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Biomedical subjects

P S Gartside

Publications and source records attributed to P S Gartside.

At least 19 recordsLinked to original sources

A comparison of exposures to refractory ceramic fibres over multiple work shifts.

As part of an ongoing, industry-wide study in the manufacture of refractory ceramic fibres (RCF), time weighted average (TWA) exposures have been collected at five facilities according to a standardised protocol. Work activities were grouped into dust zones (DZs). Persons to be sampled were randomly selected according to a protocol designed to assure that at least one sample was collected annually from each DZ; each work shift is also sampled at least annually. TWA exposures calculated over a sampling period of at least 360 min were included in the data set. DZs were combined into one of three groups (DZGs): fibre production; vacuum processes; other. The data were analysed to identify any differences by DZG between airborne fibre exposures, by the shift worked at each facility, and across all facilities. There were no statistically significant shift-related differences detected between airborne fibre exposures across the five RCF facilities when analysed as a group. Within four of the facilities, no shift-related differences were detected between airborne fibre exposures; however, at one facility, first and third shift exposures were statistically different. No documentation related to job activities was found to account for the observation. The data generally support the use of a single exposure estimate for each DZG in each of these facilities, regardless of shift worked. Researchers reconstructing exposure and not able to determine the shift worked by study subjects may find these results useful, but are cautioned that substantial differences in exposure across shifts may exist in other types of manufacturing.

Air Pollutants, Occupational

Prospective 10-year evaluation of hypobetalipoproteinemia in a cohort of 772 firefighters and cross-sectional evaluation of hypocholesterolemia in 1,479 men in the National Health and Nutrition Examination Survey I.

Our specific aim in a 10-year prospective study of 772 Cincinnati firemen (predominantly aged 26 to 46 years) was to determine the prevalence, attributes, and etiology of persistent hypobetalipoproteinemia, defined by entry low-density lipoprotein cholesterol (LDLC) less than 75 mg/dL. A second specific aim was to cross-sectionally assess hypocholesterolemia (defined by total serum cholesterol [TC] < 130 mg/dL) in 1,314 white and 165 black men aged 26 to 46 years in the National Health and Nutrition Examination Survey (NHANES I). The 141 black and 631 white firemen had 4,973 person-years of follow-up time (median, 7.1 yr/man). Of 772 men, 44 (5.7%) had entry LDL levels less than 75 mg/dL; they had a mean follow-up time of 7.3 yr/man. Of these 44 men, there were 12 (1.8% of the cohort) with entry LDLC less than 75 mg/dL, and at least 67% of their follow-up LDLC levels were less than 75. Their mean entry TC and LDLC levels were low (130 and 58 mg/dL), mean triglyceride (TG) was low (63 mg/dL), and mean high-density lipoprotein cholesterol (HDLC) was high (60 mg/dL), LDLC remained at less than 75 mg/dL in 81% of their follow-up samples. Their mean entry and follow-up cholesterol and LDLC did not differ (P > .1, 130 v 133 mg/dL and 58 v 63 mg/dL). Compared with 32 men with entry LDLC less than 75 mg/dL but with less than 87% of follow-up LDLC less than 75 mg/dL, the 12 men with persistently low LDLC had lower mean Quetelet indices and diastolic blood pressure at entry (2.36 v 2.58, P = .056; 73 v 80 mm Hg, P = .03) and on follow-up study (2.45 v 2.69, P = .04; 72 v 79 mm Hg, P = .05). Of 12 men with persistently low LDLC, two had truncated apolipoprotein (apo) B (familial hypobetalipoproteinemia, two had the apo E genotype 2/3, and two had acquired hypobetalipoproteinemia that antedated mortality from melanoma by 9 years and from alcoholism by 2 years. Comparable to white and black firemen aged 26 to 46 years, 2.9% and 3.6% of whom had entry serum TC less than 130 mg/dL, of 1,314 white and 165 black men in the NHANES I study (aged 26 to 46), 1.8% and 3.6% had hypocholesterolemia (entry TC < 130 mg/dL). Daily mean calorie, fat, and protein intake (grams per day) did not differ (P > .05) in men with entry TC less than 130 mg/dL compared with those with TC 130 to 230 or greater than 230 mg/dL. Hypocholesterolemia in white and black men in NHANES I could not be attributed to hypocaloric intake or to protein, fat, or carbohydrate undernutrition. There appear to be racial differences in the prevalence of hypocholesterolemia. Blacks comprised 18% of the firemen's cohort but 42% of those with persistent hypobetalipoproteinemia; among NHANES I subjects, 3.6% of blacks were hypocholesterolemic versus 1.8% of whites. Unless persistent hypobetalipoproteinemia reflects an underlying disease, alcoholism, etc., it is often heritable, and may be associated with a reduced likelihood of coronary heart disease (CHD) and with increased longevity.

