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Gastroenterol Jpn, 1980, 15(4), 324 - 9
Clinical basis of chemotherapy for gastric cancer with uracil and 1-(2'-tetrahydrofuryl)-5-fluorouracil; Kimura K et al.; Studies were performed on the clinical basis of chemotherapy for human cancer with uracil and 1-(2'-tetrahydrofuryl)-5-fluorouracil (FT) . In 62 operated patients with stomach, breast, and uterine cancers, the concentration of 5FU and FT were compared in serum, tumor and normal tissues 1, 2, 4, 6, 8, and 12 hours following the administration of 300 mg of UFT (300 mg of FT plus 672 mg uracil, a uracil/FT molar ratio of 4), or FT alone . It was found that the level of 5-FU in tumor tissue remained above 0.05 mcg/g over 12 hours . This value for 5-FU corresponds to a minimum inhibitory concentration in the Vitro experiment with L1210 cells . BLood levels of 5-FU increased up to 0.1 mcg/ml 1 hour after UFT administration and then decreased below 0.05 mcg/ml . The drug concentration in normal tissues was lower than that of the tumor tissues . On the basis of the above findings and phase I study, a protocol of UFT-therapy was made and applied for the treatment of gastric cancer . Our patients were given an oral dose of 300 mg of UFT twice a day per 50 kg body weight (12 mg/kg BW) . Therapeutic effects were detectable in 7 of 20 cases . In addition, a combination of mitomycin C (6 mg i.v . weekly) with UFT seemed to improve the response rate (5/7) . Diarrhea (15%) and skin pigmentation (10%) were major side effects of UFT.

Chemotherapy, 1980, 26(4), 276 - 81
Antimycobacterial activity of isoniazid + prothionamide + dapsone against a number of randomly selected 'wild' strains of Mycobacterium tuberculosis; Urbanczik R; 46 strains of Mycobacterium tuberculosis were studied as to their susceptibility to isoniazid (INH) or to INH + prothionamide (PTH) in the presence or absence of dapsone (DDS) by microdilution transfer plate technique . Synergy with DDS as defined by Berenbaum in 1978 was seen in 78% with INH and in 91% with INH + PTH . It concerned the minimal inhibitory concentration, whereas the minimal bactericidal concentration (MBC) was unaffected in the case of INH and it was increased in only 52% with INH + PTH . The latter MBC proportion mentioned would be decreased to roughly 16% accepting an only twofold decrease in the MBC as possibly due to dilution errors . The possible effect of dimethyl sulphoxide on the reported results is discussed.

Br J Ophthalmol, 1980 Jan, 64(1), 30 - 2
Keratitis due to Aspergillus flavus successfully treated with thiabendazole; Upadhyay MP et al.; A case of Aspergillus flavus keratitis treated successfully with 4% suspension of thiabendazole is reported . This seems to be the first case of successful treatment of keratomycosis with thiabendazole . All other reported cases treated with this drug either had their eyes removed or did not retain any useful vision . Its ability to penetrate ocular tissues, ability to remain in concentrations higher than the minimal inhibitory concentration of many fungi, and broad spectrum of activity make it a worthwhile drug for further investigation in keratomycosis.

Clin Ther, 1980, 3(Spec Issue), 127 - 9
Bactericidal activity of cefoperazone in comparison with other beta-lactam antibiotics and gentamicin; Welch DF et al.; Killing curves were employed to determine the in vitro bactericidal activity of cefoperazone against several aerobic bacterial species of clinical origin . Cefoperazone was bactericidal at concentrations equal to, or greater than, the minimal inhibitory concentration (MIC) but allowed regrowth of the organisms after four to six hours when tested in concentrations of one-fourth or one-half the MIC . Comparative studies with gentamicin, LY127935 (moxalactam), piperacillin, cefamandole, and cephalothin indicate that, in general, cefoperazone demonstrated similar killing activity as other beta-lactam compounds, with some strain differences noted . Gentamicin, as the representative aminoglycoside, demonstrated a greater rate of bactericidal activity than the beta-lactam compounds studied.

Clin Ther, 1980, 3(Spec Issue), 123 - 6
Regression analyses for cefoperazone on Mueller-Hinton agar and DST agar; Langmaack H et al.; A total of 142 gram-positive and 161 gram-negative bacterial strains were tested by an agar diffusion method using antibiotic disks (30 microgram/ml) and the broth dilution method in order to establish a relationship between zone diameter and minimal inhibitory concentration . Mueller-Hinton and DST-Oxoid agars were both evaluated to assess their effects on zone diameters . Computer programmed regression lines of the first and second order were determined, as well as the correlation coefficient of both regression lines . Acceptable correlation coefficients (R = 0.84-0.92) were achieved . The regression lines of the first and second order showed differences, which fell into the category of resistant/susceptible . The DST agar appeared to be better suited than the Mueller-Hinton agar (using the Bauer-Kirby method of the agar diffusion test) to show the differences in the breakpoints.

Int J Fertil, 1980, 25(1), 62 - 6
Sperm semi-autoanalysis by a combination of multiple exposure photography (MEP) and computer techniques; Makler A et al.; A semiautomatic method for sperm analysis is described . The method combines a previously developed multiple exposure photography system with a digitizer connected to a computer . An undiluted specimen is inserted into a 10-mic chamber and the sperms are microscopically photographed for 1 second while illuminated by six short light pulses . On the developed film nonmotile sperms appear very bright, while motile sperms are seen as six-ringed chains . In addition, high magnification photographs of immobilized preheated sperms are taken for morphology analysis . The photographed images are projected onto sheets of paper where the traces of the nonmotile and motile sperms as well as the normal and abnormal forms are marked by a pen . For motility determination, sheets containing the sperm tracks are placed on the digitizer tablet . By means of a sonic pen the coordinates of the ends of the tracks are automatically recorded and the number of motile and nonmotile sperms are counted . Then the percent of abnormal forms are entered at the keyboard . Within a few seconds the computer supplies a printout of the results, including sperm concentration, percent of motile sperms, average velocity and frequency distribution of velocities of moving sperms, percent of abnormal forms, and total number of analyzed sperms.

Sci Rep Res Inst Tohoku Univ {Med}, 1979 Dec, 26(3-4), 71 - 91
Resistance of Mycoplasma pneumoniae to macrolide and analogous antibiotics; Suzaki K; 1 . The susceptibility of M . pneumoniae to antibiotics can be determined by the microtiter method . The adequate technique requires that the final volume of broth medium in a well is 0.2 ml and that the dilution is made after the parent solution of antibiotic in the test tube is dropped into a well every fifth wells . 2 . M . pneumoniae was cultured on agar media containing two-fold concentrations of macrolide and analogous antibiotics, and the following results were obtained . 1) The growth of eight strains of M . pneumoniae on agar media containing two-fold concentrations of the antibiotics revealed that, in six strains, one CFU (colony forming unit) per 10(5) to 10(6) CFU of an inoculum dose was resistant to the antibiotics . 2) The MIC (minimum inhibitory concentration) of erythromycin for the subculture of thet strains of M . pneumoniae on agar media containing two-fold concentrations of the antibiotics revealed that, in six strains, one CFU (colony forming unit) per 10(5) to 10(6) CFU of an inoculum dose was resistant to the antibiotics . 2) The MIC (minimum inhibitory concentration) of erythromycin for the subculture of thet strains of M . pneumoniae on agar media containing two-fold concentrations of the antibiotics revealed that, in six strains, one CFU (colony forming unit) per 10(5) to 10(6) CFU of an inoculum dose was resistant to the antibiotics . 2) The MIC (minimum inhibitory concentration) of erythromycin for the subculture of the colony grown as an average of 0.5 to eight on agar media containing erythromycin in four strains was 0.1 to 1.6 micrograms/ml in some colonies, and 400 to 800 micrograms/ml in most colonies . The results disclosed that the broth culture contains a small number of mycoplasma cells with a definite, high degree of resistance to the antibiotics, but no cells with intermediate degrees of resistance . 3) The FH strain was made resistant to erythromycin, oleandomycin, midecamycin, acetylspiramycin, leucomycin, josamycin, tylosin, lincomycin, or clindamycin by subculture in broth medium from the colony grown at the highest concentrations of each of the antibiotics in agar media . The degree of the resistance developed was 16 to 128,000 in the MIC radio and showed high values of MIC in most strains . The resistance developed was not lost by subculturing the resistant strain in broth medium without antibiotic . 4) The FH strain made resistant to the antibiotics had cross resistance to other macrolides . Strains resistant to some of the antibiotics had cross resistance to lincomycin and clindamycin, and strains resistant to others did not . Some strains made resistant to macrolides with cross resistance to lincomycin and clindaymycin and strains made resistant to lincomycin or clindamycin had no cross resistance to vernamycin B alpha, while all the resistant strains without cross resistance to lincomycin and clindamycin had cross resistance to vernamycin B alpha . No strain had cross resistance to vernamycin A...

Z Hautkr, 1979 Oct 15, 54(20), 901 - 7
{Effect of nitroimidazole therapy on the demonstration of gonococci}; Thurner J et al.; The minimal inhibitory concentration of metronidazole and tinidazole lies between 4000 micrograms/ml and 7.8 micrograms/ml . Drug levels are present in this range for 2--5 hours in genital discharge following single dose oral therapy with 2 g tinidazole or 1.5 g metronidazole . Therefore, 5-nitroimidazole derivatives exert a bacteriostatic effect in the genital region at least on the more sensitive strains . As shown in our experiments, otherwise reliable laboratory procedures for the demonstration of gonococci may yield false negative results, if specimens for culture are obtained at an inappropriate time.

