Can J Microbiol, 1988 Nov, 34(11), 1217 - 23 Role of the carbon source in regulating chloramphenicol production by Streptomyces venezuelae: studies in batch and continuous cultures; Bhatnagar RK et al.; Both carbon- and nitrogen-limited media that supported a biphasic pattern of growth and chloramphenicol biosynthesis were devised for batch cultures of Streptomyces venezuelae . Where onset of the idiophase was associated with nitrogen depletion, a sharp peak of arylamine synthetase activity coincided with the onset of antibiotic production . The specific activity of the enzyme was highest when the carbon source in the medium was also near depletion at the trophophase-idiophase boundary . In media providing a substantial excess of carbon source through the idiophase, the peak specific activity was reduced by 75%, although the timing of enzyme synthesis was unaltered . Moreover, chemostat cultures in which the growth rate was limited by the glucose concentration in the input medium failed to show a decrease in specific production of chloramphenicol as the steady-state intracellular glucose concentration was increased . The results suggest that a form of "carbon catabolite repression" regulates synthesis of chloramphenicol biosynthetic enzymes during a trophophase-idiophase transition induced by nitrogen starvation . However, this regulatory mechanism does not establish the timing of antibiotic biosynthesis and does not function during nitrogen-sufficient growth in the presence of excess glucose. Mayo Clin Proc, 1988 Nov, 63(11), 1116 - 21 Diagnosing Lyme disease: the contribution of serologic testing; Duffy J et al.; Lyme disease is a multisystem disorder caused by a tick-transmitted spirochete, Borrelia burgdorferi . The diagnosis is based on clinical findings in most patients, particularly those with erythema migrans or exposure to geographic locations endemic for the disease . Detection of a specific antibody to B . burgdorferi is a useful confirmatory test in many patients . In atypical cases, however, a positive test result can be pivotal for determining the diagnosis and can lead to institution of definitive treatment . Serologic testing should not be used indiscriminately to diagnose Lyme disease or as the sole basis for administration of antibiotic therapy. Am J Obstet Gynecol, 1988 Nov, 159(5), 1028 - 34 How Swedish obstetricians manage premature rupture of the membranes in preterm gestations; Olofsson P et al.; Fifty-two of 53 obstetric departments in Sweden answered a questionnaire concerning preterm premature rupture of membranes . The answers formed the basis for a consensus conference and a symposium, which resulted in the following recommendations . The pregnancy should be interrupted when preterm premature rupture of membranes occurs before week 20 of gestation; individualized management is needed for preterm premature rupture of membranes between 20 and 25 weeks . After 25 weeks, institute hospitalization and bed rest, with a body temperature check twice a day, electronic fetal heart rate monitoring daily, and ultrasonography every second week . Cervical and urethral flora should be cultured once a week . Antibiotic infusion and prompt delivery should be instituted if an intrauterine infection occurs, and tocolysis is called for in cases of preterm labor in which intrauterine infection and abruptio placentae can be excluded . Labor should be induced between 32 and 34 weeks' gestation if spontaneous contractions do not occur . Cesarean section should be considered in cases of breech presentation earlier than 34 weeks, with delivery in a hospital with a neonatal intensive care unit if before 32 weeks' gestation. South Med J, 1988 Nov, 81(11), 1358 - 60 Routine bile cultures during elective cholecystectomy; Cull DL et al.; To assess antibiotic usage and the value of routine intraoperative bile cultures, we retrospectively reviewed 79 patients who had elective cholecystectomy from January to December 1986 . Forty patients (57%) received perioperative antibiotics, and 15 (19%) had positive intraoperative bile cultures . During follow-up, the only septic complications identified were wound infections in two patients (3%); one of them had received antibiotics and one had not . Each bile culture cost $60 to $80, and the cultures were not clinically useful . In the absence of risk factors associated with positive bile cultures, the incidence of wound infections or septic complications after cholecystectomy is low . We conclude that routine intraoperative bile cultures and prophylactic antibiotics are not indicated for elective cholecystectomy in low-risk patients. Int J Radiat Oncol Biol Phys, 1988 Nov, 15(5), 1153 - 9 Radiosensitivity of permanent human bone marrow stromal cell lines: effect of dose rate; FitzGerald TJ et al.; In contrast to the dose-rate independent X ray killing observed with human bone marrow hematopoietic stem cells, bone marrow adherent stromal cells from the same fresh marrow harvests demonstrate increased radiation resistance at low dose rate (LDR) (5 cGy/min), compared to high dose rate (HDR) irradiation (120-200 cGy/min) . Physiologic changes observed in plateau phase bone marrow cells after LDR irradiation in vivo and in vitro suggested that marrow stromal cells might be heterogeneous in LDR irradiation repair . Five permanent clonal bone marrow stromal lines were derived from a single human marrow donor . Each cell line was positive for markers of fibroblasts including: immunohistochemically detectable fibronectin, collagen, acid phosphatase, and nonspecific esterase, and was negative for Factor VIII, alkaline phosphatase, lysozyme and several markers of marrow macrophages . The x-irradiation survival curve of each cell line was determined at LDR and HDR in vitro . Cell lines KM102, KM103, KM104, and KM105 each demonstrated a significant (p less than .05) increase in radioresistance at LDR (D0 = 142, n = 2.9; D0 = 131, n = 2.5; D0 = 145, n = 2.1 and D0 = 127, n = 2.1 respectively) compared to HDR: (D0 = 111, n = 2.1; D0 = 94, n = 3.5; D0 = 99, n = 3.5 and D0 = 95, n = 2.1 respectively) . In contrast, cell line KM101 demonstrated no significant change in radiosensitivity relative to dose rate at LDR (D0 = 113, n = 3.3) compared to HDR, D0 = 114, n = 3.3 . Cell line KM101 was more supportive than the other lines of cocultivated hemopoietic cells in vitro . Subclones of KM101 and KM104 selected by retroviral vector transfer of the neor gene for growth in the antibiotic neomycin-analogue G418, maintained the stably associated radiobiologic properties of each parent clonal line . These data indicate significant heterogeneity in the LDR irradiation response of clonal stromal cell lines derived from human bone marrow. Dis Colon Rectum, 1988 Nov, 31(11), 854 - 6 Leukergy in inflammatory bowel disease; Goldman G et al.; In the phenomenon of leukergy, white blood cells agglomerate in peripheral blood slides . This agglomeration has been described in inflammatory infections of various causes . This study assesses this phenomenon in inflammatory bowel disease . A correlation was found between the severity of inflammatory bowel disease activity and the percentage of leukergy . Leukergy was found to parallel the clinical and endoscopic findings of inflammatory bowel disease . Furthermore, leukergy was found to be more accurate than white blood count and erythrocyte sedimentation rate . It is also found to accurately assess the course of the disease when clinical and other laboratory tests were masked by steroid and antibiotic administrations . Leukergy is a quick, inexpensive test that can easily be performed at the patient's bedside. Arch Surg, 1988 Nov, 123(11), 1320 - 7 Risk of infection after open fracture of the arm or leg; Dellinger EP et al.; Two hundred forty consecutive patients admitted for operative treatment of an open fracture of the arm or leg were followed up prospectively for the development of fracture infection . The independent risk of fracture infection was increased in patients with grade IIIB or IIIC fractures, internal or external fixation, lower-leg fracture, any blood transfusion, or injuries resulting from motorcycle accidents or motor vehicle-pedestrian accidents . By stepwise multivariate logistic regression, the most significant risk factors were the grade of the fracture, internal or external fixation, and fractures of the lower leg . These risk factors all represent local wound characteristics, and we conclude that the most important actions by the surgeon to prevent infection involve local wound care . There was no relation between the timing of antibiotic administration or duration of antibiotic therapy and infection risk. J Virol, 1988 Nov, 62(11), 4349 - 52 Retinoic acid-induced differentiation of retrovirus-infected HL-60 cells is associated with enhanced transcription from the viral long terminal repeat; Collins SJ; I infected different human leukemic cell lines with an amphotropic retrovirus vector (designated PA317/N2) which confers G418 resistance and contains the Moloney murine leukemia virus long terminal repeat . In retrovirus-infected G418-resistant HL-60 cells, induction of granulocyte differentiation by retinoic acid was invariably accompanied by a marked increase (5- to 10-fold) in the transcriptional activity of the integrated retroviral long terminal repeat. Biochimie, 1988 Nov, 70(11), 1535 - 49 Dissecting glycoprotein biosynthesis by the use of specific inhibitors; McDowell W et al.; It is possible to interfere with different steps in the dolichol pathway of protein glycosylation and in the processing of asparagine-linked oligosaccharides . Thus some clues about the role of protein-bound carbohydrate can be obtained by comparing the biochemical fates and functions of glycosylated proteins with their non-glycosylated counterparts, or with proteins exhibiting differences in the type of oligosaccharide side chains . Cells infected with enveloped viruses are good systems for studying both aspects of protein glycosylation, since they contain a limited number of different glycoproteins, often with well-defined functions . Tunicamycin, an antibiotic, as well as several sugar analogues have been found to act as inhibitors of protein glycosylation by virtue of their anti-viral properties . They interfere with various steps in the dolichol pathway resulting in a lack of functional lipid-linked oligosaccharide precursors . Compounds that interfere with oligosaccharide trimming represent a second generation of inhibitors of glycosylation . They are glycosidase inhibitors that interfere with the processing glucosidases and mannosidases and, as a result, the conversion of high-mannose into complex-type oligosaccharides is blocked . Depending upon the compound used, glycoproteins contain glucosylated-high-mannose, high-mannose or hybrid oligosaccharide structures instead of complex ones . The biological consequences of the alterations caused by the inhibitors are manifold: increased susceptibility to proteases, improper protein processing and misfolding of polypeptide chains, loss of biological activity and alteration of the site of virus-budding, to name but a few. Arch Fr Pediatr, 1988 Nov, 45(9), 623 - 8 {Hepatobiliary changes during exclusive parenteral feeding in infants with severe diarrhea}; Larchet M et al.; In order to specify the factors responsible for the hepatic changes occurring during total parenteral nutrition (TPN) and to propose a preventive treatment, 30 infants treated for severe protracted diarrhea were prospectively distributed into 4 groups: I (n = 10): controls; II (n = 7): oral administration of human milk since the 15th day of TPN; III (n = 5): oral metronidazole since the 15th day; IV (n = 8): parenteral antibiotic therapy for septicemia since the 1st day . Contrary to group IV, the first 3 groups were randomly constituted on the 15th day . Liver function tests, bile and serum biliary acids, duodenal flora, hepato-biliary ultrasonography and, in 12 cases, liver histology were sequentially studied . Liver function changes were observed on the 15th day in all groups . An improvement occurred 15 days later in the infants treated, when the control group worsened (p less than 0.02) . A significant increase of bile chenodeoxycholic acid levels was observed in the control group only (p less than 0.01), without change in lithocholic acid levels . These results lead the authors to recommend the preventive use of metronidazole or human milk during prolonged TPN in infants. Arch Mal Coeur Vaiss, 1988 Nov, 81(11), 1403 - 7 {Brucella endocarditis caused by reinfection of an aortic Starr valve . Apropos of a case with a favorable development after valvular replacement}; D'Agrosa MC et al.; We report the case of a 36-year old male patient who was admitted for subacute endocarditis on an aortic prosthetic valve implanted 14 years previously for endocarditic valve regurgitation; no pathogen had been isolated at that time . Nine blood cultures were positive for Brucella abortus . The conventional antibiotic therapy did not prevent the formation of an abscess below the aortic annulus . A third antibiotic combination (quinolone and rifampicin) resulted in pyrexia prior to surgery . An atrioventricular block initially noted raised the problem of an associated myocarditis . The risk of Brucella infection existed before the first operation, and five serological tests were positive for that organism between the two episodes, which makes reinfection highly probable . This is the third case of Brucella endocarditis on a prosthetic valve . Its originality lies in its mechanism. QRB Qual Rev Bull, 1988 Nov, 14(11), 336 - 40 An adverse drug reaction reporting program in a community hospital; Tse CS et al.; An adverse drug reaction (ADR) surveillance program implemented in a 472-bed acute care community hospital consists of three components: specific indicators that nurses and pharmacists can use to evaluate reactions for reporting, an