Interaction of Vibrio cholerae cells with beta-lactam antibiotics: emergence of resistant cells at a high frequency. Unlike other gram-negative enteric bacteria, Vibrio cholerae cells were equally susceptible to penicillin and ampicillin and in general more susceptible than Escherichia coli to most of the beta-lactam antibiotics. The turbidity of penicillin-treated cultures contained to increase exponentially for about 3 h, although the cell viability declined rapidly within 30 min of penicillin addition. Prolonged treatment with beta-lactam antibiotics produced cells resistant to these antibiotics. A fluctuation test indicated that this resistance might be due to adaptive mutation. Cells resistant to a beta-lactam exhibited broad cross-resistance to other beta-lactam antibiotics. A new 12,000-Da outer membrane protein was detected both in beta-lactam-resistant cells and in wild-type cells growing in medium containing beta-lactam antibiotics. While the penicillin-resistant cells had all of the penicillin-binding proteins (PBPs) present in the parental cells, significant differences in the relative proportion of low-molecular-weight PBPs were seen. The low-molecular-weight PBPs from resistant cells seemed to form more stable complexes with penicillin than those from the parental strain.


Imipenem versus gentamicin combined with either cefuroxime or cephalothin as initial therapy for febrile neutropenic patients. A prospective randomized study was conducted to determine the efficacy of imipenem-cilastatin (hereafter referred to as imipenem) (500 mg four times daily) versus combination therapy for febrile neutropenic patients receiving either no prophylaxis or ciprofloxacin for prevention of infections. Combination therapy consisted of gentamicin (80 mg every 8 h) plus either cefuroxime (1,500 mg every 8 h) or cephalothin (1,000 mg every 4 h) for suspected catheter-related infections. Ninety-four neutropenic fever episodes in 87 patients were evaluable for efficacy. The overall clinical rate of response to imipenem was significantly higher than that to combination therapy (91 versus 74%; P = 0.05). The difference in efficacy was most pronounced in patients with microbiologically documented infections (89 versus 53%; P = 0.025), which were predominantly caused by gram-positive bacteria. Differences in susceptibility may have caused the better rate of response to imipenem. Two of 29 gram-positive bacteria were imipenem resistant, whereas 10 were resistant to cephalothin and cefuroxime and 12 were resistant to gentamicin. No causative gram-negative bacterium and 24 gram-positive bacteria were isolated in 61 fever episodes with ciprofloxacin prophylaxis (oral). In contrast, nine causative gram-negative and five gram-positive bacteria were isolated in 33 episodes without prophylaxis. The difference in distribution proved to be statistically significant for gram-negative (P = 0.0001) as well as gram-positive (P = 0.025) bacteria, indicating that ciprofloxacin effectively prevented the occurrence of gram-negative bacteria and may have contributed to the relatively large number of gram-positive bacteria isolated. Empirical initial therapy with imipenem may be a valuable alternative to combination therapy for neutropenic fever episodes.


Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine. 3'-Fluoro-3'-deoxythymidine (FLT), a candidate anti-AIDS compound in clinical trials, showed anti-human immunodeficiency virus type 1 (HIV-1) potency (50% effective concentration, 0.0052 microM) slightly better than or equal to that of 3'-azido-3'-deoxythymidine (AZT) in MT4 cells and was threefold more potent in H9 cells. There was no FLT resistance demonstrable in the AZT-resistant HIV-1 strains. Both FLT and AZT showed low cytotoxicity for MT4 cells, with selectivity indices (efficacy/toxicity ratio) of greater than 47,000 and greater than 33,000, respectively. Cellular permeation of FLT and thymidine (dThd) was greater than that of AZT, and FLT and dThd permeated the cell membranes by a carrier-mediated mechanism as well as by simple diffusion, as indicated by the existence of nitrobenzylthioinosine-5'-monophosphate-sensitive and -insensitive components. By contrast, transport of AZT into cells was by simple diffusion. The intracellular level of the triphosphate of FLT (FLTTP) in MT4 cells was two- to threefold higher than that of AZT (AZTTP) after exposure to 1.8 microM each compound for 12 h. The elimination kinetics of FLTTP and AZTTP in HIV-1-infected MT4 cells in fresh medium showed biphasic patterns, with initial half-lives of 1.03 and 1.09 h, respectively. In phytohemagglutinin-stimulated human peripheral blood lymphocytes, the FLTTP level was increased 59-fold compared with that in unstimulated cells at 12 h, was four- to sixfold higher than the level of AZTTP in stimulated cells at 12 h, and remained four- to fivefold higher during a 4-h elimination period in fresh medium and twofold higher at the end of a 12-h elimination period. Two- to eightfold more [3H]AZT than [3H]FLT was incorporated into the host cell DNA, and both [3H]AZT and [3H]FLT remained persistently incorporated for over 24 h. The incorporated [3H]AZT and [3H]FLT were alkali labile, whereas incorporated [3H]dThd was alkali stable. Pharmacokinetics of FLT in plasma of monkeys after intravenous (i.v.) administration showed that the FLT concentration in plasma declined, with a half-life of 1.19 +/- 0.1 h; the steady-state volume of distribution was 0.93 +/- 0.2 liter/kg of body weight, and total clearance was 0.56 +/- 0.15 liter/kg. Oral bioavailability of FLT was excellent and comparable to i.v. bioavailability in terms of areas under the concentration-time curves for three monkeys. Of the total dose, 41 to 61% was excreted in urine as unchanged FLT, and only 3.2 to 7.4% of the total dose was identified as glucuronide-conjugated FLT in urine 48 h after i.v. administration to monkeys. We conclude that FLT exhibits an anti-HIV-1 potency similar to that of AZT but with slightly better selectivity of effects and with higher intracellular active metabolite levels.


Bactericidal activities of five quinolones for Escherichia coli strains with mutations in genes encoding the SOS response or cell division. The bactericidal effects of five quinolones (at the optimum bactericidal concentration for strain AB1157) on 15 strains of Escherichia coli with mutations in genes for the SOS response or cell division was studied by a viable-count method. The kill rate data were normalized for growth rate and compared to those for the wild type, AB1157. Similar MICs of enoxacin and fleroxacin were obtained for all mutants; however, different mutants had differing susceptibilities to ciprofloxacin, norfloxacin, and nalidixic acid. Killing kinetic studies showed that mutants with constitutive RecA expression (recA730 and spr-55 mutants) survived longer than AB1157 with all quinolones. Mutants deficient in SOS induction, e.g., recA430 and lexA3 mutants, also survived longer, suggesting that induction of the SOS response by quinolones is harmful to wild-type cells. Recombination repair-deficient mutants (recB21, recC22, and recD1009 mutants) were killed more rapidly than AB1157, as were excision repair mutants, except with nalidixic acid. Mutants which were unable to filament (sfiA11 and sfiB114 mutants) survived longer than AB1157 with all agents, but a mutant defective in the Lon protease was killed more quickly. It was concluded that (i) recombination and excision repair were involved in the repair of quinolone-damaged DNA and (ii) continuous induction (in response to exposure to quinolones) of the SOS response, and hence induction of the cell division inhibitor SfiA, causes cell filamentation and thereby contributes to the bactericidal activity of quinolones.


The lipid A biosynthesis mutation lpxA2 of Escherichia coli results in drastic antibiotic supersusceptibility. The conditionally lethal lpxA2 mutant of Escherichia coli, which lacks detectable UDP-N-acetylglucosamine acyltransferase activity and which produces greatly reduced amounts of lipid A after a shift to 42 degrees C (S. Galloway and C. R. H. Raetz, J. Biol. Chem. 265:6394-6402, 1990), was found to be, at conditions which promote normal growth, remarkably susceptible to a number of antibiotics. The MICs of hydrophobic antibiotics, such as rifampin, erythromycin, clindamycin, and fusidic acid, were 32- to greater than 128-fold lower for the lpxA2 strain than for the parent type strain, and those of the peptide antibiotics vancomycin and bacitracin were 32- and 256-fold lower, respectively. Futhermore, the lpxA2 strain was found to be sensitive to hypoosmotic conditions. Comparisons with the other characterized outer membrane permeability mutants, such as the heptose-deficient strains of E. coli and Salmonella typhimurium, the acrA and abs mutants of E. coli, and the ssc-1 and class SS-B mutants of S. typhimurium, indicated that the lpxA2 mutant had characteristically the most antibiotic-supersusceptible phenotype. These findings advocate the possible use of the lpxA2 strain as a tool in various fields of basic and applied bacterial research in which the impermeability of the outer membrane currently poses problems.


Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin. This study was designed to determine the effects of an aluminum hydroxide antacid and a calcium carbonate antacid on the bioavailability of ciprofloxacin (Cipro). Cipro (750 mg) was administered orally to 12 healthy volunteers in a three-way randomized crossover design. The three treatments included Cipro alone, four 850-mg calcium carbonate tablets taken 5 min before Cipro, and three 600-mg aluminum hydroxide tablets taken 5 min before Cipro. The relative bioavailability of Cipro when given with calcium carbonate was approximately 60% of the control value. When Cipro was given with aluminum hydroxide, the relative bioavailability was approximately 15%. Urinary recovery of Cipro in the aluminum hydroxide treatment group was approximately one-fourth of that in the calcium carbonate group. Although calcium carbonate decreased absorption to a lesser extent than aluminum hydroxide, these data suggest that antacids containing either aluminum or calcium should not be given concomitantly with Cipro.


Iron transport-mediated antibacterial activity of and development of resistance to hydroxamate and catechol siderophore-carbacephalosporin conjugates. Peptides containing residues of N5-acetyl-N5-hydroxy-L-ornithine were evaluated as potential artificial siderophores of beta-lactam-hypersusceptible Escherichia coli X580. Only those peptides which were capable of forming a hexadentate complex around ferric iron, which is analogous to the natural siderophore ferrichrome, were able to reverse the growth inhibition effects of the ferric iron chelator ethylenediamine di(o-hydroxyphenylacetic acid). A synthetic bis(catechol) spermidine derivative, similar to the natural siderophores enterobactin and agrobactin, also exhibited siderophore activity with this strain. Conjugation of the N5-acetyl-N5-hydroxy-L-ornithine tripeptide and the bis(catechol) siderophore to the potent carbacephalosporin loracarbef and closely related analogs provided compounds which exhibited antibacterial activity against E. coli X580. As was observed with the naturally occurring albomycins, the initial bactericidal effect was followed by the appearance of survivors that were resistant to the test compound. An enhanced killing effect was observed when the parent was incubated simultaneously with hydroxamate and catechol siderophore-antibiotic conjugates. Natural and synthetic siderophore growth promotion experiments with survivors resistant to the conjugates strongly suggested that disabled ferrichrome and enterobactin-catechol assimilation mechanisms may be responsible for the observed resistance. One isolated survivor was postulated to be a tonB mutant. The antibacterial activities of the described siderophore-carbacephalosporin conjugates appear to be related to an iron transport assimilation mechanism and would not have been detected during routine MIC testing procedures.