Br J Vener Dis, 1979 Oct, 55(5), 348 - 50
Vaginal oxytetracycline concentrations; Thin RN et al.; Although tetracycline preparations are widely used in departments of genitourinary medicine, or sexually transmitted diseases clinics, little is known of the concentrations of these preparations in genital secretions . For this reason a microbiological method was used for estimating oxytetracycline concentrations in vaginal secretions . These concentrations varied from 0.6 to 6.5 microgram/ml in 19 women who had had sexual contact with a man with non-specific urethritis and who were taking oxytetracycline dihydrate 250 mg four times daily . They were well in excess of the minimum inhibitory concentration of oxytetracycline (0.2 microgram/ml) for the strains of Chlamydia trachomatis isolated from the patients with positive culture results . Thus, oxytetracycline 250 mg four times daily appears to be a satisfactory regimen for the treatment of chlamydial genital infection in women.

J Antibiot (Tokyo), 1979 Sep, 32(9), 862 - 7
Herbicidins F and G, two new nucleoside antibiotics; Takiguchi Y et al.; A mutant of Streptomyces saganonensis No . 4075, obtained with N-methyl-N'-nitro-N-nitrosoguanidine treatment, produced herbicidins F and G without herbicidins A and B . Isolation of the antibiotics was performed by adsorption on resinous adsorbent followed by elution with aqueous MeOH . Herbicidin F was obtained as colorless needles after extraction of the eluate using methylene dichloride . Purification of herbicidin G was completed with silica-gel chromatography to give a crystalline powder . physico-chemical characterization revealed that herbicidins F and G were new nucleoside antibiotics having an adenine moiety in their structures . There was no inhibition activity at 100 micrograms/ml of herbicidins F and G against all of bacteria and yeast tested . Herbicidin F, as well as herbicidin G, are inhibitory activity against some of fungi such as Tricophyton rubrum (MIC; 6.25 micrograms/ml), T . asteroides (6.25 micrograms/ml), T . mentagrophytes (6.25 approximately 12.5 micrograms/ml), Botrytis cinerea (12.5 micrograms/ml), Blastomyces brasiliensis (12.5 approximately 25 micrograms/ml).

Antimicrob Agents Chemother, 1979 Sep, 16(3), 353 - 61
Correlation of aminoglycoside dosages with serum concentrations during therapy of serious gram-negative bacillary disease; Reymann MT et al.; We prospectively evaluated serum aminoglycoside (AMG) concentrations in 120 patients who received gentamicin or tobramycin for serious gram-negative bacillary disease . AMG serum concentrations were assayed by microbiological and radioimmunoassay techniques . Correlation between the two assay methods was good . When AMG doses were based on total body weight, there was no significant correlation between AMG dosage administered and serum concentrations in patients with either normal or abnormal renal function . The use of ideal body weight for calculation of AMG dosage improved this correlation significantly except in hemodialysis patients . AMG-induced nephrotoxicity occurred in 13 patients . No significant association was noted between the occurrence of toxicity and the specific AMG given or with other commonly recognized risk factors . Among study groups, peak AMG serum concentrations failed to exceed the minimal inhibitory concentration of the infecting organism in 17 to 33% of the cases . Serum inhibitory levels of greater than or equal to 1:8 were not associated with improved survival . There was no significant difference in mortality between the gentamicin- and tobramycin-treated groups . We advise base-line serum AMG levels in seriously ill patients with gram-negative bacillary disease and additional bacteriological studies in selected situations.

Rev Infect Dis, 1979 Sep-Oct, 1(5), 832 - 7
Suppression of bacterial adherence by subminimal inhibitory concentrations of beta-lactam and aminoglycoside antibiotics; Ofek I et al.; Nonseptate filaments of Escherichia coli obtained by growth of a temperature-sensitive mutant of the organism at its restrictive temperature in the absence of antibiotics or at its permissive temperature in the presence of approximately one-half the MIC of penicillin (27 micrograms/ml; MIC of penicillin, 50 micrograms/ml) lacked the ability both to bind to mannose and to adhere to host tissues . Addition of low concentrations (0.5-10 micrograms/ml) of streptomycin to cultures of E . coli resulted in marked suppression of the mannose-binding and adhering ability of streptomycin-sensitive E . coli (MIC, 30 micrograms/ml) . In contrast, up to 5,000 microgram of streptomycin/ml had no effect on an isogenic streptomycin-resistant mutant of E . coli (MIC, 20,000 micrograms/ml) . No concentration of penicillin or streptomycin that was tested was able to suppress either the mannose-binding or the adhering ability of E . coli once those activities had been acquired by the organism . These results suggest that subminimal inhibitory concentrations of antibiotics suppress the ability of bacteria to adhere to cells.

Postgrad Med J, 1979 Sep, 55(647), 681 - 2
Modern aspects of testing azole antifungals; Haller I; Difficulties in the in vitro testing of azole antimycotics are described . The value of minimal inhibitory concentration results are discussed and contrasted to those obtained with polyene antimycotics.

Vet Rec, 1979 Aug 11, 105(6), 122 - 4
The irritancy of chlorhexidine gluconate in the genital tract of the mare; Jackson PS et al.; Uterine irrigation was carried out in eight Welsh pony mares using 50 ml of chlorhexidine gluconate solution diluted to give active ingredient concentrations of 0.25 per cent to 2 per cent . Treatment was repeated up to twice in mares showing no adverse effects and irritancy of treatment judged on clinical symptoms and uterine biopsy . Results indicated the inadvisability of using a higher concentration than 0.25 per cent . Three daily applications of a diluted surgical scub solution containing 2 per cent chlorhexidine gluconate to the penis of an arab stallion failed to produce symptoms or irritation . An in vitro minimum inhibitory concentration test performed with the contagious equine metritis organism confirmed its high sensitivity to both chlorhexidine gluconate preparations.

Biochim Biophys Acta, 1979 Aug 7, 555(2), 337 - 48
The interaction of 3,3',4',5-tetrachlorosalicylanilide with phosphatidylcholine bilayers; Barratt MD et al.; 1 . The interaction of the germicide 3,3',4',5-tetrachlorosalicylanilide (T4CS) with vesicles and dispersions of egg phosphatidylcholine has been studied by gel permeation chromatography, electron microscopy, electron spin resonance spin labelling and ion permeability measurements . 2 . Incorporation of T4CS into vesicles of egg phosphatidylcholine gives rise to a large increase in the permeability rate of the paramagnetic cation N,N-dimethyl-N-(1'-oxyl-2',2',6',6'-tetramethyl-4'-piperidyl)-2-hydroxyethylammonium chloride through the lipid bilayer but has no significant effect on the vesicle sizes as measured by gel permeation chromatography or electron microscopy . 3 . ESR studies using a spin-labelled fatty acid have demonstrated the presence of two different environments for the spin label when T4CS is incorporated into phosphatidylcholine bilayers . These two environments are identified as (a) highly ordered areas of the bilayer, rich in T4CS and (b) areas with very similar ordering to that in pure egg phosphatidylcholine . 4 . The effectiveness of very low concentrations of the germicide in increasing vesicle permeability is explained in terms of its clustering to give rigid patches, rich in T4CS, rather than being evenly distributed throughout the bilayer . It is proposed that the increased ion permeability arises from leakage at the interfaces between the rigid and flexible regions of the lipid bilayer . 5 . Comparisons between the effective levels of T4CS in phosphatidylcholine vesicles and its minimum inhibitory concentration with a Gram-positive bacterium confirm the validity of phospholipid vesicles as a model for studies of germicidal activity.

J Antibiot (Tokyo), 1979 Aug, 32(8), 828 - 33
Antifungal activity upon Saccharomyces cerevisiae of iturin A, mycosubtilin, bacillomycin L and of their derivatives; inhibition of this antifungal activity by lipid antagonists; Besson F et al.; The antifungal activity of three antibiotics of the iturin group: iturin A, mycosubtilin, bacillomycin L and of eleven methylated and acetylated derivatives of these antibiotics was tested upon Saccharomyces cerevisiae . The lowest MIC values were found for natural antibiotics . The substitution of polar groups diminished the antifungal activity . Various lipids, sterols, fatty acids, fatty acid methyl esters and phospholipids were tested as inhibitors of the antifungal activity of iturin A, mycosubtilin and bacillomycin L . Cholesterol was the strongest inhibitor upon the three antibiotics; ergosterol, oleic acid and cis-vaccenic acid were less potent inhibitors . Among phospholipids, phosphatidyl choline inhibited bacillomycin L and iturin A while diphosphatidyl glycerol inhibited bacillomycin L and mycosubtilin . The inhibitory effect appeared to be dependent on the nature of both the hydrophilic group and the fatty acid part of phospholipids.

Can J Microbiol, 1979 Jul, 25(7), 818 - 21
Relationship between carbon source and susceptibility of Cephalosporium acremonium to selected amino acid analogues; Mehta RJ et al.; The susceptibility of Cephalosporium acremonium to selected amino acid analogues was markedly influenced by the carbon source used in the test media . Lysine hydroxamate, beta-hydroxy norvaline, and hexafluorovaline were toxic when tested with ribose, ribose or fructose, and ribose or galactose, respectively . In contrast, thialysine and thiaisoleucine inhibited C . acremonium with glucose, fructose, galactose, sucrose, mannitol, sorbitol, and soluble starch . Neither of these analogues was toxic at levels tested when glycerol was used as a carbon source . The minimal inhibitory concentrations (MIC) of thialysine, homoserine, and alpha-methylserine were greater than 1000, greater than 1000, and 250 microgram/mL, respectively, with glycerol . In contrast, the MIC values for the same three analogues were 31, 62, and 125 microgram/mL, respectively, with mannitol . The matching of the carbon sources with the specific amino acid analogues expands the number of analogues useful for selecting derepressed mutants . Thialysine-resistant mutants (tlysR) of C . acremonium which excrete lysine were isolated on a medium containing mannitol.

Lepr India, 1979 Jul, 51(3), 358 - 62
Activity and effective serum level of repository sulphones (DADDS) in lepromatous leprosy; Anand LC et al.; 35 cases of lepromatous leprosy were studied to evaluate the effective blood level and long depot action of acedapsone (DADDS) . It was revealed that serum level of this drug is maintained well above the minimum inhibitory concentration upto 60 days following single intramuscular injection . No significant untoward effects of the drug were encountered except one case of Erythema Nodosum Leprosum and six patients with mild reactional symptoms in the form of fever and arthralgia.

