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Biomedical subjects

J Hart

Publications and source records attributed to J Hart.

At least 73 records · Page 4Linked to original sources
PubMed1999

Endothelin plays a role in contractions of isolated pig pulmonary vessels induced by diaspirin cross-linked hemoglobin.

The current studies were undertaken to investigate the role of endothelin-1 (ET-1) and its receptors in contractions of isolated pulmonary vessels of the pig induced by diaspirin cross-linked hemoglobin (DCLHb). Second-order pulmonary arteries (PAs) and veins (PVs) were isolated from pigs, cut into rings (4 to 5 mm), and mounted at optimal passive tension in 37 degrees C Krebs-filled tissue baths bubbled with 95% O2/5% CO2. Isometric tension was recorded continuously. In paired rings, concentration responses to ET-1 (10(-10) to 10(-7) mol/L), DCLHb (10(-9) to 3x10(-6) mol/L), and N-nitro-L-arginine (LNA) (10(-6) to 5x10(-5) mol/L) in the presence and absence of the ET(A) receptor antagonist BQ123 (3x10(-5) mol/L) were determined. PVs and PAs with intact endothelium and rings from which the endothelium was removed (denuded) were pretreated with the ET(B) receptor antagonist BQ788 to determine the contribution of ET(B) receptors to ET-1, DCLHb, and LNA responses. ET-1, DCLHb, and LNA caused concentration-dependent increases in tension in all vessels. In the presence of BQ123, the 50% effective concentration (EC50) of ET-1 was significantly increased (by 5-fold to 10-fold) in all vessels. DCLHb concentration responses were significantly attenuated-in the PVs by 45% and in the PAs by 79%-during treatment with BQ123. BQ123 attenuated LNA responses in PVs by 35% and in PAs by 87%. Treatment with BQ788 had no effect on endothelium-intact PVs or PAs but significantly increased ET-1 EC50 (log of the molar concentration) from -9.0+/-0.22 to -7.8+/-0.05 in denuded PAs. The ET-1 EC50 was significantly decreased in denuded PAs (-9.0+/-0.22) as compared with responses in endothelium-intact PAs (-8.1+/-0.18). DCLHb concentration responses were attenuated by 71% and LNA responses by 80% during antagonism with BQ788 in the intact PAs only. These data demonstrate that ET-1 plays a role in DCLHb-induced contractions in the PA and PV. The contributions of ET are mediated by both ET(A) and ET(B) receptors in the PA but only by ET(A) receptors in the PV. These results suggest that the vasoconstrictor actions of DCLHb, which have previously been shown to depend on its interference with endothelium-generated NO, may also involve ET. This may reflect the importance of the interaction of these two endothelium-generated physiologic antagonists in the pulmonary circulation.

Animals↗
PubMed1999

Hemodialysis prognostic nutrition index as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. Council on Renal Nutrition National Research Question Collaborative Study Group.

OBJECTIVE: Prospectively examine the use of a hemodialysis prognostic nutrition index (HD-PNI) as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. DESIGN: Prospective randomized collaborative study group. SETTING: There were 211 chronic hemodialysis centers; 202 from 43 United States, 9 from Canada. PATIENTS: There were 1527 hemodialysis patients undergoing treatment a minimum of 3 months and at least 18 years of age. Sample mirrored United States Renal Data System data for age, sex, race, and etiology of renal failure. INTERVENTIONS: None; routinely collected demographic, biochemical, and clinical data for 8-month baseline and 3-month predictive phases. METHODS: HD-PNI calculated from baseline data as linear mathematical equation using level of serum albumin, level of serum creatinine, and number of days and times hospitalized; HD-PNI risk defined as >/=0.8. Adequacy of dialysis calculated as urea reduction ratio (URR) from baseline data; adequacy risk defined as URR of </=65%. MAIN OUTCOME MEASURES: Number of times and days hospitalized, mortality. RESULTS: For this research, 1167 patients completed the study (76%) with 360 (24%) dropped due to death, incomplete data, transfer, or change in modality. Patients completing study with HD-PNI risk (n = 208, 18%) compared with patients who had no HD-PNI risk (n = 959, 82%) were hospitalized more often (57.2% v 28.5%, P <. 01), hospitalized with infection more often (14.6% v 4.6%, P <.01), and had greater mortality (7.7% v 2.5%, P <.01). Stratification of HD-PNI risk by URR of >/=65% did not significantly improve prediction. CONCLUSIONS: Use of HD-PNI is an effective screening tool to identify hemodialysis patients at risk for morbidity and mortality. No correlation was found between URR and HD-PNI.

