Determination of gallium concentration in "blood-free" tissues using a radiolabeled blood marker

Radioiodinated serum albumin has been used as a blood marker to define and quantitate physiological volumes for 12 organs and tissue types. The concentration of gallium-67 in "blood-free" tissues of rats was also determined at various times after intravenous administration. Tissues were divided into two kinetically distinguishable types based on reported nonuniform distribution of the blood marker and the gallium distribution observed in the present study. Gallium distribution into the liver and spleen was observed to be slow, with a discernable accumulation phase followed by monoexponential elimination. In contrast, gallium accumulation into the stomach, small and large intestines, heart, lung, skin/adipose tissue, and muscle was rapid and elimination was monophasic.     

Pharmacokinetics of vindesine bolus and infusion

Summary The pharmacokinetics of vindesine were investigated during treatment of 15 patients with progressive malignancies refractory to conventional treatment. Patients were administered one of three IV dose schedules: 3.0 mg/m² bolus injection, 1.2 mg/m²/day infusion for 5 days, or 2.0 mg/m²/day infusion for 2 days. Concentrations of the drug in the serum and urine were determined by radioimmunoassay. Serum concentrations were highest (5×10^-7 M) in patients receiving a bolus injection, but fell to nondetectable levels by 48 h in four of five patients (terminal t_1/2 15.0±9.4 h). Compared with bolus injection, 1.2-to 1.4-fold greater areas under the blood concentration curve were observed during infusions of 2.0 mg/m² and 1.2 mg/m². Whereas steady-state concentrations (1×10^-8 M) were maintained throughout the infusion of 1.2 mg/m²/day progressively increasing serum levels were observed during the infusion of 2.0 mg/m²/day. Serum concentrations fell rapidly following discontinuation of the 2.0-mg/m² infusion, but were somewhat more sustained in the 1.2-mg/m² infusion group. The average urinary excretion was similar for each dose-schedule (8%–11% of the total dose). The pharmacokinetics of vindesine are influenced by variations in dose schedule.     

Rabbit antithymocyte globulin. A 10-year experience in cardiac transplantation

Rabbit antithymocyte globulin, a "custom-made" pan-anti-T-cell antibody produced in rabbits, is currently being evaluated in the United States and may, within several years, become approved by the Food and Drug Administration. Because we have used this agent for induction of immunosuppression for 10 years in cardiac recipients and because the results appear to be more favorable than those obtained with other agents (horse antithymocyte globulin, antilymphocyte globulin, OKT3), we have reviewed our experience. For the purpose of analysis, all non-bridge-to-transplant cardiac recipients have been divided into three groups on the basis of immunosuppression protocol: group I (March 1979 to January 1983), 28 patients treated with rabbit antithymocyte globulin, steroids, and azathioprine; group II (January 1983 to March 1985), 29 patients treated with rabbit antithymocyte globulin, cyclosporine, and steroids; and group III (March 1985 to January 1989), 98 patients treated with rabbit antithymocyte globulin, cyclosporine, steroids, and azathioprine. Actuarial data showed advantage for group III in survival rate (1 year 94%, 2 years 91%, 3 years 88%), freedom from rejection (30% free at 1 year), freedom from infection (50% free at 1 year), freedom from death from rejection (99% free at 1 year), and freedom from death from infection (97% freedom at 1 year). Actuarial survival rates and freedom from death from rejection and infection are comparable for any of our groups with contemporary published data. In the past 3 years, we have had no death from acute rejection or from posttransplant infection. Time-related rates of infection by etiologic agents have shown a significant reduction in early bacterial, viral, and nocardial infections between groups I and III. With rabbit antithymocyte globulin 200 mg intramuscularly every day for 3 days, our current protocol, T-cells are significantly reduced and local and systemic toxicity is almost unnoticeable. A progressively increasing cyclosporine dose along with rapid tapering steroid and maintenance azathioprine immunosuppressive induction appears to be the therapy of choice in cardiac transplantation.     

Investigation of under-ascertainment in epidemiological studies based in general practice

