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Biomedical subjects

P Gartside

Publications and source records attributed to P Gartside.

16 recordsLinked to original sources

Effects of an IL-1 receptor antagonist on acute myeloid leukemia cells.

The effect of an interleukin 1 receptor antagonist (IL-1ra) on the proliferation of acute myelogenous leukemia (AML) cells was investigated. The antagonist reduced the spontaneous clonogenicity of these cells as well as the clonogenicity of these cells subsequent to exposure to the antagonist. The effects of the IL-1ra on the clonogenicity of leukemia cells was observed even when the antagonist failed to inhibit DNA synthesis by the leukemia cell population as a whole. The data are consistent with the concept that the administration of IL-1ra subsequent to cytotoxic therapy has the potential of slowing the regrowth of leukemia cells thereby potentiating the effects of chemotherapy.

Bromodeoxyuridine

Biological significance of cell cycle kinetics in 128 standard risk newly diagnosed patients with acute myelocytic leukemia.

Bromodeoxyuridine (BrdU) was administered to 128 newly diagnosed patients with standard risk acute myelocytic leukaemia (AML) for cell cycle measurements. Labelling indices (LI) were obtained from both the bone marrow aspirate (BMasp) and biopsies (bx) and durations of S-phase (Ts) and total cell cycle time (Tc) were measured by double-labelling the S-phase cells in vitro with tritiated thymidine. Median LI BMasp was 8% and from BMbx was 25%. The median Ts was 12 h (range 3.1-35 h) and Tc was 48 h (range 11.5-211 h). All patients received induction therapy with a combination of cytosine arabinoside and an anthracycline. Outcome of therapy or FAB type were not related to cell cycle characteristics. Patients with above median LI BMasp, however, had longer remission durations (P = 0.03) as did patients with above median Ts (P = 0.03) and Tc (P = 0.03). Upon longer follow-ups, even some of the patients with slowly cycling myeloblasts have relapsed (log rank P = 0.453 and 0.203 for Ts and Tc respectively). We conclude that patients with rapidly cycling cells tend to relapse faster; however, slowly cycling nature of myeloblasts is not associated with curability.

Adult

Prognostic factors in alcoholic liver disease. VA Cooperative Study Group.

Two hundred eighty-one alcoholic patients were prospectively evaluated by clinical, biochemical, and histologic parameters during a 4-yr period to assess their prognosis. They were stratified into four categories of injury: 1) fatty liver (26 patients), 2) acute alcoholic hepatitis (106), 3) cirrhosis (39), and 4) cirrhosis with superimposed alcoholic hepatitis (111). The rate of survival and variables correlating with survival varied according to the group. At 48 months, 70% of the patients with fatty liver were alive, 58% in the alcoholic hepatitis group, 49% in cirrhosis, and 35% in alcoholic hepatitis superimposed upon cirrhosis. Within group one, deaths were due to causes unrelated to liver disease. In the alcoholic hepatitis group, factors significantly correlating with survival were ascites, alanine amino-transferase levels, grams of alcohol consumed, continuation of alcohol intake, and clinical severity of disease. Survival in patients of group three correlated significantly with prothrombin time and histologic severity score. Patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis, with the most significant predictors of survival being age, grams of alcohol consumed, the ratio of serum aminotransferases (AST:ALT) and the histologic and clinical severity of the disease. Although a different pattern of correlates was observed for each pathologic level of injury, knowledge of the various correlates aids in prognostic assessment.

Acute Disease

Prognostic significance of cholestatic alcoholic hepatitis. VA Cooperative Study Group #119.

Tissue cholestasis is a histologic feature in some patients with alcoholic liver disease, but its significance is unknown. We studied prospectively the clinical, laboratory, and histologic findings of 306 chronic male alcoholics in whom liver tissue was available. Tissue cholestasis permitted identification of two groups: group I, absent or mild cholestasis (239 patients), and group II, moderate to severe cholestasis (67 patients). Statistical evaluation was performed by Student's t test and regression analyses. In patients with tissue cholestasis, 97% had elevated serum cholylglycine levels, while only 61% had significant jaundice (serum bilirubin greater than 5 mg/dl). In patients without tissue cholestasis, 66% had elevated serum cholylglycine and 13.5% jaundice. Highly significant statistical correlations (P less than 0.0001) were found between cholestasis and malnutrition, prothrombin time, AST, alkaline phosphatase, bilirubin, Maddrey's discriminant function, serum cholylglycine level, albumin, and histologic severity score. In group I, 54% survived 60 months versus 22% in group II (P less than 0.0001). Highly significant statistical correlations (P less than 0.0001) were noted between serum cholylglycine levels and the parameters enumerated earlier, but not with survival. We conclude that tissue cholestasis is a highly significant prognostic indicator of outcome in alcoholic hepatitis and is more consistently associated with bile salt retention than jaundice.

