Pigmentation phenotype, photosensitivity and skin neoplasms in patients with myotonic dystrophy.

BACKGROUND AND PURPOSE: Recent studies have suggested a possible excess risk of skin neoplasms in patients with myotonic dystrophy (DM). Risk factors related to this observation have not been defined. METHOD: Information regarding personal history of skin tumors, pigmentation phenotype, and skin reaction to sun exposure were collected from 266 DM patients who were enrolled in the US National Institutes of Health National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members. RESULTS: Seventy-seven subjects reported having skin tumors that were either benign (n = 31), malignant (n = 32) or both (n = 14). Female gender [odds ratio (OR) = 2.27, 95% confidence interval (CI) 1.02-5.05, P = 0.04], older age (OR = 1.10, 95% CI 1.05-1.16, P < 0.001) and DM1 subtype (OR = 3.42, 95% CI 1.27-9.26, P = 0.02) were associated with a malignant skin tumor. The associations between malignant skin tumors and known risk factors [light eye color (OR = 1.62, 95% CI 0.78-3.39, P = 0.20), light skin complexion (OR = 1.31, 95% CI 0.63-2.73, P = 0.48) and moderate/extensive face freckles (OR = 1.47, 95% CI 0.50-4.34, P = 0.49)] were modest. Strong, but not statistically significant, associations were noted with sunburn reactions when exposed to sunlight (OR = 4.28, 95% CI 0.91-19.95, P = 0.06, and OR = 2.19, 95% CI 0.67-7.09, P = 0.19, for sunburn with and without blistering, respectively). CONCLUSIONS: Although our study was limited by small sample size, the risk factors for malignant skin tumors in DM strongly resemble the general population. It is recommended that DM patients adhere to sun exposure protective behavior.

Nurses speaking up for mothers and children: 25 years of public policy involvement.

Public policy decisions directly affect the health care of women and children and also affect the practice of maternal and child nursing. The past quarter century has seen a shift in nursing involvement in the public policy process. Heightened awareness of the collective power of nurses, greater independence of the nursing profession, the increasing capability for generating research to guide the formulation of public policy, and nurses' better understanding of the political process have all contributed to the increasing influence of our nation's 2.6 million nurses. The passage of several significant pieces of legislation, such as expansions of the Medicaid program for pregnant women and children in the late 1980s, have opened up new opportunities for nurses to further shape the nation's health care agenda for women and children. Nurses can and should become more involved with the policy-making process at local, state, and national levels to assure that decisions are made that benefit this important population group. Leadership in the public policy arena will give nurses the best opportunities for putting forth the agendas that will accomplish these goals.

Non-metastatic Ewing's sarcoma: twenty years of experience suggests that surgery is a prime factor for successful multimodality therapy.

Eighty-five patients (37 female, 48 male; median age 14 years) with non-metastatic Ewing's sarcoma received definitive treatment at the University of Texas M.D. Anderson Cancer Center between 1969 and 1988. Multidisciplinary therapy was administered as follows: combination chemotherapy (CC) and local radiotherapy (XRT): 65 patients; CC, XRT and surgery, 19 patients; and XRT and surgery, 1 patient. This permitted a 10-20 year follow-up for 75% of our patients. The overall survival at 5 and 10-20 years was 46.1%, and 37.2%, respectively. At 5 years, 80.5% of live patients had control of local disease. The influence of sex, age, ethnicity, primary site, size, lactic dehydrogenase (LDH) level, presence or absence of systemic symptoms, and XRT dose (<60 Gy and

Evolution of the CANDA at Roche.

Computer-assisted NDAs (CANDAs) have evolved from an instrument that provides information to regulators to also providing information to internal researchers. They are still not as useful internally during the NDA process as they will be in the future. The portion of CANDA that allows summary, display, and query of the raw data is the most complicated part of the CANDA. Roche's current CANDA system, as well as the challenges in using, documenting, and validating such a system, is described, stressing the features that make it usable in-house. Roche's vision of the future is outlined, covering the strategies, targets, and expected savings.

Quantification of p53 in epithelial ovarian cancer.