BACKGROUND: One of the aims of the Study of Infectious Intestinal Disease (IID) in England is to estimate the incidence of IID presenting to general practice. This sub-study aims to estimate and correct the degree of under-ascertainment in the national study. METHODS: Cases of presumed IID which presented to general practice in the national study had been ascertained by their GP. In 26 general practices, cases with computerized diagnoses suggestive of IID were identified retrospectively. Cases which fulfilled the case definition of IID and should have been ascertained to the coordinating centre but were not, represented the under-ascertainment. Logistic regression modelling was used to identify independent factors which influenced under-ascertainment. RESULTS: The records of 2021 patients were examined, 1514 were eligible and should have been ascertained but only 974 (64%) were. There was variation in ascertainment between the practices (30% to 93%). Patient-related factors independently associated with ascertainment were: i) vomiting only as opposed to diarrhoea with and without vomiting (OR 0.37) and ii) consultation in the surgery as opposed to at home (OR 2.18). Practice-related factors independently associated with ascertainment were: i) participation in the enumeration study component (OR 1.78), ii) a larger number of partners (OR 0.3 for 7-8 partners); iii) rural location (OR 2.27) and iv) previous research experience (OR 1.92). Predicted ascertainment percentages were calculated according to practice characteristics. CONCLUSION: Under-ascertainment of IID was substantial (36%) and non-random and had to be corrected. Practice characteristics influencing variation in ascertainment were identified and a multivariate model developed to identify adjustment factors which could be applied to individual practices. Researchers need to be aware of factors which influence ascertainment in acute epidemiological studies based in general practice.     

Surgical management of the cardiovascular complications of Kawasaki's disease

During a 31-year period, 54 patients were treated for Kawasaki's disease at the Texas Heart Institute and Texas Children's Hospital. Classically, the illness is characterized by prolonged fever, conjunctivitis, oral mucosal inflammation, exanthema, and later skin desquamation and cervical lymphoadenopathy. Seventy percent of patients have electrocardiographic abnormalities consisting of prolongation of the PR and QT intervals and ST-T wave changes. Most deaths occur within 1 to 2 months after onset of the disease. The risk of coronary abnormalities and cardiac death appear to be higher in those patients under 1 year of age with prolonged fever, elevated white blood count, and erythrocyte sedimentation rate.     

RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer.

PURPOSE: RRM1 has important functions in the determination of the malignant phenotype. It controls cell proliferation through deoxynucleotide production and metastatic propensity through PTEN induction. It is located in a region of loss of heterozygosity in non-small-cell lung cancer (NSCLC), which is a predictor of poor survival. We hypothesized that RRM1 expression would be a significant predictor of outcome in NSCLC. PATIENTS AND METHODS: A retrospective data set of 49 patients and a prospective data set of 77 patients with resectable NSCLC were studied. RNA was extracted from tumor and normal lung tissue, and expression of the genes RRM1, PTEN, and RRM2 was determined by real-time quantitative polymerase chain reaction. RESULTS: RRM1 expression was significantly correlated with PTEN and RRM2 expression in tumor tissue. RRM1 and PTEN expression in tumor tissue was highly predictive of overall (P =.011 and.018, respectively) and disease-free survival (P =.002 and.026, respectively). Patients with high levels of expression lived longer and had disease recurrence later than patients with low levels of RRM1 and PTEN. In a multivariate analysis, high RRM1 expression was predictive of long survival independent of tumor stage, performance status, and weight loss. CONCLUSION: RRM1 is a biologically and clinically important determinant of malignant behavior in NSCLC. Knowing the level of expression of this gene adds significant information to management decisions independent of the currently used outcome predictors of tumor stage, performance status, and weight loss. Future clinical trials should stratify patients based on expression of this gene to avoid unwanted biases.     

Antenatal corticosteroid therapy and risk of osteoporosis

Objective To assess the risk of maternal osteoporosis associated with antenatal corticosterioid administration for neonatal respiratory distress syndrome prophylaxis.
Design Prospective longitudinal study.
Setting Maternity unit of Chelsea and Westminster Hospital, London.
Population Fourteen pregnant women who received dexamethasone therapy for fetal lung maturation in anticipation of delivery before 34 completed weeks of gestation.
Methods Blood samples were collected before dexamethasone administration, 24 hours and 48 hours after the course of dexamethasone, and within 24 hours of delivery. Serum levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) were measured to monitor the rate of bone formation, and serum levels of cross-linked carboxy terminal telopeptide (ICTP) were measured as a marker of bone resorption.
Main outcome measures Changes in the markers of bone turnover following dexamethasone administration.
Results Serum PICP levels dropped 24 hours after dexamethasone therapy (   P = 0.001  ), but partially recovered by 48 hours (   P = 0.014  ) to reach higher than pre-therapy levels at delivery (   P = 0.044  ). Although there were no corresponding changes in the serum levels of ICTP after 24 and 48 hours of therapy, levels increased from pretherapy to delivery (   P = 0.006  ).
Conclusion Antenatal corticosteroid therapy leads to a transient suppression of, followed by an increase in, bone formation without any significant alteration in the pattern of bone resorption expected during pregnancy.     

Waardenburg syndrome Type II

Two rare cases of Waardenburg type II are reported. First case had three main features of WS-profound SN hearing loss, hetrochromia iris and white forelock of hair. Second case had moderate SNHL and depigmentation of hair. Key words: Hetrochromia iris, white forelock hair.