ADR reporting form and procedure, and innovative computerized screening for ADRs . In the program's first year, ADR reporting has increased 13-fold, and an important ADR to an antibiotic has been detected and publicized, resulting in modified prescribing patterns . Careful planning and frequent, intensive in-service training are key to the program's success. Hautarzt, 1988 Nov, 39(11), 717 - 26 {Cutaneous B cell lymphoma in chronic Borrelia burgdorferi infection . Report of 2 cases and a review of the literature}; Garbe C et al.; Low-grade malignant B-cell lymphomas of the skin can be distinguished from lymphadenosis benigna cutis (Bafverstedt) by immunohistological methods developed in the last few years . Its coexistence with Borrelia burgdorferi infection can be shown by clinical and serological findings . In the chronic stage of this infection, lymphocytic cell infiltrations consistent with histological and immunohistological findings of malignant B-cell lymphoma can be found . Predominantly at the extremities, multiple plaque-shaped or nodular lesions are seen, showing a follicular pattern in their periphery . The tumors do not respond to antibiotic therapy . They regress totally after X-ray treatment, but local recurrences are rather common . They show a long persistent course with only slow progression and seem to be of low-grade malignancy independent from the cytological findings . In most cases the tumors remain limited to the skin and to one anatomical site; nevertheless, the development of systemic involvement has been reported . We present two cases of malignant B-cell lymphoma of the skin in patients with chronic B . burgdorferi infection . Both cases showed the typical clinical and histological features of this entity . Similar reports from the literature indicate close relationships with the chronic stage of Borrelia infection, with the simultaneous presence of acrodermatitis chronica atrophicans as an indicator . We conclude that an elevated titer indicating Borrelia infection is an important finding for the diagnosis and prognosis of this particular type of cutaneous B-cell lymphoma. J Allergy Clin Immunol, 1988 Nov, 82(5 Pt 2), 950 - 6 Sinusitis in adults and its relation to allergic rhinitis, asthma, and nasal polyps; Slavin RG; Sinusitis, an infection of the paranasal sinuses, has been linked to allergic rhinitis, asthma, and nasal polyps . Sinusitis is a common complication of allergic rhinitis, which can lead to inflammation of the sinus mucosa, obstruction of the sinus opening or ostium, and generally favorable conditions for bacterial growth . Sinusitis can trigger asthma . Stimulated nerves in an infected sinus may result in parasympathetic stimulation to the bronchial tree and in smooth muscle contraction . Sinusitis may be a cause of nasal polyps, which are common when sinusitis complicates allergic rhinitis and even more common in nonallergic rhinitis . Treatment of sinusitis strives to eliminate infection and promote drainage . Ampicillin or amoxicillin is the antibiotic of choice . All patients with sinusitis should be treated with antibiotic to encourage drainage . Fluids, expectorants, and decongestants, both oral and topical, should be used . As many as half of patients with sinusitis also have marked rhinitis (either allergic or nonallergic), nasal polyps, or swollen, edematous mucosa; these patients should also receive topical steroids, such as flunisolide . Flunisolide promotes drainage and aeration by decreasing inflammation, swelling, and the influx of white blood cells . Persistent sinusitis may need to be treated surgically. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Nov, 270(1-2), 66 - 75 New inhibitors for aminoglycoside-adenylyltransferase; Saleh NA et al.; Two hydroxymethyltropolones and two tropolone acetate derivatives were found to inhibit an aminoglycoside-adenylyltranferase in a gentamicin-resistant Escherichia coli strain . The inhibitory effect of tropolones depends on the nature of the aminoglycoside antibiotic subject to adenylation . Combinations of hydroxymethyltropolones with tobramycin were more active compared with tropolone acetates against gentamicin-resistant strains displaying adenylyltransferase activity . On the contrary a combination of the investigated acetate with gentamicin was of lower activity . It could be shown that these inhibitors inhibit, to a varying degree, the transfer of radioactive ATP to different aminoglycoside molecules. Horm Metab Res, 1988 Nov, 20(11), 713 - 6 A direct assay for oestrone sulphate and its use to investigate the effect of ampicillin on plasma levels of oestrone sulphate; Reed MJ et al.; A direct radioimmunoassay for measuring plasma levels of oestrone sulphate has been developed using 8-anilino-2-naphthalene sulphonic acid to displace oestrone sulphate from plasma binding proteins . Oestrone sulphate was assayed by using an antiserum raised against glucuronide which cross-reacted 100% with oestrone sulphate . The direct assay gave a good analytical recovery of oestrone sulphate and there was a good correlation (r = 0.82, P less than 0.001) for plasma levels of oestrone sulphate measured by the direct assay and a method involving steroid conjugate extraction and enzyme hydrolysis . The mean (+/- S.D.) plasma level of oestrone sulphate in men was 1100 +/- 280 pg/ml . The effect of taking the antibiotic, Ampicillin, on plasma levels of oestrone sulphate was investigated in four men . Plasma levels of oestrone sulphate were significantly reduced after taking Ampicillin for 5 days . Ampicillin may act to lower plasma levels of oestrone sulphate by reducing the growth of bacteria in the gut or by inhibiting oestrogen sulphotransferase activity. Biochem Pharmacol, 1988 Nov 1, 37(21), 4063 - 8 Inhibition of type II topoisomerase by fostriecin; Boritzki TJ et al.; Fostriecin is a new antitumor antibiotic which is being developed further as an anticancer agent based on its marked activity in murine leukemias . Its mechanism of action, however, has thus far remained unknown . The present study demonstrates that fostriecin inhibits the catalytic activity of partially purified type II topoisomerase from Ehrlich ascites carcinoma . Under the experimental conditions employed, fostriecin completely inhibited the enzyme at 100 microM . A general kinetic analysis showed that fostriecin inhibited topoisomerase in an uncompetitive manner with a Ki,app of 110 microM and produced kinetics that were distinctly different from those of VM-26 which exhibited noncompetitive inhibition . Fostriecin did not cause DNA strand breaks in L1210 cells, suggesting that it did not stabilize a cleavable complex as do other known inhibitors of this enzyme . Fostriecin, however, did partially inhibit DNA strand breaks produced by amsacrine . An analysis by flow cytometry showed that L1210 cells exposed to 5 microM fostriecin for 12 hr caused a block in the G2 phase of the cell cycle . These studies thus suggest that the mechanism by which fostriecin produces its antitumor effects may be through inhibition of topoisomerase II and that the type of inhibition is markedly different from existing antitumor agents which inhibit this enzyme. J Virol, 1988 Nov, 62(11), 4353 - 7 Increased expression of CD4 molecules on Jurkat cells mediated by human immunodeficiency virus tat protein; Koka P et al.; The tat gene of the human immunodeficiency virus, tat-III, when introduced into T-lymphoblastoid Jurkat cells by a Moloney retroviral recombinant DNA vector expressed high levels of the functional tat protein as measured by the chloramphenicol acetyltransferase assay . Immunofluorescence analysis with CD4-specific monoclonal antibodies demonstrated that the cell surface levels of the CD4 antigen were increased by 5- to 10-fold in the tat-III-infected Jurkat cells . Cellular cytoplasmic RNA analysis indicated that the enhanced CD4 expression was mediated at the mRNA level . Our findings suggest that the single expression of the human immunodeficiency virus tat protein in the absence of the other viral proteins causes an upregulation of CD4 gene expression on helper T cells, although infection of these cells by the virus, thus expressing all the viral gene products including tat, is known to downregulate CD4 antigen expression. Presse Med, 1988 Oct 26, 17(37), 1925 - 7 {Pharmacokinetics of ceftazidime in cystic fibrosis}; Saint Raymond A et al.; Ceftazidime has been recognized as an invaluable antibiotic for the treatment of lower respiratory infections in patients with cystic fibrosis . In these patients the apparent volume of distribution of ceftazidime is increased . Its clearance is besides increased, with a significant reduction in the area under concentrations curve . The distribution of ceftazidime in the bronchi seems to be very satisfactory . It results from these data that dosage in children with cystic fibrosis may reach 200 to 300 mg/kg/day divided into 3 or 4 injections . The intrabronchial administration of ceftazidime has not proved effective. J Mol Biol, 1988 Oct 20, 203(4), 939 - 47 Recognition of the DNA helix stabilizing anthramycin-N2 guanine adduct by UVRABC nuclease; Walter RB et al.; The binding of the anti-tumor antibiotic anthramycin to a defined linear DNA fragment was investigated using both exonuclease III and lambda exonuclease . We show that most of the guanine residues are reactive toward anthramycin; however, several guanine residues showed preferential reactivity for the drug . Using purified UVRA, UVRB and UVRC proteins we present evidence that these three proteins in concert are able to recognize and produce specific strand cleavage flanking anthramycin-DNA adducts . The cleavage of anthramycin adducts by UVRABC nuclease is specific and results in strand breaks at five or six bases 5' and three or four bases 3'-flanking an adduct . At some guanine residues single incisions were observed only on one side of the adduct . The 5' strand breaks observed often occurred as doublet bands on sequencing gels, indicating plasticity in the site of 5' cleavage whereas the 3' cleavage did not show this effect . When DNA fragments modified with elevated levels of anthramycin were used as substrates the activity of the UVRABC nuclease toward the anthramycin adducts decreased . Possible mechanisms for the recognition and specific cleavage of the helix-stabilizing anthramycin DNA adduct and other helix destabilizing lesions by the UVRABC nuclease are discussed. J Mol Biol, 1988 Oct 20, 203(4), 961 - 70 Mutations that alter the pore function of the OmpF porin of Escherichia coli K12; Benson SA et al.; We describe the isolation and characterization of mutations in ompF that alter the pore properties of the OmpF porin . The selection makes use of the fact that maltodextrins larger than maltotriose are too large to diffuse through the normal OmpF pore . By demanding growth on maltodextrins (Dex+) in the absence of the LamB protein, which is normally required for the uptake of these large sugars, we are able to obtain ompF mutations . These include transversions, transitions and small deletions . We obtained almost exclusively ompF mutations in spite of the fact that analogous alterations in ompC can result in similar phenotypes . Fifteen independent point mutations identify residues R42, R82, D113 and R132 of the mature peptide as important in pore function . The alterations result in uncharged amino acids being substituted for charged amino acids . Growth tests, antibiotic sensitivities and rates of {14C}maltose uptake suggest that the alterations result in an increased pore size . Small deletions of six to 15 amino acid residues in the region between A108 and V133 of mature OmpF dramatically alter outer membrane permeability to hydrophobic antibiotics and detergents as well as conferring a Dex+ phenotype . We suggest that these mutations affect both the pore function and interactions with other outer membrane components . A model of OmpF protein structure based on general rules for folding membrane proteins and these mutations is presented. Biochemistry, 1988 Oct 18, 27(21), 8106 - 14 Sites in the diyne-ene bicyclic core of neocarzinostatin chromophore responsible for hydrogen abstraction from DNA; Chin DH et al.; The antitumor antibiotic neocarzinostatin exhibits its main drug action by abstracting hydrogen from DNA deoxyribose with consequent strand breakage or related lesions . All biological activities of the drug derive solely from a nonprotein chromophoric substance (NCS-chrom) consisting of a novel epoxy-bicyclo-diyne-ene system . Thiol or sodium borohydride activates NCS-chrom into a labile, reactive species that induces DNA damage but causes inactivation of the drug in the absence of the target DNA . Mass spectrometric studies indicate that the isolated thiol-activated NCS-chrom product in the presence of DNA has the same molecular weight as the thiol-inactivated NCS-chrom product in the absence of DNA . No deuterium is incorporated into the chromophore from the deuterium-labeled sulfhydryl group . Since three deuterium atoms can be incorporated into the drug by treatment with sodium borodeuteride without DNA, adding an unlabeled DNA under parallel conditions permitted the ready identification of the activated NCS-chrom product that abstracted hydrogen from the DNA . Not only does the activated NCS-chrom product have the same structure as the inactivated drug without DNA, but two of the incorporated deuterium atoms have been substituted by hydrogen . With the aid of NMR spectrometry, the two replaced hydrogen atoms are found to be incorporated into the C-2 and C-6 positions of the bicyclo-diyne-ene ring of NCS-chrom and are derived neither from borodeuteride nor from the hydroxyl functions of the solvents . In accord with current proposals, the two hydrogens incorporated into the drug may come from closely opposed sites on the complementary strands of the DNA at which the drug is bound.