 to 28), both daily gain and feed conversion were not significantly affected by dietary tiamulin concentrations . For the post-treatment period (d 28 to 42), tiamulin improved daily gain (P less than .05) and feed conversion (P less than .05) over those of nonmedicated controls, and the responses of both daily gain and feed efficiency increased linearly (P less than .05) as dietary tiamulin levels increased.

J Antimicrob Chemother, 1983 Dec, 12(6), 623 - 7
Comparative penetration of latamoxef (moxalactam) and cefazolin into human knee following simultaneous administration; Hume AL et al.; The penetration of latamoxef (moxalactam) and cefazolin into cancellous bone was compared in ten adult patients undergoing total knee replacement . Each patient received a ten milligram per kilogram bolus dose of both antibiotics at the induction of anaesthesia . Antibiotic bone concentrations were determined by HPLC . The mean serum concentrations of cefazolin were significantly greater (P less than 0.01) than those of latamoxef at all time periods . The absolute bone concentrations of cefazolin and latamoxef did not differ significantly (P greater than 0.05) . The method of simultaneous administration offers significant advantages over the conventional two group study design.

J Antibiot (Tokyo), 1983 Dec, 36(12), 1755 - 61
The mode of action of a novel 18-membered macrolide, virustomycin A (AM-2604 A), on Trichomonas foetus; Omura S et al.; The mode of action of virustomycin A, a novel 18-membered macrolide, on Trichomonas foetus was investigated . The antibiotic inhibited the biosynthesis of RNA, DNA and protein in the organism . The inhibition of RNA biosynthesis was the most severe . Virustomycin A repressed the incorporation of {3H}uridine into both acid-soluble and insoluble fractions, whereas actinomycin D inhibited the incorporation of {3H}uridine into acid-insoluble fraction alone . Furthermore, it was found that virustomycin A interfered with nucleotide formation from uridine and adenosine but not with their transport to the cells . On the other hand, the antibiotic did not inhibit the activities of uridine kinase and uracil phosphoribosyltransferase in a cell-free extract from the organism . These data suggest that the antibiotic interferes with the formation of phosphate donor(s) (possibly ATP-forming system) of the organism.

J Clin Microbiol, 1983 Dec, 18(6), 1424 - 6
Rapid diagnosis of septic arthritis by coagglutination; Mayer ME et al.; Pneumococcal capsular antigens were detected and serotyped by coagglutination in joint fluids and serum of a patient with septic arthritis within 1 h of obtaining the specimens . Pneumococcal antigens continued to be detected by coagglutination for 3 days, whereas cultures and Gram stains were negative after 1 day of antibiotic therapy.

Am Fam Physician, 1983 Dec, 28(6), 113 - 6
Carotidynia; Fox GN; Carotidynia is a common but seldom recognized syndrome in which the patient typically complains of a sore throat . Closer questioning usually reveals the soreness to be in the neck . On physical examination, tenderness is noted along a localized segment of the carotid artery . Often the syndrome is misdiagnosed as cervical adenitis and inappropriately treated with an antibiotic . Etiology is unknown . Anti-inflammatory therapy is effective.

South Med J, 1983 Dec, 76(12), 1572 - 4
Medical treatment of splenic abscess; Tooke MC; I have described the first reported patient with a diagnosis of splenic abscess treated medically who survived . Another unusual aspect of this case was the establishment of the diagnosis of splenic abscess by ultrasonic examination . Some typical features of splenic abscess illustrated by this case were compromised patient, known abnormal spleen, febrile illness of uncertain cause, and a low index of suspicion causing delay in correct diagnosis . Despite this patient's survival, splenectomy with antibiotic coverage is the preferred treatment of splenic abscess.