Blood, 1979 Jul, 54(1), 245 - 53
Erythropoietin levels in the course of a patient with erythropoietin-producing renal cell carcinoma and transplantation of this tumor in nude mice; Toyama K et al.; Erythropoietin was measured by exhypoxic polycythemic mouse method in the course of a 64-yr-old male with renal cell carcinoma associated with erythrocytosis . Serum erythropoietin fluctuated with progression of the disease . Preoperative elevated erythropoietin (0.11 U/ml, p greater than 0.05) subsided after nephrectomy and again increased with developing lung metastasis (0.1 U/ml, p greater than 0.02) . Erythropoietin was markedly increased in the tumorous extracts from primary renal cell carcinoma in the kidney (0.2 U/g, p greater than 0.01) and lung metastasis (0.8 U/g, p greater than 0.01) . Renal cell carcinoma from the lung metastasis was transplanted into nude mice, resulting in erythrocytosis in some of these mic . In the erythrocytotic mice, erythropoietin was elevated to levels of 0.25--0.9 U/g (p greater than 0.01) in the tumorous extracts and increased (0.67 U/ml, p greater than 0.02) in the serum . These results indicate that this renal cell carcinoma is an erythropoietin-producing tumor, and this tumor has been successfully transplanted in nude mice for the first time.

J Rheumatol, 1979 Jul-Aug, 6(4), 451 - 5
Results of combined amphotericin B-5-fluorcytosine therapy for prosthetic knee joint infected with Candida parapsilosis; MacGregor RR et al.; A prosthetic knee joint became infected with Candida parapsilosis, apparently introduced by arthrocentesis . The infection was quite indolent, present for several months before treatment . Although the joint fluid contained antibiotic concentrations in excess of the organism's minimum inhibitory concentration, medical therapy failed, and cure required removing the prosthesis and fusion of the knee.

J Am Dent Assoc, 1979 Jul, 99(1), 47 - 50
Concentrations of cephalexin in mandibular alveolar bone, blood, and oral fluids; Shuford GM; Results from this study of 16 patients who underwent extractions and alveoloplasty indicate that cephalexin effectively penetrates alveolar bone . After cephalexin had been administered, 500 mg four times a day for 48 hours, the average concentration in bone exceeded the average minimal inhibitory concentration of six organisms commonly encountered in infections and bacteremias of dental origin . These data and the current knowledge of cephalexin suggest that cephalosporins may have a unique use in dental infections or potentially harmful bacteremias caused by susceptible organisms.

Experientia, 1979 Jun 15, 35(6), 795 - 6
Antibiotic sensitivity testing by flow microcalorimetry; Beezer AE et al.; The proposed flow microcalorimetric method for the diagnosis of bacteriuria has been extended to include antibiotic sensitivity testing . Sensitive organisms rapidly (4-8 min) show thermal responses to the added antibiotics over the normal range of concentrations (1 x, 2x, MIC value).

J Am Diet Assoc, 1979 Jun, 74(6), 667 - 9
Nutrition services for pregnant adolescents within a public high school; Alton IR; PIP: The St . Paul Maternal and Infant Care Project (MIC) was begun in 1973 in response to the recognition that pregnant adolescents were medically, nutritionally, and socially at risk . The program provides prenatal care as well as adolescent health care and drug screening . It operates within 3 inner city public high schools and has a strong educational component for parents and for infants and children . Funds come from state-allocated Title V Maternal and Child Health funds, Title XIX EPSDT funds, and grants from the Minnesota Community Health Services Act and the St . Paul-Ramsey Hospital Medical Education and Research Foundation . Title XX monies are used to support the day care component . In-kind contributions from the St . Paul Schools provide physical facilities for the school health clinics and the day care center . Since implementation, the program has secured a 50% reduction in school fertility rates, there have been fewer obstetric complications, and a lower incidence of low-birth-weight infants compared with adolescents served by the MIC Project in non-school clinics . 85% have completed high school . The article then describes the nutritional problems of pregnant adolescents and the measures taken to deal with these .

Quad Sclavo Diagn, 1979 Jun, 15 Suppl 1, 770 - 6
{"S . wien" and "S . bredeney" plasmidic resistance to disinfectant agents and antibiotics (author's transl)}; Levre E et al.; Several antiseptic and disinfectant compounds have been investigated for their minimal inhibitory concentration (MIC) against antibiotic multiresistant strains of S . wien and S . bredeney as well as S . typhi and S . typhimurium strains characterized by wide spectrum of antibiotic sensitivity . The MICs of AgNO3, merthiolate, NaN3, phenol, Zephiran and Desogen were not substantially different for the former and the latter strains; on the contrary, the HgCl2 minimal inhibitory concentration was significantly higher against S . wien and S . bredeney than against the other strains . The mercury resistance appeared plasmid controlled and transferable to E . coli K-12, always associated with antibiotic resistance . The findings, which confirm the results of other AA., seem unrestrictive of the use of HgCl2, because its not probable selective role in the hospital environment.

Pol J Pharmacol Pharm, 1979 May-Jun, 31(3), 227 - 37
Some remarks of penicillin and desacetylcephalosporin synthesis by mixed anhydrides method; Borowicz P et al.; The possibilities of 6-APA and 7-ADCA acylation by means of mixed anhydrides from ethyl chloroformate and cyclic carboxylic acids were investigated . The complexity of acylation course was observed, which depends upon kind of aminoderivative and structure of starting acid, respectively . In the case of mixed anhydrides formed from acid derivatives of which vicinal carbon atoms of ethylene bond built on into appropriate cyclic system were connected with methyl and carboxylic group (-C)CH3=C(COOH(-), it was found, that the main reaction products were: the suitable ureids and ethoxypenicillin or ethoxydesacetylcephalosporin . After treatment of 6-APA or 7-ADCA with different esters of chloroformic acid the corresponding alkoxy-, aralkoxy- or aryloxyderivatives were obtained . The MIC estamination showed, that only penicillin derivatives may be considered as interesting microbicides.

Jpn J Antibiot, 1979 May, 32(5), 598 - 605
{Treatment of E . coli meningitis with cefmetazole . Report of two cases with favorable response and determination of the concentrations in CSF (author's transl)}; Kobayashi Y et al.; Two patients with purulent meningitis, of which causative organism was presumed to be E . coli, were treated with intravenous administration of cefmetazole, 300 approximately 400 mg/kg/day in 4 approximately 6 divided doses, and the following conclusions were obtained . 1) Clinical response was favorable and a complete cure was obtained without sequelae in both patients . There were no adverse reactions noted except for a mild and transient eosinophilia (12%) in one case . 2) Of two strains of E . coli recovered from CSF, one was sensitive to ampicillin, cefazolin and cefmetazole, among which cefmetazole had the highest bacterial activity . Although another strain was sensitive to cefmetazole, it showed resistance to cefazolin (greater than 12.5 microgram/ml) and to ampicillin (greater than 100 microgram/ml) . 3) Concentrations of cefmetazole in CSF following 1 approximately 2 hours of its intravenous administration were either equal to or higher than those of ampicillin, which was given to the same patient for a short period of time . The concentrations in CSF were higher than 3.1 microgram/ml on each occasion except for in some specimens during the convalescent phase and exceeded well the MIC of the causative organism . 4) Based on the above results, cefmetazole is considered to be a potent antibiotic in the treatment of E . coli meningitis . Although further studies are needed as to the dosage, an intravenous administration at 4-hour interval appears to be warranted based on the studies that the half-life of the drug is short in CSF in animal experiments.

J Histochem Cytochem, 1979 May, 27(5), 942 - 6
The histochemical distribution of protein bound sulfhydryl groups in human epidermis by the new staining method; Ogawa H et al.; Recently, we synthesized a new fluorescent thiol reagent, N-(7-dimethylamino-4-methylcoumarinyl)-maleimide (DACM) which is nonfluorescent by itself but will react readily with -SH groups to form highly fluorescent addition products . By the use of this reagent, we studied the localization and concentration of -SH groups and S--S linkages in the human epidermis . The distribution of -SH groups in living layers was abundant in cytoplasm but not in nuclei . The fluorescence was concentrated on the cell membrane or intercellular spaces (MIC parts) and was increased at the spino-granular junction . In the horny layer, the fluorescence of the MIC parts appeared brilliantly in the lower layers and decreased gradually . On the other hand, the fluorescence of cytoplasm in keratinized cells in the stratum corneum was faint . The localization of S--S linkages was not a characteristic of the living layers, but appeared abruptly at the junction of living and horny layers . The fluorescence was localized to the MIC parts and disappeared gradually . The distribution of S--S linkages appeared to be very low in the cytoplasm of keratinized cells . No substantial fluorescence was localized on keratohyalin granules even after reduction.

J Pharm Sci, 1979 Apr, 68(4), 529 - 30
Synthesis of methyl 1-(3,4-dichlorobenzyl)-hexahydro-2,3-dioxo-4-pyridinecarboxylate; Schwan TJ et al.; Methyl 1-(3,4-dichlorobenzyl)-hexahydro-2,3-dioxo-4-pyridinecarboxylate was prepared by alkylation of methyl hexahydro-2,3-dioxo-4-pyridinecarboxylate with alpha,3,4-trichlorotoluene . The compound showed significant antifungal activity when challenged by a spectrum of pathogenic yeast species in a minimum inhibitory concentration test . It was active against some dermatophytic fungi and Aspergillus niger.