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Biochem, 1988 Oct 15, 177(1), 219 - 23 Neomycin inhibits platelet functions and inositol phospholipid metabolism upon stimulation with thrombin, but not with ionomycin or 12-O-tetradecanoyl-phorbol 13-acetate; Tysnes OB et al.; Gel-filtered human platelets that had been pre-labelled with {32P}Pi were stimulated with thrombin, ionomycin or the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) . The effect of the hexacationic aminoglycoside antibiotic, neomycin, on platelet physiological responses, such as aggregation and secretion, as well as changes in phosphoinositide metabolism was studied . Neomycin strongly inhibited thrombin-induced aggregation and secretion whereas the antibiotic had no effect on ionomycin- or TPA-induced platelet functions . The thrombin-induced enhancement of inositol phospholipid metabolism was strongly inhibited by the presence of neomycin whereas the TPA- or ionomycin-induced increase in inositol {32P}polyphospholipids remained unaffected . The inhibitory effect of some other aminoglycoside antibiotics was compared to that of neomycin and the data demonstrate that the inhibition of platelet secretion and phosphatidic acid production was dependent on the cationic charge of the antibiotic . It is suggested that neomycin inhibits signal transduction in platelets at a level prior to the inositol-phospholipid-specific phosphodiesterase. Biochem Biophys Res Commun, 1988 Oct 14, 156(1), 517 - 23 Molecular cloning of the nosiheptide resistance gene from Streptomyces actuosus ATCC 25421; Dosch DC et al.; An 8.5 kb BamHI DNA fragment conferring resistance to nosiheptide, a peptide antibiotic of the 'thiostrepton group', was cloned from Streptomyces actuosus ATCC 25421 in Streptomyces lividans 1326 . Two BamHI fragments of S . actuosus, the 8.5 kb fragment and an additional 3.0 kb fragment, hybridized with a thiostrepton resistance gene probe (pIJ30) . The 8.5 kb fragment showed a relatively low degree of homology with the thiostrepton resistance gene . The restriction map of the nosiheptide resistance gene isolated here was significantly different from the map of the thiostrepton resistance gene previously published. Hosp Pharm, 1988 Nov, 23(11), 976 - 8, 981-3 A practical approach enabling staff pharmacists to prospectively review and dose aminoglycoside therapy; Possidente CJ et al.; A simple and effective approach for staff pharmacists to prospectively review and dose aminoglycoside therapy is presented . A departmental policy was established requiring pharmacists to review each adult aminoglycoside order for appropriateness by means of a written audit form . Specific patient data and the aminoglycoside dose is obtained from an antibiotic order form and the patient's creatinine clearance is estimated using a modified Cockcoft and Gault equation . Proper initial dosage regimens are assessed by use of a modified Sarubbi and Hull nomogram or an in-house developed pharmacokinetic software program . The results demonstrate pharmacists were required to intervene in 26.8% of adult aminoglycoside orders . To determine if the percentage of pharmacist intervention changed over time, the results were compared to a sample period selected almost two years later . The percentage of pharmacists intervention was almost identical (25.3%) . In both groups, over 90% of the pharmacists's dosing recommendations were accepted by the physician . The outcome of pharmacist's reviews were analyzed during the first study period . In courses of therapy with dosages recommended by pharmacists, therapeutic, non-toxic concentrations of gentamicin and tobramycin (peak 5-10 micrograms/ml, trough less than 2 micrograms/ml) comprised 47/54 (87%) of the interpretable levels . Patients judged by the pharmacist to have an appropriate dose during the initial review had 85/119 (71.4%) of interpretable serum levels in the therapeutic, non-toxic range . Without benefit of a formalized pharmacokinetic service, this program enables all staff pharmacists to perform a review of aminoglycoside therapy which ensures an appropriate initial dosage regimen . The completed aminoglycoside initial audit form serves as a communication tool as well as documentation for the department's quality assurance program. Biomed Environ Mass Spectrom, 1988 Oct, 16(1-12), 419 - 22 Soft ionization techniques in mass spectrometry of distamycin and some analogues; Arlandini E et al.; The results obtained using three different soft ionization techniques (field desorption (FD), fast atom bombardment (FAB) and desorption chemical ionization (DCI} on the antiviral antibiotic distamycin and on some analogues are reported . FAB mass spectra show more intense molecular ion and more regular fragmentation while FD and DCI mass spectra are dominated by thermally originated fragments . Information furnished by the three systems are different and complementary. Diagn Microbiol Infect Dis, 1988 Oct, 11(2), 87 - 100 Diagnostic efficacy of a nasotracheal protected specimen brush in patients with suspected bacterial pneumonia; Gong H Jr et al.; The diagnostic yield and safety of a novel nasotracheal protected specimen brush (PSB) were evaluated in 15 nonintubated adult patients with suspected bacterial pneumonia . A double-catheter PSB was passed directly through the anesthetized nose and into the trachea without bronchoscopy or fluoroscopy . Endotracheal brushing was performed in less than 10 sec, and the brush was immediately processed for Gram staining and quantitative aerobic and anaerobic cultures . According to clinical follow-up and response to therapy, 11 episodes of bacterial pneumonia and five cases of nonbacterial lung disease were established . The PSB Gram stain confirmed lower respiratory sampling in all cases . The PSB cultures indicated respiratory pathogens in 9/11 (82%) cases of pneumonia, with greater than 10(3) colony-forming units (cfu)/ml in all but two specimens . All patients with pneumonia responded to specific antibiotics . All patients with nonbacterial disorders had PSB cultures of less than 10(3) CFU/ml, and their pulmonary processes improved without antibiotic therapy . The procedure was well tolerated, although two patients had transient bronchospasm or apnea . Experience with the nasotracheal PSB is limited, but the procedure appears to be a reliable and relatively safe alternative diagnostic method in selected patients with suspected bacterial pneumonia . Quantitative cultures are necessary to improve its diagnostic accuracy. Microbiologica, 1988 Oct, 11(4), 279 - 88 An in vitro comparative study on the effect of amphotericin B, econazole, and 5-fluorocytosine on Naegleria fowleri, Naegleria australiensis, and Naegleria australiensis s.sp . italica; Scaglia M et al.; We tested in vitro amphotericin B (AMP-B), econazole (ECO), and 5-fluorocytosine (5-FC) on pathogenic Naegleria fowleri (KUL strain), Naegleria australiensis s.sp . italica (AB-T-F3, original strain) to assess their sensitivity to chemotherapeutic compounds . Previous reports have shown the polyene antibiotic AMP-B to be the most active agent . It was, however, much more active on N . fowleri than on N . australiensis and N . australiensis s.sp italica . 5-FC and ECO gave rise to non appreciable effect at non-toxic corresponding dosages in vivo . The results of these in vitro tests are discussed. Am Rev Respir Dis, 1988 Oct, 138(4), 886 - 90 Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy . II . Two-month, daily administration study; Acocella G et al.; The time course of the plasma concentrations of isoniazid, rifampin, and pyrazinamide was assessed in a group of 13 patients with lung tuberculosis treated over a period of 2 months on a continuous daily basis with a fixed triple combination of the same drugs . The blood kinetics of the three antituberculosis drugs were determined on Days 1, 15, 30, and 60 of treatment . The triple combination employed in this study contained 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet, the number of tablets ranging from four to seven per day according to the body weight of the patients . Almost superimposable plasma concentration curves for isoniazid were observed during the 4 days of the study . For rifampin, a fall in the plasma concentrations at the time intervals after the peak was observed comparing the data on Day 1 with those on Days 15, 30, and 60, which did not differ from each other . This finding is thought to be due to the well-known phenomenon of self-induction, which leads to an increased rate of disposal of the antibiotic from the blood compartment within the first and second weeks of continuous treatment . For pyrazinamide, an equilibrium in the opposite sense as that of rifampin seemed to take place within the 2 months of the study . Because of the relatively high plasma levels observed 24 h after each administration, an increase in plasma concentrations with respect to those observed on Day 1 was found on Days 15, 30, and 60, the levels on these days no differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS) Laryngoscope, 1988 Oct, 98(10), 1050 - 4 Use of bacitracin for neurotologic surgery; Kartush JM et al.; Wound infection, cerebrospinal fluid leak, and meningitis are serious potential complications of neurotologic procedures that transgress the posterior cranial fossa dura . A study of 236 patients was made to determine the effect of perioperative intravenous antibiotics and topical bacitracin irrigation on the incidence of these complications . Of the 236 patients, 170 (72%) underwent translabyrinthine resection of acoustic tumors, while 66 (28%) underwent retrolabyrinthine vestibular nerve section . Patients were divided into four groups: those who received no antibiotics, those who received perioperative intravenous antibiotics only, those who received topical bacitracin irrigation only, and those who received a combination of perioperative intravenous antibiotics and topical bacitracin irrigation . There were no untoward effects of either perioperative intravenous antibiotics or topical bacitracin . The results indicate that bacitracin irrigation reduced the incidence of wound infection from 9% to 2% (p less than 0.05); of cerebrospinal fluid leak from 12% to 5% (p less than 0.04); and of all targeted complications combined from 22% to 9% (p less than 0.006) . Furthermore, the topical bacitracin irrigation only group showed a statistically significant reduction in wound infections compared to the perioperative intravenous antibiotic only group (p less than 0.02) . The incidence of meningitis was statistically unaffected by any of our treatment protocols. J Vasc Surg, 1988 Oct, 8(4), 428 - 33 One-stage versus two-stage amputation for wet gangrene of the lower extremity: a randomized study; Fisher DF Jr et al.; Although the two-stage amputation technique entails an additional operation, several authors have advocated this approach to deal with wet gangrene because it allows primary wound closure with a reduced chance of wound infection . To examine this issue, 47 patients with necrotizing wet gangrene of the foot were randomized prospectively to receive either a one-stage amputation (definitive below- or above-knee amputation with delayed secondary skin closure in 3 to 5 days) or a two-stage amputation (open ankle guillotine amputation followed by definitive, closed below- or above-knee amputation) . Antibiotic coverage was standardized with clindamycin and gentamicin used in all patients . Preoperative blood cultures and intraoperative foot cultures were obtained, as well as cultures from the deep muscle and lymphatic area along the saphenous vein to determine the presence of bacteria at the level of initial amputation . Twenty-four patients (11 diabetic and 13 nondiabetic) were randomized to the one-stage procedure . Twenty-three patients (14 diabetic and nine nondiabetic) were randomized to the two-stage procedure . Five of 24 patients in the one-stage group (21%) had positive muscle cultures vs 10 of 23 patients in the two-stage group (43%) . Two of 24 patients in the one-stage group (8%) had positive lymphatic cultures vs 7 of 23 patients in the two-stage group (30%) . Five of 24 patients in the one-stage group (21%) had wound complications attributable to the amputation technique vs none of 23 patients in the two-stage group (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) Antibiot Khimioter, 1988 Oct, 33(10), 723 - 6 {Hybridization of A-factor deficient mutants of Streptomyces griseus by means of fusion of protoplasts}; Efremenkova OV et al.; Characteristics of 6 A-factor deficient mutants of S . griseus are presented . The common feature of the mutants was impairment of sporulation, formation of aerial mycelium and streptomycin synthesis . Pair-by-pair hybridization of the mutants was performed with protoplast fusion followed by regeneration . 