Search PubMed⌕ Search

Biomedical subjects

J Hart

Publications and source records attributed to J Hart.

At least 109 records · Page 6Linked to original sources
PubMed1996

Complete lymphoid chimerism and chronic graft-versus-host disease in an infant recipient of a hepatic allograft from an HLA-homozygous parental living donor.

Living-related donor liver transplantation (LDLT) is an accepted approach to pediatric liver transplantation. Parental donation imposes a significant risk of chimerism with graft-versus-host disease (GVHD) because donors homozygous at all HLA loci (1.6% of the population) present no mismatched HLA antigens to be recognized by their offspring's immune system. The case of a 9-month-old who underwent LDLT with her 23-year-old HLA-homozygous mother as a donor demonstrates the consequences of this occurrence. The patient developed GVHD with aplastic anemia; the patient's nucleated peripheral blood elements were shown to be entirely derived from the donor. Later, after some marrow recovery, the patient's circulating lymphocytes had a donor origin, while the marrow-derived neutrophils had a recipient origin. The patient suffers from chronic GVHD and debilitating skin disease several years posttransplant. Our current protocol calls for HLA typing to eliminate parents who are homozygous at all HLA loci as donors of hepatic allografts to their children.

Chronic Disease↗
PubMed1996

Posttransplant lymphoproliferative disease in pediatric liver transplantation. Interplay between primary Epstein-Barr virus infection and immunosuppression.

The incidence, risk factors, and outcome of posttransplant lymphoproliferative disease (PTLD) were examined for 298 children undergoing liver transplantation. The overall incidence of PTLD was 8.4% (25 of 298). Intensity of immunosuppression was found to be a major risk factor for the development of PTLD. Cyclosporine and tacrolimus when used as primary immunosuppression were associated with the development of PTLD in 4.3% and 6.6% of cases (P=NS). OKT3 and tacrolimus, when used as rescue therapy for steroid-resistant rejection, were associated with a comparable increase in the risk of developing PTLD (10.9% and 11.1%, P=NS). Patients requiring both OKT3 and tacrolimus to treat refractory rejection were at significantly increased risk for PTLD (28.1% vs. 4.3% or 6.6%, P<0.0001). PTLD was more common in patients who received transplants for Langerhans cell histiocytosis relative to other indications for transplantation (66% vs. 8.4%, P=0.0005). The data also support an association between primary Epstein-Barr virus (EBV) infections following transplantation and the development of PTLD. While only three patients were EBV seropositive before transplantation (14%), 19 patients were EBV seropositive at the time of diagnosis of PTLD (90%), confirming a high incidence of primary EBV infections in patients with PTLD (21 patients had both pre- and posttransplant EBV serologies). In this series, PTLD was associated with a mortality rate of 60%, and 12 of the 15 patients who died had persistent tumor at the time of death. Five of the 13 patients rendered disease-free developed ductopenic rejection. Of the four with severe liver dysfunction, two have undergone successful retransplantation and are alive without evidence of PTLD. In conclusion, intense immunosuppression using OKT3 and tacrolimus as rescue agents was associated with a significant increase in the incidence of PTLD. Primary EBV infection after transplantation further accentuated this risk. Independent of these risk factors, patients with Langerhans cell histiocytosis were at significantly increased risk for PTLD. The identification of high-risk patients should allow the development of protocols to screen patients for primary EBV infections and early indications of PTLD, as well as the institution of preemptive antiviral and antitumor therapies.

Adolescent↗
PubMed1996

Tacrolimus for primary treatment of steroid-resistant hepatic allograft rejection.