Exp Cell Res, 1983 Dec, 149(2), 335 - 45
Role of glycoproteins in neuronal differentiation . Inhibition of neurite outgrowth and the major cell surface glycoprotein of murine neuroblastoma cells by a purified tunicamycin homologue; Richter-Landsberg C et al.; Mouse neuroblastoma cells in culture can be induced to differentiate morphologically by serum deprivation or by dibutyryl cyclic AMP (db-cAMP), e.g . they appear flattened, adhere more firmly to the culture substratum and extend long neuritic processes, and thus represent a widely used model system for neuronal cells . This differentiation is accompanied by modulation of cell surface components, such as the induction of a high molecular weight (HMW) glycoprotein (200 kD) . We have studied the role of glycoproteins in the process of neuronal differentiation, using a purified homologue of the antibiotic tunicamycin (Al-tunicamycin) and neuroblastoma N115 cells grown in culture . Al-tunicamycin markedly inhibited (up to 60-75%) the incorporation of radioactively labelled sugars into cellular proteins of differentiating neuroblastoma cells . Concomitantly, the cells altered their morphology, they became rounded and less adhesive and retracted their neurites . Changes in the appearance, glycosylation and electrophoretic mobility of several cellular and secreted glycoproteins were observed, when cells were incubated in the presence of Al-tunicamycin . The most striking effect of Al-tunicamycin on the composition of cellular glycoproteins was the marked reduction in appearance of the 200 kD glycoprotein . The findings suggest that glycoproteins and in particular the neuron-specific 200 kD glycoprotein, are related to morphological differentiation processes, mainly to cellular adhesion and neurite outgrowth.

Radiology, 1983 Dec, 149(3), 835 - 9
Aclarubicin (aclacinomycin A) and irradiation: evaluation using HeLa cells; Miyamoto T et al.; Aclarubicin (aclacinomycin A), an anthracyclic anti-tumor antibiotic, was examined as a possible factor to improve survival of proliferating HeLa cells following irradiation . After irradiation followed by exposure to 5 micrograms/ml of aclarubicin for 1 hour, cell killing was significantly enhanced from 2 hours onward, reaching a maximum at 24 hours . The maximum enhancement ratio, determined from comparison of D0 values (mean lethal radiation doses), was 2.3 . Aclarubicin did not potentiate cell killing appreciably when it was given prior to or simultaneously with irradiation . Potentiation cannot be attributed to suppression of recovery from sublethal radiation damage, but rather is due to interaction between radiation and drug damage and lasts through approximately 10 divisions . A recall effect may be predicted on the basis of these findings.

Anal Biochem, 1983 Dec, 135(2), 383 - 91
The use of amphotericin B to detect inhibitors of cellular cholesterol biosynthesis; Krieger M; Pores formed in the membranes of animal cells by complexes of sterols and the polyene antibiotic amphotericin B can efficiently kill the cells . Thus, in the absence of exogenous sources of cholesterol, inhibitors of enzymes in the cholesterol biosynthetic pathway render cells resistant to amphotericin B . Preincubation of Chinese hamster ovary cells with compactin or 25-hydroxycholesterol, inhibitors of the synthesis of the key intermediate mevalonate, protected cells from amphotericin B killing and this protection was reversed by the addition of exogenous mevalonate . The ability of compactin to confer amphotericin B resistance on normal cells was abolished when cells were provided exogenous cholesterol by the receptor-mediated endocytosis of low density lipoprotein . Low density lipoprotein receptor-defective Chinese hamster ovary cells were not subject to this low density lipoprotein-dependent amphotericin B killing . Exogenous mevalonate did not prevent 4,4,10 beta-trimethyl-trans-decal-3 beta-ol, an inhibitor of mevalonate conversion to sterols, from protecting cells from amphotericin B . A simple two-step protocol in which cells are preincubated (15-24 h) with potential inhibitors and then treated (3-6 h) with amphotericin B was devised to provide a sensitive method for detecting direct (e.g., competitive) and regulatory inhibitors of cholesterol biosynthesis . This protocol may prove useful in detecting potential antihypercholesterolemia drugs and is currently being used to isolate mutants in receptor-mediated endocytosis.