Adult↗
PubMed1999

Plasmapheresis, intravenous cytomegalovirus-specific immunoglobulin and reversal of antibody-mediated rejection in a pediatric renal transplant recipient: a case report.

This is a pediatric case report illustrating the development of antibody (Ab)-mediated rejection in a patient with low levels of pretransplant anti-human leucocyte antigen (HLA) panel reactive antibodies (PRA). The clinical course of this patient suggests that aggressive use of a combination of plasmapheresis, monoclonal anti-T-lymphocyte antibody therapy, and intravenous immunoglobulin (IVIG) therapy can reverse Ab-mediated rejection in previously allosensitized pediatric transplant recipients.

Adolescent↗
PubMed1999

The effect of drug cost on hypertension treatment decision.

The cost of medical care is constantly increasing. Therefore, ways of saving expenses should be considered. The aim of the present study is to evaluate the possibility than an awareness of the cost of drugs for treatment of hypertension may affect physicians' prescription decisions. A questionnaire containing the clinical data of a young and an elderly imaginary patient with moderate hypertension was given to 30 family physicians and 30 hospital physicians together with a list of appropriate drugs (phase I). This was repeated as phase II except that for this stage the cost of the drugs was brought to the participants' attention. Knowing the cost of the drugs caused a decrease in prescription of the more expensive drugs for the younger patients; of 60% (family physicians) and 87% (hospital physicians). For their elderly patients family physicians preferred the less expensive drugs at both phases. 25% of the hospital doctors changed their preference towards less expensive drugs at phase II. For the younger patient, no correlation was found between the number of years of physicians' practice and the cost of the drugs chosen. For the elderly patient, physicians from both groups preferred less expensive drugs at phase II without any relation to their years of practice. The results of this study indicate that a knowledge of the price of the drugs may affect physicians' prescription decisions, a fact that may result in considerable saving by health providing organizations.

Adult↗
PubMed1999

Histologic features associated with lymph node metastasis in stage T1 and superficial T2 rectal adenocarcinomas in abdominoperineal resection specimens. Identifying a subset of patients for whom treatment with adjuvant therapy or completion abdominoperineal resection should be considered after local excision.

Local excision of rectal adenocarcinomas that are confined to the submucosa is an accepted method of surgical excision. Adjuvant therapy and possibly completion abdominoperineal resection (APR) may be appropriate if lymph node (LN) metastases are present. Identifying the patients at high risk of having LN metastases would assist in disease management. We retrospectively examined 73 APR resection specimens with T1 or superficial T2 adenocarcinomas. The leading edge of the tumor was evaluated for budding, microacinar structures, or isolated or small clusters of undifferentiated cells. The features were correlated with LN metastases. Eleven specimens had LN metastases. Extensive budding, microacinar structures, or undifferentiated cells, tumor grade 3, and small vessel vascular space invasion were associated with LN metastases. Limiting the comparison to grade 1 and 2 adenocarcinomas showed association of extensive budding, microtubular architecture, and undifferentiated cells along the advancing edge with LN-metastases. If these histologic features are extensively present, the patient may be a candidate for adjuvant therapy or completion APR. The morphologic features of the advancing edge are independent of the tumor grade of the neoplastic glands within the body of the tumor; they can be incorporated into the evaluation of overall tumor grade.

Adenocarcinoma↗
PubMed1999

Inhibition of O(6)-methylguanine-DNA methyltransferase increases azoxymethane-induced colonic tumors in rats.

