Melanoma and occupation: results of a case-control study

OBJECTIVES: Associations between occupational exposures and the occurrence of cutaneous melanoma were examined as part of a large population based case-control study of 19 cancer sites. METHODS: Cases were men aged 35 to 70 years old, resident in Montreal, Canada, with a new histologically confirmed cutaneous melanoma (n = 103). There were two control groups, a randomly selected population control group (n = 533), and a cancer control group (n = 533) randomly selected from among subjects with other types of cancer in the large study. Odds ratios for the occurrence of melanoma were calculated for each exposure circumstance for which there were more than four exposed cases (85 substances, 13 occupations, and 20 industries) adjusting for age, ethnicity, and number of years of schooling. RESULTS: Significantly increased risk of melanoma was found for exposure to four substances (fabric dust, plastic dust, trichloroethylene, and a group containing paints used on surfaces other than metal and varnishes used on surfaces other than wood), three occupations (warehouse clerks, salesmen, and miners and quarrymen), and two industries (clothing and non-metallic mineral products). CONCLUSIONS: Most of the occupational circumstances examined were not associated with melanoma, nor is there any strong evidence from previous research that any of those are risk factors. For the few occupational circumstances which were associated in our data with melanoma, the statistical evidence was weak, and there is little or no supporting evidence in the scientific literature. On the whole, there is no persuasive evidence of occupational risk factors for melanoma, but the studies have been too small or have involved too much misclassification of exposure for this conclusion to be definitive.     

Lymphoma, myeloma and occupation: results of a case-control study

The known risk factors for lymphoma and myeloma cannot account for the current incidence rates of these cancers, and there is increasing interest in exploring occupational causes. We present results regarding lymphoma and myeloma from a large case-control study of hundreds of occupational exposures and 19 cancer sites. We examine in more detail those exposures previously considered to be related to these cancers, as well as exposures which were strongly related in our initial analyses. Lymphoma was not associated in our data with exposure to solvents or pesticides, or employment in agriculture or wood-related occupations, although numbers of exposed cases were sometimes small. Hodgkin's lymphoma was associated with exposure to fabric dust, and non-Hodgkin's lymphoma was associated with exposure to copper dust, ammonia and a number of fabric and textile-related occupations and exposures. Employment as a sheet metal worker was associated with development of myeloma.     

Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study

We report a non-randomized Phase II clinical trial to assess the efficacy and safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were entered in the trial. Changes in size, colour and associated oedema of selected 'target' lesions were measured. Clinical, biochemical and haematological toxicities were assessed. Ten subjects were evaluated. A partial response was achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's sarcoma occurred in the remaining six, maintained until the end of the trial period in four. The drug was generally well tolerated, with few mild symptoms of toxicity. The main problem encountered was haematological toxicity, with three subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)/l). There was no evidence of cardiotoxicity. In this small patient sample, liposomal daunorubicin was an effective and well tolerated agent in the treatment of Kaposi's sarcoma.     

Epidemiology, etiology and pathogenesis, clinical presentations and therapeutic approaches in Kaposi's sarcoma: 15-year lessons from AIDS

Kaposi's sarcoma (KS) is a leading cause of morbidity among 25-30% of AIDS patients and is by far the most common AIDS-associated malignancy. Since the beginning of the 1990s the incidence of KS continuously declined, but it was the introduction of protease inhibitors that markedly reinforced this phenomenon. In our experience, the annual incidence was 59/1,000 patient-years in 1984 vs 21.2/1,000 patient-years in 1990, 12.5/1,000 patient-years in 1996, with a drop to 3.2/1,000 patient-years in 1997. One of the peculiar characteristic of this tumor is the sexual susceptibility, which could be the consequence of a hormonal protection in females. The in vitro models of KS-like cell culture promoted and sustained in vitro with a conditioned medium containing several pro-inflammatory cytokines, the characterization of human herpes virus-8 (HHV-8) in almost all the cases of AIDS-KS as the putative KS-agent and the determination of a putative role of hCG-associated factors in the control of KS growth are among the leading discoveries of this last decade in this field.     

