The impact of COVID-19 on cancer patients, their carers and oncology health professionals: A qualitative study.

OBJECTIVE: Cancer patients, carers and oncology health professionals have been impacted by the COVID-19 pandemic in many ways, but their experiences and psychosocial responses to the pandemic are still being explored. This study aimed to document the experience of Australians living with cancer, family carers, and Oncology health professionals (HPs) when COVID-19 first emerged. METHODS: In this qualitative study, participants (cancer patients currently receiving treatment, family carers and HPs) completed a semi-structured interview exploring their experiences of COVID-19 and the impact it had on cancer care. Participants also completed the Hospital Anxiety and Depression Scale (patients) and the Depression, Anxiety and Stress Scale (carers and HPs) to assess emotional morbidity. Thematic analysis was undertaken on qualitative data. RESULTS: 32 patients, 16 carers and 29 HPs participated. Qualitative analysis yielded three shared themes: fear and death anxiety, isolation, and uncertainty. For HPs, uncertainty incorporated the potential for moral distress and work-stress. Patients and carers scoring high on anxiety/depression measures were more likely to have advanced disease, expressed greater death anxiety, talked about taking more extreme precautionary measures, and felt more impacted by isolation. CONCLUSION: Cancer and COVID-19 can have compounding psychological impacts on all those receiving or giving care. PRACTICE IMPLICATIONS: Screening for distress in patients, and burnout in HPs, is recommended. Increased compassionate access and provision of creative alternatives to face-to-face support are warrented.

Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial.

Patients with symptomatic idiopathic venous thromboembolism and apparently cancer-free have an approximate 10% incidence of subsequent cancer. Apparently cancer-free patients with acute idiopathic venous thromboembolism were randomized to either the strategy of extensive screening for occult cancer or to no further testing. Patients had a 2-year follow-up period. Of the 201 patients, 99 were allocated to the extensive screening group and 102 to the control group. In 13 (13.1%) patients, the extensive screening identified occult cancer. In the extensive screening group, a single (1.0%) malignancy became apparent during follow-up, whereas in the control group a total of 10 (9.8%) malignancies became symptomatic [relative risk, 9.7 (95% CI, 1.3-36.8; P < 0.01]. Overall, malignancies identified in the extensive screening group were at an earlier stage and the mean delay to diagnosis was reduced from 11.6 to 1.0 months (P < 0.001). Cancer-related mortality during the 2 years follow-up period occurred in two (2.0%) of the 99 patients of the extensive screening group vs. four (3.9%) of the 102 control patients [absolute difference, 1.9% (95% CI, -5.5-10.9)]. Although early detection of occult cancers may be associated with improved treatment possibilities, it is uncertain whether this improves the prognosis.

Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-alpha?

Elevated plasminogen activator inhibitor-1 (PAI-1) plasma levels, responsible for reduced fibrinolysis, are associated with animal and human obesity and with increased cardiovascular disease. The expression of PAI-1 has been found recently in animal and human adipose tissue. Factors and mechanisms regulating such an expression remain to be elucidated. In omental and/or subcutaneous biopsies from obese non-diabetic patients, incubated in Medium 199, we have confirmed that human adipose tissue expresses PAI-1 protein and mRNA; furthermore we have demonstrated that such an expression is clearly evident also in collagenase isolated human adipocytes and that it is stimulated by incubation itself and enhanced by exogenous human tumor necrosis factor-alpha (h-TNF-alpha). Since human adipose tissue produces TNF-alpha, to further characterize the relationship of PAI-1 to TNF-alpha, human fat biopsies were also incubated with Pentoxifylline (PTX) or Genistein, both known to inhibit endogenous TNF-alpha through different mechanisms. PTX caused a dose-dependent decrease of basal PAI-1 protein release, reaching 80% maximal inhibitory effect at 10(-3)M, the same inhibitory effect caused by Genistein at 100 microg/ml. This was associated to a marked inhibition of PAI-1 mRNA and of endogenous TNF-alpha production. Furthermore, when human fat biopsies were incubated in the presence of polyclonal rabbit neutralizing anti-human TNF-alpha antibody (at a concentration able to inhibit 100 UI/ml human TNF-alpha activity), a modest but significant decrease of the incubation induced expression of PAI-1 mRNA was observed (19.8+/-19.0% decrease, P = 0.04, n = 7). In conclusion, the results of this study demonstrate that PAI-I expression is present in human isolated adipocytes and that it is enhanced in human adipose tissue in vitro by exogenous TNF-alpha. Furthermore our data support the possibility of a main role of endogenous TNF-alpha on human adipose tissue PAI-1 expression. This cytokine, produced by human adipose tissue and causing insulin resistance, may be a link in the clinical relationship between insulin-resistance syndrome and increased PAI-1 plasma levels.

