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Biomedical subjects

S L Gorbach

Publications and source records attributed to S L Gorbach.

At least 19 recordsLinked to original sources

Survival of Lactobacillus species (strain GG) in human gastrointestinal tract.

A newly isolated strain of a species of Lactobacillus of human origin, designated GG (Lactobacillus GG), has been studied to determine its ability to survive in the human gastrointestinal tract. When fed to 76 volunteers as a frozen concentrate or as a fermented preparation in milk or whey, Lactobacillus GG was recovered in the feces of all subjects receiving the fermented milk or whey and in 86% receiving the frozen concentrate when a single fecal specimen was cultured. The organism was also present in the feces of subjects concurrently receiving ampicillin. After terminating feeding of the organism, Lactobacillus GG persisted in the feces of 87% of volunteers four days later and in 33% of subjects seven days later. Lactobacillus GG lowered fecal bacterial beta-glucuronidase activity by approximately 80% in volunteers given the organism for four weeks. These studies demonstrate that Lactobacillus GG can survive and temporarily colonize the human gastrointestinal tract and can affect the metabolic activity of the resident microflora.

Digestive System

Enhancing the level of nutrition education at Tufts University's Medical and Dental Schools.

The current medical and dental curricula at Tufts were evaluated to ascertain the breadth and depth of their nutrition programs. The program, which both schools plan to initiate, to enhance the level of nutrition education involves (1) development of nutrition units for the first and second year, (2) expansion of required nutrition courses in the second year, (3) diet lunches in the third year introducing the role of nutrition in the clinical setting, and (4) nutrition rounds in the fourth year. A combined medical-dental seminar will be presented each year. At the end of the five-year funding period, it is anticipated that a manual will be available to all medical and dental schools that includes (1) nutrition units, (2) methods of dietary assessment in medical-dental practices, (3) nutrition interaction for the prevention of chronic disease in medical-dental practices, and (4) nutrition support for chronic disease and cancer, and case studies on nutrition and disease. The success of this program will be evaluated on the basis of goals and a national nutritional literacy exam.

Boston

Evaluation of new anti-infective drugs for surgical prophylaxis. Infectious Diseases Society of America and the Food and Drug Administration.

It has been established by substantial research that antimicrobial prophylaxis for various surgical procedures can reduce the risk of postoperative morbidity and mortality. When the incidence of infectious complications is high, the reduction with prophylaxis is most dramatic. However, even for many "clean" procedures (vascular procedures, total joint replacement), the small reduction in potentially calamitous complications justifies the use of prophylaxis. Many issues of detail remain unanswered: timing and duration of administration of antimicrobial drug; type of drug; use of topical anti-infective agents as ancillary measures; and choices for high-risk individuals and others ordinarily excluded from clinical trials. An approach to the conduct of clinical trials of anti-infective drugs for surgical prophylaxis is provided. Both general guidelines and specific recommendations for total hip replacement, colorectal operations, appendectomy, and transurethral resection of the prostate are included.

Anti-Infective Agents

Food use and health effects of soybean and sunflower oils.

This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oils.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women.

Fifteen young (22-35 y) and 10 older (51-71 y) women received six capsules of fish oil (Pro-Mega)/d, providing a total of 1,680 mg eicosapentaenoic (EPA), 720 mg docosahexaenoic (DHA), 600 mg other fatty acids, and 6 IU vitamin E. Blood was collected before and after 1, 2 and 3 mo of supplementation. Compliance was confirmed by the significant increase in plasma EPA and DHA in all women. Older women had a significantly higher increase in EPA and DHA than did young women (10-fold increases in EPA and 2.5-fold increases in DHA vs. 8-fold in EPA and 2-fold in DHA for older and young women, respectively). The decrease in the arachidonic acid:EPA ratio was more dramatic in the older women. Plasma total triglycerides (TG) decreased significantly, and the ratio of polyunsaturated fatty acids to saturated fatty acids was significantly (P less than 0.01) increased. Plasma vitamin E levels did not change significantly after supplementation; however, after 3 mo of supplementation by young women, plasma vitamin E was significantly lower than after 1 mo. The vitamin E: TG ratio was significantly increased and vitamin E:(EPA + DHA) significantly decreased. All women showed a significant increase in plasma lipid peroxide through mo 2 of supplementation. After 2 mo, older women had significantly higher lipid peroxide levels than young women. The lipid peroxide:TG ratio, which declined by mo 3, was still significantly higher than baseline. These data indicate that although long-term fish oil supplementation may be beneficial in reducing plasma total TG, susceptibility of plasma lipids to free radical attack is potentiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women.

