Tumour dormancy: initiation, maintenance and termination in animals and humans

The authors review the natural occurrence of tumour dormancy in man and animal models, which show the importance of cellular defence mechanisms in inducing and maintaining the state of tumour dormancy. Six cases of non-small-cell lung cancer are described. The patients exhibited moderate to very strong delayed hypersensitivity reactions to soluble lung-cancer antigen after specific immunotherapy. Three patients had nonregional metastases at 11, 12 and 14 years. Two had regional recurrence after 9 years, and in one patient a small hilar-node metastasis was found at autopsy after 7.6 years. In each case an immunodepressive event or drug treatment preceded resurgent growth. The effect of renal transplantation in patients with a history of surgery for cancer supports the conclusion that cellular defence mechanisms are crucial for the maintenance of tumour dormancy in man.     

Effect of cholesterol deprivation on piglet small intestine and serum lipids

Using the neonatal piglet, the effects of dietary cholesterol deprivation on growth, intestinal enzyme activity, intestinal and hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and serum lipid were studied. Six litters of piglets were randomly assigned to one of two feeding regimens: restricted (800 ml of formula/24 h) versus unrestricted (1,200 ml of formula/24 h). Within litters, piglets were separated by sex, then randomly assigned to a formula containing low cholesterol (less than 2 mg/dl) or high cholesterol (145 mg/dl). Piglets were fed for 2 weeks. Male piglets in the restricted low cholesterol group gained significantly less weight per milliliter of formula than the restricted high cholesterol males. No effect was observed in the females. Microvillus membrane lactase activity was greater in males fed a high versus low cholesterol diet. Intestinal and hepatic HMG-CoA reductase activities and serum lipid profiles showed a trend toward compensation for dietary cholesterol deprivation but did not differ statistically between the cholesterol-fed versus -deprived groups. It is concluded that dietary cholesterol deprivation in the male neonatal pig causes alterations in growth, but no other statistically significant responses were detectable in this study.     

Nasofacial conidiobolomycosis.

A case of Nasofacial Zygomycosis in a 15-year-old male patient from South India is reported. This patient had typical thickening of the nasofacial mucosa and the skin overlying it. The diagnosis was confirmed with fungal cultures. Although initially good response to treatment with potassium iodide was achieved, later the response was unsatisfactory, probably partly due to irregularity in treatment. Treatment with sulphamethoxazole--trimethoprim and prednisolone combination has resulted in remarkable improvement.     

Iron nutritional status of preschool children

Low hemoglobin and low MCHC levels were indicative of high incidence of iron deficiency in preschool children. The extent of iron deficiency as assessed by serum ferritin and free erythrocyte protoporphyrin showed a different trend. While FEP levels were highly suggestive of extensive iron deficiency (in 40–45% of children below the age of 5 years), low serum ferritin was seen in only 16–20% of children. The discrepant finding of high serum ferritin, and high erythrocyte protoporphyrin despite low MCHC in the present study, possibly reflects iron deficiency status along with chronic infection resulting in hyperferritinemia and hyperprotoporphyrinemia. It may be also due to associated folate deficiency resulting in non utilization of iron leading to the elevated levels of protoporphyrin.     

Mefenamic acid-induced bilateral transient myopia, secondary angle closure glaucoma and choroidal detachment

Drug-induced secondary angle closure is quite common and in the majority of cases simply stopping the medication leads to rapid reversal of the condition and resolution of glaucoma. We describe here a patient who presented with secondary angle closure glaucoma and myopia following mefenamic acid ingestion which was managed successfully by stopping the medication, symptomatic treatment and reassurance.     

Commercialization of BRCA1/2 testing: practitioner awareness and use of a new genetic test

It was our purpose to determine the characteristics of practitioners in the United States who were among the first to inquire about and use the BRCA1 and BRCA2 (BRCA1/2) genetic tests outside of a research protocol. Questionnaires were mailed to all practitioners who requested information on or ordered a BRCA1/2 test from the University of Pennsylvania (UPenn) Genetic Diagnostics Laboratory (GDL) between October 1, 1995 and January 1, 1997 (the first 15 months the test was available for clinical use). The response rate was 67% of practitioners; 54% (121/225) were genetic counselors, 39% (87/225) were physicians or lab directors. Most physicians were oncologists, pathologists, or obstetrician/gynecologists, but 20% practiced surgery or internal or general medicine. Fifty-six percent (125/225) had ordered a BRCA1/2 test for a patient; most of the rest had offered or were willing to offer testing. Of those who had offered testing, 70% had a patient decline BRCA1/2 testing when offered. Practitioners perceived that patients' fear of loss of confidentiality was a major reason for declining. Nearly 60% of practitioners reported that their patients had access to a genetic counselor, but 28% of physicians who ordered a BRCA1/2 test reported having no such access, despite the GDL's counseling requirement. The proportion of physicians reporting no access to genetic counselors for their patients increased from 22.4% in the first half of the study to 50% in the last half. Many practitioners have an interest in BRCA1/2 testing, despite policy statements that discourage its use outside of research protocols. Practitioner responses suggest that patient interest in testing seems to be tempered by knowledge of potential risks. An apparent increase in patient concern about confidentiality and inability to pay for testing could indicate growing barriers to testing. Although most practitioners reported having access to counseling facilities, perceived lack of such access among an increasing proportion of practitioners indicates that lab requirements for counseling are difficult to enforce and suggests that an increasing proportion of patients may not be getting access to counseling.     

Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas(lpr) mice from autoimmune disease

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LFA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas(lpr) mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(lpr) mice, suggesting a lack of redundancy among the beta(2) integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE.     

Reduction of FK-506 requirements by combination with polyethylene glycol superoxide dismutase in orthotopic rat liver transplantation

Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506. Mean survival time was increased significantly in these animals (p < 0.007) to 40.6 ± 25.6 days as compared with either untreated rats (10.0 ± 2.7 days) or rats treated with 0.04 mg/kg FK-506 alone (13.7 ± 4.2 days). Histologic examination demonstrated a significant reduction in the cellular infiltrate in rats treated with PEG-SOD plus FK-506, as compared with recipients treated with either agent alone or left untreated. Our results therefore suggest a potential approach to reducing immunosuppression in transplantation. (J ALLERGY CLIN IMMUNOL 1995;95:1276-81.)