In vitro antistaphylococcal activity and testing of RP 59500, a new streptogramin, by two methods. The in vitro antistaphylococcal activity of RP 59500, a new streptogramin, was comparable to those of vancomycin and teicoplanin against Staphylococcus aureus, and RP 59500 was the most active agent against coagulase-negative staphylococci. All staphylococcal strains were inhibited by 4 micrograms of RP 59500 per ml, including multiply resistant strains. Broth microdilution and agar dilution testing gave comparable results in 97% of the tests with RP 59500.


In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin. The antibacterial activity of levofloxacin was compared with those of ofloxacin, ciprofloxacin, and other antibiotics. In general, levofloxacin was equally active or up to fourfold more active than ofloxacin against all 801 organisms tested. Levofloxacin was twofold [corrected] more active than ciprofloxacin against Streptococcus pneumoniae and 2- to 4-fold more active than ciprofloxacin against Staphylococcus aureus, Xanthomonas maltophilia, and Bacteroides fragilis. Levofloxacin was two- to eightfold more active than ciprofloxacin against coagulase-negative staphylococci and Acinetobacter spp., although these improvements in potency may not be clinically relevant. Levofloxacin inhibited 90% of streptococci when it was used at concentrations of 1 to 2 micrograms/ml. Levofloxacin was two- to fourfold less active than ciprofloxacin against most members of the family Enterobacteriaceae, such as Escherichia coli; Klebsiella pneumoniae; Citrobacter, Proteus, Providencia, Salmonella, and Yersinia spp.; and Pseudomonas aeruginosa. Both compounds were equally active against Pseudomonas cepacia. The in vitro DNA gyrase inhibitory activity of levofloxacin was as potent as that of ciprofloxacin, with a 50% inhibitory concentration of 0.65 micrograms/ml against an E. coli enzyme. In vivo, oral treatment with levofloxacin was as efficacious or more efficacious than that with ciprofloxacin in systemic as well as pyelonephritis infections in mice. Levofloxacin achieved higher concentrations in the serum and tissue of mice than did ciprofloxacin. This study presents some potential advantages of the pure L isomer of ofloxacin over ciprofloxacin and other quinolones.


Evidence for in vivo incorporation of D-lactate into peptidoglycan precursors of vancomycin-resistant enterococci. The VanA ligase encoded by the vancomycin resistance plasmid pIP816 of Enterococcus faecium BM4147 condenses D-alanine with various D-2-hydroxy and D-2-amino acids in vitro. D-Lactate added to the culture medium restored the vancomycin resistance of a strain that does not produce the VanH dehydrogenase and therefore appears to be a substrate of VanA in vivo.


In vitro susceptibilities of Mycoplasma genitalium to antibiotics. The susceptibilities of seven clinical isolates of Mycoplasma genitalium and three strains of Mycoplasma pneumoniae to a variety of antibiotics were examined by an agar dilution method. Macrolides, pristinamycin, and tetracyclines were very active against both species. Sparfloxacin was the most active quinolone tested. None of the 21 antibiotics tested had differential activity toward the two organisms.


Tet determinants provide poor protection against some tetracyclines: further evidence for division of tetracyclines into two classes. Atypical tetracyclines were active against Escherichia coli and Staphylococcus aureus strains containing determinants that mediate resistance to typical tetracyclines by efflux (Tet B and Tet K) or ribosomal protection (Tet M) mechanisms. The results support recently published data that tetracyclines are divisible into at least two classes on the basis of their modes of action.


In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents. The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients.


A pneumococcal clinical isolate with high-level resistance to cefotaxime and ceftriaxone. A beta-lactam-resistant serotype 23F Streptococcus pneumoniae clinical isolate from the cerebrospinal fluid of a pediatric patient from California is unusual in that the MICs of cefotaxime and ceftriaxone (2.5 micrograms/ml each) are higher than that of benzylpenicillin (0.3 micrograms/ml); the isolate also has patterns of penicillin-binding proteins and of cell wall peptides which are atypical compared with those of previously examined penicillin-resistant pneumococci.


Kinetic interaction of biofilm cells of Staphylococcus aureus with cephalexin and tobramycin in a chemostat system. Planktonic and young biofilm cells were completely eradicated after exposure of these cells to drug levels representing one loading and two maintenance doses of tobramycin and cephalexin. A very different picture was observed when antibiotic exposure was initiated on day 21. Complete eradication of the old biofilm cells was not observed even when the antibiotic exposure was continued for an extra 6 days. Regrowth of the organism was observed when the antibiotic exposure was terminated.


In vitro studies of activities of some antifungal agents against Candida albicans ATCC 10231 by the turbidimetric method. Different criteria (the drug concentration which inhibited 50% of growth [IC1/2], the lowest drug concentration at which growth was just less than 30% of that in a positive control well [IC30], the visual inhibitory concentration [ICv], and the minimum fungicidal concentration [MFC]) were applied to study the effects of some antifungal agents against Candida albicans. Amphotericin B, flucytosine, and bifonazole produced total growth inhibition. Clotrimazole, itraconazole, ketoconazole, and miconazole produced partial growth inhibition. The values of IC1/2 and IC30 were similar for all agents and avoided the problems of partial inhibition; the values of ICv and MFC were higher than those of IC1/2 and IC30.


Effects of amino acids on expression of enterococcal vancomycin resistance. The effects of various amino acids on vancomycin MICs obtained with resistant enterococci was investigated by using broth dilution testing. For both the type A (i.e., possessing transferable resistance to teicoplanin and vancomycin) and the type B (i.e., possessing teicoplanin susceptibility and nontransferable vancomycin resistance) resistant strains, vancomycin MICs in the presence of glycine were substantially lower than those in unsupplemented broth (range of MIC decrease, 8- to 128-fold). No such effect was seen with Enterococcus gallinarum AIB-39 or with the susceptible control Enterococcus faecalis ATCC 29212. Further testing of two type B strains (E. faecalis V583 and V583-2) showed that certain other amino acids (i.e., D-methionine, D-serine, D-alanine, and D-phenylalanine) had effects similar to that of glycine. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis with membrane preparations from these strains revealed the production of vancomycin-inducible proteins of sizes comparable to those describe for other enterococcal isolates that exhibit acquired vancomycin resistance. Even in the presence of 0.2 M glycine, the inducible proteins were produced. These results indicate that certain amino acids specifically interfere with the mechanism(s) of acquired vancomycin resistance in enterococci and that the nature of interference probably involves inhibition or circumvention of the inducible proteins' functions.


Postoperative orthopedic autotransfusion. Successful management for the total knee arthroplasty patient. Orthopedic autotransfusion is an effective technique that should be available to patients having total knee arthroplasty. Patient safety, however, must not be compromised simply because the blood is autologous. Blood products, in any form, require close observation and careful administration. The best results are achieved when the physician and all nursing departments involved have comprehensive knowledge of the system and the guidelines for its safe use.


Autologous blood transfusion. Current trends, nursing implications. Developing a quality perioperative autologous blood recovery program is a team effort. Members of transfusion committees, hospital blood bank personnel, OR staff members, and the members of the surgery committee are all possible sources of information. Your local blood center also may have literature or services that could be of assistance. Knowledge of current autologous transfusion alternatives will help nurses communicate with patients regarding transfusion therapy and will make nurses more valuable participants in the crucial decisions necessary to deliver optimal patient care in the perioperative period.


[The need for death education].

[The need for death education]. "Death Education" is at the same time "Life Education." For many years I have endeavored to create an awareness of the need for death education in Japan. In this paper I would like to stress the necessity of death education for the following three groups. 1. For medical personnel. Three objectives of death education: 1) Learn to understand the fears and anxieties of the patients facing death and try to reduce their excessive fears and anxieties. 2) Familiarize yourself with the ethical issues related to terminal care and try to establish a warm relationship based on trust and continue communication with the dying patient till the end. 2. For patients. 1) Be aware that the time of your life is limited and try to discover the preciousness of the remaining time. Meditate on the uniqueness of your own death. 2) Finish your unfinished business, reevaluate your human relationships and benefit from a life review therapy. 3) Remove the taboo on death, arrange your own funeral and consider the possibility of another life after death. 3. For the patient's family and friends. 1) Continue warm communication with the dying patient till the end. 2) Prepare for your own bereavement and grief. 3) Try to make your own grief process an opportunity for personal growth. When a cure is no longer possible for a dying patient, the focus of our endeavors should be loving care of the person. Death education can help us to provide better terminal care during the final stage of life.


[Endoscopic treatment of esophageal cancer]. With the advance of endoscopic equipment the number of superficial cases of esophageal cancer has been increasing dramatically. It has been clarified as to which cancer can be treated as an early cancer with desirable results as in gastric cases. Endoscopic treatment for early cancer already established in gastric or colorectal cases have been applied to esophageal cases with nationwide popularity. Especially endoscopic mucosal resection, which can assure accurate pathological findings, can be the treatment of choice for endoscopic procedures for early cancer. In this paper, our methodology of endoscopic treatment of early esophageal cancer is introduced and our endoscopic approach to advanced cases which is still to be established is reported.


[Endoscopic treatment of lung cancer].