Adult

Effect of food palatability on early (cephalic) phase of diet-induced thermogenesis in nonobese and obese man.

OBJECTIVE: To study the effect on the early (cephalic) phase of diet-induced thermogenesis (EDT) of palatable vs unpalatable food, in nonobese and obese man. SUBJECTS: Twenty-four nonobese volunteers and 19 obese clinic patients. DESIGN AND MEASUREMENTS: A palatable, liquid formula meal of Ensure (1048 KJ, 450 ml), and of Ensure made unpalatable by addition of aqueous KCl, were sipped on nonconsecutive mornings. O2 consumption (ml/min) was measured before, and starting 30, 60 and 90 min after beginning the test meal, from which EDT was calculated as KJ/min. RESULTS: Palatability of the test meal significantly increased EDT (palatability effect, P = 0.004) but obesity status per se, did not affect EDT. Nevertheless, the effect of palatability on EDT was dependent on obesity status, being seen only in the nonobese. EDT was significantly greater in the nonobese after the palatable than the unpalatable meal: (mean +/- s.e.m.) 2.45 +/- 0.14 vs 1.83 +/- 0.14; P < 0.0001, but not in the obese: 1.93 +/- 0.28 vs 1.73 +/- 0.20; P < 0.21. Therefore only after the palatable meal was EDT less in the obese compared with the nonobese: P < 0.05. The threshold for the unpleasant taste of added KCI was 31% higher in the obese than the nonobese: 4.2 +/- 0.4 vs 3.2 +/- 0.2 [g KCI]; P < 0.025. CONCLUSIONS: The early (cephalic) phase of dietary thermogenesis (EDT) is significantly increased in the nonobese by palatability, but not in the obese, so that only after a palatable meal is EDT less, or 'deficient,' in the obese compared with the nonobese. Also, the obese have a higher threshold for the unpleasant taste of KCI (in Ensure) than the nonobese.

Adolescent

Attention-deficit hyperactivity disorder among homeless veterans.

Among 100 participants in a Department of Veterans Affairs domiciliary program for chronic mentally ill homeless veterans who were consecutively referred for psychiatric consultation, 81 who were not psychotic and did not have central nervous system damage were screened for attention-deficit hyperactivity disorder (ADHD). The screening instrument was a four-item questionnaire. Fifty of the 81 participants screened positive, yet none of the patients or their clinicians had considered ADHD a possible influence on their lives. The study results suggest that clinical staff working with homeless veterans should receive better training in recognizing the various presentations of ADHD among adults.

Adult

Risk factors for coronary heart disease among firefighters in Cincinnati.

Since 1984, coronary heart disease (CHD) risk factors have been prospectively assessed among Cincinnati firefighters free of CHD at study entry. In total, 806 firemen with a mean age of 37 years at entry have been followed for 6.4 years on average, contributing 5,173 person-years. CHD risk factors were measured every 1-4 years and included weight, blood pressure, cigarette use, fasting glucose, and lipid profile. When, in aggregate, these CHD risk factors were found to be in a high risk range, suggestions were made serially to reduce CHD risk. A composite high CHD risk factor score led to an exercise electrocardiogram (ECG) with thallium scan, which was repeated every 1-4 years. Myocardial infarction (MI) occurred in 7 men, with 1.35 MIs/1,000 man-years; 15 others developed CHD, with 4.25 MI + CHD/1,000 man-years. The firefighters' MI event rate (1.35 MIs/1,000 man-years) was lower (but not significantly, p > 0.1) than that for employed 30- to 39-year-old men free of CHD at entry (2.07/1,000 man years), who had an average follow-up of 5.4 years in the NHANES I study. At study entry, the 22 men who later developed CHD (vs. the 784 who did not develop CHD) were older (p = .0001), smoked more (p = .0001), and were more likely to have first degree relatives with CHD before age 60 (p = .017). After covariance adjusting for age, race, and Quetelet index, men with CHD (vs. those CHD free) had higher systolic and diastolic blood pressures (p = .0001, .0001), higher LDL cholesterol (p = .04), higher total cholesterol (p = .014), and higher triglycerides (p = .03). By Poisson regression, significant independent predictors of CHD events were age (p = .0007), cigarette smoking (p = .001), diastolic blood pressure (p = .056), and family history of CHD at age < or = 60 (p = .048). Men who later developed CHD and those without CHD did not differ by history of smoke inhalation (p > 0.3). The calculated ratio of savings to cost attributable to the program per year was 5.9/1 ($258,500/$43,600). In the current study, firefighting as an occupation was not associated with increased CHD event rates. CHD events that did develop were, for the most part, associated with modifiable CHD risk factors.

