Decreased fat and nitrogen losses in patients with AIDS receiving medium-chain-triglyceride-enriched formula vs those receiving long-chain-triglyceride-containing formula.

OBJECTIVE: The purpose of this study was to compare two enteral formulas, differing only in fat source, for product acceptance, tolerance, and effect on fat malabsorption and nutritional status in subjects with acquired immune deficiency syndrome (AIDS). DESIGN: The double-blind, randomized 15-day trial was divided into a 3-day period in which solid food was consumed followed by a 12-day experimental period in which liquid formulas were consumed. SETTING/SUBJECTS: Twenty-three men and one woman with AIDS and fat malabsorption completed the study. The study was conducted in the General Clinical Research Center, University of Alabama Hospital, University of Alabama at Birmingham. Laboratory assays were performed in the Department of Nutrition Sciences. INTERVENTIONS: After 3 days of consuming a controlled, solid food diet containing 100 g fat per day from mixed sources to document fat malabsorption, subjects were randomly assigned to one of two groups. Each group received a liquid formula containing 35% of energy as fat for 12 days. One group received a formula containing 85% medium-chain triglycerides (MCTs) and the control group received a formula containing 100% long-chain triglycerides. MAIN OUTCOME MEASURES: Determinations included stool number, consistency, weight, and fat and nitrogen content; urine nitrogen and creatinine levels; and body weight. STATISTICAL ANALYSIS PERFORMED: Subject demographic and other baseline characteristics were compared using two-sample t tests; stool and urine assessments were compared between groups at the initial experimental period using two-sample t tests; changes from initial to final experimental periods were assessed by means of analysis of covariance; changes in pooled intake, body weight, and the number and consistency of bowel movements were also assessed using analysis of covariance. All statistical tests were two-tailed and considered significant at P < .05. RESULTS: Within-group comparisons indicated that subjects fed the MCT formula showed significantly decreased stool fat and stool nitrogen content (P = .01 and P = .03, respectively) and increased fat absorption (P = .03), whereas those fed the control formula did not. Differences in stool fat between the groups were not statistically significant. However, the difference in fat absorption from the initial to final formula period was significant (P = .04). Subjects consuming the MCT formula also tended to have a decreased number of bowel movements and abdominal symptoms, whereas subjects fed the control formula showed no improvement. All subjects maintained their body weights. APPLICATIONS: There may be advantages to using an MCT-based formula in the treatment of AIDS-associated malabsorption.

Dietary habits of first-year medical students assessed during clinical nutrition course.

To enhance the Introduction to Clinical Nutrition course at the University of Alabama at Birmingham, medical students taking the course from 1989 to 1992 (n = 616) were required to analyze by computer the nutrient composition of their own diets for a 24-h period. In 1991 and 1992, they were required to repeat the analysis at the completion of the course. Overall, fat comprised 30% of energy intake, and along with saturated fat and the cholesterol-saturated fat index, it declined virtually each year compared with the previous year. Significant changes were noted by the end of the course in 1991 and 1992 compared with the beginning, when fat comprised 26% of energy, and more students adhered to recommendations for dietary fat, saturated fat, and fiber. Vitamin C intakes exceeded the recommended dietary allowance by more than twofold and increased further by the end of the course in 1991 and 1992, probably indicating an increase in fruit and vegetable intake. Each year, most students rated the dietary assessment as moderately or very useful. These data suggest that dietary self-assessment is a useful tool for teaching clinical nutrition in medical schools and that, even before instruction in clinical nutrition, medical students are favorably altering their dietary patterns to a greater extent than the general population.

Peptides from multiple regions of the lectin domain of P-selectin inhibiting neutrophil adhesion.

The selectins are a family of three structurally related glycoproteins that are integral components of leukocyte adhesion to the vascular endothelium. Their involvement in the recruitment and extravasation of neutrophils is critical in mounting an inflammatory reaction. The carbohydrate nature of the selectin ligands suggests that the binding regions of the selectins are contained within the lectin-like domains of the selectins. The synthesis and evaluation for inhibition of selectin binding of overlapping peptides of the lectin and adjacent EGF-like domains of P-selectin have been used to identify small peptides that completely inhibit P-selectin-dependent neutrophil adhesion. These peptides span a region of more than 100 amino acids and may define the carbohydrate recognition domain of P-selectin.