Gann, 1979 Apr, 70(2), 165 - 71
Effect of blood, ascites, and tumor cell density on cytocidal action of neocarzinostatin; Shimoyama M et al.; Cytocidal activity of Neocarzinostatin (NCS) was analyzed in vitro by using cultured and ascitic L1210 cells . NCS shows rapid and typical concentration-dependent cytocidal action against L1210 cells . The concentration required for 90% cell-kill (MLD90) and for all 10(6) cell-kill (MIC/10(6)) was 5 x 10(-2) and 4 x 10(-1) microgram/ml, respectively, when L1210/C cells were exposed to NCS at the concentration of 2 x 10(5)/ml in RPMI-1640 medium . When L1210/C cells at the concentration of 1.3 x 10(7)/ml were exposed to NCS, cytocidal activity of NCS decreased, and MLD90 and MIC/10(6) increased to 1.75 x 10(-1) microgram/ml (3.4x) and 2.83 microgram/ml (6.5x), respectively . Also, when a small fraction of whole BDF1 mouse blood, red blood cells, or spleen cells was present in the reaction mixture, cytocidal activity of NCS appeared to decrease . Furthermore, when washed hemorrhagic ascitic L1210 cell suspension was exposed to NCS, 100 times or more concentration of NCS was required for 90% cell-kill or all 10(6) cell-kill . The effect of plasma or serum on cytocidal activity of NCS was minimum . These results indicate that cytocidal activity of NCS is greatly inhibited through contact with tumor cells, blood cells, spleen cells, and/or hemorrhagic ascites . This may be one of the reasons why L1210 cells, which show high sensitivity against NCS in vitro, are less sensitive in vivo . In order to explain these findings, the possibility of inactivation of NCS by the cells or reduction of free active NCS molecules by the binding or adsorption with the cells is discussed . This characteristics in action of NCS should be take into account in clinical use.

Mutat Res, 1979 Mar, 66(3), 277 - 90
Chromosomal aberration tests on 29 chemicals combined with S9 mix in vitro; Matsuoka A et al.; A metabolic activation system with rat-liver microsome fraction plus cofactors (S9 mix) was applied to chromosomal aberration tests in vitro for the screening of chemical mutagens or carcinogens in the environment . Dialkylnitrosamines only induced chromosomal aberrations in Chinese hamster cells (CHL) when treated with S9 mix . The incidence of chromosomal aberrations in CHL varied with experimental conditions, e.g . incubation time, recovery time, components of S9 mic and inducers used for preparation of S9 . For dimethylnitrosamine (DMN), the maximal incidence was obtained when the cells were incubated with S9 mix for 3 h and harvested 24 h after treatment . Therefore, this system (3 h incubation and 24 h recovery) was routinely applied to further screening of other chemicals with S9 prepared from PCB-pretreated rats . 10 carcinogens (e.g . 7,12-dimethylbenz{a}anthracene, benzo{a}pyrene, quinoline, etc.) out of 16 induced aberrations when they were treated with S9 mix, whereas the remaining 6 carcinogens (e.g., 3-methyl-cholanthrene, 4-o-tolylazo-o-toluidine, etc.) induced few or no aberrations even after activation . Two insecticides, allethrin and diazinon, were strongly positive at relatively low doses only when they were activated with the S9 mix . Medical drugs, such as ethenzamide, methyl p-hydroxybenzoate and nitrofurazone, and a food additive, sodium hypochlorite, were positive on activation . Chemicals used for industry, such as styrene monomer and tris-dichloropropylphosphate, were also positive in our activation system.

Endocrinology, 1979 Feb, 104(2), 448 - 53
Gonadotropin-releasing hormone action in cultured pituicytes: independence of luteinizing hormone release and adenosine 3',5'-monophosphate production; Conn PM et al.; The secretory response of pituitary gonadotropes to stimulation by gonadotropin-releasing hormone (GnRH) has been extensively studied, but the mechanism by which GnRH evokes gonadotropin synthesis and release has not been clarified . In particular, there has been conflicting evidence about the role of cAMP in GnRH-induced release of LH . To examine this question in more detail, the actions of GnRH on LH release and cAMP production were analyzed in primary cultures of collagenase-dispersed rat pituitary cells . In this system, addition of 10(-10)--10(-6) M GnRh to cultured pituicytes caused rapid release of LH into the incubation medium . In contrast, GnRH caused no significant change in intracellular or extracellular cAMP or in occupancy by cAMP of the regulatory subunit of protein kinse . Neither dibutyryl cAMP nor methyl isobutylxanthine (MIC) stimulated LH production to the same level as GnRH, and neither agent potentiated the effect of the releasing hormone . Cholera toxin and prostaglandin E1 (PGE1), both of which stimulated cAMP production in cultured pituicytes, did not raise LH levels as markedly as GnRH . These results demonstrate the independence of LH release from cAMP accumulation in cultured pituicytes, suggesting that cAMP is not required for stimulation of LH release from these cells and that GnRH acts on LH secretion by a different mechanism.

Antibiotiki, 1979 Feb, 24(2), 97 - 9
{Development of an accelerated method of determining the antibiotic sensitivity of Cl . perfringens type A}; Zemlianitskaia EP et al.; An express method for determination of antibiotic sensitivity in the strains of Cl . perfringens of type A using Soviet dry nutrient media and antibiotics is proposed . The criteria for estimation of the level of the antibiotic sensitivity of the causative agent of gas gangrene in short periods on the basis of comparison of the data of the antibiotic agar diffusion procedure and the antibiotic MIC were worked out . Twelve antibiotics and 45 collection strains of Cl . perfringens of type A were used in the experiment . The antibiotic agar diffusion method with the use of the nutrient media, microbial load and cultivation conditions developed by the authors is recommended for tentative determination of the antibiotic sensitivity in Cl . perfringens of type A for 4 hours . The use of the agar diffusion method and determination of the antibiotic MIC provided complete estimation of tha antibiotic sensitivity of Cl . perfringens of type A within not more than 24 hours.

Am J Dis Child, 1979 Feb, 133(2), 187 - 91
Penicillin-insensitive pneumococci . Case report and review; Ahronheim GA et al.; Infections due to pneumococci with decreased susceptibility (or resistance) to penicillin have been infrequently recognized . Our experience and that of others suggest that (1) penicillin susceptibility testing of significant pneumococcal isolates should become routine; (2) penicillin may not be adequate therapy for CNS infections due to pneumococci whose penicillin minimal inhibitory concentration is greater than 0.1 microgram/ml; and (3) long-term penicillin "prophylaxis" may be inappropriate in the splenectomized patient in areas where these organisms are prevalent.

Vet Rec, 1979 Jan 27, 104(4), 73 - 4
Sensitivity in vitro to dimetridazole of treponemes associated with swine dysentery; Griffin RM; The minimum inhibitory concentration (MIC) of dimetridazole (DMZ) against Treponema hyodysenteriae (55 isolates) obtained over the period 1974-77 from individual pigs with swine dysentery from 41 herds where DMZ had been in use was determined . The MIC was less than or equal to 5.0 microgram per ml for 54 of the isolates and differences in the distribution of MICs between the annual sampling periods were not significant (P less than 0.05) . There was no decrease in sensitivity of T hyodysenteriae to DMZ during the survey.

Comput Programs Biomed, 1979 Jan, 9(1), 19 - 38
MIC-II - a program for the determination of cardiac output, arterio-venous shunt and regional blood flow using the radioactive microsphere method; Schosser R et al.; MIC-II is a versatile BASIC computer program designed to calculate the cardiac output, the arterio-venous shunt and the regional blood flow from data obtained by the radioactive microsphere method . The samples are measured in a gammaspectrometer with a multichannel pulse height analyzer and the data are recorded on tape . Up to 10 different nuclides may be used simultaneously, including tracers which are not bound to microspheres . The nuclides may have overlapping energy spectra . The analysis of the energy spectra is performed according to the matrix method . Standard samples, each containing one pure nuclide, are measured to obtained the overlap matrix . The unkown amounts of the nuclides in the samples are obtained by solving a system of simultaneous linear equations . Up to 100 organ samples may be taken in one experiment . Up to 10 different organ maps, containing a text label for each organ specimen, may be created, edited, modified and stored on tape for convenient identification of input and output . Numerous validity checks for imput and output make MIC-II easy to use, even for non-computer trained personel.

Arzneimittelforschung, 1979, 29(2a), 384 - 7
MIC determination, disc sensitivity testing, and analysis of regression in cefazedone and cefazolin; Dingeldein E et al.; Minimum inhibitory concentrations (MIC) of (6R,7R)-7-(2-{3,5-dichloro-4-oxo-1(4H)-pyridyl-a1-acetamido)-3-({(5-methyl-1,3,4-thiadiazol-2-yl)-thio}methyl)-8-oxo-5-thia-1-azabicyclo{4,2,0}oct-2-ene-2-carboxylic acid (cefazedone, Refosporen)), a new semisynthetic cephalosporin derivative were determined by a broth dilution technique . In comparison with cefazolin 130 gram-positive and gram-negative bacteria, recent clinical isolates, were tested . In parallel, inhibition zones for the same organisms were determined by a standardized disc technique using 30-micrograms discs . According to the calculated regression lines a good correlation was found for cefazedone and cefazolin between the MIC values and the diameters of the inhibition zones (correlation coefficients r = --0.90 and --0.92, respectively) . Taking into account the dosages recommended for cefazedone and the mean serum concentrations to which they give rise, appropriate categories of sensitivity (break points) for susceptibility testing are recommended.

Infection, 1979, 7(3), 129 - 45
{Tissue penetration of erythromycin (author's transl)}; Dette GA; Although erythromycin has been used in therapy for more than 25 years, until now there has been no paper summarizing the data on tissue penetration . The present review documents in detail dose- and time-related peak serum levels of erythromycin derivatives after oral administration, in addition to the erythromycin tissue levels . The erythromycin tissue levels often manifoldly exceed the corresponding MIC values of pathogens sensitive to erythromycin . However, erythromycin does not penetrate the central nervous system, or only penetrates in small, incalculable amounts . The same applies for the placental passage of erythromycin . The tissue levels confirm, with respect to the MIC values of the pathogen spectrum, clinical experience with erythromycin in the treatment of ear, nose and throat infections, respiratory tract infections and, with some limitations Chlamydia urethritis.