[Endoscopic treatment of lung cancer]. There are many kinds of endoscopic treatment for lung cancer. In this paper the authors describe these methods and present representative cases. The first is laser treatment. There are three methods of endoscopic laser treatment. One is vaporization using high-power lasers, for example, the Nd-YAG laser. Indications for high-power laser treatment include obstructive lesions of the trachea or large bronchi with no recognizable peripheral focus. The second is photodynamic therapy (PDT) using tumor-specific photosensitizers, and low-power lasers. PDT has potential for the treatment of early stage lung cancer. The third is "laser chemotherapy," which is a new method developed by the authors using low-power lasers, e.g., He-Ne lasers, combined with chemotherapy. It is possible that antitumor drugs could be administered in doses lower than used at present. The second method is bronchofiberscopic ethanol injection therapy for stenosis or obstruction of central airways in order to obtain airway dilatation or hemostasis. The third method is brachytherapy or endobronchial radiation for central type lung cancer. We use a bronchofiberscope to place the applicator into the target bronchial lumen. Radiation therapy is performed with 60Co high dose-rate endobronchial radiation by a remote after-loading system. The value of laser treatment has been amply demonstrated and the other methods are also yielding encouraging results in the treatment of lung cancer.


[Endoscopic treatment of early gastric cancer]. We assessed the results of endoscopic resection (ER) of early gastric cancer using electrocoagulation with high frequency current. Resection was performed utilizing endoscopic double-snare polypectomy (EDSP) and electrocoagulation. The initial endoscopic total resection rate was 65.0% (119/183 lesions). There were 32 lesions in which no residual cancer was present at follow-up biopsy or surgery, and when these were included the endoscopic resection cure rate was 82.5%. Extensive tissue necrosis and degeneration occurred in the resected stump as a result of using electrocoagulation. Since an increase in suitable patients and an expansion of the indications for endoscopic resection are anticipated in the future, careful clinical evaluation of endoscopic resection based on the results of pathological assessment of the resected tissue is needed.


[Endoscopic treatment of early colorectal cancer]. Early cancer of the colon and rectum is currently treated by endoscopic or surgical resection. We studied the indications for endoscopic treatment of early colorectal cancers (80 lesions) in relation to the size and macroscopic findings. The endoscopic treatment consists of polypectomy for a pedunculated or a sessile polyp and strip biopsy for a plaque-like or a depressive lesion. Microscopic or most small cancers were completely treated endoscopically. From macroscopic findings of the early cancers, type Ip (less than 2cm and 2cm in diameter) was completely treated by polypectomy, type I s and type II a (less than 1cm and 1cm in diameter) by polypectomy or strip biopsy, and type II c (less than 0.5cm and 0.5cm in diameter) by strip biopsy.


[Phase III study of DWA2114R for ovarian cancer]. A phase III study of DWA2114R for ovarian cancer was carried out in CAP regimen by a cooperative study group consisting of 42 institutions. The response rate of 31 cases for DWA2114R regimen was 38.7% and out of 30 cases for CDDP regimen 46.7%. No significant differences were observed between the two regimens in efficacy, adverse reactions, and abnormalities in laboratory findings except for red blood cell and creatinine clearance, but the incidence of thrombocytopenia was likely to be lower in DWA2114R than in CDDP regimen. Since the DWA2114R regimen did not need hydration, or require diuretics, DWA2114R is more useful in the treatment of ovarian cancer than cisplatin.


[Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract]. The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi-institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder.


[Evaluation of 58 patients with acute leukemia]. We made a retrospective study of 44 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) admitted to our hospital from September 1984 to May 1991. The complete remission (CR) rate of ANLL was 90.9%, against 85.7% for ALL. The 5-year survival of ANLL was 50.7%, and that of ANLL under age 60 years was 70.3%. The 2-year median survival of ALL was 35.1%. These results were obtained with response-oriented individualized therapy, and intensive chemotherapy with a view to eradication of residual leukemic cells. Eight elderly patients with ANLL were treated with cytosine arabinoside in low doses. Complete remission was achieved in 6 patients, but these cases relapsed. These treatments should be reconsidered for long CR duration. Our schedules of response-oriented individualized therapy were too flexible to apply at another institute so they should be arranged for general application.


[Intensive induction chemotherapy of adult acute myelogenous leukemia by continuing daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone until marrow aplasia]. Intensive induction chemotherapy was applied to 25 patients with acute myelogenous leukemia by continuing drugs (daunorubicin, behenoyl-cytosine arabinoside, 6-mercaptopurine and prednisolone) until the achievement of severe bone marrow aplasia (leukemic cells less than 1,000/microliters). Complete remission (CR) was achieved in 18 (72%). Numbers of partial remission and an early death were 5 (20%) and 2 (8%), respectively. Although median nadirs of white blood cells (WBC) and platelet counts (Pl) (205/microliters and 8,200/microliters, respectively) were remarkably low, recovery of WBC (over 1,000/microliters) and Pl (over 50,000/microliters) were achieved in 23.8 and 24.5 days, after an initiation of the chemotherapy. Sepsis was a most frequently observed complication during induction stage and a duration of fever was 2-48 days (median 15). Median duration of CR was 22.9 months. Unexpectedly, 11 of 17 CR (except one with bone marrow transplanted) relapsed after 4.2-41.4 months (median; 9.4), but 6 (35.3%) still remain in first CR for 30.5-72.9 months (median; 51.4). A long-term survival might be obtained by intensifying induction chemotherapy in about one fourth of patients, but the intensification or application of non-cross resistant anti-leukemic agents in post-remission therapy may be required to avoid relapses even if induction is intensified.


[Comparative study of cefpiramide + amikacin versus piperacillin + amikacin in granulocytopenic patients: a randomized, prospective study]. Cefpiramide + amikacin (CPM + AMK) was compared in a prospective randomized trial with our standard regimen of piperacillin plus amikacin (PIPC + AMK) as an empiric therapy for fever in 252 episodes of 141 patients with granulocytopenia. Initial profound granulocytopenia (fewer than 100/mm3 mature granulocytes) was present in approximately 69% of the patient trials in both treatment groups. Both groups were equally distributed in regard to age, disease, pretreatment WBC count and duration of antibiotic treatment, although septic shock was more frequently seen in CPM + AMK. Responses to PIPC + AMK and CPM + AMK were similar for microbiologically and clinically documented infection, while the response rate for clinically documented infections treated with PIPC + AMK was superior to CPM + AMK (63% vs. 52%). Patients with persistent granulocytopenia of less than 100/mm3 of mature granulocytes without a rise during therapy responded significantly less in both groups (22% vs. 9%) than those in whom the granulocyte count rose (79% vs. 79%). Toxicities of jaundice or disordered hepatic function test were infrequent in both groups. Disordered renal function test occurred in one case in PIPC + AMK groups.


[Effects of UFT and loxiglumide (CR1505) on liver metastasis of human pancreatic cancer cell line, KP-1 N in nude mice]. Effects of caerulein (CCK), 5-FU and CCK antagonist, loxiglumide (CR1505), were studied on the growth of human pancreatic cancer cell line, KP-1 N, in vitro. And effects of UFT and CR 1505 were also studied on liver metastasis in nude mice. The growth of KP-1 N was stimulated approximately 40% by addition of 10(-10) M of CCK in vitro. CR1505 antagonized the action of CCK, that is, the 40% growth rate increase was suppressed by addition of 25 microM of CR1505. Moreover, the growth rate of the cells dose-dependently decreased by the addition of CR1505. 5-FU also dose-dependently inhibited the growth of KP-1 N in culture. 5-FU additionally decreased the growth rate of KP-1 N in combination with CR1505. A number of metastatic nodules were found in the liver of nude mice a month after injections of KP-1 N cells into the spleen CR1505 suppressed the liver metastasis in nude mice which were administered with UFT. These results suggest that CR1505 would be useful for the treatment of human pancreatic cancer in combination with UFT.


[Ototoxicity of cis-diammine glycolato platinum, 254-S]. Ototoxicity of cis-diammine glycolato platinum, 254-S, was evaluated from the results obtained in phase II studies for head & neck cancer, lung cancer, breast cancer, gastrointestinal cancer, urogenital cancer and gynecological cancer at 114 institutions, and in randomized comparative study of 254-S plus vindesine vs. cisplatin plus vindesine for advanced non-small cell lung cancer conducted at 41 institutions. In these studies, 254-S was administered at doses ranging from 80 to 100 mg/m2, repeated at least 2 times at 4-week intervals. Impaired hearing was examined in a hearing audiometry test before and after 254-S administration. The incidence of impaired hearing was 25.8% (16/62) in the 254-S phase II studies. The incidences in the randomized comparative study were 17.6% (3/17) for the 254-S/vindesine group and 20.0% (3/15) for the cisplatin/vindesine group. From these results, the ototoxicity of 254-S was thought to be similar to that of cisplatin in incidence and type.


[A case of advanced breast cancer effectively treated with tamoxifen]. A 69-year-old female with advanced breast cancer was daily administered 20 mg of tamoxifen. After 4 months, her left breast tumor decreased in size. Left breast tumor and metastatic lymph nodes disappeared completely (CR) 7 months later. CR has been continued for 6 months up to the present, and the patient has been enjoying favorable quality of life.


[A bladder cancer with complete remission after arterial infusion of anti-cancer agents (CDDP and THP) and balloon-catheter occlusion of the internal iliac artery: a case report]. The case was a 63-year-old male with the chief complaint of hematuria. A local doctor made the diagnosis of a bladder tumor (egg-sized) on the basis of the results of ultrasonography. CT-scan and cystoscopy. He was thus referred to our Department for treatment. Histopathological study of the biopsied tumor specimen revealed that the tumor was a squamous cell carcinoma. The bilateral internal iliac arteries were occluded for 48 hours, and 100 mg of CDDP and 40 mg of THP were arterially infused. After 7 days, hematuria disappeared, as did the tumor 5 weeks after treatment. No malignancy was noted from histological examination of a biopsy specimen obtained from the cured cancer region using a cystoscope. Since then, there was no recurrence for 12 months. Thus, this approach is thought to be an effective treatment for primary bladder cancer.


[Cell culture and its application primary culture of human hepatocytes and its application]. Difficulty in obtaining human liver specimens has made a delay in the development of methodology for isolation and primary culture of human hepatocytes compared to animal hepatocyte cultures. Recently the collagenase-liver-perfusion technique, which was developed for rat hepatocyte isolation, has been applied to prepare isolated human hepatocytes. This method greatly improved the yield and viability of hepatocytes of human liver tissues. Since then, the isolated human hepatocytes and their primary culture have been widely used for studies of hepatic metabolism, regeneration, transplantation, hepatitis B virus infection, hepatotoxins, detection of human carcinogens, hepatocarcinogenesis and so forth. These current studies were reviewed.