OBJECTIVE: The perceived function of wild-type p53 is suppression of cell proliferation. An alteration in the p53 tumor suppressor gene is a common defect in human malignancies. The purpose of this study was to prospectively determine whether p53 expression, as quantified by image analysis, was related to traditional prognostic indicators as well as survival in patients epithelial ovarian cancer. METHODS: Eighty-three consecutive patients with epithelial ovarian cancer had their p53 expression studied by immunohistochemical staining and quantified by image analysis. Unless otherwise noted, p53 expression was reported as the percentage positive nuclear area staining. RESULTS: The mean follow-up was 37 months (median, 30 months; range 24-55 months). In patients with serous carcinomas of the ovary, the mean p53 expression was 29.4%, whereas in patients with other histologies, the mean was 10.5% (P < 0.001). The tumors of patients with stage III or IV tumors stained significantly higher (mean 28. 7%) than the tumors of patients with stage I or II disease (mean 8. 36%) (P < 0.001). The tumors of patients with disease which could be optimally cytoreduced stained significantly lower (mean 23.0%) than the tumors of patients whose disease was unable to be optimally cytoreduced (mean 28.6%) (P = 0.041). Utilizing survival as the endpoint for multivariate analysis, FIGO stage (P = 0.006), p53 expression (P = 0.046), and the level of cytoreduction (P < 0.001) were independent prognostic indicators. CONCLUSION: Image analysis allows quantitative measurements of p53 staining. p53 staining is significantly higher in advanced-stage, high-grade tumors which are unable to be cytoreduced than in early-stage, low-grade tumors which can be optimally cytoreduced. p53 expression is an independent prognostic indicator of survival in patients with epithelial ovarian carcinomas.

Status report on maternal and child health indicators.

The health of pregnant women and children has improved substantially since the 1960s. In the past decade, however, progress in preventing infant deaths, reducing the incidence of low-birth-weight infants, and ensuring first trimester prenatal care has slowed. African-American infants suffer a significantly higher risk of poor pregnancy outcome. Immunization rates for preschoolers remain low. Changing social conditions including a rising child poverty rate, a high teenage birth rate, an increased rate of births to unmarried women, and higher levels of unintended pregnancy may be contributing to stalled progress.

Treatment of lower torso stages I and II Hodgkin's disease with radiation with or without adjuvant mechlorethamine, vincristine, procarbazine, and prednisone.

From 1956 to 1987, 60 patients with either lymphangiogram-staged or laparotomy-staged I-II lower torso presentations of Hodgkin's disease were treated with radiation with or without Mustargen (mechlorethamine), vincristine, procarbazine, and prednisone (MOPP). In 22 with inguinal/femoral or pelvic disease and 24 with abdominal disease, treatment consisted of radiation only. Fourteen other patients with abdominal disease received MOPP chemotherapy before radiotherapy. In 11, the chemotherapy was limited to two cycles. At 10 years, the determinate survival and freedom from progression rates for all patients were 82% and 72%, respectively. For patients with inguinal/femoral or pelvic disease who were treated with radiation only, the corresponding rates were 90% and 86%. For patients with abdominal disease who received radiation only, the determinate survival and the freedom from progression rates were only 66% and 50%, respectively. However, corresponding results for 14 patients with abdominal disease who were treated with MOPP and radiation were 100% and 92% (P = 0.033 and P = 0.009, respectively.

Angiosarcoma arising in an irradiated breast. A case report and review of the literature.

The authors discuss an angiosarcoma that developed in a 50-year-old woman's breast 10 years after she underwent conventional postoperative irradiation with cobalt 60 teletherapy. Although angiosarcoma developing in a lymphedematous arm after radical mastectomy is a well-known phenomenon, and several cases of angiosarcoma are known to have occurred in the chest wall after mastectomy with or without irradiation, only one other case of angiosarcoma in an irradiated breast has been reported. The possible role of therapeutic irradiation in inducing this malignancy is discussed.

Evaluation of methods of administering tyramine to raise systolic blood pressure.