The white blood cell count: its relationship to plasma insulin and other cardiovascular risk factors in healthy male individuals.

OBJECTIVES: To evaluate the relationships of total and differential white blood cell (WBC) count to the components of the so-called insulin resistance syndrome. SUBJECTS AND DESIGN: The study population consisted of a random sample of 90 38-year-old healthy men with normal glucose tolerance. INTERVENTIONS: A 75 g oral glucose tolerance test was performed in all participants. MAIN OUTCOME MEASURES: Total and differential WBC count, lipids, blood pressure, plasma glucose, C-peptide and insulin (at fasting and 2 h after glucose load). RESULTS: Total WBC count correlated consistently with plasma 2-h glucose (r = 0.38; P < 0.001), fasting and 2-h postload insulin (r = 0.26 and r = 0.33; P < 0.01-0.001, respectively) and C-peptide (r = 0.28 and r = 0.32; P < 0.01-0.001) concentrations. Smokers had significantly higher total leukocytes (P < 0.01), neutrophils and lymphocytes than nonsmokers. Furthermore, total WBC count correlated positively with body mass index, blood pressure, plasma triglycerides, fibrinogen, and negatively with HDL cholesterol concentration. As differential WBC count, most variables correlated essentially to neutrophils and/or lymphocytes, whereas plasma insulin and C-peptide concentrations correlated essentially to lymphocytes and monocytes, but not to neutrophils. In a multiple linear regression analysis, only 2-h plasma glucose (P < 0.01) and fibrinogen (P < 0.05) were positive predictors of total WBC count after adjusting for all potentially confounding variables. CONCLUSIONS: The results indicate that increased, albeit normal, WBC count associates with the cluster of metabolic and haemodynamic disorders typical of the insulin resistance syndrome, and suggest that increased WBC count may be yet another component of this syndrome.

Plasma factor VII and its relation to adipose tissue fatty acids and other atherogenic risk factors in healthy men.

In this study the authors examined the relationships of plasma factor VII (F-VII) to adipose tissue fatty acid composition, as an objective index of the habitual dietary fat intake, as well as to a number of other atherogenic risk factors in 60 healthy male volunteers (aged 38 years). Significant positive correlations were found between plasma F-VII [measured as antigen (F-VIIAg) and coagulant activity, using bovine thromboplastin (F-VIIbt)] and body mass index (BMI), waist-thigh girth ratio (WTR), cigarette smoking and plasma triglyceride concentration. After adjustment for BMI, only plasma triglycerides remained positively correlated with F-VII (r = 0 center dot 27, P = 0 center dot 03, and r = 0 center dot 29, P < 0 center dot 01, for F-VIIbt and F-VIIAg respectively). A significant positive relation was found between F-VII and the total proportion of fatty acid as monounsaturated fatty acid (r = 0 center dot 26, P < 0 center dot 05, for F-VIIAg), whereas inverse relations were found between F-VII, the total proportion of fatty acid as polyunsaturated fatty acid (r = -0 center dot 26 and r = -0 center dot 25, P < 0 center dot 05, for F-VIIbt and F-VIIAg respectively), polyunsaturated-saturated fat ratio (r = -0 center dot 25, P < 0 center dot 05, for F-VIIbt) and, more significantly, between F-VII and adipose-tissue alpha-linolenic acid (r = -0 center dot 29, P < 0 center dot 01, for F-VIIbt and r = -0 center dot 49, P < 0 center dot 001, for F-VIIAg). All these correlations remained significant after matching for BMI. In a multiple linear regression analysis, only adipose tissue alpha-linolenic acid was a negative and independent predictor of F-VIIAg (P = 0 center dot 004) and, at borderline significance, of F-VIIbt (P = 0 center dot 061) when allowance was made for BMI, WTR, smoking and plasma triglycerides. In conclusion, this study shows significant relations between F-VII and adipose tissue fatty acid composition in healthy male individuals; it supports the possibility that adipose tissue poly-unsaturated fatty acids, derived from dietary intake, play a role in the relation between F-VII and coronary heart disease (CHD), thus suggesting that high dietary polyunsaturated fatty acid intake (especially alpha-linolenic acid) may reduce the risk for CHD by an improvement of a number of risk factors, including a lowering of plasma F-VII (both activity and antigen).