Adult

The loss of heterozygosity in retinoblastoma and p53 suppressor genes as a prognostic indicator for head and neck cancer.

Inactivation of tumor suppressor genes, including p53 and retinoblastoma (Rb), are commonly found in all cancers, including head and neck squamous cell carcinoma. Alterations at either p53 or Rb, however, are only weakly associated with tumor aggressiveness. In many cancers loss of heterozygosity (LOH) at multiple loci is associated with decreased survival. The polymerase chain reaction and highly informative microsatellite markers were used to compare DNA from matched sets of 63 head and neck squamous cell cancers and normal tissue for LOH at the p53 and Rb loci. At p53, 50 were informative, with LOH occurring in 19 (38%). Of the 57 that were informative at Rb, LOH occurred in 21 (37%). Of the 46 that were informative at both p53 and Rb, LOH occurred in 10 (22%) at both loci. When LOH for p53 and Rb individually was compared to stage, differentiation, and survival, there was no correlation. However, the patients with LOH at both loci had a significantly poorer survival (P = .009). This strongly supports the contention that simultaneous alterations of these two tumor suppressor genes favor tumor aggressiveness and can be used as a prognostic indicator.

Carcinoma, Squamous Cell

Pulmonary function in obese subjects with a normal FEV1/FVC ratio.

STUDY OBJECTIVE: To determine pulmonary function test (PFT) profile and respiratory muscle strength (RMS) of a group of obese individuals who did not have evidence of obstructive airway disease or other underlying diseases affecting their respiratory system. DESIGN: Prospective, open. SETTING: PFT laboratory, VA Medical Center. PARTICIPANTS: Sixty-three consecutive obese (body mass index greater than 27.8 kg/m2) male subjects without overt obstructive airway disease (FEV1/FVC ratio greater than 80%). MEASUREMENTS AND RESULTS: Standard PFTs and maximum static inspiratory (PImax) and expiratory (PEmax) mouth pressures were determined. RMS was calculated from the following formula: (PImax+PEmax):2. Two distinct groups were identified, those with normal maximum voluntary ventilation (MVV) (> 80% predicted) and those with low MVV. Both inspiratory and expiratory flow rates (FVC, FEV1, forced expiratory flow at 50% vital capacity [V50], maximum inspiratory flow rate [MIFR]), lung volumes (vital capacity [VC], inspiratory capacity [IC], expiratory reserve volume), PImax, and RMS were significantly lower, and residual volume/total lung capacity (RV/TLC) ratio was significantly higher in obese subjects with low MVV compared with those in whom MVV was normal. MVV correlated significantly with FVC, FEV1, V50, MIFR, TLC, VC, IC, RV/TLC, and RMS; the strongest correlation was with MIFR (r = 0.76, p < 0.0001). CONCLUSIONS: Standard PFTs allow recognition of a subgroup of obese subjects without overt obstructive airway disease who have more severe lung dysfunction, the marker of which is a low MVV. Peripheral airway abnormalities may be responsible for these observations.

Adult

The important role of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease hospitalization and mortality: the prospective NHANES I follow-up study.

OBJECTIVE: Our specific aim in the prospective, longitudinal assessment of 8,251 subjects in the National Health and Nutrition Examination Survey, NHANES I, followup study was to assess the important roles of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease (CHD). METHODS: Using NHANES I prospective 10 year followup data, we studied 8,251 subjects; 492 with cardiovascular events and 7,759 without events during the followup period (1971-75 to 1982-84). Using general linear models and logistic regression, we assessed the relationships of CHD risk factors to CHD morbidity and mortality. RESULTS: By logistic regression, the following factors were independently, significantly, and inversely associated with coronary heart and vascular disease deaths and hospitalizations: alcohol intake, dietary riboflavin, dietary iron, serum magnesium, leisure time exercise, habitual physical activity, and female gender. Positive significant independent determinants of CHD events included cigarette smoking, sedimentation rate, Quetelet index, maximum body weight, and age. CONCLUSIONS: These associations emphasize the important role of modifiable dietary and behavioral characteristics in the causation and prevention of CHD.