J Appl Biochem, 1983 Dec, 5(6), 420 - 8
Proteinase affinity chromatography on bacitracin-Sepharose; Stepanov VM et al.; Antibiotic-cyclopeptide bacitracin covalently bound to Sepharose proved to be an efficient general ligand for affinity chromatography of aspartyl, serine, and metalloproteinases from various sources . The yields of purified enzymes varied from 50 to 180% . New experimental data extend the application of bacitracin-Sepharose for affinity chromatography of cysteine proteinases--papain, bromelain, and ficin . Hence, bacitracin acts as a ligand which more or less efficiently binds proteinases that belong to all the main classes of these enzymes . Bacitracin, being a weak proteinase inhibitor of broad specificity, interacts with the substrate-binding sites of proteinases, which explains its efficiency as a ligand.

Am J Hosp Pharm, 1983 Dec, 40(12), 2149 - 53
Work analysis of an admixture service; Sebastian G et al.; The use of work analysis to identify problems and measure the effect of procedural changes in a hospital pharmacy i.v . admixture service is described . Problems in the work flow in the sterile-products area (SPA) were identified by process analysis, and a work-sampling study was conducted to quantify the time spent in various activities . The number of unused and expired large-volume parenterals (LVPs) that were received by the pharmacy during the work-sampling period was determined, and the lag times between writing of LVP orders and preparation of these LVPs were measured . After reviewing the major activities in the SPA, four procedural changes (automated label typing, use of a new total parenteral nutrient (TPN) base solution, batch production and storage of antibiotic minibags in a freezer, and scheduling changes in the SPA) were implemented . Subsequently, the percentage of time spent in label typing, preparation of TPN solutions, and minibag production decreased . The small decrease in returned LVPs attributed to scheduling changes was related to the failure of decentralized pharmacists to notify SPA personnel about discontinued orders . Monitoring and enforcement of policies regarding notification of discontinued i.v . orders were recommended to management as a means of increasing work flow efficiency . Work analysis was helpful in evaluating and improving the efficiency of an i.v . admixture service . This technique can be applied to other areas of the pharmacy department as well.

Proc Natl Acad Sci U S A, 1983 Dec, 80(23), 7075 - 9
Tunicamycin inhibits ganglioside biosynthesis in rat liver Golgi apparatus by blocking sugar nucleotide transport across the membrane vesicles; Yusuf HK et al.; The synthesis of ganglioside GM1 in intact rat liver Golgi-derived vesicles is stimulated by phosphatidylglycerol as much (about 20-fold) as by Triton X-100 . The antibiotic tunicamycin inhibits strongly the synthesis, in the presence as well as in the absence of the phospholipid, but has no effect when Golgi membranes are solubilized with detergent . In Pronase-treated Golgi vesicles, which retain full enzyme activity, both phospholipid dependence and tunicamycin inhibition of the synthesis disappear completely . When freshly prepared Golgi vesicles are incubated with 125 microM UDP-{3H}Gal for 10 min at 30 degrees C, the nucleotide sugar is found to be transported into the vesicles at an approximate rate of about 85 pmol/mg of protein per min, 92% of which remains firmly bound to the membrane . Tunicamycin inhibits this transport in a concentration-dependent manner . These results indicate the existence of carrier proteins in rat liver Golgi vesicles, which mediate the transport of the sugar nucleotide UDP-Gal, and that the carriers face the cytoplasmic side of the vesicles . The results also show that, although the mechanism of phosphatidylglycerol-induced stimulation of the synthetic activity remains unclear, tunicamycin inhibits ganglioside biosynthesis by blocking the transport of the nucleotide sugar and not by inhibiting the transferase directly.