Moderate alcohol consumption and its relation to visceral fat and plasma androgens in healthy women.

OBJECTIVE: To study the inter-relationships between daily alcohol intake, fat distribution and plasma androgens in order to verify whether daily alcohol intake correlates with abdominal body fat and, if so, to what extent such a relation is mediated by plasma androgens. SUBJECTS: A random sample of 87 clinically healthy women (aged 38 y) with a light-moderate alcohol consumption and without clinical evidence suggestive of any endocrine disorder. MEASUREMENTS: Anthropometric and computed tomography (CT scans made at the level of L4-L5 in a subgroup of 18 women) measurements of body fatness and adipose tissue distribution, main behavioural factors, including daily alcohol intake and plasma androgens (i.e. total and free testosterone levels). RESULTS: After adjustment for BMI, cigarette smoking and physical activity, significant differences were found in waist circumference and waist-hip ratio as well as in plasma androgens with increasing daily alcohol intake. Waist-thigh ratio tended to parallel waist-hip ratio, but did not achieve statistical significance. In simple linear regression analysis, abdominal visceral fat area, derived from CT, correlated positively with both plasma free testosterone and alcohol intake. While the above reported difference in body fat distribution totally disappeared after controlling also for free testosterone level, the differences in plasma androgens with increasing alcohol intake remained essentially unchanged when allowance was made also for waist-hip ratio. In multiple linear regression analysis, daily alcohol intake appeared to be positively and independently correlated to both plasma total and free testosterone levels. Neither BMI nor waist-hip ratio nor fasting insulin made any significant contribution to the prediction of plasma androgens after daily alcohol intake had been taken into account. CONCLUSIONS: The results of this study show that moderate alcohol consumption correlates with abdominal distribution of body fat, likely due to enlarged visceral fat area, and increased plasma androgenicity (i.e. higher total and free testosterone levels) in adult healthy women. These data also suggest that the relation between alcohol intake and fat distribution may be, at least in part, mediated by plasma androgens.

Cardiovascular risk profile in 38-year and 18-year-old men. Contribution of body fat content and regional fat distribution.