Azoxymethane (AOM) causes O(6)-methylguanine adduct formation which leads to G-->A transitions. Their repair is carried out by O(6)-methylguanine-DNA methyltransferase (MGMT). To evaluate the importance of this repair event in AOM-induced carcinogenesis, we examined the effect of O(6)-benzylguanine (BG), a potent inhibitor of MGMT, on colonic tumor development. Rats were treated weekly for 2 weeks at 0 and 24 h with BG (60 mg/kg body wt i.p.) or vehicle (40% polyethylene glycol, PEG-400), followed 2 h after the first dose of BG with AOM (15 mg/kg body wt) or vehicle (saline) i.p. Rats were killed 35 weeks later and tumors harvested and DNA extracted. In the AOM-treated groups, BG caused a significant increase in tumor incidence with tumors in 65.9%, versus 30.8% in the AOM/PEG-treated group (P < 0.05). In the BG/AOM group there was also a significant increase in tumor multiplicity, with 2.3 tumors/tumor-bearing rat, versus 1.6 tumors/tumor- bearing rat in the AOM/PEG group (P < 0.05). Since O(6)-methylguanine adducts can cause activating mutations in the K-ras and beta-catenin genes, we examined the effects of BG on these mutations. In the BG group there were seven mutations in codon 12 or 13 of exon 1 of the K-ras gene in 51 tumors examined, compared with no K-ras mutations in 17 tumors analyzed in the AOM/PEG group (P = 0.12). In the BG/AOM group there were 10 mutations in exon 3 of the beta-catenin gene among 48 tumors evaluated, compared with six mutations in 16 tumors analyzed in the PEG/AOM group (P = 0.16). In summary, MGMT inhibition increases AOM-induced colonic tumor incidence and multiplicity in rats.

Animals↗
PubMed1999

Fulminant hepatic failure secondary to malignant melanoma: case report and review of the literature.

Malignant melanoma has a propensity to metastasize widely to many organs, involving the liver in up to one-third of cases. Fulminant hepatic failure is an unusual presentation of hepatic neoplasms, whether primary or metastatic. We describe a case of malignant melanoma with liver metastases that rapidly progressed to fulminant hepatic failure and death. Striking elevations of liver tests, particularly lactate dehydrogenase, were seen. Liver biopsy showed diffuse intrasinusoidal infiltration with melanoma cells. In patients with malignant melanoma, raised serum lactate dehydrogenase levels may suggest hepatic involvement, with extreme elevations possibly predictive of liver failure.

Hepatic Encephalopathy↗
PubMed1999

Apoptotic and mitotic indices predict survival rates in lymph node-negative colon carcinomas.

An imbalance between apoptosis and mitosis is believed to underlie colon cancer development and progression. These processes regulate the growth of normal and neoplastic epithelia, and in tumors, may confer prognostic information. To test this hypothesis, we determined apoptotic and mitotic indices (AI, MI) by morphology in H&E sections of 154 lymph node-negative, sporadic colon carcinomas. The relationship of these indices to genetic (p53 and Bcl-2) and biological features (DNA ploidy and cell kinetics) and patient survival rates was determined. Tumor features were compared in proximal and distal tumors, given postulated differences in their pathogenesis. Bcl-2 and p53 proteins were examined using immunohistochemistry and DNA ploidy and proliferative indices (PIs) by flow cytometry. Tumor features were dichotomized for analysis of relapse-free survival and overall survival (OS) rates using a Cox proportional hazards model. Median patient follow-up was 8.8 years. The median AI and MI were 1.2% (0-7.6) and 0.40% (0-1.8), respectively, and did not differ by tumor site. AI correlated with histological grade (P = 0.03); MI correlated with PI (P = 0.02) and inversely with Bcl-2 in distal tumors (P = 0.02). p53 and Bcl-2 expression were detected in 52 and 53% of tumors, respectively. Distal tumor site was associated with aneuploidy (P = 0.001), p53 (P = 0.001), and PI > 15% (P = 0.002). In a univariate analysis, colon cancers with high MIs (>0.5%) had a poor prognosis (P = 0.04). Bcl-2 overexpression (>20% + tumor cells) was associated with more favorable OS (P = 0.04). The association of ploidy and PI with outcome was of borderline significance for all tumors; however, diploidy predicted better survival in proximal cancers. In distal cancers, low AIs (< or = 0.25%) and high MIs (>0.5%) were adverse prognostic markers. After adjustment for other variables, an increased MI predicted shorter OS with a hazard ratio (HR) for death of 2.70; 95% confidence interval (CI) was 1.23-5.91 (P = 0.01). Expression of Bcl-2 was associated with more favorable OS (HR, 0.46; 95% CI, 0.21-1.0; P = 0.06). In proximal cancers, Bcl-2 expression was the most important predictor of OS (HR, 0.17; 95% CI, 0.03-0.85; P = 0.03). In distal tumors, low AIs (HR, 3.33; 95% CI, 1.27-9.09; P = 0.01) and high MIs predicted poor survival. In conclusion, increased mitosis and low or absent Bcl-2 expression are significant risk factors for death in node-negative colon cancers, as are low rates of apoptosis in distal tumors. If validated prospectively, our results may identify patient subsets than can benefit from adjuvant chemotherapy.