A meal conference format to teach ambulatory nutrition concepts.

Third-year medical students participated in a program using a meal conference approach to teach ambulatory nutrition concepts called "Building Better Health Through Nutrition." The series of three interactive presentations was given during the required family medicine clerkship. A pretest and posttest were used to measure acquisition of nutrition knowledge. There was a statistically significant (P less than 0.05) average increase in posttest compared to pretest scores. Seventy percent of students rated the meal conference approach as "effective" or "very effective" and 76% stated that the series expanded their knowledge of nutrition's role in clinical medicine. We conclude that the meal conference format is an effective way to teach nutrition during the clinical years in medical school.

Tc-99m antifibrin Fab' fragments for imaging venous thrombi: evaluation in a canine model.

An antifibrin antibody (T2G1s) Fab' fragment labeled with technetium-99m was tested for its ability to produce images of fresh thrombi in dogs. In gamma camera images, all thrombi were evident by 2-4 hours after injection. Mean thrombus-to-blood and thrombus-to-muscle ratios averaged 4.0 and 69 at four hours after injection and increased to 24 and 270, respectively, by 24 hours after injection. When compared with I-125 fibrinogen injected into the same dogs, Tc-99m-antifibrin Fab' had lower absolute uptake in thrombus but higher thrombus-to-blood ratios due to a faster rate of disappearance from the blood. The primary route of excretion was through the kidneys. Tc-99m-antifibrin Fab' was highly stable in vivo, with an average of 82% of the circulating radioactivity able to bind to fibrin at 4 hours after injection. When compared with an In-111-labeled Fab fragment of antifibrin antibody 59D8, thrombus-to-blood and thrombus-to-muscle ratios were slightly higher for the Tc-99m-labeled antibody, and the blood disappearance rate was slightly faster. The absolute uptake in thrombus, however, was not significantly different, and the thrombus was visualized at about the same time after injection. These studies suggest that Tc-99m T2G1s Fab' is a potential agent for detecting thrombi in a clinical setting.

The efficacy of sighs in patients with COPD undergoing general anesthesia and controlled ventilation.

Fourteen patients with COPD underwent elective procedures below the umbilicus, all receiving a standard anesthetic. They were randomized to one of four groups differentiated by the presence or absence of sighing during mechanical ventilation. Patients who were sighed experienced both statistically and clinically significant improvement in their oxygenation efficiency as measured by the alveolar to arterial oxygen gradient.

(3,6-Dimethyl-3,6-diazaoctan-1,8-dithiolato-S1,N3,N6,S8)oxotechnetium(V) pertechnetate.

[TcO(C8H18N2S2)]TcO4, Mr = 484.2, monoclinic, P2(1)/c, a = 7.447 (2), b = 16.952 (8), c = 12.236 (3) A, beta = 99.63 (2) degrees, V = 1523 (1) A3, Z = 4, D chi = 2.112, Dm = 2.09 (1) Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.06 mm-1, F(000) = 952, T = 295 (1) K, final R = 0.071 for 2496 significant reflections and 173 parameters. The Tc atom is bound to the oxo group and the N and S atoms of the complex ligand in a rough square pyramid. The Tc atom lies 0.770 (3) A out of the S,N,N',S' plane. This plane is significantly distorted such that N and N' lie nearly 0.25 A out of the plane on opposite sides. The Tc-S bonds [2.238 (3), 2.266 (3) A] are short but other bond lengths and angles are normal.

Cocaine: long-term administration depletes cardiac enzymes in the rat.

Arterioles and myocytes of the cardiac ventricle were examined histochemically to determine their metabolic profiles in normal rats and in rats treated either acutely or chronically with cocaine. Following long-term, but not acute, cocaine administration, enzymes involved in both aerobic and anaerobic metabolism as well as in hexosemonophosphate shunt were greatly decreased. These data suggest that long-term usage of cocaine leads to severely impaired coronary metabolism.

Brain imaging agents: synthesis and characterization of (N-piperidinylethyl) hexamethyl diaminodithiolate oxo technetium(V) complexes.