OBJECTIVE: To evaluate whether young and middle-age men differ in blood pressure and serum lipid profiles and, if so, to what extent these differences are dependent on total body fat, regional fat distribution, plasma insulin and behavioural variables. SUBJECTS: Random samples of 94 young (18 year-old) and 94 middle-age (38 year-old) healthy men matched for body mass index (BMI). MEASUREMENTS: BMI, total body fat (by bioelectrical impedance), regional fat distribution (by anthropometry), serum lipids, blood pressure, fasting insulin and some behavioural variables. RESULTS: Total body fat was similar in the two groups (mean +/- s.e.: 16.6 +/- 0.5 vs 16.0 +/- 0.6 kg and 20.8 +/- 0.5 vs 20 +/- 0.5%), while waist/hip circumference ratio (WHR) was significantly higher in middle-age as compared to young men (0.96 +/- 0.001 vs 0.92 +/- 0.003, P < 0.0001). The former also had significantly higher serum concentrations of total cholesterol (6.21 +/- 0.13 vs 4.10 +/- 0.10 mmol/l; P < 0.0001). LDL-cholesterol (4.24 +/- 0.11 vs 2.34 +/- 0.10 mmol/l; P < 0.0001), triglycerides 1.40 +/- 0.09 vs 1.02 +/- 0.06 mmol/l; P < 0.01) as well as higher systolic (134.0 +/- 1.6 vs 126.3 +/- 1.4 mmHg; P < 0.0001) and diastolic (86.8 +/- 0.9 vs 82.0 +/- 1.1 mmHg; P < 0.001) blood pressure values. HDL-cholesterol and fasting insulin concentrations were similar in the two groups (1.33 +/- 0.03 vs 1.28 +/- 0.03 mmol/l and 13.7 +/- 0.6 vs 14.7 +/- 0.7 mU/l, respectively). Significant differences in the two groups also were found in daily alcohol consumption (49.6 +/- 5.7 vs 20.0 +/- 3.4 g/day; P < 0.0001), whereas no significant differences were found in smoking and physical activity level. The comparison of subgroups (n = 41) of young and middle-age men matched for both BMI and WHR showed virtually unchanged differences in serum lipids and blood pressure. When age, BMI, WHR, fasting insulin and behavioural variables were included as independent variables in a multiple linear regression analysis in which subjects of the two groups were pooled, age was a significant predictor of total and LDL cholesterol, triglycerides and systolic blood pressure, insulin predicted HDL cholesterol and systolic blood pressure, BMI predicted triglycerides and diastolic blood pressure and WHR was not an independent predictor of any risk factor. CONCLUSIONS: These results indicate that middle-age men have a cardiovascular risk profile less favourable than young men, which is largely independent of differences in total body fat content, regional fat distribution and behavioural variables.

Serum retinol levels throughout 2 years of cholesterol-lowering therapy.

Some studies have reported an inverse correlation between serum cholesterol level and risk of cancer. This correlation might be due to a decrease in serum retinol, a lipid-soluble vitamin that controls cell proliferation and differentiation. We evaluated the influence of cholesterol-lowering therapy on serum retinol in 102 subjects (mean +/- SE: aged 47.1 +/- 4.1 years; body mass index, 23.8 +/- 0.6 kg/m2) with primary hypercholesterolemia treated for 2 years with different therapeutic protocols. Twenty-two subjects had been treated with diet alone, 35 with diet and fibrates, 37 with diet and hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), and eight with diet and cholestyramine. Postabsorptive serum retinol, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were determined at baseline and every 3 months. Baseline TC and LDL-C were significantly lower in the diet-treated group than in other groups. No intergroup differences were found in pretreatment levels of triglycerides and serum retinol. After 2 years of treatment, TC and LDL-C serum levels were not significantly decreased in the diet-alone group, whereas they were decreased by 20% and 24%, respectively, in the gemfibrozil group, 28% and 34% in the statins group; and 21% and 27% in the cholestyramine group. In the entire population (N = 102), serum retinol was 3.46 +/- 0.08 mumol/L before therapy and 3.76 +/- 0.07 after 2 years of therapy (P < .001). Serum retinol increased in diet- and statin-treated groups, but not in fibrate- and resin-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men.

Recent prospective studies have reported an independent association between fibrinogen plasma levels and risk of cardiovascular events. Aim of this study was to investigate the relationships between fibrinogen level and conventional cardiovascular risk factors in a random sample of 38 year-old apparently healthy men (n = 94), and to verify whether the fatty acid composition of the diet might influence those relations. Anthropometric measurements, serum lipids, blood pressure, and smoking habits were evaluated. In addition, fasting and after glucose-load serum glucose and insulin concentrations were measured. The most significant difference in fibrinogen level was found among the tertiles of fasting serum insulin (F-ANOVA = 4.5; P < 0.01) with the highest plasma fibrinogen values in the third insulin tertile, whereas body mass index (BMI), waist/hip circumference ratio (WHR) and serum triglycerides were more weakly related. The current smokers had substantially higher levels of fibrinogen than subjects who never smoked (P < 0.001). A multivariate regression analysis showed that, among the above reported variables, only serum insulin and smoking were independently associated with plasma fibrinogen. Furthermore, as the possible association between fatty acid composition of the diet and fibrinogen level regards, we have examined the fatty acid composition of adipose tissue, as a good and objective index of quality of the dietary fat intake. It was found that, fibrinogen level was not associated with any adipose tissue fatty acid. In conclusion, this study performed in a random sample of healthy men indicates an independent relationship of fasting insulin and smoking to fibrinogen plasma level.