9 pair couplings of the mutants were performed . In 3 of them sporulating recombinants were detected . The antibiotic production level in 70 hybrids was different and ranged from 0 to 1700 micrograms/ml . The morphological features of the colonies and the number of the spores formed were also different . The common feature of all the 70 sporulating hybrid strains was recovery of synthesis of A-factor, an endogenic regulator of S . griseus development . Therefore, in the A-factor deficient mutants impairment of A-factor synthesis was induced not by the plasmid elimination, as was suggested, but by mutation of separate genes. Mol Gen Genet, 1988 Oct, 214(2), 295 - 9 Point mutations in the 23 S rRNA genes of four lincomycin resistant Nicotiana plumbaginifolia mutants could provide new selectable markers for chloroplast transformation; Cseplo A et al.; Experiments designed to establish stable chloroplast transformation require selectable marker genes encoded by the chloroplast genome . The antibiotic lincomycin is a specific inhibitor of chloroplast ribosomal activity and is known to bind to the large ribosomal subunit . We have investigated a defined region of the chloroplast 23 S rRNA genes from four lincomycin resistant Nicotiana plumbaginifolia mutants and from wild-type N . plumbaginifolia . The mutants LR415, LR421 and LR446 have A to G transitions at positions equivalent to the nucleotides 2058 and 2059 in the Escherichia coli 23 S rRNA . The mutant, LR400, possesses a G to A transition at a position corresponding to nucleotide 2032 of the E . coli 23 S rRNA. Ann Vasc Surg, 1988 Oct, 2(4), 373 - 7 Mycotic cervical carotid artery aneurysms: a case report and review of the literature; Jones TR et al.; Mycotic cervical carotid artery aneurysms are rare . We report one case successfully treated by resection and reconstruction with a saphenous vein interposition graft . A review of the English world literature revealed 22 additional cases . Principles of management include appropriate and timely antibiotic use, resection of the aneurysm, debridement of all infected tissue, and restoration of arterial continuity with autogenous tissue through uninvolved tissue planes. Appl Biochem Biotechnol, 1988 Oct, 19(1), 33 - 59 Biocatalysis made to order; Tripathi G; Recombinant DNA technology is now being explored to engineer enzyme molecules . It has many far-reaching applications in biocatalytic processes of enzyme engineering . The facts have pursued certain important industrial, biomedical, and environmental problems . These current excitements are mainly focused on the basis of gene cloning and in vitro mutagenesis for overproduction and redesigning of enzymes, as well as their probable implications in industry, antibiotic research, and waste degradation. J Reprod Immunol, 1988 Oct, 14(1), 1 - 8 Evaluation of the expression of a male-specific antigen on cells of equine blastocysts; Wood TC et al.; This experiment was designed (1) to determine if H-Y antigen is expressed on the cell surface of pre-implantation equine blastocyst stage embryos, (2) if so, to identify differences in expression on inner cell mass (ICM) verses trophectoderm cells and (3) to evaluate whether the detection of this glycoprotein would aid in the identification of equine embryonic sex . A total of 33 blastocyst stage horse embryos were collected 6-7 days post-ovulation by trans-cervical flush and were immediately evaluated for the presence of H-Y antigen . Additionally, 17 embryos, collected at similar stages and cultured for 72 h, were similarly evaluated . Embryos were recovered and evaluated by use of a dissecting microscope and then washed for 5 min in phosphate buffered saline supplemented with 1 g/l glucose, 36 mg/l pyruvate, 1% antibiotic-antimycotic and 10% fetal calf serum (FCS) (PBS-2) . Embryos were placed in the primary antibody medium and cultured for 60 min . The primary antibody medium consisted of monoclonal antibodies to H-Y antigen (previously determined to have male-specific activity) dilute 1/5 (v/v) with PBS-2 (without FCS, PBS-1) . Following an additional wash, embryos were cultured in PBS-1 containing 1/10 (v/v) fluorescein isothiocyanate conjugated goat anti-mouse or rabbit antimouse IgM Fc specific antiserum . Embryos were evaluated at 200-400 x to identify cell specific fluorescence of either trophectoderm or ICM cells . Following evaluation, embryonic sex was independently verified with karyotypes to identify sex chromosomes . Of the 50 embryos evaluated, 29 were evaluated as non-fluorescent and 21 fluorescent . Expression of H-Y antigen was detected on both trophectoderm and ICM cell types in those embryos classified as fluorescent.(ABSTRACT TRUNCATED AT 250 WORDS) Mol Cell Biol, 1988 Oct, 8(10), 4204 - 11 Inducible expression and cytogenetic effects of the EcoRI restriction endonuclease in Chinese hamster ovary cells; Morgan WF et al.; The cytogenetic endpoints sister chromatid exchange (SCE) and chromosome aberrations are widely used as indicators of DNA damage induced by mutagenic carcinogens . Chromosome aberrations appear to result directly from DNA double-strand breaks, but the lesion(s) giving rise to SCE formation remains unknown . Most compounds that induce SCEs induce a spectrum of lesions in DNA . To investigate the role of double-strand breakage in SCE formation, we constructed a plasmid that gives rise to one specific lesion, a staggered-end ("cohesive") DNA double-strand break . This plasmid, designated pMENs, contains a selectable marker, neo, which is a bacterial gene for neomycin resistance, and the coding sequence for the bacterial restriction endonuclease EcoRI attached to the mouse metallothionein gene promoter . EcoRI recognizes G decreases AATTC sequences in DNA and makes DNA double-strand breaks with four nucleotides overhanging as staggered ends . Cells transfected with pMENS were resistant to the antibiotic G418 and contained an integrated copy of the EcoRI gene, detectable by DNA filter hybridization . The addition of the heavy metal CdSO4 resulted in the intracellular production of EcoRI, as measured by an anti-EcoRI antibody . Cytogenetic analysis after the addition of CdSO4 indicated a dramatic increase in the frequency of chromosome aberrations but very little effect on SCE frequency . Although there was some intercellular heterogeneity, these results confirm that DNA double-strand breaks do result in chromosome aberrations but that these breaks are not sufficient to give rise to SCE formation. Dis Colon Rectum, 1988 Oct, 31(10), 774 - 7 Cefoxitin for one day vs . ampicillin and metronidazole for three days in elective colorectal surgery . A prospective, randomized, multicenter study; Rorbaek-Madsen M et al.; In a multicenter study the prophylactic efficacy of two antibiotic regimens was tested against postoperative septic complications following elective colorectal surgery . The study was conducted in a prospective block-randomized design . Patients were preoperatively allocated to either ampicillin, 1 gm, four times daily, and metronidazole, 0.5 gm, three times daily, for 72 hours, or to cefoxitin, 2 gm, given three times in a period of 10 hours . Both regimens were initiated immediately before surgery . Forty-five patients were withdrawn from the study after randomization . Three hundred fifty two patients (175 receiving ampicillin and metronidazole and 177 receiving cefoxitin) completed the study and were followed for one month postoperatively . The frequency of septic and nonseptic complications was not statistically significant different between the two regimens . About one third of all septic complications appeared more than two weeks after surgery . It is concluded that short-term treatment with cefoxitin is at least as efficient as a three-day treatment with ampicillin and metronidazole. Geriatrics, 1988 Oct, 43(10), 51 - 6, 59-62 Pneumonia in the elderly: a review; Raju L et al.; Elderly persons are at increased risk of acquiring pneumonia . Morbidity and mortality rates from pneumonia are also higher . Clinical manifestations of pneumonia in the elderly are frequently very subtle; however, a high index of suspicion will induce the physician to obtain a chest roentgenogram . A new lung infiltrate will confirm the diagnosis . Although the Gram's stain of a sputum smear is most helpful in the initial selection of a specific antibiotic, a good quality sputum is not usually available in the elderly, and empiric therapy reduces the morbidity and mortality from pneumonia. J Antibiot (Tokyo), 1988 Oct, 41(10), 1439 - 44 Spectinomycin modification . IV . The synthesis of 3'-aminomethyldihydrospectinomycins via spectinomycin 3'-cyanohydrins; Thomas RC et al.; The C-3'-carbonyl group of N-protected spectinomycin is converted into the corresponding aminomethylalcohols via the intermediacy of cyanohydrins . Methodology for the selective synthesis of either epimer with retention of protection in the aminocyclitol ring provides valuable synthetic intermediates for the preparation of analogs of this important antibiotic . The new methodology provides an efficient synthesis of the highly active 3'-aminomethyldihydrospectinomycins. Int J Gynaecol Obstet, 1988 Oct, 27(2), 171 - 6 Characteristics of maternal deaths following cesarean section in a developing country; Ojo VA et al.; A retrospective analysis was made of 27 maternal deaths after cesarean section occurring over a 5-year period . Sepsis was the single most important cause of maternal death (81.5%) . The commonest indications for the cesarean sections were obstructed labor (59.3%) and cord prolapse (18.5%) . The causes of maternal deaths were classified as avoidable and recommendations were made for their preventionPIP: A retrospective analysis of 27 maternal deaths associated with cesarean section and occurring at Nigeria's University of Ilorin Teaching Hospital in 1982-86 was performed . The cesarean section rate for the 48,974 deliveries that took place at the hospital during the study period was 4.1% . The death rate was 18.1/1000 cesarean sections compared with 1.89/1000 vaginal deliveries . Maternal sepsis was responsible for 22 (82%) of the cesarean section-associated maternal deaths; the remaining deaths were attributed to hemorrhage (1 primary and 3 secondary) and eclampsia (1 case) . Obstructed labor was the single most important indicator for cesarean section (67%) and the most significant predisposing factor to maternal sepsis (63%) . Most deaths from sepsis occurred on the 2nd-4th postoperative days . The skill of the surgeon was not a significant factor in maternal deaths . The most common antibiotic used to combat sepsis was a combination of ampicillin and gentamicin--a regimen that does not cover anaerobic organisms . Some patients did not receive antibiotics until the 3rd postoperative day because they were not on stock in the hospital pharmacy . Administrative difficulties, most notably inadequate laboratory backing and funding, also played some role in the high maternal death rate in this series . Virology, 1988 Oct, 166(2), 561 - 72 A host-dependent temperature-sensitive mutant of Rous sarcoma virus: evidence for host factors affecting transformation; Young JC et al.; We have characterized a host range mutant of Rous sarcoma virus in order to identify host cell factors involved in transformation . This mutant, tsLA33-1, which was isolated from a stock of the temperature-sensitive mutant tsLA33, is not temperature-sensitive for transformation of chicken embryo fibroblasts, as judged by its ability to induce morphological changes and agar colony formation at both 36 and 41.5 degrees . In Rat-3 cells, however, this mutant induced a temperature-dependent transformation: infected Rat-3 cells were transformed at 34 degrees but not at 39.5 degrees . Retransformants were isolated from tsLA33-1-infected Rat-3 cells by growth in agar suspension at 39.5 degrees . Virus rescued from these retransformants induced a temperature-dependent transformation when reintroduced into rat cells . The level of expression of pp60v-src at 39.5 degrees was unchanged in the retransformants . When the retransformants were treated with herbimycin, an antibiotic which induces turnover of certain protein-tyrosine kinases, they reverted to a normal phenotype, indicating that the transformed phenotype of the retransformants was dependent on continued expression of pp60v-src . The retransformants are therefore pseudorevertants in which a cellular alteration has occurred that allows transformation at 39.5 degrees by the mutant pp60v-src . Thus the temperature-dependence of transformation by tsLA33-1 is affected by the cellular environment, and is suppressed or complemented both in chicken cells and in the rat cell pseudorevertants . No clear correlation between levels of phosphorylation at tyrosine and transformation was observed . In Rat-3 cells the pp60v-src encoded by tsLA33-1 may be defective in its interaction with low abundance substrates that are critical for transformation; alternatively the nonpermissive cells may require a higher threshold dose of pp60v-src for transformation. Proc Natl Acad Sci U S A, 1988 Oct, 85(20), 7670 - 4 Asbestos fibers mediate transformation of monkey cells by exogenous plasmid DNA; Appel JD et al.; We have tested the ability of chrysotile asbestos fibers to introduce plasmid DNA into monkey COS-7 cells and the ability of this DNA to function in both replication and gene expression . Chrysotile fibers are at least as effective as calcium phosphate in standard transfection assays at optimal ratios of asbestos to DNA . After transfection with chrysotile, a minor percentage of introduced plasmid DNA bearing a simian virus 40 origin of replication replicates after 24 hr . Fragmentation of entering DNA is more prominent with asbestos than with calcium phosphate, and after 72 hr most DNA introduced by asbestos is associated with chromosomal DNA . Cells transfected with plasmid p11-4, bearing the p53 protooncogene, express this gene . Cells transfected with pSV2-neo express a gene conferring resistance of antibiotic G418, allowing isolation of colonies of transformed cells after 18 days . The introduction of exogenous DNA into eukaryotic cells could cause mutations in several ways and thus contribute to asbestos-induced oncogenesis. Endocrinology, 1988 Oct, 123(4), 2067 - 74 HLA-DR gene expression in a proliferating human thyroid cell clone (12S); Cone RD et al.; We have used a retroviral vector carrying the adenovirus E1A oncogene and the neomycin phosphotransferase gene to establish a human thyroid-derived cell line that exhibits TSH-mediated cAMP generation as well as the differential expression of HLA class II antigens in response to recombinant gamma-interferon . Twenty-two-week gestation, histologically confirmed, human fetal thyroid was collagenase digested, cultured as a monolayer, and infected directly with 12S or 13S E1A-containing retrovirus constructs . Infected clones (n = 30) were selected in a hormone-supplemented medium containing bovine TSH (bTSH; 1 mU/ml), 