Two 99mTc complexes of (N-piperidinylethyl) hexamethyl diaminodithiol (NEP-DADT) have shown high brain uptake in rodents and lower primates. One of these 99mTc complexes has given positive images of the brain in man which are qualitatively related to regional brain blood flow (rCBF). In order to determine the structure of these 99mTc products, the corresponding 99Tc(NEP-DADT) complexes were prepared and characterized by HPLC, TLC, fast-atom-bombardment mass spectrometry (FAB MS) and other analytical techniques. These results indicate that the two 99Tc (NEP-DADT) complexes are syn and anti isomers (i.e. one isomer has the N-piperdinylethyl side chain located syn to the technetium oxo core while the other has this side chain located anti to the technetium oxo core).

Design, preparation, and biodistribution of a technetium-99m triaminedithiol complex to assess regional cerebral blood flow.

A new ligand (N-piperidinylethyl-DADT, 5) has been prepared which forms two complexes with 99mTc when stannous chloride is used as a reducing agent for [99mTc] pertechnetate. Biodistribution studies of one of the complexes in mice showed that 2.2% of the injected dose of the tracer was in the brain at 5 min postintravenous injection with 0.53% of the dose remaining in the brain at 30 min postinjection. Brain-to-blood ratios at these times were 5.3 and 3.0, respectively. Biodistribution studies of the other complex showed similar behavior with a slightly lower initial uptake by and faster clearance from the brain. Imaging studies of the more promising of the two complexes were conducted in a monkey and a baboon. In both cases, rapid uptake of the tracer in the brain was observed and clear brain images were obtained. Time-activity curves showed peak uptake in the brain at approximately 5 to 7 min postintravenous injection followed by a plateau of about 11 min. The half-lives for clearance of the tracer from the brains of the monkey and baboon were found to be 63 and 58 min, respectively. These results suggest that this tracer may be useful for brain imaging in humans.

Zinc and Chlamydia trachomatis.

Zinc was noted to have significant effects upon the infection of McCoy cells by each of two strains of Chlamydia trachomatis. With a high or low Chlamydia inoculant, the number of infected cells increased up to 200% utilizing supplemental zinc (up to 1 X 10(-4) M) in the inoculation media compared with standard Chlamydia cultivation media (8 X 10(-6) M zinc). Ferric chloride and calcium chloride did not effect any such changes. Higher concentrations of zinc, after 2 hr of incubation with Chlamydia, significantly decreased the number of inclusions. This direct effect of zinc on the Chlamydia remained constant after further repassage of the Chlamydia without supplemental zinc, suggesting a lethal effect of the zinc. Supplemental zinc (up to 10(-4)M) may prove to be a useful addition to inoculation media to increase the yield of culturing for Chlamydia trachomatis. Similarly, topical or oral zinc preparations used by people may alter their susceptivity to Chlamydia trachomatis infections.

The use of cyclosporine in living-related renal transplantation. Donor-specific hyporesponsiveness and steroid withdrawal.

Fourteen HLA-identical (HLA-ID) and 62 haploidentical (HP-ID) living-related donor (LRD) renal allograft recipients were transplanted using cyclosporine (CsA) and prednisone immunosuppression. No patients were preconditioned with pretransplant blood transfusions (third-party or donor-specific)--and, therefore, none were sensitized to their donor. Patient 93% (13/14) and graft 93% (13/14) survival for the HLA-ID patients is not significantly different (P greater than .1) compared with patient 98% (61/62) and graft 91% (56/62) survival in the HP-ID patients, with a mean follow-up of 16.3 (8-30) and 14.7 (2-35) months, respectively. A significant difference was noted in the incidence of treated rejection episodes (0% vs. 31%, P less than .01) and the mean serum (mg/dl) creatinine (1.37 vs. 1.71, P less than .05) at 18 months between the HLA-ID and the HP-ID and HP-ID recipients, respectively. Ten of 22 HP-ID recipients demonstrated donor-specific mixed lymphocyte culture hyporesponsiveness one year posttransplant that may have been due to the emergence of monocytoid suppressor cells. Nine of these HP-ID and seven HLA-ID recipients were subjected to a protocol of steroid withdrawal. Eleven of these patients are currently on CsA monodrug therapy and two are on alternate-day steroids from 9-18 months after discontinuation of prednisone. These findings suggest that CsA is an effective steroid-sparing agent in LRD renal transplantation that diminishes the frequency of treated rejection episodes and may permit monodrug therapy in selected individuals.