Chemotherapy, 1979, 25(5), 261 - 7
On the mechanism of the antimycobacterial activity of isoniazid + prothionamide + dapsone (Isoprodian); Urbanczik R; Increased antimycobacterial activity of Isoprodian (isoniazid + prothionamide + dapsone) may be due to (i) decreased mutation rate for INH resistance provoked in mycobacteria by DDS (in 2 of 3 strains tested); (ii) leakage of K+, Na+ or Ca++ caused by INH and/or by PTH (in all 3 strains tested), and (iii) indicating damages which may increase the low level penetration of DDS into the cell in sub-MIC concentrations as shown by phage proliferation changes (tested in 1 strain with 1 phage).

J Int Med Res, 1979, 7(1), 45 - 51
Amikacin concentration in the cerebrospinal fluid of children with acute bacterial meningitis; Trujillo H et al.; Penetration of the aminoglycoside, amikacin, into the cerebrospinal fluid (CSF) of twenty children with acute bacterial meningitis was studied at various times after intramuscular administration and at various stages of therapy . Six of the patients were evaluated during therapy with amikacin at 7.5 mg/kg (intramuscularly) every 12 hours plus ampicillin every 6 hours at 300 mg/kg/day (intravenously); thirteen of the remaining fourteen patients were treated with ampicillin alone, but were given a single intramuscular dose of 7.5 mg/kg of amikacin for evaluation of CSF concentration . Amikacin concentration in CSF with respect to time after administration followed essentially the same pattern as in serum . A minimum concentration of 2 microgram/ml was found in 76% of the CSF samples obtained between 0.5 and 7 hours after administration . A mean amikacin serum/CSF ratio of 3:1 was demonstrated up to 7 hours after dose in all patients who underwent clinical improvement . Patient response was predictable by a correlation of in vitro MIC values with in vivo CSF concentration in three of the six patients who received amikacin therapy.

Scan Electron Microsc, 1979, (3), 33 - 40
Correlation by scanning electron microscopy of in vitro and in vivo effects of amoxicillin and ampicillin on the morphology of Escherichia coli; Kramer MJ et al.; The effect of in vitro incubation with subinhibitory and inhibitory doses of amoxicillin or ampicillin on the morphology of E . coli 257 was evaluated by scanning electron microscopy (SEM) . No effect, with either penicillin was seen at 1/16 X MIC (0.39 microgram/ml) . Filament formation was the major effect seen with both agents at 1/8, 1/4 and 1/2 X MIC but only with ampicillin at the MIC (6.25 microgram/ml) . Cells incubated with amoxicillin at the MIC were primarily short rods with bulbous swellings . This morphological difference between the two antibiotics was dose-related since ampicillin, at 2 X MIC, also caused the formation of short rods with bulbous swellings . SEM examination of omentum from amoxicillin and ampicillin treated mice 2 h after infection with E . coli 257 indicated a correlation of morphological effects seen in vitro and in vivo with the respective antibiotics . For example, following a single subcutaneous treatment with amoxicillin and ampicillin at 250 mg/kg, the plasma concentrations 2 h later (the time of infection) were 8.2 and 7.7 microgram/ml respectively but short rods with bulbous swellings were seen in amoxicillin-treated mice whereas filaments were found in the ampicillin-treated mice.

Chemotherapy, 1979, 25(1), 48 - 53
In vitro susceptibility of pseudomonas to four beta-lactamantibiotics (ampicillin, cephalothin, carbenicillin, piperacillin), to four aminoglycosides (kanamycin, amikacin, gentamicin, tobramycin) and to colimycin; Hoogkamp-Korstanje JA et al.; Of 97 well-defined strains of Pseudomonas, isolated from sputum of patients with cystic fibrosis (CF), the minimum inhibitory concentration (MIC) of several antibiotics was determined with a broth dilution method . The majority of the strains were resistant to ampicillin and cephalothin, moderately susceptible to carbenicillin (70% to 100 microgram/ml) and highly susceptible to piperacillin (100% to 25 microgram/ml, 88% to 6.25 microgram and 60% to 3.12 microgram/ml) . If the pharmacological properties of piperacillin are comparable with those of carbenicillin, it can be expected that the sputum level of this drug will be adequate to treat Pseudomonas pulmonary infections . At the lowest concentration tested (0.78 microgram/ml) 3% of the strains were susceptible to kanamycin, 85,5% to amikacin, 95% to gentamicin, 98% of tobramycin, and 80% to colimycin . With regard to clinically attainable concentrations, 98.9% of the strains were susceptible to gentamicin and tobramycin 97.9% to amikacin, 96.9% to colimycin, 88.6% to piperacillin, 38% to carbenicillin, 25.7% to kanamycin, 12.3% to ampicillin, and 1% to cephalothin.

Dermatologica, 1979, 158(4), 249 - 56
Antibiotic sensitivity of gonococcal strains isolated from patients in Basel and environs; Fullhaas J et al.; During the first 4 months of 1977, 95 different strains of gonococcus were isolated in the out-patient department of the Dermatology Clinic of the University of Basel . These were systemically tested for sensitivity to penicillin G, spectinomycin, thiamphenicol, doxycycline and rifampicin . The MIC values and the diameter of the zones of inhibition were determined . Tests for beta-lactamase production were made . A correlation in the degree of sensitivity was observed between the following antibiotics: penicillin G/rifampicin; penicillin G/thiamphenicol; penicillin G/doxycycline; thiamphenicol/doxycycline; thiamphenicol/rifampicin; doxycycline/rifampicin . The size of the inoculum had little influence on the activity of the substances, except for that of penicillin G against the beta-lactamase-positive reference strains . No beta-lactamase-producing strains were detected amongst the clinical isolates . In the case of penicillin G, there was a correlation between the minimum inhibitory concentration and the inhibition-zone diameter.

Immun Infekt, 1978 Dec, 6(6), 244 - 8
{Comparison of regression line analysis for several antibiotics on different media (author's transl)}; Grimm H; The method for performing regression analysis is described in detail . MIC values and zone sizes are determined on agar throughout . Applying these techniques, good correlation between MIC's and zone sizes (r = greater than -0.9) were found with 82% of 59 regressions (33 different antibiotics) . Comparable results were found with DST- and Mueller-Hinton agar . In some cases a linear regression for MIC and zone size values could be demonstrated, independent from the correlation coefficient . Some theoretical aspects of regression analysis are discussed.

Tubercle, 1978 Dec, 59(4), 277 - 80
Activity of amikacin, erythromycin and doxycyline against Mycobacterium chelonei and Mycobacterium fortuitum; Garcia-Rodriguez JA et al.; The activity of amikacin, erythromycin and doxycycline was studied against 18 strains of M . fortuitum and 10 of M . chelonei . The agar dilution technique was used for the evaluation of the minimum inhibitory concentration . Between the three drugs tested, amikacin was the most active, since 66.6% of the M . fortuitum and 80% of M . chelonei strains were inhibited at 12.8 microgram/ml . It is possible that in some circumstances amikacin could be useful in the treatment of infections caused by M . fortuitum or M . chelonei.

Immun Infekt, 1978 Dec, 6(6), 240 - 3
{Relationship between MIC and Zone Size (author's transl)}; Krasemann C et al.; The one antibiotic-one disk agar diffusion test for susceptibility testing of clinical isolates, though technically similar to that used for determining antibiotic concentrations in body fluids, lacks the exactness of the latter . In correlating zone diameters to MICs, stochastic linearity should be evaluated besides the regression lines and the correlation coefficient.

Mycopathologia, 1978 Nov 10, 64(3), 147 - 51
Determination of the minimal inhibitory concentration of amphotericin B and miconazole for 21 strains of Aspergillus; Martinez J et al.; The susceptibility of 21 strains of Aspergillus (11 of A . fumigatus, 8 of A, niger, and 2 of A . flavus) isolated from human pathologic specimens to Amphotericin B and Miconazole has been comparatively studied . Determination of the minimal inhibitory concentration of both drugs in a liquid medium showed a noticeably variability for the different strains . The values obtained for Amphotericin B varied between 0.25 microgram/ml (2 strains) and 1.25 microgram/ml (5 strains) after 48 hours, and between 1,25 microgram/ml (1 strain) and 50 microgram/ml (1 strain) after 10 days . For Miconazole the results varied between 0.1 microgram/ml (1 strain) and 25 microgram/ml (1 strain) after 48 hours of incubation, and between 0.5 microgram/ml (5 strains) and greater than 100 microgram/ml after 10 days . The variability of these results indicates the usefulness of carrying our in vitro sensitivity studies whenever it is possible.

Can Med Assoc J, 1978 Nov 4, 119(9), 1044 - 6
Pneumococci resistant to erythromycin; Dixon JM et al.; Susceptibility to erythromycin was determined for all pneumococci isolated in one laboratory from clinical specimens between 1969 and 1977 . All 4724 isolates examined prior to October 1973 were susceptible to erythromycin . From October 1973 to December 1977, 64 (0.71%) of 8995 pneumococcus isolates were resistant to erythromycin . The resistant strains were isolated from 38 patients living in six widely separated communities in Alberta . The erythromycin-resistant strains were of nine capsular types, including six that often cause bacteremic disease and five for which resistance to erythromycin has not been reported hitherto . Certain strains of type 33 and of type 15 were highly resistant, the minimum inhibitory concentration (MIC) of erythromycin being 2000 microgram/mL; these strains were also highly resistant to lincomycin and clindamycin . Resistance in strains of other types was much lower, the MIC of erythromycin being 0.6 to 20 microgram/mL, and all but one of these strains were susceptible to lincomycin and clindamycin . All the erythromycin-resistant pneumococci were suspectible to penicillin.