Classic Kaposi's sarcoma in Jews living in Israel, 1961-1989: a population-based incidence study

BACKGROUND: The incidence of classic Kaposi's sarcoma (CKS) has been reported to be high in Jewish populations, mostly born in Eastern Europe. OBJECTIVE: To describe the incidence on CKS in Israeli Jews and to determine differences in incidence according to their geography origin. DESIGN: We analysed data on 1098 incident CKS cases with known country of origin occurring between 1961 and 1989 in the Jewish Israeli population. Reporting systems were the Israel Cancer Registry, the medical documentation of all-Kaposi's sarcoma cases and the registry of HIV-seropositive patients. Patients who were seropositive for HIV were excluded from the study population. Population figures for groups of migrants and natives were derived from census surveys (1961, 1972, 1983) and inter-census estimates based on the population registry. RESULTS: The overall age-standardized rate of CKS was 16.9 per million in men and 6.3 per million in women. The ratio between genders remained stable during the study period. In both genders, there was a steep increase in CKS incidence between the late 1960s (age-standardized rates per million: 8.0 in men and 2.2 in women) and the early 1970s (17.9 in men and 6.7 in women). No further increase was present after 1971. Overall, immigrants experienced a relative risk (RR) of 1.17 [95% confidence interval (CI) 0.90-1.521 compared with Jews born in Israel. Immigrants from Morocco, Algeria and Tunisia had the highest incidence (RR 2.01; 95% CI 1.52-2.65) compared with Jews born in Israel, followed by those born in Iraq (RR 1.74; CI 95% 1.27-2.37). The lowest incidence was experienced by immigrants from Iran (RR 0.37; CI 95% 0.18-0.77) and from Central European countries (RR 0.45; CI 95% 0.30-0.66). Immigrants from other countries in Asia, Africa, the Americas and Europe had similar rates as Jews born in Israel. CONCLUSIONS: Israeli Jews present one of the highest incidences of CKS reported from developed countries. The incidence varies according to geographical origin. Countries surrounding the Mediterranean sea represent the area of highest CKS incidence.     

Regression of Kaposi's sarcoma during therapy with HIV-1 protease inhibitors: a prospective pilot study

BACKGROUND: Early studies using HIV protease inhibitors (PI) showed regression of Kaposi's sarcoma (KS) lesions in some patients. OBJECTIVE: Our purpose was to determine prospectively the influence of PI on HIV-related KS. METHODS: KS lesions of nine patients with progressive cutaneous disease were prospectively evaluated clinically and by means of epiluminescence microscopy before and during PI therapy. HIV viremia and CD4 cell count were measured in parallel. RESULTS: All patients experienced reduction or initial stabilization of KS lesions during the first 4 to 8 weeks of HIV-1 PI therapy. After a median follow-up of 7 months and according to AIDS Clinical Trials Groups criteria, six patients had a partial response, two showed stable disease, and in one noncompliant patient KS progressed, requiring chemotherapy. With epiluminescence microscopy, a reduction in skin surface alterations, lesional size, and color intensity was demonstrated in six of nine patients. PI induced a median decrease in viremia of 1.66 log and a median increase in the CD4 count of 49 cells/mm3. CONCLUSION: In this series, HIV PI therapy reduced or stabilized KS. The efficacy of HIV-1 PI in KS may result from the improvement in cellular immunity. These results suggest the use of PI in AIDS-related KS regardless of the level of CD4 lymphocyte count and HIV viremia.     

Role of chewing and smoking habits in the etiology of oral submucous fibrosis (OSF): a case-control study

Oral submucous fibrosis (OSF), a premalignant and crippling condition of the oral mucous membrane, was studied to identify its relationship to various chewing and smoking habits. Two hundred and thirty-six consecutive cases of OSF were compared with 221 control subjects matched for age, sex and socio-economic conditions. It was found that chewing of areca nut/quid or pan masala (a commercial preparation of areca nuts, lime, catechu and undisclosed colouring, flavouring and sweetening agents) was directly related to OSF. Also, pan masala was chewed by a comparatively younger age group and was associated with OSF changes earlier than areca nut/quid chewing. However, chewing or smoking tobacco with various other chewing habits did not increase the risk of developing OSF. It was also found that frequency of chewing rather than the total duration of the habit was directly correlated to OSF.     