Z Kinderchir, 1983 Dec, 38 Suppl 2, 84 - 6
Infection as a cause of peritoneal catheter dysfunction in ventriculo-peritoneal shunting in children; Frykberg T et al.; Peritoneal catheter dysfunction is a significant complication of VP shunting in children . Improvement in technique and material should reduce complications such as detachment and breakage . Shunt infection, even if subclinical, should be suspected as the cause of early peritoneal catheter obstruction, especially if recurrent, as well as in cases of organ perforation . Cultures, prolonged if necessary, should be taken and infection should be treated prior to shunt revision . We have had no recurrence of infection or peritoneal catheter dysfunction after treatment with exteriorization of the infected shunt, antibiotic therapy and insertion of a new shunt on the contralateral side . In infected cases antibiotic therapy, both pre- and intra-operatively, should be a matter of course . With these precautions a better result with the ventriculo-peritoneal shunt should be achieved.

Jpn J Antibiot, 1983 Dec, 36(12), 3476 - 82
{Tissue penetration and clinical effects of ceftazidime in the field of obstetrics and gynecology}; Ogawa E et al.; To study concentrations in the gynecological organs, ceftazidime (CAZ) was given intravenously by one shot of 0.5 g to 1 patient and of 1.0 g to 10 patients who underwent simple hysterectomy because of uterine myoma . Also, clinical effect of the drug was studied in 3 cases . The levels of CAZ in sera in uterine artery and elbow vein, and tissue concentrations in various sites of the gynecological organs obtained during 50 to 425 minutes after administration were determined by the paper-disc method with P . mirabilis ATCC 21100 strain . Concentrations of CAZ at 92 minutes after administration of 1.0 g i.v . were 39.8 mcg/ml in serum of uterine artery, 47.6 mcg/ml in serum of elbow vein, 20.5 mcg/g (tissue/serum ratio 0.43) in the ovary, 18.0 mcg/g (0.38) in the fallopian tube, 16.1 mcg/g (0.34) in the endometrium, 34.5 mcg/g (0.72) in the myometrium, 30.8 mcg/g (0.65) in the uterine cervix, 36.4 mcg/g (0.76) in the portio vaginalis and then gradually decreased time-dependently . Tissue concentrations were higher than those in serum in the endometrium, uterine cervix and portio vaginalis at 147 minutes after administration . CAZ concentrations of adipose tissue between 353 and 365 minutes after injection of 1.0 g were lower than 0.8 mcg/g . The clinical responses to CAZ in intrapelvic infections were good in all cases . Slight elevation of total bilirubin, to 1.5 mg/dl, was observed in a case . In the light of these clinical findings, CAZ appears to be a potent antibiotic effective in the clinical application.

Diagn Microbiol Infect Dis, 1983 Dec, 1(4), 339 - 41
Antioxidant-stabilized amphotericin B; Beggs WH; A review of several recent reports shows that many compounds possessing antioxidant or mild reducing properties can enhance the bioactivity of amphotericin B . Antioxidants apparently retard autoxidative inactivation of this primary antifungal antibiotic . Stabilization of amphotericin B in this manner might have practical applications . Some important possibilities are identified and discussed.

Genetika, 1983 Dec, 19(12), 1925 - 33
{Cycloheximide-dependent mutants of the yeast Saccharomyces cerevisiae}; Mironova LN et al.; Selection of sup1 and sup2 mutants in the yeast Saccharomyces cerevisiae on cycloheximide containing media revealed classes of mutants that either are completely unable to grow on YAPD without cycloheximide or need this drug under high temperature incubation (30 or 36 degrees C) . Some of these mutants also exhibit the growth dependence on another antibiotic--trichodermin, and, at the same time, the osmotic dependence . A hypothesis claiming that sup1 and sup2 mutations cause conformational lability fo yeast cytoplasmic ribosomes has been put forward . It is also proposed that binding of cycloheximide and trichodermin to the mutant ribosomes cause their conformational shift, which compensates the functional defects.

Antimicrob Agents Chemother, 1983 Dec, 24(6), 856 - 9
Double-blind comparative study of two dosage regimens of cefaclor and amoxicillin-clavulanic acid in the outpatient treatment of soft tissue infections; Pien FD; A total of 88 patients were enrolled in a double-blind comparison of cefaclor and amoxicillin-clavulanic acid for the outpatient treatment of soft tissue infections (abscesses, cellulitis, and impetigo) . In 84 clinically evaluable patients, high cure rates were obtained for all treatment groups (64 to 85%) . Patients who received amoxicillin-clavulanic acid had a much higher incidence of gastrointestinal side effects than did patients who received cefaclor (34 versus 3%, P less than 0.005) . However, only five patients with gastrointestinal reactions to amoxicillin-clavulanic acid had symptoms severe enough to warrant halting the completion of antibiotic therapy.

