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Biomedical subjects

S L Gorbach

Publications and source records attributed to S L Gorbach.

At least 55 records · Page 3Linked to original sources

The effect of dietary fat and fiber on serum estrogen concentrations in premenopausal women under controlled dietary conditions.

The effect of dietary fiber and fat on serum sex hormones was studied in premenopausal women. After an initial control period during which the diet was high in fat (40% of calories as fat) and low in fiber (12 g/day), the amounts of fat and fiber were varied in the setting of a metabolic kitchen and carefully monitored meals. Forty-eight women completed 58 protocols. When the diet was changed to low-fat (20-25% calories as fat) and high fiber (40 g/day), there were significant decreases in serum concentrations of estrone, estrone sulfate, testosterone, androstenedione, and sex hormone binding globulin (SHBG) and near significant decreases in estradiol and free estradiol. When independent effects were examined, high fiber alone caused a decrease in estradiol and SHBG, whereas fat and fiber caused the observed decrease in estrone sulfate. Dietary fat independently influenced the serum concentration of androstenedione. Increased dietary fiber caused a lengthening of the menstrual cycle by 0.72 day and a lengthening of the follicular phase by 0.85 day.

Adult↗

Estrogen metabolism and excretion in Oriental and Caucasian women.

BACKGROUND: Caucasian and Oriental women have different incidence rates of breast cancer. Among the underlying risk factors for the development of breast cancer in the women of these two groups may be their different diets and patterns of estrogen metabolism and excretion. The absolute levels and relative ratios of 16 alpha-hydroxylated estrogens and 2-hydroxylated estrogens (catechol estrogens) in the body may have a role in the etiology of breast cancer, but studies so far have provided only conflicting results. PURPOSE: Our goal was to study estrogen metabolism, in particular, the extent of 2-hydroxylation and 16 alpha-hydroxylation of estrogens in two groups of women, one Caucasian and one Oriental, with inherently different breast cancer risks. METHODS: Dietary records were analyzed over 3-day periods in the mid-follicular phase, twice, at 6-month intervals for 13 premenopausal Oriental women, recent immigrant arrivals in Hawaii with presumed low risk of breast cancer, and for 12 premenopausal Finnish women with presumed higher risk. The urinary estrogen profile was measured by gas chromatography-mass spectrometry and plasma and fecal estrogens were assayed by chromatographic radioimmunoassays. RESULTS: Mean fat intake per 1000 kcal was 73% higher (P < .001) in the Finnish women, but the mean fiber intake and fecal weights were similar to those of the Oriental women. Compared with Oriental women, Finnish women had 46% higher plasma estradiol (P < .01) and 124% higher plasma estrone sulfate (P < .01); however, after adjustment for differences in age and body mass index, only the difference in estrone sulfate remained statistically significant (P < .05). Mean plasma levels of estrone and estradiol correlated with height after adjustment for body mass index (P < .05). Mean plasma levels of estrone and sex hormone-binding globulin were similar. The Finns had higher mean urinary estrone (193%), estradiol (166%), various catechol estrogens (130%-439%), and total estrogen excretion (123%) (all P < .001), but similar 16 alpha-hydroxylated estrogen excretion. As calculated, 16 alpha-hydroxylation of estrone was significantly increased (P < .01) in the Oriental women, but 2-hydroxylation, 4-hydroxylation, and 16 beta-hydroxylation of estrone were similar in both groups. The ratio of catechol estrogen to 16 alpha-hydroxylated estrogen was four to five times higher (P < .001) in the Finnish women. The Oriental women had two to three times higher fecal excretion of estrogens than the Finnish women (P < .01). CONCLUSIONS: Our results indicate that high catechol estrogen formation may be a greater risk factor for breast cancer than high 16 alpha-hydroxylation of estrogens. However, the main risk factor for the Finnish women, as opposed to the Oriental women, may be their higher estrogen levels that result from a higher fat diet, higher estrogen production related to their greater height, and lower fecal estrogen excretion.

Adult↗

Piperacillin/tazobactam in the treatment of polymicrobial infections.

Polymicrobial infections are characterized by the presence of micro-organisms from more than one group of bacteria. Empirical treatment of polymicrobial infections requires an agent active against both anaerobic and aerobic/facultative bacteria. An aminoglycoside used in combination with an anti-anaerobe agent is commonly used to treat polymicrobial infections. However, aminoglycoside nephrotoxicity and treatment failures raise questions about the use of such regimens. Among non-aminoglycoside treatment regimens such as penicillin and cephalosporins, effectiveness has been compromised by bacteria producing extended spectrum beta-lactamases. Cefoxitin shows satisfactory results for treatment of intra-abdominal infections. Other studies have shown good results with imipenem, cefotetan and piperacillin used as single agents. Piperacillin/tazobactam, a new combination broad-spectrum antibiotic and potent beta-lactamase inhibitor, can be used for the treatment of infections caused by piperacillin-sensitive micro-organisms as well as beta-lactamase-producing, piperacillin-resistant organisms. This broad-spectrum activity is appropriate for infections traditionally treated empirically by double or triple antibiotic therapy.