Twelve patients who experienced steroid-resistant rejection after primary liver transplantation while receiving cyclosporine-based therapy were converted to tacrolimus without receiving OKT3 or additional steroids. The indications for conversion were ongoing biopsy-confirmed rejection. All patients had received one course of high-dose intravenous steroids, which failed to reverse the rejection episode. No other antirejection therapy was given. Tacrolimus was initiated to reverse rejection and for maintenance therapy. The tacrolimus target level was 15-20 ng/ml (whole blood, IMX). All 12 patients had rapid reversal of the rejection episode and did not experience recurrent rejection (mean follow-up: 8.2 +/- 1.2 months). The mean bilirubin level dropped from 6.1 mg/dl at the initiation of tacrolimus therapy to 4.4 mg/dl by day 7 of therapy, 2.5 mg/dl by day 14, and 1.5 mg/dl by day 21 (P < 0.003). Serum glutamic pyruvic transaminase demonstrated a similar response. The serum creatinine level was unchanged at 1.5 mg/dl. No major adverse reactions were noted in this group of patients. Patient and graft survival rates were 100%. Four of the eight patients with a follow-up of >4 months are no longer receiving steroid therapy. Tacrolimus is effective as the primary therapy for the treatment of steroid-resistant rejection and provides a rapid and sustained biochemical response. Patients with mild to moderate rejection may be safely converted from cyclosporine to tacrolimus without an additional steroid bolus or OKT3 therapy. Early "preemptive" conversion to tacrolimus prior to the use of additional steroids or OKT3 may decrease overall rejection therapy requirements. This approach has promise for improved graft survival and fewer infectious and immunologic complications.

Adult↗
PubMed1996

Ploidy as a prognostic feature in colonic adenocarcinoma.

OBJECTIVE: To determine whether DNA content and cell-cycle kinetic characteristics in Dukes stage B colonic adenocarcinomas provide additional prognostic information in the context of clinicopathologic variables of known significance. DESIGN: Archival, paraffin-embedded tissue blocks from 210 Dukes B colonic adenocarcinomas were retrieved. After confirming stage, tumor cell nuclei were extracted, suspended, and stained. Cell nuclei from adjacent normal colon mucosa were used as controls. SETTING: University-based, tertiary cancer referral center. INTERVENTIONS: Samples obtained from tumors resected at our institution between 1965 and 1984 were analyzed by flow cytometry for DNA index (DI) and percentages of cells in synthesis (S) phase (%S) and in G2 and mitosis (M) phases (%G2M). The data were correlated with 5-year survival. Follow-up was complete in all patients to at least 5 years. RESULTS: Univariate analysis showed that the highest survival rates were associated with DI values near 1 and 2 (diploid and tetraploid tumors, P = .02) and the lowest %G2M values (tumors with fewer mitoses; P = .01). Five-year survival rates also differed significantly between patients with diploid (DI < 1.1) and those with aneuploid (1.1 < DI < 2) tumors (80% vs 64%, respectively; P = .02). Multivariate analysis revealed that race (P < .01), lymphatic or capillary microinvasion (P < .03), and ploidy (P < .05) were significantly associated with outcome. The influence of ploidy, race, and microinvasion on 5-year survival was estimated with logistic regression, and 8 subgroups of patients emerged with 5-year survival probabilities ranging from 39% for black patients with aneuploid tumors and microinvasion to 88% for white patients with diploid tumors and no microinvasion. CONCLUSIONS: Tumor DNA content provides additional independent information that allows further refinement of our prognostic ability in patients with Dukes B colonic adenocarcinoma. This may aid in the identification of a cohort of patients who may potentially benefit from aggressive adjuvant therapy.

Adenocarcinoma↗
PubMed1996

Vincristine-induced alterations in Schwann cells of mouse peripheral nerve.

The sciatic nerve of C57Bl mice was examined with a transmission electron microscope to study the ultrastructural alterations in Schwann cells following treatment with escalating doses of vincristine. Results indicated that the drug exerts a dose-related effect. Total doses up to 8 micrograms/mouse did not cause any visible damage to Schwann cells. Higher doses induced not only damage to individual cells, but also affected a greater percentage of them. The myelin sheath was the most affected organelle. Schwann cells of myelinated fibers showed greater damage than those of unmyelinated fibers.

Animals↗
PubMed1996

Effect of oral chemotherapy on the mitochondrial size of mouse intestinal cells.