Isolation of human skin-derived lymph: flow and output of cells following sodium lauryl sulphate-induced contact dermatitis. By means of microsurgery a peripheral subcutaneous lymph vessel draining a defined skin area was isolated and cannulated on the lower leg of six healthy volunteers. Lymph was collected over a period of 8 days. During the first 2 days baseline values for lymph flow and output of cells were established. A contact dermatitis was then induced in the drained skin area by the application of 10% sodium lauryl sulphate. All six probands developed a mild to moderate irritant contact dermatitis. Lymph flow as well as output of cells increased with the intensity of the skin reaction. Subsequent local treatment with clobetasol propionate decreased the cell output, but the lymph flow increased further. Neither lymph flow nor output of cells returned to the initial baseline values at the end of the study, when the clinical signs of contact dermatitis had completely disappeared. During the experiment significant individual variations were found, with means ranging from 0.10 to 0.48 ml/h for lymph flow and from 8700 to 174000/h for cells, which probably depended mainly on the different topographies and calibres of the cannulated lymph vessels.


Delayed type hypersensitivity is abnormal in patients with lichen planus. Lichen planus is characterized by the histological features of a cell-mediated attack on the epidermis. To see whether there is any defect in cutaneous immunity in non-lesional skin, we measured the response to a contact sensitizer in 17 patients with lichen planus and 27 control subjects. Sensitization was induced with 30 micrograms dinitrochlorobenzene applied to the thigh. The subjects were challenged 4 weeks later with three doses of dinitrochlorobenzene (8.8, 12.5 and 17.7 micrograms), and responses were quantified with calipers as the change in skinfold thickness at 48 h. Patients with lichen planus were significantly less responsive with smaller reactions at all challenge doses. These abnormalities suggest that the skin is abnormal in areas unaffected by the rash, and raise the possibility that there may be a primary defect in the cutaneous immune system in lichen planus.


Thermal and sweating responses in normal and atopic subjects under internal and moderate external heat stress. To compare the thermoregulatory responses of normal subjects and patients with atopic dermatitis, the effect of exercise under moderate heat stress was examined in two groups of subjects. Each group of eight subjects (controls or clinical atopics) underwent a 90-min experiment after being equipped with probes for measurement of core and skin temperatures, heart rate and overall and local sweating rates. Sweat surface tension was determined from sweat collection made at the end of the session. The experimental procedure was as follows: 30 min rest at thermoneutrality, 30 min cycling at 90 W at 36 degrees C, followed by 30 min recovery sitting at rest at 36 degrees C on the cycloergometer. None of the registered variables differed significantly between the normal and atopic subjects except for variations in mean skin temperature, core-to-skin temperature difference and sweat surface tension. Since local sweating on non-affected skin under a controlled thermal clamp was not altered by atopy, it can be concluded that the thermoregulatory modifications under heat stress is of vasomotor origin, the benefit of which, in terms of heat dissipation capacity, remains uncertain. There may be alterations in the constituents of sweat, but not in its excretion rate. Local, rather than central, factors are probably involved in this qualitative change, which remains to be investigated.


The interleukin-2 receptor in lesions and serum of bullous pemphigoid. The interleukin-2 receptor (IL-2R) is mainly expressed on activated T cells. Depending on its rate of synthesis, a portion is released from the cell surface as soluble IL-2R (sIL-2R). Since the role of mononuclear cells in the pathology of bullous pemphigoid (BP) is not well understood, we determined the sIL-2R in both blister fluid and serum of 15 BP patients with generalized disease before initiating systemic treatment. In addition, we obtained both lesional and perilesional skin biopsies and examined the mononuclear infiltrate with a panel of monoclonal antibodies. In BP blisters, sIL-2R levels were significantly increased (2070 +/- 350 U/ml), (+/- SEM) compared with serum samples taken at the time of blister puncture (1340 +/- 290 U/ml). In six patients with blisters due to second-degree burns or friction and in five suction blister volunteers, sIL-2R levels were normal in both blisters and serum. In BP, elevated serum levels decreased to normal during therapy, correlating with disease activity. The immunohistology showed that 30% of mononuclear cells in the dermal infiltrate of lesional skin expressed the IL-2R, whereas only 15% were positive in perilesional skin. IL-2R-positive cells are the most likely source of the shed receptor in BP blisters. Our results indicate the presence of activated T cells in lesions and peripheral blood of BP and thus underline the importance of cell-mediated immune mechanisms in the pathology of this disease.


Carbonic anhydrase--a marker for fenestrated capillaries in psoriasis. A strong correlation between capillary fenestrations and the demonstration of carbonic anhydrase (CA) has previously been shown. In the present histochemical study we sought to determine whether CA could serve as a marker for fenestrated capillaries in psoriasis. In normal human skin capillary staining for CA was found only in the fenestrated capillaries of the perifollicular and periglandular plexus. In psoriatic skin lesions, however, the intrapapillary capillaries also reacted for CA. From ultrastructural investigations it is known that these capillaries are fenestrated. Our findings have shown that there is a strong correlation between fenestrated and CA-positive capillaries in normal human skin as well as in the lesional skin of psoriatics. Therefore, the demonstration of CA activity may serve as a specific and sensitive marker for fenestrated capillaries in psoriasis using an uncomplicated method, which makes it possible to detect numerous fenestrated capillaries in a single histological section.


Organ culture of psoriatic skin: effect of TGF-alpha and TGF-beta on epidermal structure in vitro. Normal skin and uninvolved and involved psoriatic skin specimens were maintained in vitro in organ culture. The 3-4 mm punch-biopsied skin specimens were put freely into the culture medium with or without fetal calf serum, under an atmosphere of 95% O2 plus 5% CO2, and rotated at 60 rpm at 37 degrees C. In the serum-free culture medium (vitamin A-free) granular layers appeared in the involved psoriatic epidermis in culture. Addition of TGF-alpha caused normal skin and uninvolved and involved psoriatic skin specimens to become acanthotic and to degenerate easily almost to the full thickness of the epidermal layer in proportion to increasing concentrations of TGF-alpha as well as with the duration of the culture, but without disappearance of their granular layers. TGF-beta caused the normal skin and uninvolved psoriatic skin specimens to become thinned without disappearance of granular layers, but caused the involved psoriatic skin specimens to be thinned without appearance of granular layers in serum-containing medium or with their disappearance in the serum-free medium. TGF-beta also antagonized the acanthotic and degenerative effect of TGF-alpha. The results suggest that TGF-alpha and TGF-beta may partially be related to the induction of psoriatic epidermal lesions.


Immunohistological and immunoelectron microscopic identification of TNF alpha in normal human and murine epidermis. The presence, distribution and cellular localization of tumour necrosis factor-alpha (TNF alpha) were investigated in normal human and murine epidermis using immunohistological and immunoelectron microscopic methods with monoclonal and polyclonal antibodies. The immunostaining revealed an intercellular plasma membrane and cytoplasmic labelling of the epidermal keratinocytes, but no labelling of Langerhans cells, melanocytes and Merkel cells. Large amounts of TNF alpha were regularly found in the sebaceous glands. These findings demonstrate that epidermal keratinocytes and especially sebocytes produce and release TNF alpha and that this keratinocyte-derived cytokine may be important for the structural and functional homeostasis of normal epidermis.


Expression of cadherin cell adhesion molecules during human skin development: morphogenesis of epidermis, hair follicles and eccrine sweat ducts. Expression of E (epithelia) and P (placental) cadherin cell adhesion molecules was examined immunohistochemically using human developing skin. In adult skin, E-cadherin was expressed on cell surfaces of whole epidermal layers including skin appendages, whereas P-cadherin was expressed only on those of basal layers and the outer layers of skin appendages, which was consistent with the compartment of proliferating cells. In fetal skin, while the patterns of E- and P-cadherin expression were generally similar to those in the adult, P-cadherin temporarily showed a unique spatiotemporal expression pattern in developing sweat ducts. During this stage, the expression of P-cadherin accumulated in the epidermal ridges and showed a discrepancy with the compartment of proliferating cells. These results suggest that the expression of P-cadherin is spatiotemporally controlled, and may be closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine sweat ducts, but is not closely related to cell proliferation.


MON-150, a versatile monoclonal antibody against involucrin: characterization and applications. A monoclonal antibody, designated MON-150, was found serendipitously to react strongly with the granular layer of normal human epidermis and with the upper spinous layers of psoriatic epidermis. From analysis by flow cytometry of cultured human keratinocytes, it appeared that the percentage of MON-150-positive cells strongly increased when the cells reached confluence and the growth fraction declined. To identify the antigen recognized by MON-150, a lysate of human keratinocytes was subjected to affinity chromatography using a MON-150 Sepharose column. This yielded a single protein of approximately 350 kDa as measured on Superose 6 FPLC gel permeation chromatography using non-denaturing conditions. In Western blot analysis under denaturing and reducing conditions, a 140-kDa protein was detected. The subcellular localization and the molecular weight of the antigen recognized by MON-150 suggested that the antigen involved might be involucrin. This was confirmed using a commercial polyclonal antiserum against involucrin. We conclude that MON-150 is a new, versatile antibody against human involucrin.