Zinc and the heat-labile enterotoxin of Escherichia coli.

Enterotoxigenic Escherichia coli is a major cause of diarrhoea in man. When zinc in concentrations of 10(-6) M or 10(-5) M was added to the growth medium, there was a significant increase in heat-labile enterotoxin production by each of six toxigenic strains. Zinc in these concentrations did not alter bacterial growth or the activity of preformed toxin. Other heavy metals did not enhance toxin production and o-phenanthroline, a relatively specific zinc-chelating compound, blocked the enhancing effect. The significance of these findings is discussed in relation to the use of supplemental dietary zinc.

Nutrient chemotactic agents and the in vitro selective control of bacterial colonization.

Certain nutrient chemotactic agents after 3-18 hours of incubation with viable mammalian cells in culture can cause significant alterations in subsequent attachment of Escherichia coli to the mammalian (receptor) cells. Results were amongst the most significant with an essentially non-oxidizable amino acid analogue. Differences obtained were dependent upon the number of washings of the receptor cells after incubation with the chemotactic agents and the incubation concentrations. All E. coli isolates tested readily displayed chemotaxis, yet significant differences in adherence were observed with the minority of 16 chemotactic agents, two receptor cell lines, six E. coli and one Salmonella typhi studied. This is most likely due to poor localization of these agents in the outer layers of viable mammalian receptor cells, metabolism of the agents, or both. Some nutrient chemotactic agents may facilitate the selective control of bacterial colonization or infection.

Antibiotic and nonantibiotic ionophores can alter bacterial adherence to mammalian cells.

Epithelioid (HeLa) and fibroblastic (L) cells in culture incubated for 18 hr with the ionophores amphotericin B and amiloride were noted to bind significantly more and less bacteria, respectively, than control cells incubated without ionophores. These effects were related to dose and incubation length and were present at concentrations approximating those in vivo after administration of maximal doses of these drugs given to humans therapeutically. Electron microscopy of both receptor cell lines revealed increased length and number of cellular projections in the amphotericin-treated cells and flattening and loss of membrane individuality in the amiloride-treated cells. These findings could explain the differences in subsequent bacterial binding. The ionophores nifedipine and verapamil which block calcium transport in cells which have calcium channels did not alter bacterial binding to these receptor cells or bacterial binding to calcium channel-containing myoblasts (in culture). These data suggest that certain ionophores could alter bacterial colonization and infection in the host indirectly by altering bacterial binding; however, the clinical significance of these findings remains to be determined.

Zinc and bacterial adherence.

Zinc significantly enhances the ability of piliated Gram-negative and Gram-positive bacteria to attach to HeLa cells. This effect is related to the concentration of zinc and degree of bacterial piliation, and is not present with unpiliated organisms. Bacterial viability is not necessary for this effect, and sulfhydryl blockers decrease the response. These data suggest that zinc can bind to bacterial pili and augment bacterial adherence; in this manner, zinc may act as a virulence factor.

Effect of estrogens on bacterial adherence to HeLa cells.

Incubating confluent cell culture HeLa cells for 18 h with increasing concentrations of estrogens progressively enhanced the subsequent attachment of a variety of radiolabeled bacteria to the HeLa cells. This effect was not caused by other hormones and was not produced by 1-h incubations of HeLa cells or bacteria with hormones. Estrogens did not similarly affect two other receptor cell lines studied. The addition of metabolic inhibitors showed that this effect of estrogens on HeLa cells was energy dependent and involved protein synthesis. Concurrent incubation of the HeLa cells and estrogens with the antiestrogen nafoxidine blocked the subsequent increase in adherence. These data suggest that estrogen receptors are present in HeLa cells and that hormonally-induced alterations in the synthesis of bacterial receptor sites may modify the capacity of certain cells to bind bacteria.