Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Changes in cerebral endothelial barrier antigen, without alteration of permeability for intravenously injected leptin in diet-induced obesity in rats

Leptin, a potent anorectic, 16-kDa, adipose tissue-derived protein, predominantly acts in hypothalamic nuclei, signaling obesity and modulating ingestive behavior. To reach this brain area, leptin, probably has to cross the blood-brain barrier (BBB). In some cases of obesity, enhanced leptin levels in the blood do not result in anorectic effects, probably due to an altered leptin transport across the BBB. Therefore, we investigated the BBB in lean and diet-induced obese Lewis rats. To obtain information about the presence of microvessels with barrier dysfunction we examined three brain areas (hypothalamus, cortex, hippocampus) using a monoclonal antibody which detects intact microvessels of the BBB (anti-endothelial barrier antigen, anti-EBA). The results showed a significantly reduced EBA staining in the brain sections of the obese animals, except the hippocampus, compared to the control group. In a second step we injected I125-labeled leptin intravenously (i.v.) in permanent i.v.-cannulated, unrestrained Lewis rats (lean and obese). We measured the radioactivity in the cerebrospinal fluid after puncture of the cisterna magna, in the blood and brain tissue 90 min after injection. The leptin content in the cerebrospinal fluid and brain was not reduced in obese compared to lean rats, thus showing a similar transport capacity of the BBB in both experimental groups. Therefore, the results of the in vivo investigations do not indicate an impairment of the BBB in diet-induced obesity, despite the immunohistological findings. Further functional and morphological studies are necessary to evaluate the specific role of other organs and distinct forms of leptin (free and protein-bound) in the pathogenesis of diet-induced obesity.     

Seroprevalence of and risk factors for HIV-1 infection in injection drug users in Montreal and Toronto: a collaborative study.

OBJECTIVE: To determine the prevalence of antibodies to HIV-1 and risk factors for HIV-1 infection among injection drug users. DESIGN: Questionnaire survey. A venous blood sample was taken for HIV-1 antibody testing. SETTING: Montreal and Toronto. PARTICIPANTS: A total of 810 subjects who had used injection drugs in the previous 6 months recruited mainly from treatment centres and from the street in Montreal (425 subjects) and from treatment centres in Toronto (385 subjects) between September 1988 and September 1990. The overall participation rate was 82%. OUTCOME MEASURES: HIV-1 seropositivity, sociodemographic and behavioural risk factors for HIV-1 infection. RESULTS: The overall seroprevalence rate of HIV-1 infection was 4.8% (95% confidence limits [CL] 3.5 and 6.5). In Montreal the rate was 8.2% (95% CL 6.0 and 11.2), and in Toronto 1.0% (95% CL 0.4 and 2.6) (p < 0.001). Seropositive subjects were significantly older (p = 0.041) and were more likely to have a history of imprisonment (p = 0.006) than seronegative subjects. In univariate analysis seropositivity was associated with the following behaviours: more frequent cocaine use (p < 0.001), injecting drugs in "shooting galleries" (p = 0.002), sharing equipment with a person known to be HIV-1 seropositive (p = 0.006), "booting" fresh blood (p = 0.004), homosexual or bisexual orientation (p = 0.006), engaging in prostitution (p < 0.001) and, for men, number of male sexual partners in the previous 6 months (p = 0.007). In multivariate analysis the determinants of HIV-1 seropositivity were Montreal as the city of recruitment (odds ratio [OR] 6.7, 95% CL 2.32 and 19.42), engaging in prostitution (OR 2.13, 95% CL 1.01 and 4.75), a history of imprisonment (OR 3.51, 95% CL 1.33 and 9.29) and sharing equipment with a person known to be HIV-1 seropositive (OR 4.43, 95% CL 1.43 and 13.74). CONCLUSIONS: Our findings show that HIV-1 is circulating among injection drug users in Montreal and Toronto and that both drug use and sexual behaviours are implicated in the transmission of infection in the populations studied. Adapted preventive programs should be developed to prevent further spread of HIV-1 infection in this population.     

Indocyanine green angiography of choroidal tumors

Background: Fluorescein angiography (FA) has been widely used in the diagnostic evaluation of cboroidal tumors. Indocyanine green angiography (ICG-A), which permits better visualization of choroidal vasculature than FA, has been recently introduced into clinical practice. Only few reports exist on the ICG-A characteristics of choroidal tumors. Methods: The fluorescein and indocyanine green angiograms of 61 patients were assessed. These included 14 patients with choroidal nevi, 30 with malignant melanomas, 7 with suspected melanomas or atypical nevi, 5 with hemangiomas and 5 with metastases. Results: The outline of pigmented tumors was more accurate on ICG-A than on FA. Characteristic patterns were seen in all intra-ocular tumors with ICG-A, so it was possible to distinguish hemangiomas from malignant lesions. Characteristic features of malignant melanomas include abnormal vascular pattern and marginal late dye leakage. None of the benign lesions showed these features. In suspected melanomas, the presence of abnormal choroidal vascular patterns and/or late dye leakage on ICG-A may indicate malignancy. Conclusion: The study suggests that ICG-A can yield additional information that is useful in differentiating amongst choroidal tumors. Better delineation of pigmented lesions with ICG-A allows more accurate treatment planning and follow-up.     