Diet and Parkinson's disease. II: A possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study

In a case-control study, we compared the past dietary habits of 342 Parkinson's disease (PD) patients recruited from nine German clinics with those of 342 controls from the same neighborhood or region. Data were gathered with a structured interview and a self-administered food-frequency questionnaire. Nutrient intakes were calculated from the reported food intakes through linkage with the German Federal Food Code and analyzed using multivariate conditional logistic regression to control for total energy intake, educational status, and cigarette smoking. At the macronutrient level, patients reported higher carbohydrate intake than controls after adjustment for total energy intake, smoking, and educational status (OR = 2.74, 95% confidence interval [CI]: 1.30-6.07, for the highest versus lowest quartile, p trend = 0.02). This was reflected in higher monosaccharide and disaccharide intakes at the nutrient level. There was no difference between patients and controls in protein and fat intake after adjustment for energy intake. We found an inverse association between the intakes of beta-carotene (OR = 0.67, 95% CI: 0.37-1.19, p trend = 0.06) and ascorbic acid (OR = 0.60, 95% CI: 0.33-1.09, p trend = 0.04) by patients, although only the trend for ascorbic acid intake reached statistical significance. There was no difference between groups for alpha-tocopherol intake after adjustment for energy intake. We also found that patients reported a significantly lower intake of niacin than controls (OR = 0.15, 95% CI: 0.07-0.33, p trend < 0.00005). Our results suggest that if antioxidants play a protective role in this disease, the amounts provided by diet alone are insufficient. Although the interpretation of the inverse association between niacin intake and PD is complicated by the high niacin content in coffee and alcoholic beverages, which were also inversely associated with PD in this study, the strength of this association and its biologic plausibility warrant further investigation.     

The value of conventionally fractionated radiotherapy in the local treatment of HIV-related Kaposi's sarcoma

BACKGROUND: During the course of AIDS, 25 to 44% of homosexual patients infected with the human immunodeficiency virus develop Kaposi's sarcoma. Main manifestation is the skin. Response rates of 80 to 100% can be achieved with total dosage up to 50 Gy. Nevertheless, remissions can also be attained with 20 Gy of fractionated radiotherapy. As clinical data on low dose conventional fractionated radiotherapy are insufficient we analysed the response rates of an overall dose of 20 Gy in conventional fractionation. PATIENTS AND METHODS: From June 1991 to June 1993, 43 patients with 111 HIV-associated Kaposi's sarcoma of the skin or oral cavity were treated. Lesions were irradiated with 5 to 12 MeV electrons or 60Co gamma-rays. The fractionation scheme was 5 times 2 Gy/week for skin and endoral lesions with a total reference dosage of up to 20 Gy. Side effects were assessed during therapy and the therapeutic result 6 weeks after end of treatment. RESULTS: Thirty-eight out of 111 lesions were judged as complete response (CR) (34%), 61/111 as partial response (PR) (55%) and 12/111 were judged as no change (NC) (11%). Overall response (CR + PR) was 89%. Two patients with lesions of oral cavity suffered from RTOG grade-IV mucositis after 10 and 14 Gy. In 71/106 skin lesions (67%), radiation induced RTOG grade-1 reactions were observed. CONCLUSION: In patients with HIV associated Kaposi's sarcoma effective palliation can be achieved by means of radiotherapy with an overall dose of 20 Gy in conventional fractionation. Yet, the fraction of patients with complete responses is with 34 to 47% lower compared with doses above 20 Gy (66 to 100%). With reference to the reported data our results point to a dose-response relationship for Kaposi's sarcoma. Therefore higher total reference doses, e.g. 30 Gy with weekly 5 times 2 Gy or 24 Gy with 5 times 1.6 Gy for mucous lesions, respectively, are suggested as by this mean the complete response rate can be doubled.     

High incidence of classical Kaposi's sarcoma in Iceland and the Faroe Islands

We have examined the incidence of non-AIDS-related Kaposi's sarcoma in Iceland (1955-79) and the Faroe Islands (1974-95). In Iceland, 19 cases, nine in men and ten in women, were identified, and in the Faroe Islands four cases in men and three cases in women were found. This corresponded to surprisingly high incidence rates. In men, world standardized rates (per 100000 person-years) were 0.4 and 0.6 in Iceland and the Faroe Islands, respectively, and for women, the figures were 0.3 (Iceland) and 0.5 (the Faroe Islands). These are among the highest rates ever reported. No explanation for the high rates of Kaposi's sarcoma in these two North Atlantic communities could be identified.     