Effect of cyclosporins A, G, and H on normal and ichthyotic keratinocyte growth in culture. Cyclosporin A (CsA) was first used in organ transplantation and for the treatment of autoimmune disorders because of its strong immunosuppressant properties. Several laboratory studies have demonstrated that CsA exerts an inhibitory action on the growth of various cell types in culture, including human skin cells. Such an influence on epidermal keratinocytes, if not associated with the serious adverse effects of CsA medication, would be of interest for the treatment of hyperproliferative genodermatoses such as non-bullous congenital ichthyotic erythroderma (NBCIE). In our study, we used cyclosporin G (CsG) and H (CsH), analogues CsA, to examine the impact of these three cyclosporins on normal and ichthyotic keratinocyte growth in vitro. Epidermal cells were grown in a low-calcium, serum-free medium in the presence or absence of cyclosporins A, G or H (1-10 micrograms/ml). The effects of a 72-h exposure to the drugs were evaluated by cell counting, 3H-thymidine incorporation and cytofluorimetric analysis of the BrdU-labelled cell suspensions. Our findings indicate a dose-dependent keratinocyte growth inhibition by the three cyclosporins. The data obtained with the three quantitation methods were in agreement and the cyclosporin-mediated effects were observed in both normal and ichthyotic keratinocyte cultures. CsG and CsH proved less effective than CsA, which induced a highly significant reduction even at 1 microgram/ml. Our results suggest, however, that ichthyotic keratinocytes are more sensitive to CsG and H when compared with normal cells (50% inhibition of 3H-thymidine uptake at significantly lower doses). A possible therapeutic action of non-toxic doses of CsG and CsH on NBCIE and other hyperproliferative epidermal diseases needs to be confirmed clinically.


The antipsoriatic drug, anthralin, inhibits protein kinase C--implications for its mechanism of action. In psoriatic patients, anthralin is known to attenuate lesional inflammation, but often generates perilesional dermatitis. This phenomenon is well reflected by the contrasting action of anthralin on human leukocytes. The release of reactive oxygen species (ROS) is inhibited by anthralin in phorbol ester-activated leukocytes, whereas anthralin directly induces this cellular response in unstimulated cells. In order to elaborate further the underlying mechanisms, we compared the kinetics of anthralin and different well-characterized stimuli, including the phorbol ester, phorbol-12-myristate-13-acetate, in this test system. Compared with standard stimuli, anthralin only marginally induced the release of ROS from human leukocytes and displayed different kinetics. Protein kinase C (PKC), the major cellular phorbol ester receptor, is considered to be involved in the regulation of this cellular response. Furthermore, its involvement in the pathophysiology of psoriasis has been suggested. Therefore, we also investigated the effects of anthralin on purified PKC. Anthralin was found to inhibit the enzyme activity in a dose-dependent manner but not to display any stimulatory effects. The present results provide first evidence that the therapeutic activity of anthralin, at least in part, might be mediated by inhibition of PKC.


The long term follow-up of asymptomatic women with Chlamydia trachomatis. A community oriented intervention program was initiated in 1985 in 12 rural communities in southern Israel to identify and treat women of reproductive age with markers of Chlamydia trachomatis (CT) infection. Among 860 women tested, 21 (2.4%) had CT IgG antibody titers greater than or equal to 128, or CT IgA antibody titers greater than or equal to 16, and 9 of these women had positive cultures for CT. The 21 women, as well as their male partners, received specific anti-CT treatment, and were followed up for 5 years to assess obstetric complications, and to evaluate the effectiveness of treatment. In 9 women positive cultures became negative. In 13 out of the 17 cases with sequential follow-up a four fold decrease in IgG specific antibody titers was observed. Yet, in all but two of the cases, IgA specific antibody titers remained greater than or equal to 16.


Lactic dehydrogenase activity of platelet subpopulations during pregnancy. We determined the LDH activity of different platelet subpopulations throughout pregnancy. While no changes in LDH content occurred in large, dense platelets, a significant change was found in small, light platelets.


Creatine phosphokinase isoenzyme activity in umbilical artery, umbilical vein and capillary blood of newborn infants at term. Serum levels of creatine phosphokinase isoenzyme pattern (CPK MM, MB, BB) were measured in cord blood and capillary blood samples of 20 healthy term infants. Total CPK activity was high but similar in all samples, the main source being derived from the CPK-MM fraction. The CPK-MB fraction was absent in cord blood. Moreover, CPK-BB activity was significantly higher in capillary blood than in cord blood. These results suggest specific organ involvement in the production of CPK fractions.


Dihydroergotamine causes fetal growth retardation in guinea pigs. Dihydroergotamine is a vasoactive drug which enhances venous tone, central blood volume and cardiac output but has variable effects on arterial tone. Its effect on the uterine arterial circulation is unstudied and yet dihydroergotamine is widely used to treat postural hypotension in pregnant and nonpregnant women. For this reason we undertook studies to determine if its chronic use had any adverse effect on the placental arterial circulation and fetal growth in an animal model. We administered dihydroergotamine (14 micrograms/kg/day) to pregnant guinea pigs with 2-4 fetuses from day 30-60 of pregnancy. At term under light ketamine anaesthesia, we measured maternal arterial blood pressure and blood flow to myometrium, placenta, skin and skeletal muscle using left ventricular injection and standard sampling techniques. Vascular resistance was calculated from arterial blood pressure and blood flow. When controlled for litter size, both fetal weight and the fetal weight/placental weight ratio were significantly less (P less than 0.001) in the dihydroergotamine group (-21% and -11% respectively). Placental blood flow was decreased by 51% (P less than 0.01) whereas myometrial blood flow, skin blood flow and muscle blood flow were not significantly altered. There was no significant difference in mean arterial blood pressure but placental vascular resistance was increased (+45%, P less than 0.05) while it was unchanged in myometrium and skin and decreased in skeletal muscle (-51%, P less than 0.05). Chronic administration of dihydroergotamine at a clinical dosage level has a constrictive effect on the placental vasculature of guinea pigs with a subsequent adverse effect on flow and fetal growth.


Non-ovarian peritoneal papillary serous carcinoma with high CA125 levels. A patient with peritoneal papillary serous carcinoma involving the colon and omentum is presented. Following palliative right-sided hemicolectomy and partial omentectomy, chemotherapy was given. The patient had a second look operation after 6 months when a pelvic clearance was done and histology revealed some residual tumor in one mesosalpinx. She was well and clinically free of recurrence after a further 6 months. Serum CA125 and CEA levels were measured and CA125 levels remained high throughout.


Vaginal schwannoma.

Vaginal schwannoma. In the patient reported here, a solid tumor lying between the vagina and the rectum was detected using various imaging techniques (ultrasonography and MRI), and S100 protein was found in the tumor cells. Thus, a schwannoma was the final diagnosis. This is a slow-growing neoplasm, and its early detection is difficult.


Magnetic resonance imaging of uterine leiomyosarcoma. The magnetic resonance imaging (MRI) findings in a patient with uterine leiomyosarcoma are reported. MRI provides higher contrast resolution in soft tissues than ultrasonography or CT, and the MRI findings described in this case report suggest that MRI can be used to help differentiate between leiomyosarcoma from myoma.


Acute small bowel volvulus in adults. A sporadic form of strangulating intestinal obstruction. Small bowel volvulus is an uncommon but important cause of small intestinal obstruction. It often results in ischemia or even infarction. Delay in diagnosis and surgical intervention increases morbidity and mortality rates. Based on cause, small bowel volvulus can be divided into primary and secondary type. Goals for treatment of small bowel volvulus should include physician awareness of this uncommon diagnosis, accurate workup, and advanced surgical intervention. The presentation and subsequent management of 35 patients with small bowel volvulus confirmed by laparotomy are reviewed and discussed. The incidence of small bowel volvulus in the adult European and North American is low. The resultant mortality rate, however, makes diagnosis critically important. The cardinal presenting symptom is abdominal pain. There is no single specific diagnostic clinical sign or abnormality in laboratory or radiologic finding. In practice, the diagnosis can only be made by laparotomy. The failure to perform an exploratory laparotomy cannot be justified. Early diagnosis and early surgery are the keys for successful management of strangulation obstruction of the small bowel.


Multiple organ failure. Pathophysiology and potential future therapy. Multiple organ failure (MOF) has reached epidemic proportions in most intensive care units and is fast becoming the most common cause of death in the surgical intensive care unit. Furthermore, in spite of the development of successive generations of new and more powerful antibiotics and increasing sophisticated techniques of organ support, our ability to salvage patients once MOF has become established has not appreciably improved over the last two decades. Clearly, new therapeutic strategies aimed at preventing or limiting the development of the physiologic abnormalities that induce organ failure are needed to improve survival in these critically ill patients. Based on our rapidly increasing knowledge of the mechanisms of MOF and the fruits of molecular biology, a number of new therapeutic approaches are in various stages of development. To effectively use these new therapeutic options as they become available, it is necessary to have a clear understanding of the pathophysiology of MOF. Thus, the goals of this review are to integrate the vast amount of new information on the basic biology of MOF and to focus special attention on the potential therapeutic consequences of these recent advances in our understanding of this complex and perplexing syndrome.


Saline resuscitation after fixed-volume hemorrhage. Role of resuscitation volume and rate of infusion. The authors have reported previously that small-volume resuscitation (1.8 x bled volume) with 0.9% NaCl restores blood volume and attenuates hormonal responses after large hemorrhage without correction of arterial hypotension. The authors studied the role of rate of infusion in this observation in chronically prepared dogs (aortic flow probe, right atrial pressure and volume, and arterial catheters) after 30% hemorrhage (24.1 +/- 0.4 mL/kg). After 30 minutes, subjects were observed either without treatment (no resuscitation) or with infusion of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols: (1) impulse infusion over 10 minutes, (2) variable rate infusion, bolus with tapering infusion, or (3) constant rate infusion. Significant improvement in cardiac output and in blood volume and significant decreases of vasopressin and arterial catecholamines were observed in all fluid-treated groups. This benefit was relatively independent of rate of infusion, although impulse infusion produced greater early improvement, which dissipated with time, and constant rate infusion produced better late results. In none of the fluid-treated groups were these improvements reflected in improved mean arterial pressure compared with the no resuscitation group. The authors conclude that small-volume, slow-rate saline infusion produces physiologic benefits that cannot be assessed by easily measured clinical parameters. Thus, early resuscitation after trauma could aid patients even if arterial pressure is unchanged. This benefit might be even greater in patients with uncontrolled bleeding because arterial pressure, and hence bleeding, may not be increased by resuscitation of this type. A reassessment of the value of prehospital fluid resuscitation in the injured patient is warranted.