Since orally given cytotoxic agents may cause intestinal disfunction, the effect of oral administration of three cytotoxics, i.e., methotrexate (MTX), cyclophosphamide (CPA), and ftoral, a derivative of 5-fluorouracil (5-FU), on the gastric, liver, and small-intestine cells of C57B1 mice was studied by transmission electron microscopy. Although no ultrastructural alterations could be detected in the cells of the first two organs, the epithelial cells of the small intestine showed a marked increase in size of their mitochondria. In the control animals the mitochondrial size was in the range of 0.04-1.8 micron (mean +/- SE 0.54 +/- 0.01 micron). In the treated animals the size of the mitochondria ranged between 0.15 and 4.33 micron (mean +/- SE 0.73 micron) for those treated with MTX, 0.24-2.88 micron (mean +/- SE 0.80 +/- 0.02 micron) for those given CPA, and 0.28-5.3 micron (mean +/- SE 1.18 +/- 0.48 micron) for those treated with 5-FU. These findings were significantly different from those obtained in controls (P < 0.0001). In addition, in animals treated with MTX the mitochondria of the jejunal cells were surrounded by channels of rough endoplasmic reticulum. The cytoplasm contained long, winding channels of smooth endoplasmic reticulum, vacuoles, and myelin figures. Fluid retention in the small intestine due to administration of cytotoxic drugs is suggested as a possible mechanism for distention of the mitochondria.

Administration, Oral↗
PubMed1996

Macronutrient consumption and nutritional status in a selected well-established group of elderly people in a home for the aged in Israel.

OBJECTIVE: To evaluate the distribution pattern of the main macronutrients (protein, fat, carbohydrates) and fiber in a selected well-established group of elderly people, average age above 80 years. METHOD: Dietary consumption was evaluated in a well-established group of 21 elderly people in a home for the aged by in-person interview using a food frequency questionnaire. RESULTS: Daily energy intake was 1.87 Mcal (7.8 MJ) or 29.3 kcal/kg body weight, a value which lies within the range of 1.6 to 2.0 Mcal or 25 to 30 kcal/kg, found in 12 other studies conducted on elderly people. The average percentage of energy derived from macronutrients (with an individual range) was: protein 17.5 (13-22); fat 32.9 (25-44); and carbohydrates 49.6 (35-61). Fiber intake was 8.6 g/Mcal, lower than that found in three other studies. Positive coefficients of correlation were found between protein intake and the following parameters: serum urea (r = 0.28), cholesterol (r = 0.48) and DBP (r = 0.43). CONCLUSIONS: In our small group of elderly, energy derived from protein was higher than that in most of other studies reviewed, and that from fat was higher than in half of those studies. These values were remarkably higher than the suggested values. Energy derived from carbohydrates was close to that found in other studies. Monitoring of dietary macronutrients might improve the nutritional and the physiological status of the elderly.

Aged↗
PubMed1996

Estimation of vitamin needs--riboflavin, vitamin B6 and ascorbic acid-according to blood parameters and functional-cognitive and emotional indices in a selected well-established group of elderly in a home for the aged in Israel.

OBJECTIVE: To evaluate the vitamin status and the effects of micronutrient supplementation as determined by biochemical assays and functional, cognitive and emotional tests in a selected well-established group of elderly people, average age above 80 years. METHODS: Dietary consumption was evaluated by in-person interview using a food frequency questionnaire. Medical, biochemical, nutritional, functional, cognitive and behavioral parameters were assessed in elderly subjects (n = 12) living in a home for the aged, at baseline and after 42 days of micronutrient supplementation. The same parameters were assessed in additional subjects (n = 9), at baseline only. RESULTS: In all subjects, most of the micronutrients were not supplied at an adequate level. Supplementation of micronutrients at a level of 100% RDA improved parameters related to vitamin status, the activation coefficients (AC) of GR (glutathione reductase) and AST, blood ascorbic acid concentrations, functional-cognitive evaluation values, blood pressure, pulse rate, and serum cholesterol and triglycerides levels. At baseline, the following parameters significantly correlated with vitamin intake and were used for the estimation of vitamin needs: AC of GR, Tinetti Balance Evaluation, FIM and recorded morbidity. CONCLUSIONS: On the basis of limited available data, calculation of vitamin needs based on regression lines resulted in estimates (mg/day) of: > 150 for ascorbic acid, > 3 for riboflavin, > 3 for vitamin B6. Expanding the current practice of supplementing micronutrients at a level of 100% RDA (in tablet form) that already exists in some elderly societies should be considered after a comprehensive study in a large group of elderly people.