Adult

Structural equation modeling and nested ANOVA: effects of lead exposure on maternal and fetal growth in rats.

This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth.

Analysis of Variance

Chronic hypercapnia in obstructive sleep apnea-hypopnea syndrome.

In order to determine the relationship between chronic hypercapnia and anthropomorphic data, pulmonary function tests and slopes of ventilatory responses to hypercapnia (HVCR) and hypoxia (HVR), we studied 55 patients with sleep apnea-hypopna syndrome (SAHS). Patients were divided into hypercapnic, PaCO2 > or = 45 mm Hg (Group I, n = 23, PaO2 = 61 +/- 10 and PaCO2 = 50 +/- 5 mm Hg, and [HCO3-] = 30 +/- 4 mEq/l [means +/- SD]) and normocapnic (or eucapnic), PaCO2 < 45 mm Hg (Group II, n = 32, PaO2 = 76 +/- 10 and PaCO2 = 39 +/- 4 mm Hg and [HCO3-] = 25 +/- 3 mEq/l [means +/- SD]) groups. When compared to the normocapnic group, hypercapnic patients were significantly heavier (with greater body surface area) and had significantly more severe restrictive and obstructive defects and impaired HVR and HCVR. The means (+/- SD) of some of the data follow (* indicates p < 0.05 when Group I is compared to Group II): [table: see text] When subgroups of hypercapnic and eucapnic patients with similar lung functions were compared, the subgroups differed significantly in their weights; conversely, in subgroups with comparable weights, lung function tests differed significantly. These data suggest that the mechanisms of chronic hypercapnia are multifactorial, and we hypothesize that, in the face of repetitive apneas and hypopneas, increased weight and abnormal lung function tests interact and contribute to the generation and maintenance of hypercapnia.

Adult

Acute respiratory acidosis: large-dose furosemide and cerebrospinal fluid ions.

NaCl cotransport carrier is known to be involved in transepithelial fluid absorption and secretion in various tissues. Recent studies indicate that Na-K-2Cl cotransport carrier also exists in the choroid plexus cells and that inhibition of the carrier decreases cerebrospinal fluid (CSF) production. In this study, we used large-dose intravenous furosemide, an inhibitor of Na-K-2Cl carrier, to determine the effects on cisternal CSF ionic composition in acute respiratory acidosis. In pentobarbital-anesthetized mechanically ventilated dogs, renal pedicles were ligated to prevent furosemide-induced diuresis. The experimental group (group II, n = 7) received 400 mg/kg of furosemide intravenously, and group I (control group, n = 7) received the vehicle. In group II, serial serum and CSF furosemide concentrations were approximately 10(-3) and 10(-5) mol/l, respectively. During 5 h of acute respiratory acidosis in both groups, the mean arterial PCO2 increased approximately 25 Torr, with comparable changes in CSF PCO2. In both groups, CSF [HCO3-] and [H+] rose approximately 3 meq/l and 20 neq/l, respectively. Changes in CSF [Na+], [K+], [Cl-], and [Na(+)-Cl-] were also similar and were not significantly different from each other when the two groups were compared. These data show that furosemide at the dose that inhibits NaCl cotransport carrier does not significantly alter ionic composition of cisternal CSF.

Acid-Base Equilibrium

Growth patterns of human neuroblastoma xenografts and their relationship to treatment outcome.

BACKGROUND: Several investigators have reported the ability to establish xenografts in nude mice from children with neuroblastomas, but a correlation of prognosis with this establishment and the growth patterns of the neuroblastomas has not been reported. METHODS: Tumor specimens from 58 children with neuroblastomas were heterotransplanted into BALB/c nude mice. In 34 patients, heterotransplantation was done before therapy; in 24 patients, tumors were obtained after at least one course of chemotherapy or radiation therapy. The histology, cytogenetics, and growth characteristics of serial passages of the xenografts were studied. RESULTS: The engraftment rate was 34%. Neuroblastomas with diploid chromosome numbers did not engraft. Chromosomal abnormalities involving 1p were seen in more than 50% of the xenografts. Cytogenetic features were retained between original tumors and resultant xenografts. Xenografts could be established only from tumors with unfavorable histology, as defined by Shimada classification criteria. The histology of each xenograft line was strikingly similar, and each was highly undifferentiated. Engraftment rates, doubling times, and lag times did not vary appreciably between xenografts established from treated tumors compared with xenografts established from untreated tumors. There was no correlation between doubling or lag times and prognosis. Patients whose tumors engrafted had only a 5% 3-year survival rate. CONCLUSIONS: From these results, it appears that successful engraftment is the most important prognostic indicator for patients with neuroblastomas. Because of the commonality of the histologic features and the stability of the tumor clones from patients before and after heterotransplantation, these xenografts may be useful as an in vivo model for studying drug resistance and for designing treatment regimens.