To compare the relative merits of two different administration regimens, tyramine was administered intravenously in ascending doses to 12 healthy subjects to raise systolic blood pressure slightly more than 30 mm Hg. Six subjects received tyramine by bolus injection and six other subjects received tyramine by infusion. The bolus dose of tyramine needed was 4.34 +/- 1.51 mg (X +/- SD) and the infusion rate needed was 1.11 +/- 0.33 mg/min. Four blood pressure response patterns to continuous tyramine infusion were observed. Because different units were measured for the quantity of tyramine administered, the between-subject variance estimate to within-subject variance estimate ratios were calculated. The two techniques had equivalent consistency. With the bolus method, in contrast to the infusion procedure, the dose-response relationship was obvious in most subjects. Therefore the bolus method was judged to be more useful than the infusion method.

Effect of oral cibenzoline on steady-state digoxin concentrations in healthy volunteers.

The effect of oral cibenzoline on steady-state digoxin concentrations was studied in 12 healthy subjects ranging from 41 to 55 years of age. Each subject received an oral dose of 0.25 mg or 0.375 mg digoxin once daily for 27 days. On days 14 to 21, 160 mg of oral cibenzoline were administered concomitantly every 12 hours for a total of 15 doses. Plasma digoxin concentration-time profiles obtained before, during, and after cibenzoline coadministration were compared to determine the effect of oral cibenzoline on steady-state digoxin concentrations. The maximum plasma concentration, time of maximum concentration, area under the curve during a dosing interval and steady-state trough plasma concentration for digoxin, during and after concomitant doses of cibenzoline were similar to those before administration, indicating that cibenzoline did not affect the pharmacokinetics of digoxin. In addition, plasma cibenzoline concentration-time profiles after the first and last dose of cibenzoline were similar to those observed in previous studies in which multiple doses of cibenzoline alone were administered. The results of this study indicate that there is no pharmacokinetic interaction between digoxin and cibenzoline when the two drugs are coadministered to healthy subjects in multiple doses.

Teaching child health-care concepts to Khmer mothers.

PIP: For a course teaching western child health care to refugee Khmer mothers relocated to the U.S., the class content, process, teaching materials and evaluation are described. An average of 8 women attended each of 4 classes, 2-3 hr long, taught by nurse practitioners and an interpreter. They ranged in age from 27-48, with 2-6 children. Class outlines included: Class 1) taking temperatures, pediatrician visits, immunizations; Class 2) common childhood diseases in U.S., folk remedies, Western treatments including home remedies; Class 3) preventing accidents from burns, falls, cars, poisons, drowning and electricity; Class 4) milestones in growth and development to 5 yr, child stimulation activities. Each class was followed by a question and answer period to evaluate students. So problems included difficulty in reading thermometers, resistance against changing some traditional treatments, unfamiliarity with certain concepts such as specificity of immunizations for given diseases or medical prescription of antibiotics (drugs were available without prescription in Cambodia). Khmer mothers' concepts of child developmental milestones correlated well with western ideas. A cultural characteristic of these women that hampered evaluation was their habit of answering questions in the affirmative: Cambodians do not ask or respond to open-ended or multiple choice questions, for fear of offending the questioner. Another problem was the use of a set curriculum, without sufficiently incorporating students' own cultural health care practices into the discussion. It was felt that Khmer mothers developed a basic understanding of western health care practices.^ieng

Trimoprostil plasma concentration-gastric acid inhibition relationships in duodenal ulcer patients.

The effect of single 0.25 mg, 0.75 mg, 1.5 mg, and 3.0-mg oral doses of trimoprostil and placebo on the inhibition of meal-stimulated gastric acid secretion was investigated in duodenal ulcer patients. Drug and placebo were administered in a double-blind, randomized, crossover study under fasting conditions. A bactopeptone meal was administered 30 minutes after dosing. Gastric acid output was measured by intragastric titation (pH 5.5) and trimoprostil plasma concentrations were measured by a specific gas chromatography-negative chemical ionization-mass spectrometric method. Meal-stimulated gastric acid secretion was significantly reduced when compared to placebo for one hour after 0.25 mg, 1.5 hours after 0.75 mg, and for 2.5-3.0 hours after both 1.5 mg and 3.0 mg doses. The maximal inhibition of gastric acid ranged from 65% reduction after 0.75 mg to 74% after 1.5 mg to 82% after 3.0-mg doses. Trimoprostil was rapidly absorbed and eliminated; terminal elimination half-life ranged from 21 to 45 minutes. Both maximum concentration and area under the plasma concentration-time curve increased proportionately with an increase in the dose. The concentration-effect data at a given dose were simultaneously fit to a pharmacokinetic/pharmacologic effect model. An IC50 (plasma concentration needed to elicit a 50% inhibition effect) value of 0.2 ng/mL was observed at doses of 0.75 mg to 3.0 mg. Overall, trimoprostil was effective in inhibiting acid output in a dose-related manner in duodenal ulcer patients.