Biosynthetic human growth hormone preserves both muscle protein synthesis and the decrease in muscle-free glutamine, and improves whole-body nitrogen economy after operation. As a reproducible human trauma model, patients (n = 17) undergoing elective cholecystectomy were studied for 3 postoperative days. They were randomly allocated to receive either recombinant human growth hormone (hGH; 0.3 U/kg/24 hours) or placebo together with total parenteral nutrition, including 0.2 gN/kg/24 hours and 135 kJ/kg/24 hours. Before operation and on the third postoperative day, percutaneous muscle biopsies were performed to determine the concentration and size distribution of ribosomes and the free amino acid concentrations. The significant postoperative decrease in the total ribosome concentration (15.3 +/- 6.4%) and the polyribosome concentration (20.9 +/- 6.5%) in the control group was impeded in the group receiving synthetic hGH. Muscle free glutamine decreased by 35.6 +/- 4.2% in the control group and to a lesser extent in the group that was given hGH after operation (p less than 0.05). The protein content of skeletal muscle was unchanged. The cumulated nitrogen balance for the study period was negative in the control group (-7.09 +/- 0.71 gN), but was not different from zero in the hGH group (-2.32 +/- 1.66 gN). It is concluded that synthetic hGH administered after operation has beneficial effects on the whole-body nitrogen economy, as indicated by the unchanged capacity for protein synthesis in skeletal muscle, the preserved levels of muscle free glutamine, and improvement in the whole-body nitrogen balance. The effects of hGH on skeletal muscle protein and amino acid metabolism can explain the postoperative nitrogen-sparing effect attributed to hGH.


Preoperative and long-term cardiac risk assessment. Predictive value of 23 clinical descriptors, 7 multivariate scoring systems, and quantitative dipyridamole imaging in 360 patients. A total of 360 patients underwent preoperative cardiac risk assessment using 23 clinical parameters, seven multivariate clinical scoring systems, and quantitative dipyridamole-thallium imaging to predict postoperative and long-term myocardial infarction and cardiac death after noncardiac surgery. There were 30 postoperative and an additional 13 cumulative long-term cardiac events after an average follow-up of 15 months. Clinical descriptors were not useful in predicting the outcome of individual patients. The postoperative and long-term cardiac event rates were 1% and 3.5%, respectively, in patients with normal scans or fixed perfusion defects, and 17.5% and 22% in patients with reversible defects. Using quantitative indices reflecting the amount of jeopardized myocardium, patients could be stratified by dipyridamole imaging into multiple scintigraphic subsets, with corresponding postoperative and 1-year coronary morbidity and mortality rates ranging from 0.5% to 100% (p = 0.0001). Thus, postoperative and long-term cardiac events cannot be predicted clinically, whereas quantitative dipyridamole imaging accurately identifies high-risk patients who require preoperative coronary angiography.


Selected sperm differ from nonselected cells in their electrophoretic mobility (EPM) after demembranation. Human semen samples were first treated by swim-up migration or by Percoll density gradient centrifugation for selection of spermatozoa. The net surface charges of spermatozoa in the resulting compartments were indirectly evaluated by the electrophoretic mobility (EPM) during spermatozoal microelectrophoresis. Significantly different electrophoretic mobilities were measured between the compartments after demembranation with 0.1% (v/v) Triton X-100. However, without intermediate treatment by the detergent no significant differences were detected between the spermatozoal EPM. In addition, spermatozoa were divided into migrated and nonmigrated spermatozoal populations by the swim-up technique, and then treated with urea to remove spermatozoal coats. No significant differences in EPM were detected between these two groups. This investigation demonstrates that selected spermatozoa from semen exhibit an additional dimension of superiority, in EPM, to nonselected spermatozoa, which may better equip them for the process of fertilization. Measurements of EPM, therefore, may provide yet another, perhaps valid, means of developing a clinical tool for evaluating the potential fertilizing capacity of a semen sample in infertility studies.


A double method sperm wash for artificial insemination. Recently, there have been concerns regarding the presence of reactive oxygen species (ROS) produced during sperm processing for insemination. However, the sperm wash methods that yielded low ROS levels also had low sperm recovery after processing. The objective of this study was to compare sperm recovery after swim-up from pellet, overlay, and 2-layer Percoll wash methods with the recovery after the double method wash. The latter method consisted of a combination of 2 sperm wash methods, namely, the overlay and the Percoll method. Motile sperm were first collected through the overlay method. The leftover semen was then processed through the 2-layer Percoll method to scavenge motile sperm and the resultant pellet combined with the pellet from the overlay method. In this manner, the level of ROS was kept to a minimal, sperm recovery was improved, and a mixture of sperm with different surface properties was produced as a result of using different processing methods. The results indicated an improvement in sperm recovery and in total sperm motility in noncryopreserved sperm after using the double method wash when compared with the other wash methods. The study suggests that the double method wash is a feasible method for processing sperm for insemination.


Diet-induced changes in the male reproductive system of rats. Either quantitative or qualitative modification of diet interferes markedly with the reproductive functions of the rat. The effect of chick mash or cowpeas (Vigna unquiculata) on body growth, accessory sex organ weights, serum testosterone, and epididymal histology was studied. Body growth was markedly decreased in cowpeas fed group. Binucleated, multinucleated giant cells (MGCs), and lymphocytes were found in large numbers in the lumen of caput and cauda epididymis of the cowpea-fed group. No noticeable effect was seen in chick mash-fed group. Serum testosterone levels were significantly decreased in cowpea-fed group. Presence of MGCs in cowpea-fed animals indicates epididymal dysfunction and probably renders them infertile.


Testicular injury: late results of semen analyses after uniorchiectomy. Semen parameters from 4 patients with testicular injury after uniorchiectomy were investigated. Semen volume and sperm morphology were not affected after the operation, but sperm count and motility were severely diminished. Two of 4 cases showed azoospermia, and the other 2 cases showed low values in both sperm count and motility. After 150-300 days from the operation, 2 cases recovered to the normal range in sperm count while the other 2 remained in the abnormal range. In sperm motility, 3 cases recovered to the normal range but the rest remained abnormal. The results suggest that long-term follow-up in semen parameters is needed when unilateral orchiectomy is performed.


Glutathione therapy for male infertility. Eleven infertile men were treated with glutathione (600 mg/day IM) for 2 months. The patients were suffering from dyspermia associated with various andrological pathologies. Standard semen and computer analyses of sperm motility were carried out before treatment and after 30 and 60 days of therapy. Glutathione exerted significant effect on sperm motility patterns. Glutathione appears to have a therapeutic effect on some andrological pathologies causing male infertility.


Relatedness of the flagellins from methanogens. Purified flagellar filaments isolated from six methanogens were composed of multiple flagellins. Two flagellins were present in Methanococcus deltae (Mr = 34,000 and 32,000), Methanoculleus marisnigri (Mr = 31,000 and 25,500) and Methanococcus jannaschii (Mr = 31,000 and 27,500), three in Methanothermus fervidus (Mr = 34,000, 25,000 and 24,000) and four or more in both Methanococcus vannielii and Methanococcus maripaludis (Mr ranging from 27,500 to 32,000). The flagellins of M. fervidus and M. deltae reacted positively with glycoprotein-specific stains. The flagellins of M. deltae, M. maripaludis and M. vannielii were closely related to those of M. voltae based on cross-reactivity with antisera raised against M. voltae flagellins and homology with flagellin-specific oligonucleotide probes to the N-terminus and leader peptide of M. voltae flagellins. Similarities appear to exist among the flagellins of M. fervidus, M. marisnigri and Halobacterium halobium based on cross-reactivity with antisera produced against the flagella of Methanospirillum hungatei JF1. The N-termini of the flagellins from the mesophilic Methanococcus spp. and M. marisnigri show homology with the N-termini of other archaebacterial flagellins. These N-termini may undergo a modification involving removal of a leader peptide.


Effect of spermine on sperm capacitation of guinea pig in vitro. Spermine (Sp) 10(-5) mM had vigorous activity of guinea pig spermatozoa, while it completely abolished sperm forward motility (SFM) at a concentration of 10(-3) mM. There appeared to be a dose relationship to inhibition to motility. 2-Difluoromethylornithine 10 mM antagonized the Sp-induced inhibition of SFM after 3 h of incubation. Capacitation of a guinea pig sperm was inhibited by Sp in a concentration-dependent manner. The majority of acrosome-reacted sperm did not display hyperactivated motility. Precapacitated sperm were able to undergo the acrosome reaction (AR) in the presence of Sp. Moreover, Sp-mediated inhibition of capacitation was a reversible process. Once sperm capacitation was completed, Sp no longer inhibited AR. Before capacitation, the content of Sp in spermatozoa was 4.5 +/- 0.5 micrograms/5 x 10(7) cells, whereas in case of capacitated spermatozoa it was significantly decreased (2.1 +/- 0.4 micrograms/5 x 10(7) cells). The penetration of spermatozoa into the zona-free hamster eggs in the presence of Sp was markedly decreased, but it did not affect the fertilizability of ova as compared to the control. These results suggest that Sp may be an inhibitory agent of sperm capacitation in guinea pig in vitro, and it may also be involved in the modulation of capacitation.


Nickel-dependent reconstitution of hydrogenase apoprotein in Bradyrhizobium japonicum Hupc mutants and direct evidence for a nickel metabolism locus involved in nickel incorporation into the enzyme. A double mutant (JH103K10) was created from hydrogenase constitutive mutant (JH103) by replacement of a chromosomal 0.60 kb nickel metabolism related locus with a kanamycin resistance gene. The double mutant required 10 to 20 times more nickel (Ni) to achieve near parental strain levels of hydrogenase activity. In the absence of nickel, both JH103K10 and JH103 synthesized high levels of (inactive) hydrogenase apoprotein (large subunit, 65 kDa). With nickel, the double mutant JH103K10 synthesized the same level of hydrogenase apoenzyme (65-kDa subunit) as the JH103 parent strain; however, whole cell hydrogenase activity in JH103K10 was less than half of that in JH103, and the CPM (due to 63Ni in hydrogenase) of membranes and the calculated ratio of nickel per unit of hydrogenase enzyme of the double mutant were 40% of that in JH103. Therefore, the difference in hydrogenase activities between the double mutant and the Hupc strain can be accounted for by different abilities of the strains to incorporate nickel into the hydrogenase apoenzyme. The addition of nickel ions to previously Ni-starved and then chloramphenicol-treated Bradyrhizobium japonicum whole cells (JH103 and JH103K10) resulted in (an in vivo) restoration of hydrogenase activity, suggesting that the apoprotein synthesized in the Ni-free cultures could be activated by addition of nickel even in the absence of protein synthesis. The extent of reconstitution of active hydrogenase by nickel was greater in the absence of chloramphenicol. Hydrogenase apoprotein could not be activated by nickel in vitro even with the addition of ATP. The successful in vivo but not in vitro results suggest that enzymatic but cell-disruption labile factors are required for Ni incorporation into hydrogenase.