Antibiotiki, 1978 Nov, 23(11), 1027 - 30
{Pharmacokinetic characteristics and the effectiveness of using carbenicillin on newborn premature infants with infectious and inflammatory diseases}; Vlasova IN et al.; The results of the study on the pharmacokinetics peculiar properties of carbenicillin premature infants treated with the drug administered intravenously or intramuscularly are presented . The maximum antibiotic blood levels after intravenous administration exceeded the MIC for most of the causative agents isolated from the children . The schemes for the antibiotic use in treatment of purulent septic processes of children are recommended.

J Infect Dis, 1978 Nov, 138(5), 681 - 5
In vitro studies of amphotericin B in combination with the imidazole antifungal compounds clotrimazole and miconazole; Cosgrove RF et al.; The clinically important polyene antibiotic amphotericin B, in combination with two antifungal imidazole compounds, clotrimazole and miconazole, was studied in vitro . With use of results of cytoplasmic leakage, metabolic heat output, and minimal inhibitory concentration studies, a definite antagonistic response was demonstrated . It is suggested that, if combined antifungal drug therapy is clinically indicated, the drug combination be tested against the isolate by the simple technique of measuring cytoplasmic leakage or by the more elaborate method of flow microcalorimetry.

Exp Hematol, 1978 Nov, 6(10), 791 - 800
Experimental hypoplastic marrow failure in the mouse; Kubota K et al.; In order to study the pathogenesis of aplastic anemia in man, hemopoietic stem cells were investigated in 'aplastic mice' the aplasia being induced by the immunological method . C3H/He (H-2k, Mlsc) received 600 rad whole body x-irradiation followed by the transplantation of 10(7) lymph node cells prepared from B10.BR mic e (H-2k, Mlsb) . The C3H/He mice developed pancytopenia and marrow hypoplasia 21 days after these treatments . The total number of nucleated cells, CFU-S and CFU-C in the marrow and the wet weight and CFU-C of the spleen were markedly reduced . These findings are consistent with those of aplastic anemia in man and the model may provide a useful tool for the investigation of the pathogenesis of this anemia . Control mice that received irradiation only recovered from the damage 21 days later, while control mice that receive lymph node cells only showed no hematological changes.

Zentralbl Bakteriol {Orig A}, 1978 Oct, 241(4), 488 - 98
{Analysis of penicillin and ampicillin resistance in bacteria i . resistance and beta-lactamase production in clinical isolates (author's transl)}; Foldes J et al.; The penicillin beta-lactamase (PBL) activity of the clinical isolates was measured at the same time by colorimetric microtitration, the iodometric method and chromatographic analysis . The minimal inhibitory concentration (MIC) of ampicillin (Ap) was determined for each isolate, the character of the coupled resistances, their frequency and distribution in the PBL producing and PBL-negative strains were also investigated . It was found that 1 . the MIC value was 100 microgram/ml in 87.5 per cent of the Penicillin (P) and Ap resistant clinical isolates, 2 . PBL was produced by 55--75 per cent of the P and Ap resistant strains depending on the species of the bacteria, 3 . less than 50 per cent of the E . coli isolates produced PBL; in the case of other species this value was higher, about 65--70 per cent, 4 . resistance to Su, SM, Tc, Nm and Cm was most frequently coupled to Ap and P resistance, 5 . the distribution curve representing the number of the coupled resistance to the Ap and P shows a peak with 6 coupled antibiotics in the PBL-negative strains and 2 peaks in the PBL-producing strains.

Nouv Presse Med, 1978 Sep 23, 7(32), 2831 - 6
{Pharmacokinetic study of antibiotics in human respiratory tract (author's transl)}; Bergogne-Berezin E et al.; We report the results of the study of the bronchial concentrations of several antibiotics . The experiment included 280 patients and the concentrations achieved in bronchial secretions were measured for 11 antibiotics . The samples of bronchial secretions were taken in situ by fibroscopy or through the tracheostomy cannula . The results of the study show that the rate of penetration is variable according to the different drugs; even in the same antibiotic family such as beta-lactam antibiotics the rate of penetration is variable . The bronchial levels of aminoglycosides, macrolides and tetracyclines are worthwhile, and are often superior to the MIC of the infecting organisms; the penetration is also dependant of the inflammatory conditions of the bronchi . Otherwise the sampling conditions were the best possible since samples taken by fibroscopy or by tracheostomy are not contaminated by saliva which is a factor of dilutional error . The methodology used in this study is an approach of pharmacokinetics of antibiotics in respiratory tract.

Minerva Med, 1978 Sep 19, 69(43), 2951 - 62
{Pharmacokinetic and clinical research on a new aminoglycoside antibiotic: sisomicin}; Di Nola F et al.; Results obtained with sisomycin in 10 cases of purulent meningitis and 4 of bronchopulmonitis showed good tissue diffusion, together with CSF concentrations sufficient to inhibit the main aetiological agents in these forms: MIC 0.02 mg/ml for both D . pneumoniae (I-ATCC 6301) and N . meningitidis (C-ATCC 13101), i.e . liquor transfer of the antibiotic more than sufficient to handle these agents.

J Clin Pathol, 1978 Sep, 31(9), 855 - 8
Use of sensitivity discs as primary antibiotic standards in MIC determination; Flowers DJ; A method for the determination of minimum inhibitory concentration (MICs) is described, in which commercially prepared antibiotic sensitivity testing discs are used as primary antibiotic standards from which the necessary dilutions are prepared in WHO Perspex haemagglutination plates . The materials required are readily available in most laboratories at a cost in time and reagents that compares favourably with most traditional methods of MIC testing . The same techniques may also be used to demonstrate combined antibiotic activity and to differentiate between bacteriostatic and bactericidal activity, with little expenditure of laboratory resources.

Neurosurgery, 1978 Sep-Oct, 3(2), 146 - 50
Shunt-associated glomerulonephritis; Wald SL et al.; Six patients with glomerulonephritis in association with a ventriculovascular shunt were treated with three basic modes of therapy . Direct intraventricular instillation of antibiotic was used on seven occasions in five patients either as the definitive mode of therapy or as an adjunct to shunt removal . Ventricular fluid antibiotic concentrations were monitored in two patients and demonstrate that effective levels as compared to the specific minimal inhibitory concentration can only be achieved by this method . With resolution of the shunt infection, improvement in the clinical and laboratory parameters of renal function was noted . A recommended treatment protocol is outlined, including specific dosages for intraventricular antibiotics . The need for detailed and frequent post-treatment examination including serum immunoglobulin profile is stressed.

Am J Ophthalmol, 1978 Sep, 86(3), 359 - 67
In vitro antibiotic synergism against ocular fungal isolates; Stern GA; A microtiter method for the determination of fungal sensitivities was used to determine the minimal inhibitory and fungicidal concentrations of two antifungal agents, amphotericin B and natamycin, both alone and in combination with four different antibiotics: rifampin, gentamicin, clindamycin, and tetracycline . Synergism was defined as a fourfold or greater reduction in the minimal inhibitory concentration, minimal fungicidal concentration, or both, of the antifungal agent in the presence of antibiotic; antagonism was defined as fourfold or greater increase in the minimal inhibitory concentration, minimal fungicidal concentration, or both . Amphotericin B and rifampin were synergistic against the majority of organisms, but synergism between amphotericin B and other antibiotics was infrequent . Combinations of natamycin and rifampin or of natamycin and gentamicin were synergistic against the majority of Fusarium solani tested . Combinations of amphotericin B and tetracycline were antagonistic against 14% of the organisms.

Tubercle, 1978 Sep, 59(3), 185 - 91
Comparison of various measures of sensitivity of M . tuberculosis to ethambutol; Subbammal S et al.; A sensitivity test for ethambutol was standardised, and performed on cultures isolated from patients before and after the start of chemotherapy with ethambutol and isoniazid . A discrimination type of approach was employed and three criteria of resistance were evolved: (a) growth of 20 colonies or more on ethambutol 4 microgram/ml, using a standard inoculum; (b) a proportion of 25% or more on ethambutol 1.4 microgram/ml; (c) a proportion of 5% or more on ethambutol 2 microgram/ml . The MIC definition appears to be the best in view of its simplicity and insensitivity of the classification (as sensitive or resistant) to variations in inoculum size.

J Clin Pharmacol, 1978 Aug-Sep, 18(8-9), 432 - 8
Serum concentrations and inhibitory ratios during amikacin therapy of gram-negative infections; Farchione LA et al.; The ratio of the peak serum concentration after a 500-mg dose of amikacin to the pathogen minimum inhibitory concentration was determined for 95 patients under treatment for serious Gram-negative infections . There were 113 such ratios . The relationship of this inhibitory ratio to the clinical effectiveness and side effects of treatment with this new aminoglycoside was also studied . Mean peak serum concentration of drug was 25.8 microgram/ml, and mean inhibitory ratio was 13.0 . Ninety-six per cent of inhibitory ratios were greater than or equal to 1.0 . Therapy was rated totally effective in 85% of patients clinically evaluated and partially effective in 3% . Signs of renal or eighth cranial nerve impairment attributable to drug administration were confined to only two patients, and there were no other side effects . The reliability of amikacin therapy appears to be related to dependable serum levels and high inhibitory ratios.

Ann Surg, 1978 Aug, 188(2), 202 - 8
Antibiotic concentration in human wound fluid after intravenous administration; Bagley DH et al.; Since the wound is the most common focus of infection in the surgical patient, adequate levels of antibiotic within the wound ar essential . This study examines the concentrations of antibiotic achieved in human wounds . Fluid was collected at timed intervals on the first postoperative day from the wounds of 56 patients receiving antibiotics after regional lymph node dissection . Antibiotic concentration was determined by bioassay . Six antibiotics were studied: cephalothin, cefazolin, cephapirin, oxacillin, ampicillin and clindamycin . The cephalosporins and penicillins showed similar patterns of appearance in the wound fluid . The peak level occurred early (1--1 1/2 hours) with subsequent slow decrease . Clindamycin produced nearly constant levels in wound fluid . The concentration of each antibiotic in wound fluid surpassed the serum levels after 2.5 hours . At the dosages studied each antibiotic produced wound fluid concentrations greater than the MIC for most susceptible organisms . Higher doses provided higher wound fluid levels . The rate of appearance and the levels achieved should be considered in the choice of antibiotics in the surgical subject.