Polyunsaturated fatty acids in adipose tissue in European men aged 38 years in relation to serum lipids, smoking habits, and fat distribution.

Fat biopsies were taken from 327 men aged 38 years from five different European communities in 1988-1989. Linoleic acid content varied widely (F = 110.6, p less than 0.001) and was lowest in men from Poland (8.6%) and highest in men from Belgium (16.7%). Adipose tissue content of alpha-linolenic acid was subject to less variation (F = 13.9, p less than 0.001) and was lowest in men from Italy (0.5%) and highest in men from Sweden and the Netherlands (0.9%). In analysis combining information from all centers, linoleic acid was negatively correlated to low density lipoprotein cholesterol (r = -0.15, p less than 0.01) and total cholesterol (r = -0.17, p less than 0.01). alpha-Linolenic acid was negatively correlated to serum triglycerides only (r = -0.14, p less than 0.05). These fatty acids were not related to body mass index, waist/hip ratio, or smoking habits. The authors conclude that there are major differences in the fatty acid composition of adipose tissue in different European populations but that these do not explain the significant differences in serum high density lipoprotein cholesterol and serum triglycerides among the different populations.

Fasting serum insulin in relation to fat distribution, serum lipid profile, and blood pressure in European women: the European Fat Distribution Study.

Samples of 38-year-old women were randomly selected from five European centers: Ede (The Netherlands), Warsaw (Poland), Gothenburg (Sweden), Verona (northern Italy), and Afragola (Naples-southern Italy). In total, 452 healthy women were studied. Anthropometric measurements were taken by one operator in each country after common training of all operators and blood parameters of all women were determined in one laboratory. Body mass index (BMI) was different among centers, mainly due to the higher values in southern Italy. Women from southern Europe had more central fat distribution than women from north European centers. Fasting serum insulin was higher in women from Poland and The Netherlands than in the other three centers. After adjustment for BMI, fasting insulin was significantly related to subscapular skinfold, subscapular to triceps skinfold ratio, waist circumference, and waist to thigh circumference ratio, although the partial correlations varied somewhat between the centers. In the pooled data, waist circumference showed the highest correlations with fasting serum insulin when adjusted for BMI. Fasting serum insulin showed significant partial correlations, adjusted for BMI, with lipid profile and blood pressure only in women from the two Italian centers. In the pooled data, fasting serum insulin was significantly positively correlated with serum triglycerides and total cholesterol and negatively to high-density lipoprotein (HDL) cholesterol and HDL/total cholesterol, independently of BMI and waist circumference. While blood pressure was not related to insulin in the pooled women, when adjusted for BMI and waist circumference; here as well, there were some differences in relationships between the centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Fat distribution and gender differences in serum lipids in men and women from four European communities.

We studied male/female differences in serum lipids in randomly selected 38-year-old men (n = 337) and women (n = 342) from various cities in The Netherlands, Sweden, Italy, and Poland. Overall, men had higher triglycerides and total cholesterol levels and lower HDL-levels compared to women (P less than 0.001). Adjustment for smoking habits, city, and body mass index did not remove the gender difference. Further adjustments for waist circumference alone and waist/hip and waist/thigh circumference ratio removed the gender differences in serum triglycerides and total cholesterol. Only adjustment for waist/thigh ratio removed the gender difference in HDL-cholesterol but linear relationships were different in men and women. The average male/female difference in serum lipids, particularly for total and LDL-cholesterol varied considerably among centers. In analyses of the data from the separate centers we found that sex differences in serum triglycerides and HDL-cholesterol in all 4 centers disappeared when adjusted for waist circumference alone and for waist/hip and waist/thigh ratio. For total and LDL-cholesterol, however, adjustment for circumference ratios tended to increase the male/female difference in 2 of the 4 centers. It is concluded that, in European men and women, fat distribution may be responsible for male/female differences in serum triglycerides but that such conclusions are less clear for HDL-, total- and LDL-cholesterol.