Invest Ophthalmol Vis Sci, 1983 Dec, 24(12), 1626 - 9
The effect of K-582, a new antifungal agent, on experimental Candida keratitis; Ohno S et al.; K-582, a new basic peptide antibiotic, was tested in rabbits with experimental Candida keratitis . It was shown that the K-582-treated group showed statistically highly significant therapeutic effects on days 2 and 3, as compared with the control group (day 2: P less than 0.001; day 3: P less than 0.001) . The culture study showed that the average number of colonies was 1,573.1 in the controls and 463.3 in the treated group, and the difference was highly significant statistically (P less than 0.001) . No ocular or systemic toxic effects were observed with this drug . K-582 is a promising new drug for the treatment of Candida keratitis.

J Nucl Med, 1983 Dec, 24(12), 1154 - 7
Cardiac aneurysm complicated by E . coli abscess; Reinke FE et al.; An E . coli myocardial abscess developed in the region of an old aneurysmal myocardial scar . In spite of vigorous antibiotic therapy fever and positive blood cultures persisted . A combination of In-111 WBC scanning and Tc-99m RBC gated heart imaging located the infection in the aneurysmal scar . The abscess was resected and the patient survived.

J Am Vet Med Assoc, 1983 Dec 1, 183(11), 1179 - 81
Mastitis caused by hemolytic Escherichia coli in the ferret; Liberson AJ et al.; Hemolytic Escherichia coli was isolated from the mammary glands of 8 ferrets with gangrenous mastitis . Clinical signs included firm swelling of one or more mammary glands and discoloration of the overlying skin . Peracute disease and acute septicemia were observed, and in some cases the animals rapidly became moribund . Antibiotic therapy alone did not alter the course of the disease . Wide surgical resection of the involved glands in combination with systemic antibiotic therapy (ampicillin 10 mg/kg, BID, and gentamicin 5 mg/kg, SID) was the most successful treatment . Histopathologic changes included extensive edema, hemorrhage, and necrosis, with a mixed leukocytic infiltrate and large numbers of bacteria . The agent of this disease was isolated from rectal swab specimens from clinically normal ferrets as well as ferrets that had mastitis.

Jpn J Antibiot, 1983 Dec, 36(12), 3429 - 36
{Cefotiam excretion into the bile after radical operation of congenital biliary atresia}; Miyano T et al.; Twelve infants having undergone extrahepatic cholangiojejunostomy (SURUGA'S procedure II) after portal hepaticojejunostomy as a radical operation for congenital biliary atresia received prophylactic cefotiam (CTM) against biliary tract infection, 50 mg/kg by intravenous drip in 1 hour, followed by serial determinations of bile and serum CTM levels . The patients were evaluated as to degree of CTM excretion into the bile, by classification into 4 groups according to success or failure in establishing the anastomosis, bile outflow and persistence of jaundice . Patients with an established anastomosis, satisfactory bile flow and no longer jaundice showed high biliary antibiotic concentrations whereas lower biliary antibiotic levels were seen in those with failure in anastomosis, poor bile flow and persistent jaundice . In both cases, nevertheless, the antibiotic concentration in bile sufficiently exceeded the MIC80 values of CTM against principal bacterial pathogens causative of biliary tract infections, thus demonstrating clinical significance of the use of CTM for this purpose . The antibiotic excretion into the bile improved with normalization of liver function in an infant displaying satisfactory bile outflow from an early postoperative stage . The bile and serum CTM assay data obtained by the agar well method showed a high degree of correlation with those by high performance liquid chromatography.