An international case-control study of adult glioma and meningioma: the role of head trauma

Human glycosyl phosphatidylinositol-anchored protein CD59 was solubilized in detergent-insoluble complexes (DICs) and in post-nuclear pellets by a two-step solubilization procedure using Triton X-100 and octylglucoside. CD59 molecules are recovered in both fractions, the amount being greater in the latter fraction in all cell types tested. Specific labeling of surface CD59 molecules revealed that the CD59 detected in DICs originated from intracellular compartments, whereas that in post-nuclear pellets was in part derived from the cell surface. Cross-linking of surface proteins with chemical cross-linker followed by Western blotting with anti-CD59 antibody revealed cross-linked products with molecular masses of 28-36 kDa on HeLa and human CD59 cDNA-transfected CHO cells; the CD59-associating molecules were estimated to be 13-18 kDa in size. The cross-linked products were extracted in the post nuclear pellets, and CD59 existed mainly as a cross-linked form on the cell surface. Two-dimensional electrophoresis of the cross-linked products revealed no trace of molecules other than CD59. The cross-linked products showed the same N-terminal sequences as CD59 and a strikingly similar amino acid composition to that of CD59. Thus, most likely, the cross-linked products are CD59 dimers. The finding that CD59 localized on outer membranes is all in the form of dimers suggests the importance of dimerization for CD59 functioning.     

Kaposi's sarcoma of the head and neck in patients with acquired immunodeficiency syndrome

Kaposi's sarcoma is the most common neoplastic process in patients infected with the human immunodeficiency virus. Moreover, the occurrence of Kaposi's sarcoma in human immunodeficiency virus-infected patients advances their classification to having the acquired immunodeficiency syndrome. We reviewed the medical records of 48 patients with human immunodeficiency virus infection who had Kaposi's sarcoma documented on their initial visit to the hospital. The onset of Kaposi's sarcoma occurred independent of the Centers for Disease Control and Prevention classification of human immunodeficiency virus infection (modified to exclude Kaposi's sarcoma). This neoplasm developed more frequently in patients who acquired human immunodeficiency virus infection by sexual contact (75% of cases), but manifestations were not significantly different in any of the risk populations for human immunodeficiency virus infection. Kaposi's sarcoma lesions were unpredictable and either showed progression, remained static, or occasionally, regressed spontaneously. Moreover, the lesions were usually multifocal at presentation, with the head and neck (62.5% of cases) as the primary site of involvement. In this region cutaneous lesions predominated (66.7%), followed by mucosal (56.7%) and deep structure (13.3%) involvement. The majority of patients with acquired immunodeficiency syndrome Kaposi's sarcoma involving head and neck structures were asymptomatic (80% of cases). Mucosal lesions were associated with symptoms in 29.3% of cases, whereas cutaneous lesions had symptoms in 5% of cases.     

Endophthalmitis after cataract surgery: risk factors relating to technique and events of the operation and patient history: a retrospective case-control study

OBJECTIVE: This study aimed to investigate the relationship between postoperative endophthalmitis and current changes in the cataract operative technique. DESIGN: A retrospective case-control study. PARTICIPANTS: The 22,091 cataract operations performed from 1990 through 1993 at St Eriks Hospital formed the basis for this investigation. In a random fashion, 220 control subjects were selected to be compared with the endophthalmitis cases. MAIN OUTCOME MEASURES: Numerous variables pertaining to the cataract extraction procedure and to the ocular and general health of patients with cataracts were analyzed regarding the development of postoperative intraocular infection. Patient age, presence of diabetes or immunosuppression, type of cataract extraction and intraocular lens (IOL), and intraoperative or postoperative complications were the principal variables assessed. RESULTS: Fifty-seven patients with endophthalmitis were diagnosed, resulting in an overall frequency of 0.26%. Immunosuppressive treatment (P = 0.019), wound abnormality (P = 0.03), and the use of IOLs without a heparinized surface (P = 0.0023) were the only significant risk factors found in a logistic regression model. CONCLUSIONS: The results suggest that cataract operating practice may alter the risk for endophthalmitis in that implanting a heparinized IOL and creating a tight section both seem to provide protection against this dreaded complication. Regarding patient history, an increased susceptibility was found among subjects treated with immunosuppressants. Designing a prophylactic protocol that protects against endophthalmitis more efficiently than did the study prophylaxis of 20 mg of subconjunctival gentamicin, is important not only for this patient subgroup but also for the cataract operated population at large.     