Body fat distribution in relation to serum lipids and blood pressure in 38-year-old European men: the European fat distribution study.

A study on 512 38-year-old European men selected from 6 different towns was conducted. There were significant differences between the centers in averages of anthropometric variables (except for thigh circumference), serum lipids (except for LDL-cholesterol), and blood pressure. In the pooled material, body mass index (BMI) as well as waist circumference, waist/hip ratio and waist/thigh ratio and subscapular skinfold were positively correlated to serum triglycerides, total cholesterol, LDL-cholesterol, and blood pressure and negatively with HDL-cholesterol. After adjustment for BMI, waist, waist/hip, and waist/thigh were all still significantly correlated with serum triglycerides (P less than 0.001). In addition, waist/hip and waist/thigh ratio showed significant partial correlations with total cholesterol (r = 0.16, P less than 0.001, r = 0.10, P less than 0.05 respectively), and diastolic blood pressure (r = 0.10, P less than 0.05, r = 0.09, P less than 0.05 respectively). In addition, waist/hip was, independently of BMI, correlated to LDL-cholesterol (r = 0.12, P less than 0.01), and waist/thigh ratio with HDL-cholesterol (r = -0.12, P less than 0.01). The partial association between waist/thigh with HDL cholesterol became insignificant after adjustment for smoking habits and physical activity. Adjustment for differences in anthropometric measurements did not explain the differences in serum lipids and blood pressure between the centers. The authors conclude that indicators of body fat distribution are associated with unfavorable risk profiles for cardiovascular disease in European men covering a large geographical and cultural variety and a wide range of body measurements and cardiovascular risk factors.

Body fat distribution in relation to physical activity and smoking habits in 38-year-old European men. The European Fat Distribution Study.

The authors studied 512 European men all born in 1950 from six different towns in the period October 1988 to May 1989. Anthropometric measurements were taken, including weight, height, and circumferences (waist, hip, thigh). Educational level, activity scores and information on smoking habits were obtained from a questionnaire. Higher educational level was associated with lower body mass index, waist/hip ratio, and waist/thigh ratio. The sports activity score was negatively related to waist/hip ratio (beta +/- standard error of the mean (SEM): -0.009 +/- 0.003) and waist/thigh ratio (-0.041 +/- 0.007), and this could be attributed to a negative relation with waist circumference and a positive relation to thigh circumference. Smoking habits were not related to body mass index but heavy smokers had larger waist circumferences (difference +/- SEM: 1.4 +/- 0.5 cm) as well as higher waist/hip ratios (difference +/- SEM: 0.014 +/- 0.005) and waist/thigh ratios (0.043 +/- 0.013) compared with men who never smoked. These associations between activity scores and smoking habits and fat distribution remained after adjustment for each other and for body mass index and educational level. The authors conclude that physical activity and smoking are independently related to indicators of fat distribution and may be potential confounders in the relations between fat distribution, risk factors, and disease.

Multiple symmetric lipomatosis. Ultrastructural investigation of the tissue and preadipocytes in primary culture.

Multiple symmetric lipomatosis (MSL) is characterized by enlarging, painless fat deposits in the neck and upper trunk. The pathogenesis of MSL is unknown. Owing to localization of MSL fat deposits in the neck and interscapular region, it has been suggested that they could originate from brown fat. However, the histological appearance of MSL adipose tissue is that of white fat, with prevailing monovacuolar adipocytes. Nevertheless, MSL adipocytes are smaller than adipocytes of the common white adipose tissue and show peculiar metabolic features. The ultrastructure of MSL lesions has been not described. The present work investigated the ultrastructural morphology of MSL adipose tissue and lipomatous adipocyte precursors maintained in long-term culture. Samples of lipomatous tissue were obtained from patients affected with MSL undergoing surgical lipectomy. Portion of the tissue was processed for electron microscopy; the rest was digested with collagenase, and isolated preadipocytes from the stromal-vascular fraction were cultured up to 15 days. Cultured cells were prepared for electron microscopy in situ and their morphology compared with human white adipose tissue preadipocytes and rat brown preadipocytes cultured in parallel. Results show the following. 1) Adipocytes of MSL are not monovacuolar and resemble the largest adipocytes that can be found in rat and human brown fat. 2) Some morphological features of MSL adipocyte precursors resemble brown adipocyte more than white: cultured MSL preadipocytes transiently develop large mitochondria with parallel cristae resembling those of the brown fat cell and maintain a multivacuolar lipid deposit in culture, i.e. a typical feature of brown preadipocytes. 3) Some morphological features suggest a neoplastic nature of MSL adipocytes. Taken together, these findings suggest that MSL is a neoplastic disease which could originate in brown fat.