10% fetal bovine serum, and 0.5 mg/ml G418 antibiotic . A rapidly growing clone (designated 12S) was chosen for detailed analysis over 18 months of continuous culture . The 12S clone was sensitive to less than 10 microU/ml bTSH when assessed by extracellular accumulation of cAMP, but TSH had no influence on 72-h incorporation of {3H}thymidine . Clone 12S responded to recombinant human gamma-interferon (1-10(4) U/ml) by induction of HLA DR alpha-chain-specific mRNA and the surface expression of HLA-DR antigen detected by fluorescein isothiocyanate-labeled monoclonal antibody to nonpolymorphic HLA-DR regions using flow cytometry . These studies indicate the potential for immortalizing human thyroid cells for use as targets of anti-TSH receptor immune responses and for long term studies of human throcyte HLA gene regulation. Phys Ther, 1988 Oct, 68(10), 1541 - 5 Management of chronic pelvic inflammatory disease with shortwave diathermy . A case report; Balogun JA et al.; Patients with pelvic inflammatory disease (PID) are not routinely referred for physical therapy until the condition is found to be resistant to antibiotic therapy . A 39-year-old black woman with an eight-year history of PID was treated with shortwave diathermy (SWD) using a modified "cross-fire" technique . A thermal dosage treatment lasting between 20 and 30 minutes (for each half of the cross-fire technique treatment) was administered . At the beginning of every treatment session, the patient rated her pain perception on a 10-point ratio scale . The patient received a total of nine treatments, after which she was completely pain free . The results of this case study suggest that SWD may be effective in the management of pelvic infections that are unresponsive to chemotherapy . Further studies using larger sample sizes and a control group, however, are needed before conclusive statements can be made on the relative efficacy of SWD in the management of chronic PID. Cancer Res, 1988 Oct 1, 48(19), 5471 - 4 Modulation of the cytotoxicity of mitomycin C to EMT6 mouse mammary tumor cells by dicoumarol in vitro; Rockwell S et al.; Aerobic and hypoxic cultures of EMT6 mouse mammary tumor cells were used to study the effects of dicoumarol (DIC) on the cytotoxicity of mitomycin C (MC) . DIC protected aerobic cells from MC toxicity, but sensitized hypoxic cells to the cytotoxic actions of this antibiotic . Survival curves for cells treated with 1.5 microM MC +/- 100 microM DIC for different periods of time under aerobic or hypoxic conditions showed that DIC acted as a dose-modifying agent, that is, an agent which changed the slopes, but not the shapes, of the MC survival curves . Experiments that examined the effects of the DIC concentration on the modulation of MC cytotoxicity revealed significant perturbations in MC toxicity with a DIC concentration of 100 microM and increased sensitization/protection with increasing levels of DIC . DIC altered the toxicity of MC only when it was present during exposure of the cells to MC . Treatment with DIC before or after (but not during) MC did not alter the amount of cytotoxicity . Addition of DIC to cell cultures seconds before the addition of MC was as effective as addition of DIC 30 min to 2 h before MC . Taken together, these findings suggest that DIC reversibly inhibits one or more enzymes involved in the activation and inactivation of MC, and that this modulation of the enzymatic processing of MC alters the cytotoxicity of the drug. J Mol Biol, 1988 Sep 20, 203(2), 457 - 65 Site-directed mutagenesis of Escherichia coli 23 S ribosomal RNA at position 1067 within the GTP hydrolysis centre; Thompson J et al.; Site-directed mutagenesis has been used to change, specifically, residue 1067 within 23 S ribosomal RNA of Escherichia coli . This nucleoside (adenosine in the wild-type sequence) lies within the GTPase centre of the larger ribosomal subunit and is normally the target for the methylase enzyme responsible for resistance to the antibiotic thiostrepton . The performance of the altered ribosomes was not impaired in cell-free protein synthesis nor in GTP hydrolysis assays (although the 3 mutant strains grew somewhat more slowly than wild-type) but their responses to thiostrepton did vary . Thus, ribosomes containing the A to C or A to U substitution at residue 1067 of 23 S rRNA were highly resistant to the drug, whereas the A to G substitution resulted in much lesser impairment of thiostrepton binding and the ribosomes remained substantially sensitive to the antibiotic . These data reinforce the hypothesis that thiostrepton binds to 23 S rRNA at a site that includes residue A1067 . They also exclude any possibility that the insensitivity of eukaryotic ribosomes to the drug might be due solely to the substitution of G at the equivalent position within eukaryotic rRNA. S Afr Med J, 1988 Sep 17, 74(6), 277 - 9 Human bites of the face . Early surgical management; Venter TH; A prospective study was done on 72 cases of human bites of the face . Forty-four patients were found suitable for early surgery, which was performed under antibiotic cover within 5 days after injury . In 35 of the 44 cases antibiotics were started within the first 24 hours (group I) and the results are compared with similar studies . Further comparison is made with 9 patients (20%) (groups II and III) who arrived at hospital late and so did not receive antibiotics until over 24 hours after the bite, although surgery was still performed within the first 5 days . Infection rates were low in all three groups . Wounds were closed directly or definitive surgery done with the use of local flaps or skin grafts . No problems were experienced with these procedures. Mol Pharmacol, 1988 Sep, 34(3), 286 - 97 Interactions of liposome-incorporated amphotericin B with kidney epithelial cell cultures; Krause HJ et al.; The polyene antibiotic amphotericin B (AmB) is profoundly cytotoxic to both fungal cells and mammalian cells . We have previously shown that the incorporation of AmB into phospholipid vesicles can markedly reduce the toxicity of the drug for mammalian cells (erythrocytes) without changing its antifungal potency {Mol . Pharmacol . 31:1-11 (1987)} . Because the primary site of in vivo toxicity of AmB is the kidney, here we investigate the effects of free AmB and liposomal AmB (L-AmB) on LLCPK1 cells, a porcine kidney cell line with many characteristics typical of proximal tubule cells . Acute exposure (2 hr) to free AmB inhibits protein synthesis and causes cell detachment and protein loss in LLCPK1 cells, with an IC50 of about 30 micrograms/ml . By contrast, certain formulations of L-AmB have little effect on protein synthesis/protein loss at concentrations of up to 2 mg/ml . The action of liposomes in protecting against acute AmB toxicity extends to effects on sugar transport and on cellular morphology in differentiated cultured kidney cells . Thus, the IC50 for inhibition of sodium-stimulated glucose transport by free AmB is 1.5 micrograms/ml whereas concentrations of L-AmB up to 1 mg/ml do not inhibit this process . However, chronic exposure of cells to L-AmB results in profound toxic effects as manifested by changes in cellular transport functions and cell morphology . Our results suggest that extended periods of proximity between cells and liposomes permit the transfer to toxic amounts of AmB . This may be of importance to the therapeutic use of AmB, for which protracted courses of drug administration are common. Clin Pediatr (Phila), 1988 Sep, 27(9), 445 - 7 Acute bacterial meningitis . Cerebrospinal fluid differential count; Bonadio WA; A retrospective analysis of 112 cases of pediatric bacterial meningitis over a 3-year period was performed to determine the rate of cerebrospinal fluid (CSF) lymphocytosis at initial evaluation . Of 14 neonates and 98 children older than 1 month of age not receiving preadmission antibiotic therapy, only one instance of CSF lymphocytosis occurred . This patient's CSF exhibited pleocytosis, hypoglycorrhachia, abnormally elevated protein content, and organisms visualized on gram stain smear . In children with bacterial meningitis not receiving antibiotic therapy at the time of evaluation, CSF differential cell count with relative lymphocytosis is rare. Exp Cell Res, 1988 Sep, 178(1), 154 - 62 An improved method of electroporation for introducing biologically active foreign genes into cultured mammalian cells; Tatsuka M et al.; We have developed a modified, reproducible, and efficient method for introducing cloned genes into mammalian cells by using an electric field followed by treatment with sodium butyrate . Transfection frequencies with plasmid pSV2-neo, consisting of an antibiotic (G418) resistance gene and simian virus 40 (SV40) early promoter, by electroporation were higher than those by calcium phosphate DNA precipitation . Treatment with sodium butyrate following electroporation significantly increased the frequency of transfection in various types of cell lines and primary cultured cells including human skin fibroblasts . Treatment with sodium butyrate also increased the transient expression of the gene for chloramphenicol acetyltransferase (acetyl-CoA; chloramphenicol O3-acetyltransferase, CAT, EC 2.3.1.28) when the gene was introduced into BALB/c 3T3 cells by electroporation . Electroporation combined with sodium butyrate treatment is an improved method for stable and transient biochemical transformation of foreign genes in cultured mammalian cells. Chirurg, 1988 Sep, 59(9), 587 - 91 {Perforation of the large intestine by a contrast medium enema with barium}; Graf D et al.; This is a report about five patients who suffered a perforation of the colon during a barium-sulfate enema . In one case, barium leaked into the intraperitoneal cavity causing a barium peritonitis . In the other four cases, leakage into the retroperitoneal cavity occurred . All patients underwent surgical removal and drainage of the barium-sulfate and subsequently required a colostomy . In two cases a bowel resection was additionally performed . In one case the defect re-sutured . Antibiotic therapy was included in all cases . All patients survived the incident and were discharged between 20 days and four months postoperatively . Publications and personal experience led us to manage intraperitoneal or large retroperitoneal perforations by prompt laparotomy with removal of barium and faeces . A proximal colostomy is also required . In smaller retroperitoneal perforations conservative management is feasible, however, if the patient's condition deteriorates, they should be treated as recommended for an intraperitoneal perforation. Antibiot Khimioter, 1988 Sep, 33(9), 694 - 6 {Benzylpenicillin levels in the serum and bone tissue of the lower jaw in patients with chronic traumatic osteomyelitis after intraosseous and intramuscular administration}; Borodin IuN; Penetration of benzylpenicillin into pathological foci was studied in 48 patients with chronic traumatic osteomyelitis of the lower jaw after intramuscular and intraosseous administration of the antibiotic . A group of 10 patients operated for congenital deformations of the lower jaw was used as the control . The results showed that after intramuscular administration benzylpenicillin penetration into the inflammation focus of the lower jaw was better than that into the intact bone only for the first 30 minutes . At later periods it was detected in both the cases as traces . After intraosseous administration of the drug in doses of 50,000 and 200,000 units its accumulation in the bone tissue of the patients with chronic traumatic osteomyelitis of the lower jaw in 30 minutes was respectively 75 and 160 times higher than that after the intramuscular injections . The period of its presence in the pathological focus as the therapeutic levels was also higher i . e . up to 2 hours . Intraosseous route of benzylpenicillin administration is likely to decrease the quantity of the drug needed for treating patients with chronic osteomyelitis of the lower jaw. J Nat Prod, 1988 Sep-Oct, 51(5), 937 - 40 The biosynthetic origins of rebeccamycin; Pearce CJ et al.; Experimental evidence is presented to demonstrate that the antitumor-antibiotic rebeccamycin is biosynthesized by Saccharothrix aerocolonigenes from one unit of glucose, one of methionine, and two of tryptophan . Evidence is presented that suggests that the alpha-amino group of neither tryptophan unit provides the nitrogen of the phthalimide system. J Nat Prod, 1988 Sep-Oct, 51(5), 893 - 9 Biosynthesis of staurosporine, 2 . Incorporation of tryptophan; Meksuriyen D et al.; Following studies to define the time course, media, and nutrient parameters for the production of the potent cytotoxic antibiotic staurosporine in Streptomyces staurosporeus, biosynthetic studies of staurosporine with singly- and doubly-labeled radioactive precursors established that either one or two units of tryptophan was incorporated efficiently . From the 13C-nmr spectrum of staurosporine subsequent to stable isotope incorporation experiments, it was established that the aglycone moiety was derived from two units of tryptophan with the carbon skeleton incorporated intact. J Nat Prod, 1988 Sep-Oct, 51(5), 884 - 92 Biosynthesis of staurosporine, 1 . 1H- and 13C-NMR assignments; Meksuriyen D et al.; Complete and unambiguous assignments of the 1H- and 13C-nmr spectra of the potent antitumor antibiotic staurosporine have been accomplished using a combination of one- and two-dimensional nmr techniques, including one-bond and long-range heteronuclear multiple-quantum coherence spectroscopy (HMQC) . Staurosporine was found to be highly cytotoxic in the KB and P-388 assays but was inactive in the microtubulin assembly assay. Jpn J Pharmacol, 1988 Sep, 48(1), 1 - 6 Autoradiographic demonstration of the antagonism of anthramycin and diazepam against cholecystokinin in the mouse brain using the {14C}-2-deoxyglucose method; Sugaya K et al.; Effects of diazepam (DZP), a synthetic benzodiazepine drug, and anthramycin (ATM), a benzodiazepine antitumor antibiotic produced by a certain species of streptomyces, on the uptake of 2-deoxy-D-{14C}-glucose (2-DG) in mouse brain neurons with or without cholecystokinin were examined . 