The role of dieting in binge eating disorder: etiology and treatment implications

Dieting has been implicated as a potential contributor in the development of binge eating problems in binge eating disorder (BED). If dieting plays a causal role in the etiology of BED, this could have major implications for understanding and treating individuals with the disorder. This article reviews the existing literature on the role of dieting in BED. Retrospective studies of dieting history, research on levels of dietary restraint, and prospective studies investigating the effects of dieting on subsequent eating behavior are explored. Although the literature is inconclusive as to the exact role that dieting plays in the etiology of BED, recommendations for future research and suggestions for treatment are given.     

The risk profile of childhood leukaemia in Greece: a nationwide case-control study

The risk profile of childhood leukaemia in Greece was studied through a case-control investigation that included all 153 incident cases of the disease, ascertained throughout the country during 1993 and 1994, and two hospital controls for every case matched for gender, age and place of residence. The data were analysed using conditional logistic regression and the associations are expressed in terms of adjusted odds ratios (OR) and their 95% confidence intervals. Cases were born to mothers of a higher standard education, the OR for an increment of four schooling years being 1.48 (1.17-1.87) and had higher birth weight, the OR for an increment of 500g being 1.36 (1.04-1.77). Pet ownership and birth after a pregnancy with anaemia were associated with increased risk, the ORs being 2.18 (1.14-4.16) and 2.60 (1.39-4.86) respectively. From the frequency analyses, indicative inverse associations were found with birth order, household crowding and previous hospitalization with allergic diseases, whereas indicative positive associations were found with diabetes mellitus during pregnancy and with neonatal jaundice. Substantial or significant elevations were not found with respect to maternal smoking and coffee drinking during pregnancy, diagnostic radiography and ultrasonographic examinations or blood transfusions. A significant inverse association with maternal consumption of alcohol could be due to multiple comparisons, but a detrimental effect can probably be excluded. A non-significant positive association with total shots of viral vaccinations and a weak non-significant inverse association with breast feeding were also found. We interpret the findings of this study as being compatible with acute childhood leukaemia being linked with delayed development of herd immunity to fairly common infectious agents, in conjunction with accelerated perinatal and early post-natal growth.     

Liposomal doxorubicin in the treatment of AIDS-associated Kaposi's sarcoma: clinical, histological and cell biological evaluation

AIDS-associated Kaposi's sarcoma (KS) in eight patients was treated with the systemic application of liposomal doxorubicin (20 mg/m2 per cycle). After six cycles of treatment a significant regression of KS was observed in all patients. Tumour volume was reduced from 556 +/- 635 mm3 before therapy to 42 +/- 134 mm3 after therapy as determined by ultrasonography of selected tumours. Histological examination revealed a reduction of tumour-like structures and the absence of KS spindle cells in involved areas after therapy. In vitro experiments with KS-derived cell cultures, which most likely represent the KS spindle cells, suggested that liposomal doxorubicin may cause regression of KS via two different mechanisms: (i) by highly specific inhibition of KS spindle cell proliferation and (ii) by induction of monocyte chemoattractant protein-1 expression in KS spindle cells, which may result in increased recruitment of phagocytic cells (monocytes/macrophages) into the lesions. A cooperative action of both mechanisms may explain the high efficacy of liposomal doxorubicin in the treatment of AIDS-KS.     

The role of hyper-homocysteinemia in the etiology of some vascular diseases

About 5% of population have a highly, while other 15% a moderately elevated plasma homocysteine level. Hyperhomocysteinemia may be responsible about 10-20% of coronary artery, 40% of cerebrovascular and 60% of peripheral vascular diseases. There in an inverse relationship between folate, cobalamin and pyridoxine intake or blood level and plasma homocysteine level. In addition, the intake of these three B vitamins can reduce high plasma homocysteine level. Folate-folic acid seems to be the most important in homocysteine reduction due to the compensation of thermolabile methylenetetrahydrofolate reductase insufficiency, however, a milder impact of cobalamin any pyridoxine (mainly following a methionine load test) is also proved. There are possibilities to reduce risk associated with elevated homocysteine: e. g. dietary supplementation or food fortification. In Hungary bread enriched by folic acid, cobalamin and pyriodixine might reduce rate of vascular diseases due to hyperhomocysteinemia.