Basic principles of cancer genetics

All cancer can be described as genetic, that is, due to altered DNA. Many of these mutations will be accumulated during the normal division of cells. However, some people may inherit abnormal genes, which predispose those individuals to high risk of certain malignancies. These individuals can sometimes be identified as having a family history of affected individuals, some of which might have early age of onset or multiple malignancies. Specific genes have been identified as being associated with certain of these malignancies. The hereditary cancers include (but are not limited to) ovary, breast, colon, endometrium, and to a lesser extent, prostate, skin and pancreas. Some of these cancer predisposing genes are highly penetrant with up to 80 to 90 percent of gene carriers developing the associated malignancy within a 70 year life expectancy. Molecular testing for the presence of cancer predisposing genes is available for many of the hereditary syndromes. While there currently is no way to correct a mutant gene, early detection and some techniques of chemoprevention are of clinical value. People who fear that they are at high risk only learn that they are not, can benefit from the relief of anxiety through the genetic counseling process.     

Special care for newborns at a community hospital: a 5-year experience

Anthralin has been a consistently effective drug for the treatment of psoriasis for more than 80 years, but has not enjoyed common use in the United States because of the unwanted side effects of irritation and staining. New treatment methods such as short-contact therapy and innovative vehicle formulations minimizing these problems have allowed anthralin once again to be used effectively in psoriatic treatment programs. We review these newer adaptations and suggest that the enduring modality deserves an important place in the topical armamentarium.     

In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer

Thirteen postmenopausal women with advanced breast cancer were enrolled in an open randomized Phase I trial of a new p.o. active aromatase inhibitor, CGS 20267 (letrozole). The primary aim of the trial was to assess the impact of two doses of letrozole (0.5 and 2. 5 mg/day) on the peripheral aromatization of androstenedione to estrone. An in vivo isotopic technique was used to measure peripheral aromatization in each patient before treatment. The patients were then randomly assigned to one of the two doses, and measurements of aromatization were repeated after 6 weeks. At 0.5 mg and 2.5 mg/day, letrozole inhibited aromatization by 98.4% (97.3 to >99.1) and >98.9% (98.5 to >99.1; geometric means and ranges), respectively. Plasma estrogen levels were also measured before and during treatment. At the dose of 0.5 mg/day estrone and estradiol levels fell by 82.0% and 84.1% (geometric means), respectively. At the dose of 2.5 mg/ day, the estrogens fell by 80.8% and 68.1%, respectively. There were no significant differences between the doses in aromatase inhibition. No formal statistical analysis was performed on the estrogen data. Letrozole is therefore a highly effective inhibitor of aromatase, causing near complete inhibition of the enzyme in peripheral tissues at the doses investigated. The falls in estrogen levels were greater than those seen with earlier generation aromatase inhibitors.     

Voluntary wheel running decreases adipose tissue mass and expression of leptin mRNA in Osborne-Mendel rats

The purpose of this study was to assess the effects of voluntary wheel running on the expression of leptin mRNA in rats that are either sensitive (OM) or resistant (S5B/Pl) to diet-induced obesity. Male OM and S5B/Pl rats had ad libitum access to standard rodent diet and water. At 3-5 weeks of age, animals of both strains were randomly assigned to either an exercise or sedentary control group. The exercise groups had 24-h access to a running wheel, and they trained for 7 weeks. During weeks 1-4, animals in both OM and S5B/Pl exercise groups progressively increased their running. During weeks 5-7, S5B/Pl exercisers tended to run more than did OM (approximately 60 vs. 45 km/week), but by the end of the study both groups had an equally greater heart weight (mg/g body weight) and planteris citrate synthase activity than their sedentary controls. Oral glucose tolerance tests performed during the last week of training revealed that compared with their appropriate controls, insulin sensitivity was enhanced (P < 0.05) in OM but not in the S5B/Pl wheel-running groups. Inguinal, epididymal, and retroperitoneal fat pads weighed less in the running than in the nonrunning groups of both strains (P < 0.01). Additionally, exercised animals had an increased percentage of smaller cells (40-60 microm; P < 0.05) and a decreased percentage of larger cells (120-160 microm; P < 0.05) in the epididymal fat depot. Epididymal leptin mRNA measured by Northern blot analysis was reduced in the exercise-trained rats of both strains (P < 0.05). Furthermore, serum leptin was reduced in exercise-trained compared with the control animals of both strains. In comparison to S5B/Pl, control OM animals exhibited both a higher expression and higher circulating levels of leptin (P < 0.05). While serum leptin levels were decreased and food intake was increased in the exercise-trained animals of both strains (P < 0.05), the exact relationship between exercise, leptin, and food intake in this rat model of dietary obesity remains to be determined. Nonetheless, these results suggest that the expression and secretion of leptin can be influenced by exercise training and that these changes (i.e., reduced expression and secretion of protein) can occur independently of changes in whole-body insulin sensitivity and susceptibility to diet-induced obesity.     

Occupational risk of hepatitis C virus infection to dental health care staff: an update

In this review, we develop four topics on the relationship between blood transfusion and cancer. First, the rationale for not allowing blood donations from patients with infiltrating tumors is presented. Second, the different possibilities for autotransfusions in cancer patients are discussed. Predeposited autotransfusions are rarely possible in these patients, in addition to the high cost. The usefulness of another method, intraoperative autologous transfusion with blood saved from the surgical field, is not well established. Our third topic concerns the effect of transfusion on cancer induction. In some cases, the risk of cancer is higher after allogenic transfusion resulting from a mechanism involving alterations of the immune function. Finally, the relationship between transfusion and cancer recurrence is controversial. In spite of numerous studies attempting to elucidate this relationship, no final conclusion can be drawn at the present time. What is sure, is that patients requiring blood transfusion have a higher risk of recurrence than patients who do not need transfusion.     

Respiratory muscle work compromises leg blood flow during maximal exercise

We hypothesized that during exercise at maximal O2 consumption (VO2max), high demand for respiratory muscle blood flow (Q) would elicit locomotor muscle vasoconstriction and compromise limb Q. Seven male cyclists (VO2max 64 +/- 6 ml.kg-1.min-1) each completed 14 exercise bouts of 2.5-min duration at VO2max on a cycle ergometer during two testing sessions. Inspiratory muscle work was either 1) reduced via a proportional-assist ventilator, 2) increased via graded resistive loads, or 3) was not manipulated (control). Arterial (brachial) and venous (femoral) blood samples, arterial blood pressure, leg Q (Qlegs; thermodilution), esophageal pressure, and O2 consumption (VO2) were measured. Within each subject and across all subjects, at constant maximal work rate, significant correlations existed (r = 0.74-0.90; P < 0.05) between work of breathing (Wb) and Qlegs (inverse), leg vascular resistance (LVR), and leg VO2 (VO2legs; inverse), and between LVR and norepinephrine spillover. Mean arterial pressure did not change with changes in Wb nor did tidal volume or minute ventilation. For a +/-50% change from control in Wb, Qlegs changed 2 l/min or 11% of control, LVR changed 13% of control, and O2 extraction did not change; thus VO2legs changed 0.4 l/min or 10% of control. Total VO2max was unchanged with loading but fell 9.3% with unloading; thus VO2legs as a percentage of total VO2max was 81% in control, increased to 89% with respiratory muscle unloading, and decreased to 71% with respiratory muscle loading. We conclude that Wb normally incurred during maximal exercise causes vasoconstriction in locomotor muscles and compromises locomotor muscle perfusion and VO2.