Aged↗
PubMed1996

Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period.

Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC). This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large- (LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined.

Adult↗
PubMed1996

Effect of halothane on phenylephrine-induced vascular smooth muscle contractions in endotoxin-exposed rat aortic rings.

OBJECTIVES: a) To determine the response of endotoxin-exposed vascular smooth muscle to exogenous vasoconstrictors during concomitant exposure to an inhaled anesthetic (halothane); and b) to determine if excess nitric oxide production is responsible for any altered response. DESIGN: In vitro, prospective, repeated-measures, dose-response study. SETTING: University/medical school experimental physiology laboratory. SUBJECTS: Adult male Sprague-Dawley rats, whose aortae were studied in an in vitro preparation. INTERVENTIONS: Thoracic aortae were excised from anesthetized animals and cut into 3-mm rings. After incubation in aerated organ baths containing a modified essential medium with or without Escherichia coli lipopolysaccharide (100 micrograms/mL) at 37 degrees C for 5 hrs, the rings were removed and suspended in separate baths for isometric tension recording. Phenylephrine dose-response data (10(-10) to 10(-5) M) were determined for lipopolysaccharide- and nonlipopolysaccharide-treated rings. After washout and equilibration, two vessels (one each lipopolysaccharide- and nonlipopolysaccharide-treated) were additionally exposed to 2% halothane and phenylephrine dose-response determinations were repeated for all vessels. This procedure was repeated for 1% halothane in a separate experiment. In some experiments, the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (3 x 10(-4) M), was added to the bath after the washout from the second phenylephrine dose-response determination. Then, a third phenylephrine dose-response determination was performed, with and without 2% halothane. MEASUREMENTS AND MAIN RESULTS: Dose-response curves were evaluated using a logistic regression analysis. In addition, absolute and percentage changes in tension were compared between the first and second contractions. Exposure to lipopolysaccharide resulted in a decrease in the maximum tension from 2.07 +/- 0.03 (controls) to 1.24 +/- 0.04 g/mg of vessel dry weight and an increase in the dose at which the contraction is 50% of maximum (ED50) from 3.78 x 10(-8) to 2.05 x 10(-7) M (p < .05). Exposure to 2% halothane produced significant reductions in the maximum tensions in both groups. The lipopolysaccharide-treated vessels showed not only a proportionately larger decrease (-51 +/- 5% vs. -18 +/- 2% in the control plus halothane group), but also a significantly greater absolute decrease (0.59 +/- 0.09 vs. 0.34 +/- 0.04 g/mg in the control plus halothane group). The addition of 1% halothane produced less pronounced decreases in tension, with only an additive effect in the lipopolysaccharide-treated vessels. The addition of N omega-nitro-L-arginine resulted in a reversal of the lipopolysaccharide-induced decrease in tension. However, 2% halothane still had a significantly greater effect on the lipopolysaccharide-exposed rings. CONCLUSIONS: Exposure of rat aortic rings to lipopolysaccharide in vitro decreased the contractile response to phenylephrine. The addition of 2% halothane resulted in a more than additive decrease in tension in the lipopolysaccharide-treated vessels. Patients in septic or endotoxic shock are sensitive to most anesthetic regimens, and some of this sensitivity may be due to an altered vasoconstrictive response induced by lipopolysaccharide exposure. The inability of nitric oxide synthase inhibition to reverse this response completely suggests that induction of nitric oxide synthase and increased production of nitric oxide are not solely responsible for this finding.

Anesthetics, Inhalation↗
PubMed1996

Cognitive effects of resecting basal temporal language areas.