Adverse effects of chronic GnRH antagonist administration on seminiferous epithelium in adult rats. Seminiferous epithelium in adult rats was studied by light and electron microscopy after 5 weeks of chronic administration of GnRH antagonist (Ac-D2 Nal 1, D4ClPhe 2, DTrp 3, DArg 6, DAla 10; GnRH code-103-289-10, National Institutes of Health, USA). In these rats, the epithelium showed significant accumulation of vacuoles in more than 80% of the tubules, along with germ cell degeneration and nuclear pyknosis. Disruption in the process of spermatogenesis was also very much evident. In most of the tubules studied (greater than 90%), germ cell development was arrested beyond the pachytene spermatocyte stages. The vacuoles in the seminiferous epithelium were different sizes and when magnified were seen to consist of a thickened outer margin of solid nonfibrous coat within the Sertoli cell cytoplasm. Associated changes in the interstitium showed increased intertubular space but no inflammatory type of response. In actual cell counts, the decrease in the average number of macrophages was 32% and in Leydig cells 23%, while the total number of all types of cells in the interstitium was 30% less than that of the controls. Following the treatment, weights of testis, epididymis, seminal vesicle, and ventral prostate were drastically reduced. Rats treated with testosterone supplementation (60 micrograms/rat day) to GnRH antagonist recovered testicular and epididymal weights to approximately 57% and seminal vesicle and ventral prostate weights by 82.9 and 84%, respectively. Normalcy returned to the tubular epithelium and the interstitial cell counts were restored to original levels.


Purification and properties of a F420-nonreactive, membrane-bound hydrogenase from Methanosarcina strain Gö1. The distribution of the F420-reactive and F420-nonreactive hydrogenases from the methylotrophic Methanosarcina strain Gö1 indicated a membrane association of the F420-nonreactive enzyme. The membrane-bound F420-nonreactive hydrogenase was purified 42-fold to electrophoretic homogeneity with a yield of 26.7%. The enzyme had a specific activity of 359 mumol H2 oxidized.min-1.mg protein-1. The purification procedure involved dispersion of the membrane fraction with the detergent Chaps followed by anion exchange, hydrophobic and hydroxylapatite chromatography. The aerobically prepared enzyme had to be reactivated anaerobically. Maximal activity was observed at 80 degrees C. The molecular mass as determined by native gel electrophoresis and gel filtration was 77,000 and 79,000, respectively. SDS gel electrophoresis revealed two polypeptides with molecular masses of 60,000 and 40,000 indicating a 1:1 stoichiometry. The purified enzyme contained 13.3 mol S2-, 15.1 mol Fe and 0.8 mol Ni/mol enzyme. Flavins were not detected. The amino acid sequence of the N-termini of the subunits showed a higher degree of homology to eubacterial uptake-hydrogenases than to F420-dependent hydrogenases from other methanogenic bacteria. The physiological function of the F420-nonreactive hydrogenase from Methanosarcina strain Göl is discussed.


Accuracy in diagnosis of ectopic pregnancy by transvaginal ultrasonography. Forty patients suspected to have ectopic pregnancy by transvaginal ultrasonography had surgery. 77.5% were confirmed to have ectopic pregnancy and 10% had other abnormal pelvic findings. The transvaginal approach appears to enable us to diagnose ectopic pregnancy at an earlier date, with the earliest diagnosis made at 4 weeks 0 days of amenorrhoea. In cases of confirmed ectopic pregnancy, the presence of a complex adnexal mass was the most common feature seen on transvaginal ultrasound and its predictability of ectopic pregnancy is enhanced by a concomitant finding of an empty uterus (95%) or free fluid in the Pouch of Douglas (94%) in the presence of a positive hCG test. The significance of transvaginal ultrasound features, and the advantages of transvaginal over transabdominal ultrasound, are discussed.


Epidermal growth factor contents in seminal plasma as a marker of prostatic function. Epidermal growth factor (EGF), first identified in extracts from submaxillary salivary glands of adult male mice, acts as a potent mitogen in a wide variety of cells and tissues in culture. Human EGF, a polypeptide of 53 amino acids isolated from human urine, has been identified in several biological fluids, including prostatic fluid and seminal plasma. Epidermal growth factor content in seminal plasma was measured by RIA. The EGF content in seminal fluid did not change after bilateral vasectomy and the first fraction of sample obtained by split ejaculation contained a significantly larger amount of EGF than the second fraction. Seminal EGF originates from the prostate. There was a close correlation between EGF and zinc contents in seminal fluid. The seminal fluid EGF content was lowered in patients with prostatitis and systemic androgen deficiency. The EGF content in seminal fluid seems to be a reliable indicator of prostatic function.


Sonographic evaluation of clinical suspicion for ectopic pregnancy. Analysis of transabdominal ultrasonic findings of 167 patients presented with clinical suspicion of extrauterine pregnancies (EUP), all with measurable serum HCG, has been undertaken. Patients were divided into two main groups, namely those with demonstrable typical intrauterine gestational sac (46.7%), and those without (53.3%). This later group of patients, i.e., without intrauterine sac, was further subdivided into four other groups depending on whether or not they have adnexal mass and/or fluid in cul-de-sac. In this first subgroup of patients (21 cases), without any demonstrable mass or fluid, a positive predictive value (PPV) for EUP of only 28.6% was obtained. With ultrasound showing fluid but no mass, the PPV was 55.6%, while those with both mass and fluid, the PPV as high as 95.7% was possible. Characterization of the adnexal mass or cul-de-sac findings among those with empty uterus may further improve PPV. The results of this study indicates that ultrasonic examination can help to provide a more correct diagnosis in the investigation of EUP. EUP can be easily excluded, in the great majority of cases, with sonographic visualization of intrauterine pregnancy. In the case of empty uterus with no mass or fluid, patients should be closely followed up with HCG titer and ultrasonic examination. For those with empty uterus with fluid, culdocentesis may be indicated; whereas in the case of empty uterus with mass, laparoscopy should be considered as additional investigative procedures.


Effects of human antisperm antibodies on development of preimplantation embryos. The effects of antisperm antibodies (ASAs) present in sera of immunoinfertile patients and vasectomized men were investigated on preimplantation embryonic development in mice. Of the nine immunoinfertile sera tested, two were effective in inhibiting blastulation rates of in vitro cultured murine 2-cell embryos (p less than .05 to .002). Similarly, sera from two of the three vasectomized men were capable of affecting early embryonic development in mice (p less than .05 to .002). Specificities of the embryotoxic effects of ASAs were further confirmed by culturing embryos in the presence of affinity-purified monovalent Fab' antibodies isolated from these sera. Fab' antibodies from only one of the two immunoinfertile patients whose sera affected blastulation rates, and from one of the three vasectomized men were effective in influencing blastulation rates of in vitro cultured 2-cell murine embryos (p less than .05 to .001), mainly due to an arrest of development at 2 to 8-cell and morula stages. In the Western blot procedure, none of the immunoinfertile Fab' antibodies recognized any specific band on blots of extracts from murine ova or 2-cell embryos. However, all the immunoinfertile Fab', but not fertile control Fab', specifically recognized a protein band in the M(r) 25 +/- 2 kD region, on the Western blots of extract from murine blastocyst stage embryos. In addition, Fab' from one immunoinfertile serum, which inhibited embryonic development, reacted specifically with a protein band in the lower molecular range (approximate M(r) 12 kD) on Western blot involving exact from blastocysts. Fab' antibodies of sera from vasectomized men did not react with any specific protein band on blots of extracts from murine ova, 2-cell embryo, or blastocyst. These results suggest that ASAs from some immunoinfertile patients and vasectomized men, especially those reacting with 12-kD blastocyst protein, are capable of affecting preimplantation embryonic development in mice, and thus may contribute toward immunologically medicated infertility both at fertilization and postfertilization stages.


Sheehan's syndrome following eclampsia: a case report. A case of Sheehan's syndrome following eclampsia is presented. The clinical features were not recognised early probably because the condition was not suspected, being a rare sequel of eclampsia. Non availability of specialist care may have been partly responsible and is highlighted. Increased awareness of all possible aetiological factors in this condition is necessary for clinicians.


Prenatal diagnosis of holoprosencephaly by transvaginal ultrasonography in the first trimester. A diamniotic-monochorionic pregnancy of twins was revealed by transvaginal ultrasonography: one fetus with holoprosencephaly was diagnosed at 11 weeks of gestation. This is the first case of holoprosencephaly diagnosed in the first trimester. Prenatal diagnosis of this anomaly in the first trimester is now possible by transvaginal ultrasonography.


Clinical course of early fetal loss and its chromosomal characteristics. The relationship between types of chromosomal abnormalities and fetal development documented by ultrasonography was discussed in early spontaneous abortions. The subjects were 113 patients who had vaginal ultrasonography at least twice between 6 and 8 weeks of pregnancy, among 167 abortuses with chromosome analyzed. The results were also compared against those for 303 normally developing fetuses. The results obtained in the present study suggested that each fetus with a chromosomal abnormality succumbed at or after a specific stage of fetal development and that the fetal death might be the results of severe fetal growth suppression.


Elastase activity of endocervical mucus in normal pregnancy. Elastase activity of 294 samples of endocervical mucus taken from 125 normal pregnant women during the visits to antenatal clinic were measured. Activity of the enzyme increased gradually with the advance of gestational age. Steep rising of the enzyme was seen between 34-35 weeks of gestation and the peak was achieved at 37 week since then the enzyme activity sustained at relatively high level until deliveries. Average activity of the enzyme after 34 weeks of gestation showed significant difference over that of earlier period. To use delivery date as a referent point, the peak was reached in the last fourth week of pregnancies and then sustained until deliveries. Significantly higher average activity was also seen in these last 4 weeks of gestation. These correlated very well to the fact that cervical maturation progresses most rapidly during last month of pregnancy. Immunohistochemical staining for elastase demonstrated elastase-containing granules in polymorphonuclear leukocytes. These cells found in cervical tissue taken from immediately postpartal women were much more than in those of early pregnant women. These findings may be the evidences support roles of granulocyte elastase in the process of cervical maturation preceding spontaneous labors in normal pregnancies.