Cholestasis, Intrahepatic

Comparison of technetium-99m and iodine-123 imaging of thyroid nodules: correlation with pathologic findings.

Three hundred and sixteen patients with solitary or dominant thyroid nodules were imaged both with technetium-99m- (99mTc) pertechnetate and iodine-123 (123I). The images were preferred, but differences were small and in 27%-58% of the cases there was no difference in quality between the two radionuclides. Discrepancies between 99mTc and 123I images were found in 5%-8% of cases, twice as often in multinodular goiters as in single nodules. Cytologic/histologic examination was performed on all nodules but no correlation was found between the pathology and the type of discrepancy. Twelve carcinomas were found (4%) but none in nodules showing a discrepancy. There was great variation among the observers about the preference for radionuclides and about the existence or type of discrepancies. The slightly better overall quality of 123I scans is probably not of diagnostic significance and does not justify the routine use of 123I instead of 99mTc. Routine reimaging of 99mTc hot nodules with radioiodine for cancer detection does not appear to be necessary.

Adult

Pancreatic allograft exocrine urinary tract diversion. Pathophysiology.

Exocrine secretions of 16 of 22 pancreas allografts were drained into the urinary tract. Seven of these 16 patients have functioning allografts, six with pancreaticocystostomies and one with duct-to-ureter anastomosis. A notable problem has been a chronic metabolic acidosis, along with weight loss and hypotension, secondary to chronic bicarbonate loss and volume depletion through the urinary pancreatic fistula. This occurred as early as one week posttransplant, and intermittently thereafter up to four years. The syndrome was aggravated by episodes of renal dysfunction (acute tubular necrosis or rejection), and febrile syndromes. An inverse relationship between serum and urine bicarbonate concentrations existed, with a correlation coefficient, r = -0.746, (P less than 0.05). A negative correlation was also noted between serum bicarbonate and serum creatinine, r = 0.726, (P less than 0.05). Hyperchloremic metabolic acidosis with normal anion gap occurred despite periods of marginal pancreas allograft function resulting from ongoing rejection. Treatment consisted of intravenous and/or oral bicarbonate supplementation, and bicarbonate dialysis for uremic patients. In addition, one patient was first seen with severe balanitis and urethritis due to documented activation of trypsinogen and chymotrypsinogen, presumably caused by recurrent episodes of urinary tract infection. Urinary assay revealed a 10(2-3) increase in activated trypsin and chymotrypsin in comparison with other asymptomatic allograft recipients. Conversion to ductal enteric drainage led to resolution of both the balanitis and bicarbonate wasting. Measurement of urinary amylase levels were gross indicators of graft viability since no correlation could be found between these levels, onset of hyperglycemia, and eventual graft rejection confirmed by pathological examination.

Acidosis

Special lecture: the breast cancer screening controversy: a perspective.

Analysis of the data of the Health Insurance Plan of New York Breast Cancer Screening Study indicates that in patients whose cancers were found by screening, the case fatality rate at all ages is almost half the case fatality rate of controls. The data also strongly suggest that maximal benefit in young women resides in the detection of in situ cancers. Due to relatively low yield of these early lesions, projected 20 year survival in that study may be little different for all women screened compared to controls. We have shown that the yield of these early lesions can be increased by aggressive screening and liberal use of biopsy. Furthermore, where J.C. Bailar has indicated a net gain (or loss) of -4 to +8 lives per 20,000 women using the HIP data, using his method and our data we find a savings of 25-27 lives/20,000 women by 3 year screening to date. These are lives that have been saved by mammography alone.

Adult

Lack of efficacy of thermography as a screening tool for minimal and stage I breast cancer.

In a study of thermograms of 42 patients with Stage 1 or smaller carcinomas of the breast, 44 confounding cases and 64 randomly selected subjects being screened, we found that the ability of expert thermographers to identify the patients with carcinoma correctly (true positive = 0.238) varied little from the ability of untrained readers (true positive = 0.301). Furthermore, in the expert group, the indexes of suspicion were so high (0.436) and the true-positive levels were so relatively low (0.238, P = 0.0005) that thermography may well have a very limited role as a screening or pre-screening modality for the detection of minimal or Stage 1 breast cancers.

Breast Neoplasms

Transcendental meditation in hypertension. Individual response patterns.

Seven selected hypertensive patients were stabilized on drugs at a research clinic. Subjects learned transcendental meditation (T.M.), were seen weekly, and took their own blood pressure several times daily. After 12 weeks of T.M. six subjects showed psychological changes and reduced anxiety scores. Six subjects also showed significant reductions in home and four in clinic blood-pressures. Six months later four subjects continued to derive psychological benefit and two showed significant blood-pressure reductions attributable to T.M. at home and clinic.