Mol Cell Biol, 1983 Dec, 3(12), 2117 - 30
Efficient transformation of Dictyostelium discoideum amoebae; Barclay SL et al.; We have transformed Dictyostelium discoideum amoebae by using derivatives of a plasmid, pAG60, which was designed for transformation of mammalian cells . The plasmid carries the promoter region of the herpes simplex virus type 1 thymidine kinase gene linked to the bacterial gene kan, which codes for the enzyme aminoglycoside 3'-phosphotransferase . kan is derived from the Tn5 transposon . Expression of the phosphotransferase permits direct selection of transformed cells by their resistance to the antibiotic G-418 . pAG60 is incapable of transforming D . discoideum but is made transformation proficient by cloning D . discoideum sequences into the tetracycline resistance gene . The majority of transformed cells grow and develop normally and differentiate to give G-418-resistant spores . These transformants are unstable and rapidly lose their G-418-resistance during growth in the absence of antibiotic selection . Southern blots show that these unstable G-418-resistant transformants carry the pBR322 and kan sequences of pAG60 . The pAG60-D . discoideum recombinant plasmids used for transformation were constructed in a way that might make them mutagenic . We have isolated several developmental mutants after transformation of D . discoideum with libraries of pAG60-D . discoideum recombinant plasmids . These mutants are G-418 resistant and carry pAG60 in their nuclear DNA . We recovered a pAG60-D . discoideum recombinant plasmid from several developmental mutants . This plasmid transforms D . discoideum at an elevated frequency and integrates into the nuclear genome . We speculate that integration can result in insertional inactivation of genes that are essential for differentiation but not for growth . Mutagenic transformation occurred only if the transforming plasmid had homology with D . discoideum nuclear DNA . A mammalian cell transformation vector, pSV2-neo, carried no D . discoideum sequences and was able to transform . However, pSV2-neo transformation was not mutagenic . These results suggest that direct inactivation and recovery of genes that are essential for differentiation of D . discoideum will be possible.

Clin Nucl Med, 1983 Dec, 8(12), 630 - 1
Early diagnosis of testicular tumor using Tc-99m pertechnetate scrotal imaging; Donoghue GD et al.; Two patients who originally presented with clinical symptoms of epididymo-orchitis, with compatible findings on the Tc-99m pertechnetate scrotal images, had temporary remission of their symptoms with antibiotic therapy . After two months, both patients had repeat scrotal images, because of persistent testicular enlargement . Both now demonstrated a "cold spot" in the otherwise increased activity on the affected side . Both patients underwent orchiectomy; patient 1 had a tissue diagnosis of malignant mixed germ cell tumor and patient 2 showed teratocarcinoma.

Proc Natl Acad Sci U S A, 1983 Dec, 80(23), 7308 - 12
Construction and testing of mouse--human heteromyelomas for human monoclonal antibody production; Teng NN et al.; FU-266, a mutant human myeloma cell line sensitive to hypoxanthine/aminopterin/thymidine (HAT), was transfected by protoplast fusion with DNA of the recombinant plasmid vector pSV2-neoR, thus acquiring a dominant marker conferring resistance to the antibiotic G-418 . One of the resultant neoR clones, E-1, was fused to irradiated (500 rads) or unirradiated cells of the HAT-sensitive, G-418-sensitive, nonproducer mouse myeloma line X63-Ag8.653 . Hybrid clones were selected in G-418 plus ouabain, thus preserving their HAT sensitivity . Small numbers of human chromosomes were retained in all such hybrids, but most of them ceased secreting human myeloma (IgE(lambda) . Selected hybrid clones were then tested as malignant fusion partners in a series of fusions with polyclonally activated human B lymphocytes and with antigen-primed human B lymphocytes, in some instances after transformation of the latter with Epstein-Barr virus . The yield of viable chimeric hybridomas has been consistently high, as has the proportion of hybridomas secreting human immunoglobulin molecules unpermuted with mouse or human myeloma heavy or light chains . Secretion by many subcloned hybridomas has been stable for over 6 months, and several antigen-specific human monoclonal antibodies have been generated . Thus these heteromyeloma cell lines appear to have significant advantages for human monoclonal antibody production.