The effect of (n-3) fatty acid supplementation on cytokine production and lymphocyte proliferation was investigated in young (23-33 y) and older (51-68 y) women. Subjects supplemented their diets with 2.4 g of (n-3) fatty acid/d for 3 mo. Blood was collected before and after 1, 2 and 3 mo of supplementation. The (n-3) fatty acid supplementation reduced total interleukin (IL)-1 beta synthesis by 48% in young women but by 90% in older women; tumor necrosis factor was reduced by 58% in young and 70% in older women. Interleukin-6 was reduced in young women by 30% but by 60% in older women. Older women produced less IL-2 and had lower mitogenic responses to phytohemagglutinin (PHA) than young women prior to (n-3) fatty acid supplementation. The (n-3) fatty acid supplementation reduced IL-2 production in both groups; however, this reduction was significant only in older women. The PHA-stimulated mitogenic response was significantly reduced by (n-3) fatty acid in older women (36%). Thus, long-term (n-3) fatty acid supplementation reduced cytokine production in young women and cytokine production and T cell mitogenesis in older women. The reduction was more dramatic in older women than in young women. Although (n-3) fatty acid-induced reduction in cytokine production may have beneficial anti-inflammatory effects, its suppression of IL-2 production and lymphocyte proliferation in older women may not be desirable.

Adult

Lactic acid bacteria and human health.

Although claims for health and nutritional benefits have been made for lactic acid bacteria in fermented dairy products for nearly a century, the nutritional and therapeutic value of these organisms is still controversial. This article will review the scientific basis of these claims. There are numerous studies showing fermentation of food with lactobacilli increase the quantity, availability, digestibility, and assimilability of nutrients. The basis for this conclusion comes from direct measurements of vitamin synthesis and from increased feed efficiency when fermented products are fed to animals. There have been a number of studies showing that various fermented dairy products lower serum cholesterol levels in humans and animals. These studies are reviewed and the validity of these findings are assessed. A summary of the evidence indicating that lactase deficient individuals can eat yogurt and the mechanisms involved in this toleration is reviewed. The role of fermented dairy products in inhibiting tumor growth and chemically induced tumors in animals is discussed and the possible mechanisms involved in this protective effect are reviewed. Fermented dairy products and lypholized lactobacilli preparations have been shown to be useful in treating and preventing various intestinal infections including; salmonellosis, shigellosis and antibiotic induced diarrhea. In this context a specific lactobacillus designated GG has been shown to be useful in treating recurring diarrhea caused by a toxin produced by Clostridium difficile.

Carcinogens

Preoperative prophylactic cephalothin fails to control septic complications of colorectal operations: results of controlled clinical trial. A Veterans Administration cooperative study.

Data obtained from a survey of the membership of the Society for Surgery of the Alimentary Tract and the American Society of Colon and Rectal Surgeons indicated that concomitant administration of oral neomycin-erythromycin base and systemic cephalothin, together with mechanical colon cleansing, was the most popular method of colon preparation. We designed a prospective double blind clinical trial to compare administration of intravenous cephalothin, oral neomycin-erythromycin base, and the combination of both the intravenous and oral antibiotics. Intake of patients to the intravenous cephalothin group was stopped because the data indicated that this method of prophylaxis resulted in significantly higher numbers of septic complications. The incidence of wound infection was 30 per cent and the overall incidence of septic complications was 39 per cent in patients receiving only intravenous cephalothin combined with mechanical colon cleansing. The incidence of wound infection and the overall incidence of septic complications was only 6 per cent in the comparison group, and the differences are highly significant.

Aminoglycosides

Plasmid-mediated, transferable resistance to clindamycin and erythromycin in Bacteroides fragilis.

A clindamycin- and erythromycin-resistant strain of Bacteroides fragilis, TMP10, that had been isolated from a blood culture transferred its drug resistance in a Millipore mating procedure to another strain of B. fragilis, TM2000, and to a strain of Bacteroides thetaiotaomicron. Donor strain TMP10 contained numerous species of extrachromosomal DNA ranging from approximately 2 x 10(6) to 20 x 10(6) daltons in molecular weight, as revealed by agarose gel electrophoresis. Clindamycin- and erythromycin-resistant transcipient cells of B. fragilis strain TM2000 always contained at least two plasmid species with molecular weights of 2 x 10(6) and 20 x 10(6) daltons, respectively, although other plasmid species were also transferred.

Bacteroides

Netilmicin in gram-negative bacterial infections.