Adenocarcinoma↗
PubMed1999

Talk of the town in 1921: chiropractic and "talking sickness".

In 1921 Waukegan, Illinois, there was an eight-year-old girl who had what was called "talking sickness." She reportedly talked constantly for eight straight days and nights. After medical care failed to help, a local chiropractor was called to adjust the young girl, and she apparently experienced marked improvement thereafter. News of the seemingly spectacular recovery reached a fever pitch across the United States in the spring of 1921, in both lay and professional publications. The slightly different versions of this case, from slightly biased sources on each side of the fence (such as Fountain Head News on the one side and The Journal of the American Medical Association on the other), as well as coverage from newspaper reports are explored.

Child↗
PubMed1998

Temporal dynamics of verbal object comprehension.

Knowledge of the stage composition and the temporal dynamics of human cognitive operations is critical for building theories of higher mental activity. This information has been difficult to acquire, even with different combinations of techniques such as refined behavioral testing, electrical recording/interference, and metabolic imaging studies. Verbal object comprehension was studied herein in a single individual, by using three tasks (object naming, auditory word comprehension, and visual word comprehension), two languages (English and Farsi), and four techniques (stimulus manipulation, direct cortical electrical interference, electrocorticography, and a variation of the technique of direct cortical electrical interference to produce time-delimited effects, called timeslicing), in a subject in whom indwelling subdural electrode arrays had been placed for clinical purposes. Electrical interference at a pair of electrodes on the left lateral occipitotemporal gyrus interfered with naming in both languages and with comprehension in the language tested (English). The naming and comprehension deficit resulted from interference with processing of verbal object meaning. Electrocorticography indices of cortical activation at this site during naming started 250-300 msec after visual stimulus presentation. By using the timeslicing technique, which varies the onset of electrical interference relative to the behavioral task, we found that completion of processing for verbal object meaning varied from 450 to 750 msec after current onset. This variability was found to be a function of the subject's familiarity with the objects.

Adult↗
PubMed1998

Prognostic implications of centrilobular necrosis in pediatric liver transplant recipients.

BACKGROUND: We have observed centrilobular necrosis (CLN) in several liver allograft biopsies in our pediatric liver transplant population. The aims of this study were to describe the associated pathologic and clinical features of post-orthotopic liver transplantation CLN and determine its prognostic implications. METHODS AND RESULTS: CLN was identified and characterized in 44 allografts from 40 patients (17 males and 23 females) among our 443 pediatric recipients. Twenty episodes were associated with cellular rejection, either in the same biopsy (n=15) or within the week prior (n=5), and five were associated with ductopenic rejection. Twelve were associated with vascular thrombosis. No clear etiology was identified in seven episodes, but two also had cholangitis lenta. Of the remaining five biopsies, three showed only centrilobular dropout, suggesting a resolution of some previous insult. The outcome of 40 patients following an initial episode of CLN was poor, with graft failure in 33, chronic poor function in 2, and normal recovery in only 5 patients. The results of retransplantation for graft failure due to CLN were equally poor, with 14 deaths, 3 patients with ductopenic rejection, and only 5 with normal recovery. CLN recurred in four grafts. Overall patient outcome was very poor: 25 deaths; 3 ductopenic rejections; 2 chronic poorly functioning livers; and 10 patients alive and well. CONCLUSION: We conclude that CLN in pediatric orthotopic liver transplantation recipients is associated with cellular rejection, ductopenic rejection, or acute vessel thrombosis in the majority cases. The prognostic implications of CLN are grave, with high rates of graft failure requiring retransplantation and death.

Adolescent↗
PubMed1998

Decreased PKC-alpha expression increases cellular proliferation, decreases differentiation, and enhances the transformed phenotype of CaCo-2 cells.