Animals

Relationship of dietary intake to hospital admission for coronary heart and vascular disease: the NHANES II national probability study.

After excluding 2,908 subjects (25% of the cohort) whose diets had changed, possibly as a consequence of disease discovery, in 8,679 individuals from the NHANES II national probability study, our specific aim was to determine which nutritional factors were significant independent contributors to overnight hospitalization with coronary heart and vascular disease (CHD). Covariance adjustments were made for multiple sociodemographic, educational, geographic factors, total cholesterol, high-density lipoprotein cholesterol (HDL-C), race, age, sex, and relative ponderosity (obesity). After these adjustments, linoleic acid (p = 0.049) and alcohol (p = 0.017) were independently inversely associated with CHD hospitalizations; cigarette smoking (p = 0.054) was positively associated. Relative risk for CHD hospitalization was 1.0 for linoleate 0-6 g/day, 0.72 for 6-11.59 g/day, and 0.49 for > or = 11.6 g/day, p < or = 0.01. Relative risk for CHD hospitalization was 1.0 for no coffee intake, 0.6 for regular coffee, 1.8 for regular coffee plus decaffeinated coffee, 2.6 for decaffeinated coffee, and 5.2 when decaffeinated coffee was drunk by virtue of physicians' advice, p < or = 0.001. Unlike our extensive exclusions (25% of the cohort) for diet change, we did not exclude any subjects on the basis of self-directed or physician-recommended changes in smoking habits of initiation of decaffeinated coffee use, following, or as a consequence of disease discovery. We speculate that the relationship of decaffeinated coffee to CHD reflects behavior change after CHD hospitalization. Dietary cholesterol (p = 0.038) was an independent positive predictor of serum total cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking

Sex differences and the effects of alcohol on immune response in male and female rats.

Although it is clear that both alcohol and sex hormones impact immune function, very little information is available on the effects of alcohol on immune response in males versus females. We decided to determine if the alterations in immune response resulting from alcohol feeding might be expressed differently in males and females. To accomplish this we utilized pair-fed male and female Sprague-Dawley rats. Animals were fed a liquid diet for 60 days containing 30% of their calories as ethanol, and after 1 week this concentration was increased to 45% ethanol. Controls received liquid control diet of the same caloric and nutritional composition, and immune status was monitored with in vivo and in vitro techniques. Ethanol feeding significantly reduced the phytohemagglutinin skin response in males (p = 0.020) and females (p = 0.012). The concanavalin A blastogenic response of spleen cells prepared from female rats fed ethanol was significantly depressed with respect to spleen cells prepared from female rats fed the control diet (p = 0.0071). Alcohol also appeared to depress spleen cell blastogenic response in males, but this trend did not quite reach significance (p = 0.071). Spleen cells from groups of ethanol and control male and female rats were labeled with fluorescent monoclonal antibodies and run on a Fluorescent-Activated Cell Sorter. Ethanol significantly increased the percentage population of CD4 (T-helper cell) in males (p = 0.017), but not in females, and promoted an apparent, although nonsignificant, increase in the CD4/CD8 ratio in both sexes. An ELISA was used to measure IgM and IgG antibody elaborated by pokeweed mitogen-stimulated spleen cells in cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism

Bile duct changes in alcoholic liver disease. The Veterans Administration Cooperative Study Group.