Antibiotiki, 1978 Aug, 23(8), 751 - 6
{Pharmacokinetics of ampicillin in peritonitis in children}; Komissarov IA; Ampicillin levels in the blood serum and abdominal cavity biosubstrates of children with appendicular peritonitis were studied . The antibiotic was administered as intravenous jet infusion in single doses of 12--15 and 25--30 mg/kg and drop infusion continuously for 24 hour in doses of 150 and 250--300 mg/kg . Administration of the drug as intravenous jet infusion provided therapeutical ampicillin levels in the appendix tissue and abdominal cavity exudate . Administration of increased doses of the drug resulted in its higher biosubstrate levels . It was found that the level of the appendix destruction had a significant effect on the antibiotic level in this organ . In cases with gangrenous appendititis the ampicillin levels were 1.5--2.2 times lower than those in cases with catarrhal appendititis . The studies on the effect of the infusion therapy on ampicillin pharmacokinetics showed that the volume of the liquids administered intravenously had no significant influence on the antibiotic circulation in the blood . A continuous drop infusion provided high and stable ampicillin levels in the blood serum which significantly exceeded the antibiotic MIC . During the post-operative period the antibiotic levels in the blood serum after intraperitoneal administration were determined . The data showed that ampicillin administered intravenously 2--3 days after the operation was absorbed into the blood in insignificant amounts.

Antibiotiki, 1978 Aug, 23(8), 710 - 4
{Sensitivity of the causative agent of tularemia to antibiotics}; Kudelina RI; Sensitivity of the tularemia causative agent of different geographical races to antibiotics such as streptomycin, tetracycline, gentamicin, rifampicin (20 strains), ampicillin, polymyxin M, erythromycin, oleandomycin (361 strains) and lincomycin (294 strains) was studied . High sensitivity of the tularemi a microbe to streptomycin, tetracycline, rifampicin (MIC of 10 gamma/ml), gentamicin (MIC of 1 gamma/ml) and resistance to 50 gamma of ampicillin and 1000 gamma/ml of polymyxin M were found . Combined use of 50 gamma of ampicillin and 100 gamma/ml of polymyxin M added to the nutrient medium for growth inhibition of the foreign flora on isolation of the tularemia causative agent from the infected material including stable laboratory animal carcases was recommended . Marked differences in sensitivity of the strains of different geographical races to the macrolides and lincomycin were observed . The strains of the non-Arctic and Central Asiatic races were of low resistance to the above drugs (the MIC of erythromycin, oleandomycin and lincomycin were 10--50, 50--400 and 25--100 gamma/ml respectively . Within the holarctic race 40 per cent were low resistant and 60 per cent were highly resistant to these drugs . The above drugs should not be used for treatment of tularemia cases.

J Antibiot (Tokyo), 1978 Jun, 31(6), 539 - 45
Rapamycin (AY-22,989), a new antifungal antibiotic . III . In vitro and in vivo evaluation; Baker H et al.; The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished . The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold . Serum binding was extensive . Serum levels obtained in mice were higher on subcutaneous injection than with oral administration . Dogs absorbed rapamycin after oral administration . Rapamycin cured systemic candidosis in mice: PD50 s.c . was 9.5 mg/kg: PD50 p.o . was 11 mg/kg . In the same experimental infections amphotericin B and nystatin exhibited PD50 values of less than 0.25 mg and greater than 4,000 units/kg respectively . Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation . When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period . Vaginal candidosis in female rats was treated efficiently (91% cure) by rapamycin administered orally . No increase of resistance of C . albicans was observed during treatment.

Can J Microbiol, 1978 May, 24(5), 574 - 8
Visual micromethod for assay of fungal growth; Kerbs S et al.; A visual micromethod for measuring antifungal effects on germination and growth is described . The antifungal agent griseofulvin and the fungus Trichophyton mentagrophytes were used as materials to compare the micromethod with a standard assay based on dry mycelial weight . The micromethod was more sensitive than the weight method in detecting the minimum inhibitory concentration of griseofulvin (0.18 and 35 microgram/ml, respectively) . At higher concentrations of griseofulvin (22.5 microgram/ml), the micromethod measured minimal fungal growth that was undetectable on a weight basis . The micromethod showed that griseofulvin does not change the number of spores forming germ tubes . Progressively severe alterations in fungal morphology occured as the concentration of griseofulvin was increased from 0.09 to 22.5 microgram/ml.

J Pharm Sci, 1978 May, 67(5), 721 - 2
Chemical constituents of Gentianaceae XXIV: Anti-Mycobacterium tuberculosis activity of naturally occurring xanthones and synthetic analogs; Ghosal S et al.; Anti-Mycobacterium tuberculosis H37 RV data are presented for the individual xanthones of Canscora decussata Schult and Swertia purpurascens Wall (Gentianaceae); a few, from the former species, showed significant activity . Additionally, sturcture--activity relationships of these compounds are evaluated on the basis of the minimum inhibitory concentration data of 18 naturally occurring xanthones bearing 1,3,5- 1,3,5,6-, 1,3,6,7-, 1,3,5,8-, 1,3,5,6,7-, and 1,3.6,7,8-oxygenated patterns and six synthetic analogs.

Ann Microbiol (Paris), 1978 May-Jun, 129(4), 473 - 502
{Results of two methods for testing bacterial susceptibility to antibiotics: disk method and a new semi-automatic method in liquid medium (ABACR procedure) and comparison with the minimal inhibitory concentration (author's transl)}; Veron M et al.; A performance analysis was established between three methods for testing of bacterial susceptibility to sixteen antibiotics: agar dilution or minimal inhibitory concentration (MIC) method, agar diffusion or DISK method, and semi-automatic dilution in liquid medium or ABACR method . Precision of the three methods was determined using three reference strains in repetition experiments (9 repetitions for MIC, 60 repetitions for both DISK and ABAC) . The results show that MIC method was the most precise, and that the precision of DISK and ABAC methods was not sifnificantly different . Fidelity of both DISK and ABAC methods was compared in taking as reference the MIC of 200 wild strains of Gram-negative bacteria . Omitting the data concerning trimethoprim-sulfamethozoaxol, the results were found concordant between DISK and MIC methods in 68.6 percent of the cases, between ABAC and MIC methods in 73.6 percent, and between ABAC and DISK methods in 68.9 percent . With regard to MIC, ABAC method gave results slightly better than those of DISK method, especially for five antibiotics: gentamicin, minocyclin, doxycylin, chloramphenicol and polymyxin B . So, the ABAC method looks very interesting for a semi-automatic routine method in testing bacterial susceptibility to antibiotics.

Clin Pharmacol Ther, 1978 Apr, 23(4), 473 - 80
Cefamandole kinetics during cardiopulmonary bypass; Polk RE et al.; The kinetics of cefamandole during cardiac surgery was studied in 16 adult patients given a single intravenous infusion of 20 mg/kg at the time of anesthesia induction . Five normal volunteers who received the same dose served as controls . Cardiopulmonary bypass (CPB) was found to signficantly increase the half-life (t 1/2) of cefamandole . The mean t 1/2 during CPB (113.2 min) was longer than the terminal t 1/2 in normal volunteers (52.0 min; p less than 0.005) . Throughout CPB (maximum, 3,7 hr), cefamandole plasma levels were maintained above the minimum inhibitory concentration for those organisms most likely to cause postoperative infections . We conclude that if 20 mg/kg of cefamandole is given within an hour of the beginning of cardiovascular surgery, a supplemental dose is not needed until the patient has been on CPB for at least four hours.

Br J Vener Dis, 1978 Apr, 54(2), 77 - 80
Secnidazole . A 5-nitroimidazole derivative with a long half-life; Videau D et al.; The therapeutic activity of a single 2 g dose of secnidazole was studied in patients with urogenital trichomoniasis . In 140 patients, 97% were cured and the drug was well tolerated . In the laboratory, tests on sensitivity were made and the minimal inhibitory concentration (MIC) and the minimal trichomonacidal concentration (MTC) were determined on cultures that had recently been isolated at the clinic, and the pharmacokinetic properties of secnidazole in man were compared with those of tinidazole . The therapeutic efficacy of all the metronidazole derivatives was reviewed and a single-dose treatment is recommended . Therapeutic and prophylactic treatment is achieved by products with a long half-life . Secnidazole, with a half-life of 14.3 +/- 1.3 h (women) and 20.2 +/- 3.1 h (men), is particularly suitable for this type of treatment.

J Infect Dis, 1978 Feb, 137(2), 122 - 30
A method for testing for synergy with any number of agents; Berenbaum MC; The standard checkerboard titration for detecting synergy between antibiotics is practicable for combinations of two antibiotics, laborious for combinations of three, and not feasible for combinations of four or more . Nevertheless, methods for testing of combinations of several antibiotics are urgently needed because some combinations might be superior to those in use and enable the successful treatment of infections resistant to current therapy . A simple method for measurement of synergy (or antagonism) with combinations of any number of agents has been developed which requires less effort than the standard checkerboard titration of two agents . With this method, the concentrations of each of n agents producing some specified effect (such as minimal inhibitory concentration or minimal bactericidal concentration) are determined . A reference combination made up of 1/n of each of these concentrations is titrated to find a dilution that produces the specified effect . The degree of dilution required is equal to the sum of the fractional inhibitory concentrations (concentration of each agent in combination/concentration of each agent alone) as conventionally determined by checkerboard titrations; sums of less than 1, 1, and greater than 1 indicate synergy, additivity, and antagonism, respectively.