Aminoglycosides↗

Antibiotic treatment of anaerobic infections.

The discovery of effective antimicrobial drugs has substantially improved the therapeutic outlook for patients with anaerobic infections. In addition, the pathophysiology of anaerobic infections has been elucidated by comparative antibiotic trials and the use of antibiotic probes in experimental animal models. Facultative bacteria, such as Escherichia coli, are responsible for acute peritonitis and sepsis associated with bowel perforation. Anaerobes, particularly Bacteroides fragilis, play the seminal role in subsequent abscess formation. Treatment of only the facultative bacteria, without adequate antibiotic coverage for anaerobic bacteria, leads to clinical failures with complications of abscess formation. Such therapeutic misadventures have been witnessed in the treatment of mixed infections with cephalosporins and penicillins that lack significant activity against anaerobes. Similarly, use of metronidazole or clindamycin as a single agent is associated with failures caused by infection with facultative bacteria. Mixed infections involve complex interactions between facultative bacteria and strict anaerobes, many of which possess intrinsic pathogenicity. The best therapeutic results are realized with antimicrobial drugs that are active against both types of microorganisms.

Animals↗

Nutritional aspects of HIV infection.

Wasting may not be an inevitable consequence of HIV infection but may be a consequence of multiple nutritional insults that are additive without periods of replenishment in between. Protein energy malnutrition in AIDS patients may be consequential to underlying illness and concomitant to death as a result of that illness or may hasten a patient's demise, that is, starvation with fatal loss of body cell mass. Mortality is closely related to weight loss. Malnutrition may be a result of decreased intake, malabsorption, altered metabolism, or any combination of the three. Nutritional strategies to prevent PEM include appetite stimulation, early nutritional supplementation with oral supplements, and the diagnosis and treatment of malabsorption and underlying infections. More aggressive measures such as gastrostomy or jejunostomy tube placement and total parenteral feedings are still being evaluated. Nutritional supplementation to enhance the immune system or manipulate metabolism may be adjunctive to the above strategies. Early intervention and attention to nutritional status may have long-term benefits to patients with this disease.

HIV Infections↗

Treatment of intra-abdominal infections.

Intra-abdominal infections are caused by a mixture of aerobic, anaerobic and facultatively anaerobic bacteria. Experimental studies in animals and clinical trials indicate that antimicrobial therapy should provide adequate coverage for the whole range of isolates. Penicillins and cephalosporins with relatively limited activity against anaerobes have been associated with clinical failures in treating various types of mixed infections. Aminoglycosides are often used in combination with other drugs in the treatment of intra-abdominal infections. Recent studies have cast doubt on this practice because of increased resistance of Gram-negative bacilli to aminoglycosides and high rates of renal toxicity. Regimens that do not include an aminoglycoside have given good results in treatment of appendicitis, penetrating abdominal trauma, and peritonitis. Enterococci are frequently isolated from intra-abdominal infections, but evidence suggests that it is not necessary to direct treatment at this organism initially.

Abdomen↗

Interactions between nutrition and infection with human immunodeficiency virus.

Nutritional status is severely compromised in persons infected with the human immunodeficiency virus (HIV). One or a combination of several disease-related factors can contribute to substantial weight loss and malnutrition, accelerating the downhill course of the disease. Efforts to prevent weight loss should include early intervention aimed at appetite stimulation, nutritional supplementation with high-calorie, high-protein oral supplements, and diagnosis and treatment of underlying infections and malabsorption. Although enteral or parenteral feedings may be warranted, these forms of nutritional support pose special problems in HIV-infected persons, and the ultimate benefits of these measures are not yet clear. The recent use of pharmacologic agents to stimulate appetite or improve body composition shows promise, but more research is needed before these drugs can be widely recommended as adjuncts to therapy. In general, unproven remedies should be avoided, as their risks may well outweigh their benefits.

Body Composition↗

Perturbation of intestinal microflora.

This paper discusses the effects of antibiotics on the intestinal microflora, focusing on the microbial constituents, their antibiotic sensitivities, and their metabolic activities. Many of these effects relate to therapeutic doses of antibiotics, not to the very small concentrations found as residues in food. The alterations associated with lower levels of antibiotics are generally unknown because they have not been studied. In the 18th century, Augustus Flemming said: "And it is truly wonderful that a substance, the very aspect and odor of which are sufficient to induce an inevitable nausea, should be regarded not merely as a matter of curiosity and study, but held in the highest repute as a unique and most precious treasure for the preservation of health." Such is the philosophy of the many investigators of the intestinal microflora on whose work this article is based.

Aging↗

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↗