Previous studies have shown that PKC-alpha protein expression is decreased in sporadic human colon cancers, as well as in colonic tumors of rats induced by chemical carcinogens. To elucidate the potential role of PKC-alpha on several phenotypic characteristics of colon cancer cells, we have transfected cDNAs for PKC-alpha in sense or antisense orientations into CaCo-2 cells, a human colonic adenocarcinoma cell line. Transfected clones were isolated that demonstrated approximately 3-fold increases (sense transfectants) and approximately 95% decreases (antisense transfectants) in PKC-alpha expression with no significant alterations in other PKC isoforms. Transfection of CaCo-2 cells with PKC-alpha in the antisense orientation resulted in enhanced proliferation and decreased differentiation, as well as in a more aggressive transformed phenotype compared with empty vector-transfected control cells. In contrast, cells transfected with PKC-alpha cDNA in the sense orientation demonstrated decreased proliferation, enhanced differentiation, and an attenuated tumor phenotype compared with these control cells. These data show that alterations in the expression of PKC-alpha induce changes in the proliferation, differentiation, and tumorigenicity of CaCo-2 cells. Furthermore, these findings indicate that loss of PKC-alpha expression in sporadic human and chemically induced colonic cancers may confer a relative growth advantage during colonic malignant transformation.

Animals↗
PubMed1998

Familiar and novel contexts yield different associations between cortisol and behavior among 2-year-old children.

We examined 10:30 a.m. salivary cortisol levels in twenty-four 2-year-old children at home, and then at several points during transition into preschool: Week 1, Weeks 6-9, and the 1st week following a month-long holiday break. Cortisol levels did not increase when the children first started school as compared to either home or later school levels. Cortisol levels were correlated across similar, but not across dissimilar, psychosocial contexts. Home levels were correlated wit more shy, anxious, internalizing behavior while the response to starting school was correlated with more assertive, angry, and aggressive behavior. Behavior was assessed using parent temperament reports, teacher reports, and observational measures. We conclude that HPA activity as indexed by salivary cortisol measures is differentially associated with behavior in familiar and novel contexts. Consistent with our prior work, shy/anxious behavior is not significantly associated with elevations in cortisol when young children enter new social situations.

Child Behavior Disorders↗
PubMed1998

Modified surgical model of paratopic small bowel transplantation in mice.

A murine paratopic model of intestinal transplantation was developed and used to study the immune response to allografts in normal C57BL/6 recipients (H2(b)) and C57BL/6 recipients treated with tacrolimus (1 mg/kg, Days 0-7). B6C3F1 mice (C57BL/6 x C3H/HeJ, H2(bxk)) were used as donors. The paratopic model differed from the standard heterotopic model in that continuity of the intestine graft with the recipient intestine was established by anastomosing the graft ileum to the side of the recipient jejunum. The success rate of this modified procedure was 82% (94/114). Major complications included hypovolemic shock and/or anesthetic-related deaths (8%), infection (8%), and vascular thrombosis (2%). Rejection was assessed using both clinical features (i.e., edema and closure of the stoma, mucous discharge, and a palpable mass) and histologic features (apoptosis of crypt cells, crypt destruction, lymphocytic infiltrate, and mucosal ulceration). Syngeneic grafts appeared clinically and histologically normal throughout the study period. Untreated recipients of allografts developed clinical and histologic evidence of rejection by Day 4 which progressed to severe rejection and graft destruction by Day 18. After initially developing evidence of mild to moderate graft rejection on Day 8, the severity of allograft rejection decreased significantly by Days 10 to 14 in tacrolimus-treated mice. By Day 28 evidence of moderate rejection had recurred in mice treated with an 8-day course of tacrolimus. Consistent with these observations, graft function, as assessed by maltose absorption, was impaired in rejecting allografts when compared with syngeneic grafts. Allografts in mice treated with tacrolimus demonstrated improved maltose absorption relative to allografts from untreated mice. These studies describe a modified technique for intestinal transplantation in mice and provide a detailed analysis of complications as well as an assessment of rejection and its functional consequences. Based on these results, we conclude that the paratopic model of intestinal transplantation in mice is a useful tool for studying the host immune response to intestinal allografts.

Animals↗