2-DG uptake in neurons was evaluated by using an autoradiographic technique . The sulfated octapeptide CCK (CCK8) was injected intracisternally; DZP and ATM, intraperitoneally; and 2-DG, intravenously to mice . Autoradiograms prepared from the slices of the brain were converted to false color images . CCK8 (1 microgram/mouse) markedly stimulated the 2-DG uptake in neurons in the various regions of the brain, but the stimulative effects of CCK8 was almost completely suppressed after an intraperitoneal administration of 1.0 mg/kg of DZP or 0.5 mg/kg of ATM . Since it has been previously shown that these doses of DZP and ATM almost completely reversed the antinociception produced by 1 microgram/mouse of CCK8, the present results on the 2-DG uptake in the mouse brain are considered to further support the antagonism between CCK8 and DZP or ATM in the central nervous system. Antimicrob Agents Chemother, 1988 Sep, 32(9), 1446 - 9 Comparative effects of cefoxitin and cefotetan on vitamin K metabolism; Sieradzan RR et al.; The effects of cefoxitin and cefotetan on vitamin K metabolism and clotting parameters in five healthy subjects were investigated . No changes in prothrombin time or in the formation of abnormal prothrombin were seen either during or following the cefoxitin or cefotetan phase . However, when phytonadione (10 mg) (vitamin K1) was administered at the completion of each course of antibiotics, formation of vitamin K 2,3-epoxide was observed only during the cefotetan phase . It is probable, therefore, that cefotetan, a cephamycin antibiotic containing the N-methylthiotetrazole side chain, inhibits hepatic vitamin K 2,3-epoxide reductase . While hypoprothrombinemia and formation of abnormal prothrombin were not seen in healthy subjects, the effect of cefotetan on the coagulation status of vitamin K-depleted patients may be adverse. Pediatr Emerg Care, 1988 Sep, 4(3), 180 - 2 Significance of polymorphonuclear leukocytes in CSF of bacteremic children; Bonadio WA et al.; A retrospective study was performed of 32 bacteremic children not receiving preadmission antibiotic therapy who had a diagnostic lumbar puncture for analysis of cerebrospinal fluid at the time of initial evaluation for an acute illness . In each instance, the CSF contained polymorphonuclear leukocytes without pleocytosis . Of these 32 bacteremic patients, 88% had a CSF differential cell count with 20% or fewer polymorphonuclear cells, and greater than 90% had glucose and protein concentration within the range of normal limits . All patients had a Gram-stained smear of CSF which revealed no organisms . In no instance was a CSF culture positive for a bacterial pathogen . In the bacteremic child not pretreated with antibiotics, cerebrospinal fluid which contains total white blood cell, glucose, and protein concentrations within limits of normal, a differential cell count with 20% or fewer polymorphonuclear leukocytes, and Gram-stained smear which reveals no organisms is not indicative of risk for bacterial meningitis. J R Soc Med, 1988 Sep, 81(9), 523 - 5 The use of acrylic bone cement for cervical fusion in patients with rheumatoid arthritis; Wilde GP et al.; We report on 14 patients with instability of the cervical spine secondary to rheumatoid arthritis treated by fusion using a combination of traditional bone grafting techniques and methylmethacrylate bone cement . Successful fusion was achieved in all cases with few complications . The high infection rate reported by other authors was avoided by reducing the bulk of the cement mass and the use of antibiotic impregnated cement . We recommend this method of fusion to all orthopaedic surgeons involved in the treatment of patients with rheumatoid arthritis. J Infect, 1988 Sep, 17(2), 155 - 8 Rabies presenting with myocarditis and encephalitis; Raman GV et al.; We report a case of rabies acquired in Zambia by a 45-year-old woman who presented with a history of an influenza-like illness, abnormal behaviour and signs of myocarditis . A provisional diagnosis of systemic viral infection was made . Within 12 h of admission the patient developed features of rabies that included hydrophobia . She was artificially paralysed and ventilated electively . Empirical antibiotic therapy was given also . Signs of myocarditis and fever disappeared within 48 h . Her clinical condition remained stable but she required heavy sedation . On the ninth day after admission the patient developed features of inappropriate secretion of antidiuretic hormone and gradually became water-logged . Intake of fluid was therefore restricted . Her level of consciousness deteriorated progressively to the point where sedation was no longer required . Brain death was diagnosed 14 days after admission. J Am Dent Assoc, 1988 Sep, 117(3), 453 - 5 Brain abscess from chronic odontogenic cause: report of case; Saal CJ et al.; A case of a chronic odontogenic abscess that probably precipitated a frontopatrietal brain abscess by hematogenous spread has been presented . A thorough examination of the patient showed no other source of infection . Peptostreptococcus sp was found as the common pathogen despite 6 days of broad-spectrum antibiotic therapy . This case emphasizes the important role of dentistry in medical diagnosis and treatment implemented in the hospital setting. J Antimicrob Chemother, 1988 Sep, 22(3), 371 - 5 Oral treatment of peritonitis in CAPD patients with two dosage regimens of ofloxacin; Chan MK et al.; Two open studies of oral treatment of peritonitis in CAPD patients with ofloxacin are described . The first study included 10 episodes of peritonitis treated with ofloxacin 400 mg followed by 200 mg daily for a total of seven days . In the second study of 18 peritonitis episodes, the treatment was ofloxacin 400 mg followed by 300 mg daily for a total of ten days . The cure rate was 50% in the first study and 83% in the second . There was significant accumulation of ofloxacin in the serum but the mean serum trough level with the second treatment regimen plateaued at 6 mg/l on day 10 . Peritoneal effluent ofloxacin levels correlated well with the prevailing serum concentrations of the antibiotic and, except on day 1, the mean peritoneal effluent ofloxacin levels all exceeded 3 mg/l with the second dosing scheme . Side effects were mainly nausea and dizziness. EMBO J, 1988 Sep, 7(9), 2861 - 7 Structure-function relationships in the GTP binding domain of EF-Tu: mutation of Val20, the residue homologous to position 12 in p21; Jacquet E et al.; Val20 of elongation factor Tu (EF-Tu), one of the best-characterized GTP binding proteins, is a variable residue within the consensus motif G-X-X-X-X-G-K involved in the interaction with the phosphates of GDP/GTP . To investigate the structure-function relationships of EF-Tu, which is widely used as a model protein, Val20 has been substituted by Gly using oligonucleotide-directed mutagenesis . The most important effects are: (i) a strong reduction of the intrinsic GTPase activity, (ii) a remarkable enhancement of the association and dissociation rates of EF-TuGly20-GDP, mimicking the effect of elongation factor Ts (EF-Ts) and (iii) the inability of ribosomes to influence the intrinsic GTPase of EF-Tu uncoupled from poly(Phe) synthesis . EF-TuGly20 can sustain poly(Phe) synthesis, albeit at a much lower rate than wild-type EF-TuVal20 . As with the latter, poly(Phe) synthesis by EF-TuGly20 is inhibited by the antibiotic kirromycin, but differs remarkably in that it is largely independent of the presence of EF-Ts . According to primary sequence alignment, position 20 is homologous to position 12 of ras protein p21 . As in p21, this position in EF-Tu is critical, influencing specifically the GDP/GTP interaction as well as other functions . The effect of the mutation displays diversities but also similarities with the situation reported for p21 having the corresponding residues in position 12 . The differences observed with two homologous residues, Gly20 and Gly12 in EF-Tu and p21 respectively, show the importance of a variable residue in a consensus element in defining specific functions of GTP binding proteins. Br J Surg, 1988 Sep, 75(9), 857 - 61 Ten-year computerized audit of infection after abdominal surgery; Krukowski ZH et al.; A prospective audit of the frequency of infective complications after all abdominal operations was carried out between January 1977 and December 1986 . A total of 3100 abdominal procedures (2041 elective; 1059 emergency) were performed in 3056 patients . There were 50 (1.6 per cent) in-hospital and 66 (2.1 per cent) late wound infections (overall 3.7 per cent) . Fifty-four (1.8 per cent) patients developed postoperative intraperitoneal sepsis . Ninety-eight patients died (overall mortality 3.2 per cent) and intraperitoneal sepsis was a related factor in twelve (0.4 per cent) . Wound infection, peritoneal sepsis and mortality were related to the degree of operative contamination and to reoperation . The results support the traditional, although sometimes inadequately stressed, teaching that technique is an important factor in preventing infection . Infection is also reduced by peroperative antibiotic lavage . The limited value and the potential difficulties of the unstructured introduction of computerized audit should be recognized. J Antibiot (Tokyo), 1988 Sep, 41(9), 1196 - 204 Isolation, physico-chemical properties and biological activity of pamamycin-607, an aerial mycelium-inducing substance from Streptomyces alboniger; Kondo S et al.; Pamamycin-607, which showed aerial mycelium-inducing activity, has been isolated from Streptomyces alboniger IFO 12738 . At 0.1 microgram/disc it induces aerial mycelia in the aerial mycelium-negative strain of S . alboniger but inhibits growth of the substrate mycelia at 10 micrograms/disc . It also acts as an antibiotic against some fungi and bacteria . When KMnO4 was partitioned with pamamycin-607 between benzene and water, MnO4- but no K+ was transferred from the water to the benzene layer; pamamycin-607 was thus shown to be a novel anion-transfer antibiotic. Mutagenesis, 1988 Sep, 3(5), 409 - 13 Expression of an E.coli O6-alkylguanine DNA alkyltransferase gene in Chinese hamster cells protects against N-methyl and N-ethylnitrosourea induced reverse mutation at the hypoxanthine phosphoribosyl transferase locus; Fox M et al.; The spontaneous hypoxanthine phosphoribosyl transferase deficient (HPRT-) mutants of V79 cells (TG11 and TG15) were transfected with a retrovirus-based plasmid containing a truncated form of the Escherichia coli gene which codes for O6-alkylguanine (O6-AG) DNA alkyltransferase (ATase) . The resultant cell lines TG11SB5 and TG15SB7 were G418 resistant and expressed high levels of O6-AG ATase activity . The frequency of revertants induced by equitoxic doses of N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) was 10- to 50-fold higher in TG11 than in TG15 . In TG11SB5 and TG15SB7 induced revertant frequencies were reduced relative to TG11 and TG15 by factors of 6-8 and 1.5-3.0, respectively, immediately after treatment . On delayed plating the frequency of MNU-induced revertant colonies decreased at a rate inversely proportional to dose in both TG11 and TG11SB5 . In contrast, after exposure of TG11SB5 to ENU (50 or 75 micrograms/ml) initial reversion frequencies were low compared with TG11, but then rose to a plateau frequency by 24 h, which was maintained for up to 72 h . The frequency of reversion observed, the degree of protection afforded by the E.coli O6-AG ATase and the kinetics of expression of revertants were thus cell line specific suggesting that DNA sequence specific alkylation and/or preferential repair may be responsible . The initial protection against mutagenesis is consistent with the hypothesis that MNU- and ENU-induced reversion is the result of miscoding opposite O6-AG or O4-alkylthymine residues . Expression of O6-AG ATase activity was variable when cells were continually cultured over long periods despite the presence of the selective antibiotic G418. Rev Med Interne, 1988 Sep-Oct, 9(4), 369 - 76 {Cerebral abscess . Analysis of 41 cases over a 10-year period}; Harle JR et al.; Although treatment with antibiotics and computerized tomography (CT) of the brain have considerably improved the prognosis of intracranial purulent collections, brain abscess remains a lethal disease in about one out of ten cases . We present a series of 41 brain abscesses diagnosed between 1976 and 1986 and treated surgically . The clinical signs were more often neurological than infectious . Among the exploratory methods, only CT has a real diagnostic value . Treatment is both medical and surgical . Simple aspiration seems to have the triple advantage of producing prompt and effective decompression of brain tissue, enabling the pathogen(s) to be isolated so that the appropriate antibiotic can be chosen, and being a repeatable and little traumatic procedure with less sequelae than surgical excision. J Pediatr Gastroenterol Nutr, 1988 Sep-Oct, 7(5), 780 - 2 Ascites complicating ventriculoperitoneal shunts; Goodman GM et al.; Ventriculoperitoneal shunts are currently a standard therapy for obstructive hydrocephalus . These shunts are associated with a variety of abdominal complications, one of which is the development of ascites . We report an 11-year-old girl with a ventriculoperitoneal shunt in whom a low-grade peritoneal infection presented with ascites . This case demonstrates the importance of diagnostic paracenteses, appropriate antibiotic therapy and the potential need to establish an alternative route for cerebrospinal fluid diversion in patients with ventriculoperitoneal shunts and ascites. J Dairy Sci, 