Radiat Res, 1983 Dec, 96(3), 518 - 22
Hyperthermic modification of bleomycin--DNA interaction detected by electron spin resonance; Chapman IV et al.; Electron spin resonance spectra of DNA labeled with each of four spin-labeling compounds have been studied to detect interaction between the antibiotic bleomycin and DNA . Only one of these labels, compound IV, resulted in a modified spectrum when bound to DNA and the latter was subjected to bleomycin . This property has been used to monitor DNA-bleomycin interactions under physiological and hyperthermic conditions . Bleomycin produced an increase in rotational correlation time of the residue bound to DNA at 37 degrees C and a significantly higher increase at 43 degrees C . Some effect was still detected with bleomycin at 37 degrees C after preheating at 43 degrees C . Parallel studies have revealed enhanced binding of 59Fe-bleomycin to DNA during and after hyperthermic treatment.

Cancer Lett, 1983 Dec, 21(2), 149 - 53
Bleomycin cytotoxicity is prevented by superoxide dismutase in vitro; Cunningham ML et al.; The cytotoxicity of the antitumor antibiotic bleomycin (BLM) on Chinese hamster ovary cells in vitro was studied . Approximately 50% of the cells were killed by exposure to 9.6 micrograms/ml BLM for 1 h . The cytotoxicity could be partially reversed by the prior addition of superoxide dismutase (SOD) or catalase, but not with the addition of mannitol or histidine . These results indicate that superoxide anion and hydrogen peroxide but not hydroxyl radical are involved in the cytotoxic action of BLM.

J Bacteriol, 1983 Dec, 156(3), 1322 - 31
Effect of cerulenin on macromolecule synthesis in chemoheterotrophically and photoheterotrophically grown Rhodopseudomonas sphaeroides; Shepherd WD et al.; The antibiotic cerulenin causes the immediate cessation of phospholipid biosynthesis in both chemoheterotrophic and photoheterotrophic cultures of Rhodopseudomonas sphaeroides . Macromolecule biosynthesis in photoheterotrophic cells was unaffected by cerulenin for the first 2 h after antibiotic addition and then continued at a reduced rate for an additional 8 h . In contrast, macromolecule biosynthesis in chemoheterotrophic cells was severely affected by cerulenin within the first 2 h of treatment . Pulse-labeling of protein after cerulenin addition revealed that all subcellular fractions were equally affected by the action of cerulenin with chemoheterotrophic cell fractions more profoundly affected than those derived from photoheterotrophic cells . Protein insertion into the intracytoplasmic membrane of photoheterotrophic cells continued for up to 6 h after the onset of cerulenin treatment . Residual macromolecule synthesis was correlated with the presence of the photosynthetic membrane system under all conditions of growth.

Can J Microbiol, 1983 Dec, 29(12), 1706 - 14
Nitrogen metabolism and chloramphenicol production in Streptomyces venezuelae; Shapiro S et al.; The relationship between chloramphenicol production and nitrogen metabolism in Streptomyces venezuelae was examined in stirred jar cultures under pH control . Nitrogen sources that supported rapid biomass accumulation gave low rates of antibiotic synthesis during growth . This was consistent with a general incompatibility between fast growth and high yields of chloramphenicol . In media where the growth rate was reduced below the attainable maximum by the rate at which nitrogen could be assimilated, chloramphenicol production was associated with biomass accumulation . Enzymes that are potentially associated with nitrogen assimilation pathways were assayed in cultures supplied with nitrogen sources supporting markedly different growth rates . The results indicated that glutamine synthetase and alanine dehydrogenase levels were relatively insensitive to changes in growth rate and nitrogen source depletion . Glutamate dehydrogenase and glutamate synthase, on the other hand, showed high activity in cultures assimilating ammonium nitrogen and markedly decreased activity with poorer nitrogen sources or when ammonium was depleted . If chloramphenicol biosynthesis is coordinately controlled by mechanisms that regulate nitrogen assimilation, glutamate synthase and glutamate dehydrogenase are the most likely enzymes that manifest the regulatory linkage.