Trimoprostil plasma concentration--gastric acid inhibition relationships: potentiation by food.

A single, oral, 1.5-mg dose of trimoprostil was taken before a standard meal and a matching placebo was taken after a standard meal by 10 subjects (group A). A second group of 10 subjects took placebo before a meal and trimoprostil after the meal (group B), while a third group took placebo both before and after the standard meal (group C). Food-stimulated gastric acid production was measured by intragastric titration for 6.5 hr after dosing. Trimoprostil taken after the meal had a greater effect on gastric acid secretion than when taken before the meal: Duration of effect was 5 to 5.5 hr in group B and 2 to 2.5 hr in group A. Blood samples were drawn and assayed for trimoprostil by gas chromatography-mass spectrometry. Mean trimoprostil plasma concentration and mean inhibition of gastric acid secretion data were fit to two models by the Hill equation. The mean plasma concentration associated with 50% inhibition of gastric acid secretion was 1.25 ng/ml. Trimoprostil plasma concentrations between 3 and 4 ng/ml were associated with 70% to 80% gastric acid inhibition. Overall, there appears to be a pharmacokinetic-pharmacologic correlation between trimoprostil plasma concentrations and inhibition of gastric acid secretion. Trimoprostil (1.5 mg) in the presence of food appears to have a therapeutic advantage, in that it decreases acid secretion longer than when taken without food and suffers no loss of bioavailability.

Branhamella catarrhalis pneumonia: report of two cases and review of the literature.

Branhamella (Neisseria) catarrhalis is a saprophytic inhabitant of the human oropharynx with the capacity to cause infection, particularly in immunodeficient hosts. There have been 2 cases of Branhamella catarrhalis pneumonia reported in the literature. Two additional cases are described and the subject reviewed. An 80-yr-old woman with chronic lymphocytic leukemia presented with left lower lobe pneumonia. Gram stain of transtracheal aspirate revealed intraleukocytic and extraleukocytic gram-negative diplococci, and a beta-lactamase producing strain of Branhamella catarrhalis was cultured. Therapy with erythromycin resulted in resolution of symptoms and eradication of the organism. A 64-ye-old alcoholic man presented with fever and multiple seizures. Chest roentgenogram revealed left lower lobe pneumonia. Cultures of endotracheal aspirate and blood grew a strain of Branhamella catarrhalis sensitive to penicillin. Penicillin treatment resulted in resolution of pulmonary infiltrate and eradication of the organism. The potential for Branhamella catarrhalis to produce pneumonia and the choice of antimicrobial therapy is discussed. It is emphasized that this organism should not be assumed to be a "normal" isolate and that penicillin may be ineffective in the treatment of Branhamella catarrhalis infections.

Toxic effects of lasalocid in horses.

Lasalocid was given to horses in a series of sequentially increasing single oral doses ranging between 5 and 30 mg/kg of body weight, with an appropriate washout period between treatments. One of the 5 horses died after a dosage of 15 mg/kg, 1 of 3 horses died after 21 mg/kg, 1 of 3 horses died after 22 mg/kg, and 1 of 2 horses died after 26 mg/kg. The LD50 of lasalocid for horses was estimated to be 21.5 mg/kg. Monensin was given to horses in a similar manner at dosages of 1, 2, and 3 mg/kg of body weight. One of the 2 horses died after a dosage of 2 mg/kg and 1 horse died after a dosage of 3 mg/kg. The clinical signs of toxicosis observed in horses given either drug were progressive and included depression, ataxia, paresis, and paralysis with partial anorexia. Intermittent profuse sweating was observed before death in horses given monensin.