The histologic significance of various changes in the bile ductal structures as observed by cytokeratin immunoperoxidase assay was studied in 122 patients with alcoholic liver disease (ALD) as a part of a large Veterans Administration Cooperative Study on alcoholic hepatitis. Four types of morphologic changes in the biliary structures were observed: 1) proliferation of interlobular bile ducts in the portal tracts; 2) marginal bile ductular proliferation at the periphery of the portal tracts; 3) appearance of bile duct type cells ("oval cells") in the liver parenchyma; and 4) metaplasia of bile duct epithelium to cells resembling hepatocytes. These bile ductal changes correlated strongly with liver fibrosis (p = 0.0003; 0.0003; 0.05; 0.0035, for 1, 2, 3, and 4, respectively), cirrhosis (p < 0.0001 for all four parameters), portal inflammation (p < 0.0001 for 1, 2, and 4; p = 0.0024 for "oval cells"), and with overall histologic severity scores (p < 0.0001; p = 0.0001; p = 0.0017; p = 0.0005, respectively). However, these changes did not correlate significantly with fatty change, parenchymal degeneration and necrosis, cellular infiltrate or Kupffer cell hyperplasia, suggesting that they are probably not the direct consequences of liver cell necrosis. Periportal piecemeal necrosis correlated significantly with both portal bile duct (p = 0.0041) and marginal (p = 0.0078) bile ductular proliferation. Among all these changes, only marginal bile ductular proliferation correlated significantly with Mallory bodies present both in the hepatocytes (p = 0.05) and the bile ducts (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Ducts

Antibodies to hepatitis B virus and hepatitis C virus in alcoholic hepatitis and cirrhosis: their prevalence and clinical relevance. The VA Cooperative Study Group (No. 119)

Patients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis B virus and hepatitis C virus antibodies to determine the prevalence of these antibodies to determine the prevalence of these antibodies and any clinical association in the progression and outcome of alcoholic liver disease. Antibodies to hepatitis B (anti-HBs and/or anti-HBc) were found in 29.2% of patients with alcoholic liver disease, in 26.1% of hospitalized alcoholic patients without liver disease and in 24.2% of hospitalized nonalcoholic patients without liver disease; frequencies were not significantly different from one another. HBsAg was not evaluated because HBsAg+ patients had been excluded from the original trial. The presence of these antibody markers correlated with ethnic origin of and immunoglobulin levels in the patients. In contrast, antibody to hepatitis C, as detected by enzyme immunoassay, was positive in 27.1%, 4.8% and 3.0% of the three groups, respectively, the first differing significantly from the other two. Antibody to hepatitis C virus positivity correlated significantly with clinical severity of the disease and with the presence of histological features that imply chronic viral infection (periportal inflammation, cirrhosis), despite the fact that the supplementary assay for antibody to hepatitis C virus, using recombinant immunoblot assay, reduced the positive rate by 79%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Alpha-fetoprotein alterations in alcoholics with liver disease. V.A. Cooperative Study Groups.

Sera on 409 male alcoholics with liver injury were assayed for alpha-fetoprotein (AFP) as part of a VA co-operative study on the natural history and therapy of alcoholic liver disease. In 78% of the patients values below normal were observed and 42% had undetectable levels. Clinically the lowest AFP concentrations were observed in the more severely ill patients with the poorest 1 year survival. Furthermore, improvement in AFP was associated with improved survival. Correlation analysis showed a relationship of AFP to (1) visceral protein concentrations (i.e. albumin, transferrin, retinal binding protein); (2) variables related to hepatic fibrogenesis (i.e. Ito cell activity, quantitative estimates of fibrosis and Kupffer cell abnormalities); and (3) changes in immunoglobulin levels particularly IgG. These findings suggest that AFP is a good index of disease prognosis.

Alcoholism

Effect of 1,25-dihydroxyvitamin D3 on mesangial cell proliferation.

We have studied the effect of 1,25-dihydroxyvitamin D3 (1,25, (OH)2D3) on mesangial cell growth. Previous studies have shown that the monocyte-macrophage is the principal effector cell in immune-mediated nephritis; this cell infiltrates the glomerular mesangium, and its products may have important effects on the physiology of the mesangial cell. One of the substances produced by the activated macrophage is 1,25,(OH)2D3. We have investigated the effect of 1,25,(OH)2D3 on mesangial cell growth and found that this vitamin D metabolite suppresses the proliferation of mouse mesangial cells as assessed by mesangial cell tritiated thymidine uptake and by cell counts; this substance also antagonizes the mitogenic effect of epidermal growth factor on mesangial cell growth. By comparison, the vitamin D metabolite 25 hydroxyvitamin D3 has no significant suppressive effect on the proliferation of mesangial cells. It has also been possible to demonstrate that 1,25,(OH)2D3 could suppress the growth of mesangial cells that had been committed to proliferate by the prior addition of epidermal growth factor. The results of these studies are relevant to our understanding of the pathogenesis of the cellular abnormalities that occur in immune-mediated nephritis, and especially in subjects who have concurrent hypertension, because a segment of subjects with hypertension have demonstrable abnormalities in the levels of circulating 1,25,(OH)2D3.

Animals