1988 Sep, 71(9), 2584 - 606 Udder health in the periparturient period; Oliver SP et al.; The periparturient period is associated with rapid differentiation of secretory parenchyma, intense mammary growth, copious synthesis and secretion, and marked accumulation of colostrum and milk . Udder health during this time is an important factor associated with the production of maximum quantities of high quality milk . Intramammary infections that occur during the dry period can adversely affect udder health, resulting in decreased milk production, altered milk composition, and impaired mammary function . Bovine mammary glands are markedly susceptible to new infections during the periparturient period, especially prior to parturition . Many infections that occur at this time are associated with clinical mastitis during early lactation . Methods of controlling mastitis in the dry period have focused primarily on the use of antibiotics . However, antibiotic therapy at drying off does not appear to prevent new infections in the periparturient period . This is most likely due to lack of persistence of antibiotics . Furthermore, antibiotics used currently are less effective against environmental pathogens, in particular coliform bacteria, which can cause a high proportion of intramammary infections during the periparturient period . Methods of controlling bovine mastitis during the periparturient period is an important area that requires additional research . Procedures need to be developed that are effective against a variety of bacteria, including environmental mastitis pathogens, if additional control is to be achieved. J Urol, 1988 Sep, 140(3), 528 - 31 Local antibody in semen for rapid diagnosis of Chlamydia trachomatis epididymitis; Kojima H et al.; Etiologic studies including micro-immunofluorescence serology for Chlamydia trachomatis were done on 45 consecutive men with acute epididymitis . Of the men 21, all less than 35 years old, had type specific Chlamydia trachomatis antibody in the semen . All patients with semen antibody also had Chlamydia trachomatis antibody in the serum, while only a few of the patients without semen antibody had serum antibody . Chlamydia antibody titers in the semen specimens were higher than those in the sera and they persisted longer . In only 1 patient with semen antibody was another potential etiological agent for epididymitis demonstrated, while most of the patients without semen antibody had bacterial causes for the epididymitis . It was concluded that measurement of Chlamydia trachomatis antibody in semen offered a noninvasive, sensitive and specific method, useful despite prior antibiotic therapy, for diagnosis of the etiology of epididymitis in young men. J Card Surg, 1988 Sep, 3(3 Suppl), 309 - 12 Homograft valve preparation and predicting viability at implantation; Gonzalez-Lavin L et al.; An experimental study was performed using C14 proline uptake in order to: (1) assess the effects of current sterilization and storage methods on fibroblast viability, and (2) establish a control tissue that could be used to determine viability of each homograft valve at the time of implantation in the clinical setting . The results were expressed as disintegrations per minute per milligram of tissue (DPM/mg) . Swine aortic (AV), pulmonary (PV), and tricuspid leaflets (TV), and adjacent AV and PV arterial wall were procured sterile and subjected to routine sterilization and storage . Thirty samples of AV were analyzed for incorporation of labeled proline at procurement (208 +/- 7 DPM/mg), following 48-hour antibiotic exposure (87 +/- 6 DPM/mg, P less than .0001), and following controlled rate cryopreservation and storage for 12 days at -80 degrees C (78 +/- 8 DPM/mg, P = .42) . Proline uptake of the other tissues at the same intervals disclosed that only the TV resulted in the same degree of viability at implantation (AV 78 +/- 8, PV 68 +/- 3, TV 75 +/- 2, P = NS) . The homograft valves were obtained under sterile conditions from brain dead, multiorgan donors (homovital) . It has been postulated that these valves are sterile and ready for implantation . Of 17 homovital valves cultured at procurement, 9 had positive cultures within 48 hours (53%) . We conclude that: (1) the TV can be processed as a control tissue with each homograft and then utilized to predict viability at the time of implantation in the clinical setting; (2) antibiotic exposure is an essential step in the preparation of all homografts, however, modification of the antibiotic solution is necessary. J Card Surg, 1988 Sep, 3(3 Suppl), 289 - 96 Long-term results of the viable cryopreserved allograft aortic valve: continuing evidence for superior valve durability; McGiffin DC et al.; From December 1969 to May 1975, 124 patients underwent aortic valve replacement with an allograft aortic valve sterilized by incubation in a low dose antibiotic solution and stored by refrigeration at 4 degrees C (4 degrees C stored valve group) . From June 1975 to December 1987, 231 patients received an allograft aortic valve, sterilized by the same low dose antibiotic solution, but stored by cryopreservation in liquid nitrogen at -196 degrees C (cryopreserved valve group) . The 4 degrees C stored valves were essentially nonviable, whereas the cryopreserved valves were viable at implantation . Of the 355 aortic valve replacements, associated procedures were performed in 127 patients . The 30-day mortality was 8.9% (confidence limits {C.L.} 6.2% .. . 12.3%) (4 degrees C stored) and 4.8% (C.L . 3.3% .. . 6.7%) (cryopreserved) . Actuarial survival was similar in both groups, being 71% and 67% at 10 years in the 4 degrees C stored and cryopreserved valve groups, respectively (P = .18) . The probability of a thromboembolic event was low, but appeared higher in the 4 degrees C stored valve group (actuarial freedom at 10 years, 90%) than the cryopreserved valve group (actuarial freedom at 10 years, 98%) (P = .01) probably related to associated mitral valve surgery . The actuarial freedom from allograft valve endocarditis at 10 years was 94% and 95% for the 4 degrees C stored and cryopreserved valve groups, respectively (P = .23) . Reoperation was undertaken in 34 patients in the 4 degrees C stored group and 12 patients in the cryopreserved valve group for leaflet degeneration, endocarditis, or technical reasons.(ABSTRACT TRUNCATED AT 250 WORDS) J Card Surg, 1988 Sep, 3(3 Suppl), 279 - 87 A study of the cells in the explanted viable cryopreserved allograft valve; O'Brien MF et al.; From June 1975 to December 1987, 231 patients underwent aortic valve replacement with a viable cryopreserved allograft aortic valve . Throughout this era, a uniform procurement and preservation was used to maintain leaflet fibroblast viability . The allograft valve was obtained from coroner's autopsies within 24 hours of death, and more recently from organ donors, incubated for 24 hours in low dose antibiotic solution followed immediately by cryopreservation (mean time interval 39 hours after donor death) . Viability was ensured by monitoring glucose utilization of the aortic and pulmonary valves and by demonstrating fibroblast growth in tissue cultured from the pulmonary valve . A uniform protocol for valve preparation was used during the entire experience . Nine allograft aortic valves have been obtained by eight reoperations (two were for leaflet degeneration) and one autopsy . The time intervals from implantation to explantation were 2 months, 10 months, 20 months, 22 months, 2.2 years, 5 years, 8.3 years, 9.2 years, and 10.8 years . Histologic examination of the leaflet tissue disclosed a variable degree of cellularity, ranging from a highly cellular matrix (9.2 years) to minimal cellularity (20 months) . Within the same valve (10 months), one leaflet was completely acellular with a moderate degree of cellularity in the other two leaflets . The competent valve recovered at autopsy (8.2 years) was essentially acellular . Fibroblasts could consistently be cultured from leaflets in which viable cells were seen histologically . Chromosomal analysis of cultured cells from a valve leaflet (9.2 years) that was implanted with a donor and recipient sex mismatch demonstrated persistence of donor cells.(ABSTRACT TRUNCATED AT 250 WORDS) Invest New Drugs, 1988 Sep, 6(3), 227 - 30 Phase II trial of menogaril in advanced colorectal cancer; Holdener EE et al.; Menogaril, a new semisynthetic anthracycline antibiotic, was administered to 35 patients with advanced colorectal cancer . The drug was infused over 2 hr at a dose of 160 mg/sqm or 200 mg/sqm repeated every 4 weeks . Twenty-seven patients were evaluable for response and no objective responses were achieved . Myelosuppression, only leukopenia, was usually of mild-moderate degree and occurred in 63% of the patients . Twenty-seven percent of the patients experienced severe leukopenia . Local erythema and phlebitis were frequently observed and were severe in 13% of the patients . Nausea/vomiting (66%) and alopecia (50%) were . of mild-moderate degree . This study suggests that menogaril at these doses and schedule had no activity in advanced colorectal cancer. Mol Biol (Mosk), 1988 Sep-Oct, 22(5), 1315 - 34 {Design and synthesis of peptides capable of specific binding to DNA}; Grokhovskii SL et al.; In the present communication, design, synthesis and DNA binding activities of the following two peptides are reported: Dns-Gly-Ala-Gln-Lys-Leu-Ala-Cly-Lys-Val-Gly-Thr-Lys-Val-Lys-Val-Gl y-Thr-Lys-Thr - Val-OH (I) and {(H-Ala-Lys-Leu-Ala-Thr-Lys-Ala-Gly-Val-Lys-Gln-Gln-Ser-Ile-Gln-Leu-Ile- Thr- Ala-Aca-Lys-Aca)2Lys-Aca}2Lys-Val-OH (II), where Aca = NH(CH2)5CO--; Dns is a residue of 5-dimethylaminonaphtalene-1-sulfonic acid . Peptide I contains a large fraction (ca.30%) of valyl and threonyl residues, which possess a high potential for beta structure formation . Peptide II contains four repeats of the amino acid sequence present in the presumed DNA binding helix-turn-helix unit of 434 Cro repressor . These four domains are linked in such a way that two domains can interact with two halves a 14 base pair long operator site on DNA . From CD studies we have found that peptide I is in a random coil conformation in the aqueous solution in the presence of 20% trifluoroethanol . By contrast, amino acid residues of peptide II assume alpha helical, beta and random coiled conformations under the same conditions . A change in the secondary structure of the two peptides upon binding to DNA is observed . The difference CD spectra obtained by subtracting the spectra of free DNA from the spectra of peptide I--DNA complexes gives rise to a beta-like pattern . The difference CD spectra obtained for complexes of peptide II with various natural and synthetic DNAs suggest that alpha-beta-transition takes place in the presumed helix-turn-helix repeat units of peptide II upon binding to DNA . Peptide I binds more strongly to poly(dG).poly(dC) than to poly(dA).poly(dT) and poly{d(GC)}.poly{d(GC)} . The binding takes place in the minor DNA groove because minor groove binding antibiotic sibiromycin can displace peptide I from a complex with poly(dG).poly(dC) . Analysis of footprinting diagramms shows that peptide I specifically protects phosphodiester bonds within operator sites OR1 and OR2 of phage lambda from nuclease cleavage . By contrast, peptide II does not react specifically with operators OR1, OR2 and OR3 of phage 434 although it forms very tight complexes with DNA which are stable in the presence of 1M NH4F. Afr J Med Med Sci, 1988 Sep, 17(3), 145 - 8 Post-operative wound infection in thoracic patients: a preliminary report; Adebo OA et al.; A retrospective study of 37 patients undergoing pulmonary resection, between 1975 and 1980, was performed to establish the incidence of wound infection and to determine contributory factors . Sixteen patients had suppurative lung disease while 11 had pulmonary tuberculosis . The majority of the patients received prophylactic antibiotic (Ampicillin and Cloxacillin) given intramuscularly or intravenously, prior to thoracotomy, and continued for several days post-operatively . Twenty of the 37 cases (54%) developed wound infection, defined as any purulent wound drainage in the post-operative period . The patients with infection (group A) did not differ from those without (group B) as regards presence of pyorrhoea or haemoptysis, the duration of operation or the quantity of blood infused during surgery . A significant difference in the duration of chest intubation was identified between group A (6 +/- 1.3 days) and group B (3 +/- 1.5 days) (P less than 0.001) . The implication of the results towards the modification of post-operative management of patients is discussed. Virology, 1988 Sep, 166(1), 154 - 65 Expression and rescue of a nonselected marker from an integrated AAV vector; Mendelson E et al.; We used rep+ and rep- recombinant AAV-plasmid vectors containing the nonselectable marker chloramphenicol acetyltransferase (CAT) driven by the AAV p40 promoter, and having a selectable marker, neo, inserted in the plasmid genome, and driven by a herpesvirus thymidine kinase gene promoter . Each vector was transfected into human 293 cells or HeLa cells and the neo gene was used to select geneticin-resistant (genr) cells containing integrated vectors . The genr cells were then screened for expression of the unselected marker CAT . For 293 cells, most clones from the rep- vector gave high CAT expression whereas only 50% of those from the rep+ vector expressed CAT, generally at low level . For HeLa cells about 25% of the clones derived from either the rep+ or rep- vector expressed CAT, and several clones from the rep+ vector gave very high yields . We also analyzed integrated rep+ vectors by rescue after superinfection with adenovirus and by Southern blotting . The AAV-CAT genome could be rescued from 50% of HeLa cell clones but not from 293 cell clones . Lack of rescuability reflected rearrangement of the AAV