S-100 protein in white preadipocytes: an immunoelectronmicroscopic study.

Differentiation of adipocytes from their precursor cells (preadipocytes) is an important problem in the study of the pathogenesis of obesity. Unfortunately, among the immature stages of adipocytes, only relatively differentiated forms can be identified by their fine structure; because early preadipocytes cannot be distinguished from fibroblasts solely on the basis of their morphology, it is impossible to assess the size of the preadipocyte population. S-100 protein has been identified in various mammalian tissues and recently mature adipocytes have been shown to be positive for this protein. Because fibroblasts are negative for S-100 protein, the present study tested the S-100 immunoreactivity of preadipocytes by the peroxidase-antiperoxidase (PAP) preembedding method at the ultrastructural level both in vivo and in culture. Mature adipocytes and early preadipocytes, including fibroblast-like cells devoid of lipid droplets, were positive both in vivo and in culture. Endothelial cells and pericytes were negative; but flattened, lipid-free, fibroblast-like cells surrounding the pericytes were positive. True fibroblasts both in vivo and in culture were negative. Therefore, S-100 protein can be a useful biochemical marker in distinguishing fibroblasts from early preadipocytes.

An ultrastructural study on muciparous microcysts of the human adenohypophysis.

The microcysts found in two adenohypophyses removed from patients with nonsecreting adenomas of this gland have been studied. In one case the cysts were completely surrounded by neoplastic tissue, whereas in the second they were located within the normal parenchyma. The cysts were surrounded by a basement membrane, and appeared to contain a finely granular weakly electron-dense substance. Their walls were lined by mostly cubic cells with microvilli, joined by junctional complexes. Intracytoplasmic microlumina could be seen in some of these cells. Cells showing cilia with a 9 + 2 fibrillar pattern and cells with mucosecretory differentiation were also present. Furthermore endocrine cells were also found in the cyst-lining epithelium. The ultrastructural aspects of the cyst cells lead to reject the hypothesis that these are derived from folliculostellate cells. Besides, intermediate aspects between cyst cells and tumor cells were never visible. Therefore it seems likely that a relationship between adenoma and cyst cells does not exist and that cyst cells originate from remnants of Rathke's pouch with a ciliate or mucosecretory differentiation. The presence of endocrine cells in the cyst-lining epithelium deserves further study, for it seems to indicate that an endocrine differentiation may occur in the adult, too. To our knowledge this is the first ultrastructural study of these structures in adult human pituitary gland.

Ultrastructural features of cultured mature adipocyte precursors from adipose tissue in multiple symmetric lipomatosis.

The pathogenesis of multiple symmetric lipomatosis (MSL) is as yet unknown; however, some studies seem to indicate the neoplastic nature of this lesion. In this study we have examined the ultrastructural features of the adipocyte precursors of patients with MSL. The cells were isolated by collagenase, cultured, and then examined at the moment of their confluence in a monolayer. Their ultrastructural features were compared with those of cells of the abdominal subcutaneous adipose tissue taken from patients with nonsystemic, surgically treated illnesses. When examined immediately after isolation, the cells from normal tissue did not show significant differences from MSL cells. In culture, however, MSL grew more quickly into a monolayer and showed numerous nuclear pockets and cytoplasmic microfilaments, which were not seen in cells from normal tissue. These differences appear compatible with the neoplastic nature of the MSL adipocyte precursors.