Electrical stimulation of the basal temporal region of the dominant hemisphere before partial temporal lobectomy for epilepsy sometimes produces temporary interruption of language function, but the significance of removal of this area is unknown. We evaluated the correlation between resection of the basal temporal language areas (BTLA) and certain types of postoperative language deficits. In a population of 25 patients, we mapped the inferolateral temporal lobe with cortical electrical stimulation, verifying the positions of the stimulating electrodes with three-dimensional computed tomography (CT). Eighty percent of the patients developed transient language deficits with stimulation, particularly with tests of confrontation naming and comprehension. BTLA was primarily located in the fusiform gyrus, from 1 to 9 cm from the temporal tip. At testing 6-12 months after operation, patients with BTLA resection performed worse (mean 9% decrease) than those with no BTLA resection (mean 4% improvement) on tests of confrontation naming (p = 0.03). Resection size accounted for less of the variance in decrease in confrontation naming than did resection of the BTLA. Tests of performance I.Q. (PIQ), verbal I.Q. (VIQ), or recognition memory for word and verbal learning showed no significant difference between these groups. Most patients do not have language decrease with removal of basal temporal lobe 5-6 cm from the tip, even with removal of BTLA. Some patients, however, have persistent decrease in naming.

Adolescent↗
PubMed1996

Mixed maternal-paternal lymphocyte cultures before and after immunotherapy for recurrent spontaneous abortions.

PROBLEM: The increased reactivity of maternal lymphocytes in reciprocal mixed-maternal-paternal lymphocyte cultures (MMPLC), observed in the presence of control serum after immunotherapy, suggests that immunization with paternal lymphocytes may induce a highly significant cell mediated immune response in specifically alloactivated maternal lymphocytes. METHOD: Reciprocal one-way MMPLC were set up with responding maternal or paternal lymphocytes and mitomycin C-treated stimulating lymphocytes. Cultures were set up for 6 days in the presence of 15% maternal or control serum. The degree of lymphocyte stimulation was measured by tritiated thymidine uptake. RESULTS: In maternal serum, after immunotherapy, a highly significant blocking effect on MMPLC was observed in both directions. The extent of the blocking effect in maternal serum and the stimulation in control serum was much higher, after immunotherapy, in two cases of abortions, as compared to cases with normal pregnancy outcome. CONCLUSIONS: Although the number of cases is very small, it may be that in abortions, in the presence of maternal serum, disturbances in the balance of cytokines or/and specific antibodies could have cytotoxic effects on MMPLC and down regulate, or "block" the specific response. For a possibly better utilization of the MMPLC test in the prediction of pregnancy outcome after immunotherapy, it may be important to examine specific antibodies in maternal serum, to investigate specifically induced cytokines in MMPLC and to evaluate T cell subsets in MMPLC in the presence of maternal and control serum.

Abortion, Habitual↗
PubMed1996

Human colostrum stimulates cytokine production.

The effect of human colostrum on the production of IL-1, IL-3 and IL-6 by peripheral blood mononuclear cells (PBMCs) has been investigated. The aqueous phase of human colostrum significantly stimulated the production of these three cytokines. These findings show the importance of breast feeding not only as a well-balanced nutrient supply but also as a source for growth-promoting factors. It is suggested that the enhanced secretion of IL-1, IL-3 and IL-6 induced by human colostrum may compensate for the lower capacity of neonatal PBMCs to produce these cytokines. It is also possible that, by stimulating the secretion of these cytokines, breast feeding may provide an additional mechanism for the regulation of the neonatal immune system and hematopoiesis.

Colostrum↗
PubMed1996

Survey of patient satisfaction in a community hospital.

To assess the satisfaction with the department and hospital services provided by a medium-size community hospital during a 2 month period (April-May 1995), 118 randomly chosen patients were asked to complete a questionnaire designed to reflect their opinions during hospitalization. The principal points of the survey concerned the general perception regarding the services in the department and the hospital, the admission and discharge procedures, the quality of food and sanitary conditions, an evaluation of the physicians' and nurses' skill and attitude, as well as their compliance to patients' needs. Overall satisfaction with the medical care was very high, the physicians' attitude and nurses' compliance being the two most important determinants. The role of this type of questionnaire as an instrument for improving health services is emphasized.

Adult↗