genome termini or the rep gene . Western blotting showed low level constitutive expression of rep protein in one 293 cell clone and two HeLa cell clones . Thus, the AAV p40 promoter (as well as p5 and p19) can function in integrated vectors to express unselected markers which can subsequently be rescued . Expression and rescue depended upon several parameters including the cell type, the initial structure of the vector (rep+ or rep-) but not continued expression of rep, and possibly global effects of the surrounding chromatin. Arch Otolaryngol Head Neck Surg, 1988 Sep, 114(9), 1007 - 11 Effects of otic drops on chinchilla tympanic membrane; Masaki M et al.; Experimental studies have shown that if antibiotic otic drops reach the middle ear cavity they produce severe inflammation . However, the effects of these preparations on the tympanic membrane have not been thoroughly investigated . This study was designed to assess morphological changes in the chinchilla tympanic membrane two to 21 days after a single 0.2-mL application of an antibiotic otic preparation (Cortisporin Otic Suspension) to the middle ear cavity . At two days, the epidermal and the mucosal layers were destroyed . By four days, reepithelialization had occurred and all layers of the tympanic membrane subsequently became markedly hyperplastic . Disruption of the fibrous layer, invasion of keratinizing epidermis to the medial surface, and perforation were observed at three weeks . These findings indicate that tympanic membrane damage is a potentially significant aspect of the ototoxic properties of topical otic preparations. Hokkaido Igaku Zasshi, 1988 Sep, 63(5), 772 - 80 {Enhancement of antitumor immune responses by bleomycin}; Morikawa K; We examined the therapeutic effect of antitumor antibiotic, bleomycin (BLM), using an experimental model of WKA rats and KMT-17 tumor . BLM (5 mg/kg/day) was administered ip for 5 days . The therapeutic effect of BLM was found to be dependent upon the timing of BLM-administration . A remarkable difference in therapeutic effect was observed when BLM was administered from the eighth day after tumor inoculation (late BLM-treatment) rather than when BLM was administered from the day following tumor inoculation (early BLM-treatment) (cured rats/treated rats: 10/21 and 2/16 respectively) . By means of a Winn assay, enhancement of tumor neutralizing activity observed in spleen cells from rats given late BLM-treatment but not in spleen from rats given early BLM-treatment . The enhanced tumor neutralizing activity of spleen cells from rats given late BLM-treatment were suppressed by adding spleen cells from untreated tumor bearing rats . The antitumor transplantation resistance in rats immunized with irradiated KMT-17 cells was abrogated by an adoptive transfer of spleen cells from untreated tumor bearing rats or from rats given early BLM-treatment, but not by the spleen cells from rats given late BLM-treatment . These results suggest that BLM-administration during the late stage of tumor bearing eliminates immuno-suppressor cells and results in the enhancement of antitumor immune responses . The enhanced tumor neutralizing activity of spleen cells from rats given late BLM-treatment was mediated by both T-cell fraction and adherent macrophage fraction . The BLM treatment enhanced the in vitro cytolytic activity of splenic and peritoneal macrophages {( 125I} iododeoxyuridine release assay).(ABSTRACT TRUNCATED AT 250 WORDS) Biofizika, 1988 Sep-Oct, 33(5), 794 - 9 {Computer analysis of the spatial structure of the amphotericin channel}; Khutorskii VE et al.; Energy of Amphotericin B cholesterol complex in a membrane was calculated by the method of atom--atomic potentials . The complex is shown to have two stable states . One of them is stabilized by electrostatic interactions between charged groups of neighbouring antibiotic molecules due to a decline of the molecules to the pore radius . Another state with radial orientation of antibiotic molecules and smaller pore diameter is stabilized mainly by van-der-Waals forces . A conclusion is made that transitions between open and closed states may result from small shifts and turn of all the antibiotic molecules in the complex. Antibiot Khimioter, 1988 Sep, 33(9), 661 - 5 {Effect of salts on the lytic activity of gramicidin S and its derivatives}; Bulgakova VG et al.; Potassium and sodium chlorides, sulfates, acetates and phosphates activated the lytic action of gramicidin S and its derivatives on protoplasts of M . lysodeikticus . The derivatives used were positively charged and neutral by the free amino groups in the ornithine moieties . The salts had no effect on lysis of the bacillar protoplasts by gramicidin S and its positively charged derivatives . The lytic effect of the neutral derivative on the bacillar protoplasts markedly increased in the presence of the salts, activation of the lysis by the phosphates being more pronounced than that by the other salts . Increased membrane activity of gramicidin S in the presence of the salts was not connected with association of the substance molecules in solution . Probably it was due to increased destruction of the membranes at the account of activated detergent effect of the antibiotic and its derivatives. Brain Res, 1988 Aug 23, 458(2), 269 - 77 Clindamycin-induced alteration of ganglionic function . I . Direct effects on ganglion cell properties; Konopka LM et al.; The influence of the lincosamide antibiotic, clindamycin, on the properties of bullfrog sympathetic ganglion B cells has been determined in vitro using conventional voltage recording methods or single microelectrode voltage-clamp recording techniques . Individual neurons were depolarized with both bath application or local perfusion of clindamycin . The amplitude of the depolarization was not altered by pretreatment with 50 microM (+)-tubocurarine, 10-microM atropine, or 1.5 microM tetrodotoxin (TTX), indicating that the clindamycin-induced depolarization does not result from either the activation of (1) nicotinic receptors, (2) muscarinic receptors, or (3) voltage-gated sodium channels . Clindamycin partially inhibited IM, an action which accounts for part of the clindamycin-induced depolarization . The duration of the hyperpolarizing afterpotential (HAP) following the action potential was decreased in the presence of clindamycin . Clindamycin decreased the amplitude and maximum rate of rise (MRR) of TTX-insensitive action potentials . As calcium influx is thought to contribute to the depolarizing phase of the TTX-insensitive spikes, we suggest that the decrease in HAP duration by clindamycin results from a decrease in the somal calcium current . Further, it is suggested that a decrease in IM and HAP duration may be responsible for the increased excitability exhibited during exposure to clindamycin. Cancer Res, 1988 Aug 15, 48(16), 4633 - 8 Protein-tyrosine kinase activity and pp60v-src expression in whole cells measured by flow cytometry; Preis PN et al.; The expression and phosphotyrosine activity of pp60v-src were measured in the B31 avian sarcoma virus-transformed rat cell line by flow cytometry using monoclonal antibodies against pp60v-src (EB7) and phosphotyrosine (1G2) . Although the immunocytochemical staining was markedly heterogeneous, binding of both antibodies was significantly greater to B31 cells than to untransformed Rat 1 cells . Binding of 1G2 to phosphotyrosine residues was specific; it was entirely inhibited by adding excess phenylphosphate but was not affected by phosphoserine or phosphothreonine . The relationship between the amount of phosphorylated tyrosine measured by our FCM technique and total cellular phosphotyrosine measured by phosphoamino acid analysis was linear in vanadate-treated BALB/c 3T3 cells . Treatment of B31 cells for 48 h with herbimycin A, a benzenoid ansamycin antibiotic, to decrease the expression and tyrosine kinase activity of pp60v-src caused reductions of 42% in anti-pp60v-src and 58% in anti-phosphotyrosine antibody immunofluorescence . DNA staining with the fluorescent dye propidium iodide showed no cell cycle specificity in the binding of either antibody . Herbimycin A also caused the transformed cell line to revert to the morphology, actin configuration, and growth behavior of untransformed cells; these changes were reversed within 12 h after removal of the drug . Flow cytometric evaluation of tyrosine kinase expression and activity was fast and easy, and the results correlated well with other measures of cell phenotype . This technique can be used to quantitate the effects of drugs on oncogenic proteins such as pp60v-src and their associated tyrosine kinase activity. J Chromatogr, 1988 Aug 5, 447(1), 65 - 79 High-performance liquid chromatographic separation of subcomponents of antimycin A; Abidi SL; Using a reversed-phase high-performance liquid chromatographic (HPLC) technique, a mixture of antimycins A was separated into eight hitherto unreported subcomponents, A1a, A1b, A2a, A2b, A3a, A3b, A4a, and A4b . Although a base-line resolution of the known four major antimycins A1, A2, A3, and A4 was readily achieved with mobile phases containing acetate buffers, the separation of the new antibiotic subcomponents was highly sensitive to variation in mobile phase conditions . The type and composition of organic modifers, the nature of buffer salts, and the concentration of added electrolytes had profound effects on capacity factors, separation factors, and peak resolution values . Of the numerous chromatographic systems examined, a mobile phase consisting of methanol-water (70:30) and 0.005 M tetrabutylammonium phosphate at pH 3.0 yielded the most satisfactory results for the separation of the subcomponents . Reversed-phase gradient HPLC separation of the dansylated or methylated antibiotic compounds produced superior chromatographic characteristics and the presence of added electrolytes was not a critical factor for achieving separation . Differences in the chromatographic outcome between homologous and structural isomers were interpreted based on a differential solvophobic interaction rationale . Preparative reversed-phase HPLC under optimal conditions enabled isolation of pure samples of the methylated antimycin subcomponents for use in structural studies. Biochim Biophys Acta, 1988 Aug 4, 943(1), 76 - 86 The effect of polyphosphoinositides and phosphatidic acid on the phosphatidylinositol transfer protein from bovine brain: a kinetic study; Van Paridon PA et al.; The phosphatidylinositol transfer protein from bovine brain (PI-TP) has lipid transfer characteristics which make it well suited to maintain phosphatidylinositol (PI) levels in intracellular membranes (Van Paridon, P.A., Gadella, Jr., T.W.J., Somerharju, P.J . and Wirtz, K.W.A . (1987) Biochim . Biophys . Acta 903, 68-77) . Using a continuous fluorimetric transfer assay we have investigated in what way phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA) affect the transfer activity of this protein in model systems . The effects were analysed by application of a kinetic model which yielded the association constant (K) and dissociation rate constant (k-) for the PI-TP/vesicle complex . Incorporation of PA, PIP and PIP2 into the phosphatidylcholine-containing vesicles increased the association constant solely by diminishing the dissociation rate constant . This effect could be completely accounted for by changes in the membrane surface charge density . In contrast to the inhibitory effect of PA, the inhibition caused by PIP2 was completely abolished by the addition of neomycin, in agreement with the observed preferential binding of this polyamine antibiotic to PIP2 . A rise in pH from 5.5 to 8 drastically reduced the association constant for vesicles containing 16 mol% PA (e.g., from 38 to 2 mM-1), without affecting the Vmax . This effect could be mainly attributed to an increase in the negative charge on PI-TP (isoelectric point 5.5), resulting in an enhanced repulsion . Increasing the negative membrane surface charge at pH 7.4 had the opposite effect . This is interpreted to indicate that the membrane interaction site on PI-TP must be positively charged, overcoming the repulsive forces between PI-TP and the vesicle . Addition of PIP2 micelles as a third component in the transfer assay strongly inhibited PI-TP transfer activity . The extent of inhibition suggests a very high affinity of PI-TP for this lipid. Br J Ophthalmol, 1988 Aug, 72(8), 584 - 90 N-3-pyridylmethyl-N'-p-nitrophenylurea ocular toxicity in man and rabbits; Mindel JS et al.; Ingestion of the rat poison N-3-pyridylmethyl-N'-p-nitrophenylurea (PNU) produced ocular toxicity in three humans and in an animal model, the Dutch Belted rabbit . The electroretinogram b wave was especially susceptible to the effects of the rodenticide, and the target tissue appeared to be the retinal pigment epithelium . Injection of PNU itself did not produce ocular toxicity . The poison had to be administered orally . Gentamicin administered orally with PNU prevented the ocular toxicity . Presumably this antibiotic killed those gastrointestinal bacteria responsible for PNU's metabolism into an ocular toxin . L-tryptophan, a known antidote for the lethal effects of PNU, was an antidote for the ocular toxicity when administered orally but not when administered parenterally. Surg Gynecol Obstet, 1988 Aug, 167(2), 109 - 13 Indications and results for splenectomy for beta thalassemia in two hundred and twenty-one pediatric patients; Pinna AD et al.; To determine the advantages and complications of splenectomy in the treatment of beta thalassemia, 221 splenectomies for thalassemia performed upon pediatric patients from 1971 to 1982 are evaluated . There were 125 boys and 96 girls with a mean age of 8.2 +/- 2.5 years at the time of the operation . Sixty-one other patients who underwent splenectomy for other diseases served as the controls . Early and late complications after splenectomy are