HNO, 1983 Dec, 31(12), 415 - 9
{Intracranial complications in sinusitis}; Fenner T et al.; Between 1931 und 1981 a total of 60 patients with endocranial complications of paranasal sinus infections was observed at the ENT clinic of the University Hospital in Zurich . The symptomatology, clinical findings, incidence and eventual course of the different endocranial complications are discussed in relation to treatment before and after the availability of antibiotics . A dramatic decrease in incidence of endocranial complications occurred following the advent of antibiotic use and early surgical drainage of the involved cavities . The mortality rate between 1931 an 1945 was 86%, between 1945 and 1949 40% and between 1950 and 1981 5%.

Biochem Pharmacol, 1983 Dec 1, 32(23), 3547 - 53
Genetic and biochemical studies on the activation and cytotoxic mechanism of bredinin, a potent inhibitor of purine biosynthesis in mammalian cells; Koyama H et al.; To study the activation and cytotoxic mechanism of bredinin (4-carbamoyl-1-beta-D-ribofuranosylimidazolium-5-olate), a novel nucleoside antibiotic with potent cytotoxic and immunosuppressive effects, we isolated in a single-step manner five mutants resistant to 10 microM bredinin from cultured mouse mammary carcinoma FM3A cells mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) . Such resistant (Brdr) mutants were 15- to 19-fold less sensitive to the antibiotic than wild-type cells and maintained stably their resistant phenotypes in the absence of bredinin for more than 3 months . They were cross-resistant to tubercidin, an adenosine analog . Like wild-type cells, Brdr mutants were capable of incorporating radioactivity from ring-labeled adenosine into the acid-insoluble macromolecular fraction . However, hypoxanthine-guanine phosphoribosyltransferase-deficient (HGPRT-) mutants derived from the Brdr cells did not incorporate the radioactivity at all or at a markedly reduced rate, indicating that blockade of the pathway via adenosine deaminase present in the Brdr cells resulted in loss of their ability to utilize adenosine . Enzyme assays using cell-free extracts revealed that all the Brdr mutants had less than 3% of the adenosine kinase (AK) activity found in wild-type cells . These results demonstrate that the bredinin resistance is attributed to a defective AK activity and, therefore, that bredinin is metabolized by AK, which may phosphorylate it to a toxic nucleotide, bredinin 5'-monophosphate (Brd-MP), in sensitive cells . Among exogenously added purine bases, guanine was able to reverse the cytotoxic effect of bredinin on both wild-type cells and F5 cells carrying the vector pSV2-Escherichia coli xanthine-guanine phosphoribosyltransferase (XGPRT) gene, while xanthine was able to do so only in F5 cells because the base was metabolized to XMP by the cells . These results support the mechanism of bredinin cytotoxicity, that Brd-MP formed in sensitive cells exposed to the antibiotic blocks the conversion of IMP to XMP by inhibiting IMP dehydrogenase.

J Biomol Struct Dyn, 1983 Dec, 1(3), 809 - 27
Studies on bleomycin-DNA and bleomycin-iron interactions; Sakai TT et al.; The bleomycins, a group of antitumor antibiotics (Figure 1), cause the degradation of DNA by a process requiring iron(II) and dioxygen (1,2) . DNA degradation appears to involve two steps: association of the drug with the nucleic acid and degradation of the DNA . As part of studies directed toward achieving an understanding of how the bleomycins degrade DNA, we have examined various properties of the drug using a variety of chemical and physico-chemical techniques, including NMR and Mossbauer spectroscopy . We have studied both the interaction of the antibiotic with its target (DNA) as well as its association with its metal ion cofactor . This work has been performed on the intact drug and its derivatives as well as on synthetic models of the parent drug . This paper reviews and updates the recent work from this laboratory on the bleomycinsPublication Types:

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