Antibiotiki, 1978 Feb, 23(2), 118 - 22
{Development of a method for the quantitative evaluation of microorganism sensitivity to antibiotics utilizing disks . The determination of the minimal doxycycline concentration that depresses microorganism growth using disks containing this antibiotic}; Chaikovskaia SM et al.; A quantitative method for estimation of microbial sensitivity to doxycycline with the use of discs containing 10 gamma of the antibiotic was developed . The antibiotic concentrations in the agar were determined at a distance equal to the radius of the growth inhibition zone with the help of a curve of the dependence of the logarithm of the doxycycline concentration in agar at the period of the average critical time of the zone formation equal to 5 hours and the distance from the disc center . The antibiotic concentration in the agar at the zone edges was almost the same as the MIC of doxycycline against the test-cultures determined with the method of serial dilutions in agar.

Biochim Biophys Acta, 1978 Jan 4, 506(1), 119 - 35
Galactose transport in human erythrocytes . The transport mechanism is resolved into two simple asymmetric antiparallel carriers; Ginsburg H; The kinetic properties of the mediated transport of galactose in human erythrocytes are investigated at 20 degrees C . Different methodological procedures are used to acquire a complete kinetic description of the system . Under zero-trans conditions the uptake of galactose is mediated by two distinctly different carriers (defined as alpha and beta) having significantly different Mic;aelis parameters: alpha K = 12.7 mM and beta K = 81.5 mM, but similar maximal velocities, approx . 40 nM.min-1 . The zero-trans efflux procedure reveals apparently one single carrier with K = 74.4 mM and V = 241 mM.min-1 . Under equilibrium-exchange conditions the galactose transport is mediated apparently by a single site with K = 146 mM and V = 521 mM.min-1 . The data for the alpha-carrier are analyzed in terms of the simple carrier model as formulated by Lieb and Stein (Biochim . Biophys . Acta (1974) 373, 178) . Application of several rejection criteria for the simple carrier failed to indicate lack of fitness of the alpha-carrier to a simple asymmetric carrier . From the analysis of the kinetic data it is inferred that the transport of galactose across the human erythrocyte membrane is mediated by two simple asymmetric carriers operating in antiparallel fashion . Using this model and the data of zero-trans and equilibrium-exchange, it is shown that the predicted half-saturation constants for both uptake and efflux in infinite-cis conditions fully agree with the experimentally derived values . Further analysis of the kinetic data indicate that the translocation of the unloaded alpha-carrier is the rate-limiting step in galactose uptake . Under equilibrium-exchange conditions the unloaded carrier is asymmetrically distributed across the membrane so that its concentration is 8 times higher on the inner side of the membrane . Using the value of 3.3.10(5) hexose carriers per cell, the turnover number of galactose exchange is 6.5.10(4) molecules/carriers per min.

Chemotherapy, 1978, 24(6), 364 - 7
In vitro comparison of the antifungal activities of R34,000, miconazole and amphotericin B; Dixon DM et al.; In vitro susceptibilities of 78 isolates of pathogenic filamentous fungi to the imidazole compounds R34,000 and miconazole and to amphotericin B were determined using an agar dilution technique . Allescheria boydii, Sporothrix schenckii and the dematiaceous fungi (Cladosporium, Fonsecaea and Phialophora spp.) were most susceptible to miconazole with minimum inhibitory concentration (MIC) values ranging from less than or equal to 0.25 to 32 microgram/ml and with geometric mean MIC (G-MIC) values of 0.56-1.24 microgram/ml . Isolates of Aspergillus fumigatus were more susceptible to amphotericin B and miconazole than to R34,000 with G-MIC values of 1.20 and 3.48 microgram/ml, respectively . Coccidioides immitis, Histoplasma capsulatum and Blastomyces dermatitidis were highly susceptible to all three drugs (G-MICs greater than 1 microgram/ml); R34,000 was the most active of the three compounds against C . immitis (G-MIC = 0.44 microgram/ml).

J Immunol Methods, 1978, 22(1-2), 123 - 9
Monolayer immune complex (MIC) fractionation of Fc receptor bearing human spontaneous killer cells; Targan S et al.; A simple high recovery method is described for depletion and enrichment of Fc receptor bearing human spontaneous killer cells . The technique is called monolayer immune complex (MIC) fractionation and is based on the fact that Fc receptor positive cells will bind to immune complexes bound to plastic surface and that bound cells can be partially recovered by protein A elution.

Childs Brain, 1978, 4(2), 74 - 82
Cerebrospinal fluid antibiotic concentrations in ventricular shunt infections; Wilson HD et al.; The concentration of antibiotic in cerebrospinal fluid was measured during treatment of seven children with infected ventricular shunts . Antibiotics were administered via the ventricular shunt or through an external ventricular drain . 53 CSF samples were obtained 7-19 h after antibiotic administration . Wide variation in cerebrospinal fluid antibiotic concentration occurred from patient to patient following either route of administration . For optimal management of shunt infections, we recommend periodic assessment of antibiotic concentration or activity in ventricular fluid and determination of the minimum inhibitory concentration of antibiotic required for each pathogen.

Mayo Clin Proc, 1978 Jan, 53(1), 49 - 53
Cardiobacterium hominis endocarditis . Four cases with clinical and laboratory observations; Geraci JE et al.; The clinical and microbiologic features of Cardiobacterium hominis endocarditis in four patients seen at the Mayo Clinic from 1971 through 1976 are described . All four were men ranging in age from 39 to 60 years . The precipitating factor in three was a dental procedure, and the illness was a prolonged, chronic one, with symptoms having been present 10 to 18 months before diagnosis . The other patient had a late prosthetic valve endocarditis and had had symptoms for only 3 months . Three patients were cured; the fourth died after 32 days of adequate therapy and what was considered a bacteriologic cure . Because of the pronounced fastidiousness of these bacteria, in vitro susceptibility tests could be done in only two of the four; the minimum inhibitory concentration for penicillin G was 0.07 microgram/ml in both . The therapeutic regimens were penicillin G plus streptomycin in the first case, predominantly penicillin G alone in the second, penicillin G for 2 weeks in the third, and ampicillin for 4 weeks in the fourth (prosthetic valve case) in addition to valve replacement . Clinical and laboratory experiences in the total reported cases lead us to believe that 3 weeks of therapy with penicillin G or ampicillin alone is adequate therapy for C . hominis endocarditis of natural valves.

Arzneimittelforschung, 1978, 28(5), 735 - 8
{In vitro investigations of rifampicin . Correlation between minimal inhibitory concentration and minimal inhibitory zone}; Grimm H; Regression analyses demonstrated a good correlation between the minimum inhibitory concentrations of rifampicin determined by the agar dilution method in Mueller-Hinton or Iso-Sensitest agar and the diameters of the inhibition zones produced by the antibiotic in the agar diffusion test on the same two media . The inhibition zone diameters produced in cultures of gram-positive bacteria most of which are highly sensitive to rifampicin (MIC less than 0.125 microgram/ml), are greater than 32 mm . Clearly discernible zones of inhibition ranging from 9 to 24 mm in diameter are, however, also found with gram-negative bacteria, which are less sensitive to the drug (MIC 4--32 microgram/ml . The simple agar diffusion method consequently provides a reliable indication of the sensitivity of bacteria to rifampicin.

Arzneimittelforschung, 1978, 28(1), 87 - 90
{Tissue levels in human tonsils (tonsillae palatinae) following administration of different antibiotics (penicillin G, ampicillin, lincomycin)}; Gabka J et al.; For determination of tissue levels of different antibiotics in human tonsils penicillin G, ampicillin or lincomycin is given i.v . to patients before tonsillectomy . The concentration of the individual substances is determined in tonsils and serum by agar diffusion method . The results are compared by diagrams of tissue and serum levels and statistically assessed . For therapeutic evaluation the absolute tissue levels at tonsillectomy are compared to the values of minimum inhibitory concentration (MIC) for most frequent germs in the stomato-maxillo-facial region . According to these results recommendations for antibiotic therapy of inflammatory processes of buccal cavity are given.

Zentralbl Bakteriol {Orig A}, 1978, 242(3), 375 - 86
{In-vitro-effect of constant and varying concentrations of beta-lactam-antibiotics on bacteria . I . Quantitative studies on the kinetics of bactericidal effects (author's transl)}; Neussel H; On the basis of a continuous culture method using the Biostat apparatus (Braun Melsungen) during a six hours interval the kinetics of growth inhibition and killing of E . coli were studied under the influence of varying concentrations of carbenicillin and cephalotin . The bacteria were incubated with the antibiotic at 37 degrees C, either in the broth of the culture vessel or incorporated into the depth of the agar of a dip slide which was brought into the uninoculated broth . Constant inhibitory concentrations (1 X MIC-4 X MIC) caused a bactericidal effect with both antibiotics . The recovery of the bacteria from the toxic effects of carbenicillin and cephalotin was slow if the concentrations were decreased to subinhibitory concentrations after initial contact with inhibitory peak levels . Scanning electron microscope studies demonstrated with both antibiotics a rapid filament formation with partial lysis.

Scand J Infect Dis Suppl, 1978, (14), 274 - 8
Concentrations of ampicillin in pleural fluid and serum after single and repetitive doses of bacampicillin; Bronsveld W et al.; In patients with pleural effusions due to malignant disease, estimations of ampicillin were made on simultaneously obtained samples of blood and pleural fluid: (1) from patients (n=11) after the administration of a single dose of 400 mg of bacampicillin, and (2) from patients undergoing treatment with 800 mg of bacampicillin twice daily (a) during the 12 hours after the first dose (n=10) and (b) during the 7 hours after the third dose (n=9) . Bacampicillin gave concentrations in the pleural fluid well above the MIC of common pathogens including H . influenzae . Mean peak levels were 1.2 microgram/ml after the 400 mg dose and 3.8 microgram/ml after the first and third doses of 800 mg . The peak appeared later in the pleural fluid in comparison with serum peak levels . The elimination half life was considerably longer in the pleural fluid.






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