The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists

The use of angiotensin II receptor subtype-1 antagonists (ARA), recently introduced as antihypertensive drugs, is becoming more prevalent. We studied the prevalence and severity of hypotension after the induction of general anesthesia in 12 patients treated with ARA until the morning of surgery. The hemodynamic response to induction was compared with that of patients treated with beta-adrenergic blockers (BB) and/or calcium channel blockers (CB) (BB/CB group, n = 45) and angiotensin-converting enzyme inhibitors (ACEI) (ACEI group, n = 27). A standardized anesthesia induction protocol was followed for all patients. Hypotension occurred significantly (p < or = 0.05) more often in ARA-treated patients (12 of 12) compared with BB/CB-treated patients (27 of 45) or with ACEI-treated patients (18 of 27). There was a significantly (P < or = 0.001) increased ephedrine requirement in the ARA group (21+/-3 mg) compared with the BB/CB group (10+/-6 mg) or the ACEI group (7+/-4 mg). Hypotension refractory to repeated ephedrine or phenylephrine administration occurred significantly (P < or = 0.05) more in the ARA group (4 of 12) compared with the BB/CB group (0 of 45) or the ACEI group (1 of 27), but it was treated successfully by using a vasopressin system agonist. Treatment with angiotensin II antagonism until the day of surgery is associated with severe hypotension after the induction of anesthesia, which, in some cases, can only be treated with an agonist of the vasopressin system. IMPLICATIONS: Hypotensive episodes occur more frequently after anesthetic induction in patients receiving Angiotensin II receptor subtype-1 antagonists under anesthesia than with other hypotensive drugs. They are less responsive to the vasopressors ephedrine and phenylephrine. The use of a vasopressin system agonist was effective in restoring blood pressure when hypotension was refractory to conventional therapy.     

Heat exposure standards and women's work: equitable or debatable?

Although there is an abundant literature on the health effects of occupational heat exposure, very few authors have addressed the question of the effects of heat stress on women workers. Knowledge about the effects of work in hot environments is mainly derived from the study of "heavy" muscular activity and current heat exposure standards are based on an energy criterion according to metabolic load. Metabolic load does not reflect cardiac strain associated with sedentary, repetitive work, involving static effort. The research presented here was conducted in an industrial laundry with 11 women mangle operators exposed to moderate heat stress during the summer months and whose work activity is classified as light on the basis of energy expenditure. Physiological and symptomatological responses, work activity and ambient temperature were assessed over 3 complete work days in summer and in winter. Recorded and perceived temperature, discomfort, feelings of fatigue and symptoms of thermal stress were significantly higher in summer than in winter. Symptoms of drowsiness and musculo-skeletal aches were reported equally in both seasons. Heart rate was high in both seasons, as were calculated indices of cardiac strain. Recommended limits for cardiac strain were surpassed significantly more often in summer than in winter. It is suggested that threshold levels should be redefined to include the prevention of cardiac strain resulting from cumulative effects of heat stress and sedentary, repetitive activity, typical of many women's job with low energy requirement.     

Investigation of three new mouse mammary tumor cell lines as models for transforming growth factor (TGF)-β and Neu pathway signaling studies: identification of a novel model for TGF-β-induced epithelial-to-mesenchymal transition

Introduction  

This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line).     

Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes

Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. BACKGROUND: More than half of the new patients admitted to dialysis therapy in some centers are diagnosed with type IIb diabetes, that is, diabetes associated with obesity. This study searched for a common final pathway of renal damage in this progressive renal disease. METHODS: The evolution of biochemical and morphological renal changes was examined in 6- to 60-week-old Zucker rats (fa/fa-rats), a model of obesity associated with type II diabetes. RESULTS: fa/fa-rats exhibited pronounced hyperinsulinemia and hyperlipidemia at 6 weeks and became diabetic after 14 weeks of age. Significant focal segmental glomerulosclerosis was first noted in 18-week-old fa/fa-rats and tubulointerstitial damage and proteinuria in 40-week-old fa/fa-rats. A comparison of kidneys of six-week-old fa/fa-and lean control (Fa/?) rats by immunohistology revealed a 1.8-fold increase in glomerular monocyte/macrophage counts in fa/fa-rats and a significant increase in de novo desmin expression in podocytes. Electron microscopy demonstrated an increase in the number of podocyte mitochondria and intracytoplasmic protein and fat droplets. Podocyte desmin scores markedly increased until week 18 in fa/fa-rats, whereas glomerular monocyte/macrophage counts peaked at 3.2-fold at week 14. Podocyte desmin expression, but not glomerular macrophage infiltration, correlated with damage in adjacent tubular cells, as evidenced by their de novo expression of vimentin. Progressive glomerular hypertrophy was detected in fa/fa-rats after 10 weeks. GBM width was significantly increased in 14-week-old fa/fa-rats as compared with lean controls. Mesangial cell activation (de novo expression of alpha-smooth muscle actin) and proliferation was low to absent throughout the observation period in fa/fa-rats. Renal cell death counts (TUNEL) remained unchanged in 6- to 40-week-old fa/fa-rats. Tubulointerstitial myofibroblast formation and matrix accumulation occurred late during the study duration in fa/fa-rats. CONCLUSION: These data suggest that early progressive podocyte damage and macrophage infiltration is associated with hyperlipidemia and type IIb diabetes mellitus, and antedates both the development of glomerulosclerosis and tubulointerstitial damage.