Adult

Effect of sex hormones on protamine inactivated and resistant postheparin plasma lipases.

Effects of estrogens and the synthetic anabolic-androgenic steroid, Oxandrolone, on extrahepatic (protamine inactivated) and hepatic (protamine resistant) lipases in postheparin plasma, were assessed in 15 subjects with familial hypertriglyceridemia. In six women receiving conjugated equine estrogen (1.25 mg/day), mean (+/- SE) postheparin protemine inactivated triglyceride lipase (PI-TGL) was depressed to 0.23 +/- 0.10 mumol FFA/ml/hr, and protamine resistant lipase was depressed to 5.3 +/- 0.5 mumol FFA/ml/hr. In the 2-wk period after estrogens were discontinued, PI-TGL remained depressed, 0.54 +/- 0.24, while PR-TGL increased to 7.3 +/- 0.88, p=less than 0.05. Mean triglycerides fell insignificantly from 628 +/- 136 to 447 +/- 44 mg/100 ml when estrogens were discontinued. There was no significant correlation between changes in PR-TGL and triglycerides when estrogens were stopped. In four women with familial hypertriglyceridemia, Oxandrolone significantly increased PR-TGL in two, increased PI-TGL in three, and reduced triglycerides in two. In five men with familial hypertriglyceridemia, Oxandrolone reduced triglycerides in four, increased PR-TGL in four, but had no effect on PI-TGL. For the nine hypertriglyceridemic subjects increments in PR-TGL failed to correlate significantly with decrements in triglyceride, (r=0.309, p is greater than 0.1). Selective alteration of PR-TGL and PI-TGL by estrogens and Oxandrolone may provide an approach to better understanding of the interaction of lipases and triglycerides in familial and acquired hypertriglyceridemia.

Adult

Longevity syndromes: familial hypobeta and familial hyperalpha lipoproteinemia.

Longevity and morbidity and death from myocardial infarction were examined in eight kindreds with familial hypobeta lipoproteinemia and in 18 kindreds with familial hyperalpha lipoproteinemia. Expectation of life for males and females from kindreds with hypobeta lipoproteinemia was 9 and 12 years longer (p less than or equal to 0.002) than that indicated by population statistics for U.S. white populations, whereas expectation of life for males and females from kindreds with hyperalpha lipoproteinemia was 5 and 7 years longer (p less than 0.02). Morbidity from myocardial infarction in 115 living first-degree adult relatives of probands with hypobeta and hyperalpha lipoproteinemia and in 364 living first-degree adult relatives of normolipemic spouse controls were compared. Nonfatal myocardial infarction (MI) was reported for 18 of 364 (5 per cent) relatives of normal spouse controls and in 0 of 115 relatives of hypobeta and hyperalpha subjects (p less than 0.05). The ratios (mean+/-S.E.) of C-LDL to C-HDL in familial hypobeta and hyperalpha lipoproteinemia were 0.79+/-0.06 and 1.21+/-0.06, as compared to 2.41+/-0.12 in a control population (p less than 0.001). If high-density lipoproteins confer protection against development of atherosclerosis, whereas low-density lipoproteins have opposite effects, then we speculate that the low ratio of C-LDL:C-HDL may be related to prolonged longevity and decreased morbidity from myocardial infarction in familial hypobeta and hyperalpha lipoproteinemia.

Adolescent

Familial hyper-alpha-lipoproteinemia: studies in eighteen kindreds.

A newly recognized familial hyperlipoproteinemia, familial hyper-alpha-lipoproteinemia, is described in 18 kindreds. Affected probands and relatives had distinctive elevations of alpha-lipoprotein cholesterol (C-HDL), slight elevations of total cholesterol, no elevation of LDL and VLDL cholesterol, and normal triglyceride levels. The proband and at least one additional first degree relative had distinctive elevations of C-HDL in 16 of 18 kindreds. Simple segregation analysis involving 84 offspring of 22 hyper-alpha X normal-alpha matings from these 16 kindreds revealed a ratio of hyper-alpha to normal of 37:47, a ratio not significantly different from 1:1 (chi 2(1) = 1.2), the ratio consistent with autosomal dominant transmission. Despite the suggestion of a major gene effect by this analysis, evaluation of the C-HDL distribution in kindred members failed to reveal bimodality, and familial correlation analysis revealed no parent-offspring correlation. The present data suggest that an environmental cause common to sibships is possibly important in causing the disorder. Longevity analysis demonstrated elongation of life expectancy for kindred members, and there was an apparent rarity of premature cardiac events.

Adolescent