Netilmicin, a new semisynthetic aminoglycoside, was used in the treatment of 42 patients with serious gram-negative bacterial infections. Of the 40 evaluable patients, 24 (60%) were cured, and 8 (20%) had a favorable clinical response, for a total clinical response rate of 80%. Eight patients failed to respond; of these, three had undrained abscesses and two had severe granulocytopenia. Three of the patients who failed had organisms in which resistance to netilmicin developed during therapy, and in two of these three netilmicin was the only aminoglycoside to which resistance developed. Of the 37 patients evaluable for toxicity, 8 (22%) developed renal insufficiency. Two patients had mild but persistant elevation in serum creatinine. Three patients had nephrotoxicity while on gentamicin in the past. Pre- and posttherapy audiograms were done on 26 patients; none had hearing loss. Four patients had mild, transient asymptomatic elevations in alkaline phosphatase. The pretreatment clinical isolates were tested for in vitro susceptibility. The median minimal inhibitory concentration of netilmicin, gentamicin, and tobramycin ranged between 0.5 and 2 mug/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.

Bacterial Infections

In vitro activity of LY127935.

The activity of LY127935, a beta-lactam antibiotic of novel structure, was studied in vitro against facultative gram-negative bacilli, Staphylococcus aureus, and Bacteroides fragilis. The strains were recent clinical isolates, many of which were relatively resistant to other antibiotics. LY127935 exhibited striking activity against Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Proteus sp., Serratia marcescens, and B. fragilis with median minimum inhibitory concentrations of less than or equal to 1.0 micrograms/ml. It was somewhat less active against Pseudomonas aeruginosa and S. aureus. Cefotaxime (HR 756) showed very similar activity except that it was substantially weaker against B. fragilis. LY127935 was more active than cefamandole, cefoxitin, or piperacillin; it was also as potent as tobramycin or amikacin against all species except for P. aeruginosa.

Anti-Bacterial Agents

Inactivation of cephalosporins by Bacteroides.

We investigated the relationship between beta-lactamases of Bacteroides fragilis organisms and their resistance to cephalosporins. Timed killing curves were used to study the in vitro activity of three cephalosporins, cephalothin, cefazolin, and cefamandole, and a semisynthetic cephamycin, cefoxitin. Measurements of residual antibiotic concentrations in culture supernatants were made, and they were compared with the beta-lactamase activity of the microorganism. A cephalosporin-susceptible strain was rapidly killed by cephalothin, cefazolin, cefamandole, and cefoxitin. Four cephalosporin-resistant strains were not killed by cephalothin, cefazolin, or cefamandole but were killed by cefoxitin. An inoculum effect was noted with cefazolin and not with cefoxitin. The resistant strains of Bacteroides inactivated the three cephalosporins, but there was no inactivation of cefoxitin. A constitutive beta-lactamase was detected in all the isolates of the B. fragilis group that were resistant to the cephalosporins. There was no distinction of the species based on isoelectric focusing of the enzyme. These data suggest that inactivation by beta-lactamase may be the mechanism for resistance of B. fragilis to the cephalosporins and would explain the enhanced in vitro activity of cefoxitin.

Bacteroides

Hemagglutination and adhesiveness of toxigenic Escherichia coli isolated from humans.

Toxigenic strains of Escherichia coli isolated from humans were studied for adherence to human buccal mucosal epithelial cells. The E. coli strains were labeled with 3H-amino acids or fluorescein isothiocyanate. Toxigenic E. coli strains varied in their ability to adhere in the presence of mannose. Of 32 toxigenic strains examined, 52% bound to the buccal cells, whereas none of 8 control strains did so (Mann-Whitney U test, P =0.007). The control strains were nontoxigenic E. coli isolates from humans, enterotoxigenic E. coli isolates from animals, and E. coli K-12 containing the K88 or K99 plasmid; these strains exhibited only background-level adherence in this assay. Among the toxigenic E. coli strains that bound to human buccal mucosal cells, there was no correlation with mannose-resistant hemagglutination (MR-HA) of guinea pig and human erythrocytes. Screening 32 strains, we found the following phenotypes: (i) MR-HA+, buccal adherent; (ii) MR-HA+, buccal nonadherent; (iii) MR-HA-, buccal adherent. Presumably the third group represents strains with another type(s) of surface attachment components not involved in the MR-HA reaction. Our findings indicate that a number of bacterial surface structures can function in MR-HA and buccal adherence.

Agglutinins

Ultrastructural changes of cultured human amnion cells by Clostridiu difficile toxin.

The ultrastructure of the surface of primary human amnion monolayer cells undergoing cytopathology induced by Clostridium difficile toxin was examined by scanning electron microscopy. Our observations indicated that the type and distribution of cell surface projections were altered dramatically by this toxin. The patterns of such surface changes were specific for the two different types of cells found in this cell culture. Cells with demarcated borders showed rearrangement of microvilli into globular chains or ridges which lined up with the branching membrane. Cells without demarcated borders exhibited studlike microvilli, all arranged into ridges or globular chains. These changes were noted after 1 h of toxin exposure and persisted without further progression, in spite of continued toxin exposure, up to 48 h. These data indicate that C. difficile produces a cytolytic toxin and that scanning electron microscopy may be useful in determining toxin-cell interactions.

Amnion