The Israel perinatal census.

The Israel perinatal census. A nation-wide perinatal census which included 22,815 deliveries was carried out. The cesarean section rate was 9.6% and the perinatal mortality rate was 13.5/1000. Using a logistic regression analysis the risk factors for cesarean section and for perinatal mortality were ranked. Breech presentation and one uterine scar were found to be the most important risk factors for cesarean section and breech presentation, maternal disease and multiple pregnancy for perinatal mortality. Low birth weight rate was 6.9% with nonsignificant differences between the various ethnic groups. The national cesarean section rate in breech presentation was 57.8%. It was performed mainly at the extremes of birth weight. From those with one previous cesarean section 55.1% delivered vaginally and 44.9% abdominally. The chance for vaginal delivery is higher (67.2%) providing the woman had delivered vaginally in the past. Comparison between primiparae and multiparae showed that preeclampsia, hypertension and diabetes mellitus were all significantly more frequent among older parturients and among primiparae.


The immunohistochemical localization of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in human and cynomolgus monkey placentae. New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated by avidin-biotin immunoperoxidase technique in the human and cynomolgus monkey placentae, decidua and umbilical cords. In human early placentae, MP2 A, B, C, and E were localized mainly in the membrane of villous syncytiotrophoblasts and cytotrophoblasts. Histiocytes in the villous stroma were positive for MP2 A, B, D, and E. In human term placentae, obvious positive staining for MP2 A, B, C, and E was observed in the membrane of villous syncytiotrophoblasts, in the amniotic epithelium, and in the umbilical cord sheath. Histiocytes in the villous stroma were positive for MP2 A, B, C, E, and especially for MP2 D. Importantly, MP2 A, C, and E were positive in polymorphonuclear neutrophils, since most of these common antigens are also carcinoma-associated, suggesting clinical usage of MP2 proteins as a new tumor marker. In the cynomolgus monkey placentae, similar immuno-staining results were obtained. The monkey can thus serve as a experimental model for the investigation of the placental proteins.


Cell-mediated immunity in cervical intraepithelial neoplasia. Various immune parameters, i.e., peripheral T and B cell distribution, T cell subpopulation, interleukin 2 (IL-2) activity and in vitro lymphocyte responses to phytohemagglutinin (PHA) and concanavalin A (Con A), were investigated in 24 pretreated patients with cervical intraepithelial neoplasia (CIN) and in 35 normal controls. Of the measured parameters, lymphocyte response to PHA was significantly lower in the CIN than control group (P less than 0.05). The values of all other measured parameters were similar in both groups.


The effect of nifedipine and dipyridamole on the Doppler blood flow waveforms of umbilical and uterine arteries in hypertensive pregnant women. In a study of 45 hypertensive pregnant women, the systolic velocity/diastolic velocity ratio and pulsatility index of the umbilical and uterine arteries showed good correlation with the maternal blood pressure, and they appeared to provide a good parameter for the fetoplacental condition. Using the pulse Doppler method, we studied the effects of the antihypertensive agent nifedipine and of dipyridamole (an agent used to treat proteinuria) on the blood flow of the umbilical and uterine arteries in 16 hypertensive pregnant women. The results proved that both drugs caused a decrease in the vascular resistance of the umbilical artery and suggested that they increased the blood flow volume of this artery and were useful in the treatment of hypertension during pregnancy.


Malakoplakia of the omentum and endometrium. A rare case of malakoplakia involving the omentum and endometrium is presented. This is the first documented case of malakoplakia in the Thai population.


Experience with screening for abnormal glucose tolerance in pregnancy: maternal and perinatal outcome. In order to determine the prevalence of glucose intolerance in pregnancy, 2,230 consecutive women attending the antenatal clinic at the Aga Khan University Medical Centre in Karachi, Pakistan were subjected on the first antenatal visit, irrespective of gestational age, to a 75 g glucose challenge followed 2 hr later by plasma glucose determination. The test, was repeated at 28-32 weeks of gestation for those patients who had an abnormal initial screen at less than 28 weeks gestation followed by a normal glucose tolerance test and for those who had a risk factor for gestational diabetes even though the initial screen at less than 28 weeks gestation was normal. The initial glucose challenge test was abnormal (2 hr plasma glucose greater than 140 mg%) in 8.6% of the screened population. An oral glucose tolerance test on these patients revealed a prevalence for the entire population of 3.5% of gestational diabetes and 1.9% of impaired glucose tolerance test based on the modified O'Sullivan criteria. Patients with abnormal glucose tolerance test were older, had higher parity, a past history of macrosomia and a family history of diabetes compared to the controls. These patients also had a higher incidence of preterm labour and caesarean section. In the neonates hypoglycemia and hyperbilirubinemia were similarly higher. The fetal abnormality rate was 5.6% and the perinatal mortality was 28/1,000 which were higher than the controls.


Analysis of relative mRNA levels and protein patterns in brains of rat strains bred for differing levels of emotionality. mRNA and protein populations were studied in the brains of Maudsley reactive (MR) and Maudsley nonreactive (MNR) rat strains, which exhibit differing levels of emotionality. Translational analysis of forebrain mRNA indicated that the relative levels of two translation products (42 kDA, pI 5.0; 30 kDa, pI 5.8) were increased in the MR compared to the MNR strain. In addition, a charge-shift variant of a 36 kDa protein was present in the MR strain. Analysis of brain protein patterns indicated that a protein of 39 kDa, pI 5.0, was found to be more abundant in MR compared with MNR strains in both frontal cortex and hippocampus and the relative level of one protein (40 kDa, pI 5.8) was decreased in the frontal cortex.


The hyperactive spontaneously hypertensive rat learns to sit still, but not to stop bursts of responses with short interresponse times. The spontaneously hypertensive rat (SHR) is hyperactive and has been proposed as an animal model of attention-deficit hyperactivity disorder (ADHD). Although ADHD in most cases is treated with central stimulants, behavior therapy has also been used, but with relatively limited success. The purpose of the present study was to investigate suppression of SHR hyperactivity by differentially reinforcing immobility (DRI) using a positive reinforcer. The DRI schedule required that the rat remain immobile in a particular part of an operant chamber, the target, in order to obtain the reinforcer. The time requirement, the DRI value, of these periods was increased progressively. The results showed that time spent on the target increased by increasing DRI value in both hyperactive and control rats. However, the total number of movements, on as well as outside the target, was higher for the hyperactive rats. The behavior grouped into two independent response components. One component consisted of immobility responses with durations less than 1 s, actually bursts of active responses; the other component consisted of immobility responses with durations more or less matching the DRI requirement. The reinforcement schedule modified the long-lasting immobility component in both groups. SHR received more reinforcers than WKY as long as the schedule did not require too long periods of immobility. However, the total number of movements on target was not reduced in SHR; on the contrary, it increased somewhat as the schedule requirements increased. If the behavior of ADHD children consists of two, or more, independent components similar to the ones observed in the present study, the present results may offer an explanation of why behavior therapy has limited success in the treatment of ADHD.


Are paw preference differences in HI and LO mice the result of specific genes or of heterosis and fluctuating asymmetry? Collins (1985) has described two separate mouse strains, obtained by selective breeding, which differ in having high (HI) or low (LO) degrees of paw preference on a standard test. In this paper I argue that the differences between these strains may not be due to a specific gene (or genes) but, instead, probably reflect differences in the total heterozygosity of the strains, such that the HI strain is more heterotic than the LO strain. Greater degrees of heterozygosity are argued to buffer against fluctuating asymmetry and hence result in a greater degree of paw preference.


A biometrical genetic approach to chromosome analysis in Drosophila: detection of epistatic interactions in geotaxis. Chromosome analysis has been widely used as a first step in elucidating the genetic architecture of several behaviors of Drosophila melanogaster. These chromosome studies have generally used incomplete designs or fairly simple statistical analyses. Here I reanalyze two data sets on geotaxis from Pyle (1978) and Ksander (1966) using a biometrical genetic design. Results from the biometrical genetic reanalysis suggest that individual differences in geotaxis might be due to genes on all three major chromosomes which show extensive epistatic interactions.


Male sexual signaling is defective in mutants of the apterous gene of Drosophila melanogaster. The apterous (ap) gene of Drosophila melanogaster exhibits extreme pleiotrophy: its functioning is essential for life, normal wing structure, juvenile hormone production, female fertility, and normal development of female sexual receptivity. Four mutant ap alleles (ap4, ap56f, apc, and apblt) were characterized for three additional phenotypes: male mating success, courtship behavior, and immature male sex appeal (the ability of males to stimulate homosexual courtship). Mating success with mature wild-type virgin females is reduced in males mutant for the ap gene, the extreme case being ap4/ap4 males, which are behaviorally sterile. In ap mutants, nonwing courtship elements are qualitatively like those of ap+/ap+ males. However, the mean rate of nonwing courtship directed toward virgin wild-type females (i.e., the mean temporal frequency of these displays) is reduced in males homozygous for ap4, ap56f, or apc alleles. In contrast, the apblt allele makes for wild-type rates of nonwing courtship. Immature male sex appeal persists for at least 3 days in males homozygous for apc and, to a lesser extent, in ap56f or ap4 homozygotes; apblt/apblt and wild-type males lose immature male sex appeal after 1 day. All three male phenotypes map to the ap locus, which is therefore essential for the development of normal levels of male courtship and male mating success and for the timely loss of immature male sex appeal. For each phenotype, ap+ is dominant to ap alleles making for behavioral abnormalities, with a single exception (for rate of nonwing courtship, ap+/apc was low). For mating success and frequency of nonwing courtship, each allele pair exhibits at least partial complementation, except for ap4 and ap56f, which fail to complement. For immature male sex appeal, apc, ap4, and ap56f fall into the same complementation group. Juvenile hormone production is not correlated with effects on male reproductive behavior.