Time course of plasma levels and electrophysiologic effects of propranolol in man

We studied the time course of three electrophysiologic effects of propranolol after intravenous and oral administration and their relationship with plasma levels within the same subjects. Ten patients who had undergone cardiac catheterization for diagnostic purposes received 0.1 mg/kg of propranolol intravenously. Blood was drawn at intervals for 12 hr and heart rate and the effective refractory periods of the atrium (ERPA) and the atrioventricular node (ERPAVN) were determined at the same time. Eight patients continued treatment with propranolol by the oral route for up to 4 days (40 mg every 12 hr). Blood was sampled after each morning dose. Plasma concentrations of propranolol were measured by gas chromatography. Maximal lengthening of ERPA after propranolol (15.1% i.v. and 9.4% oral) was much less marked than that of ERPAVN (23.2% i.v. and 19.4% oral). Heart rate decreased 23.5% (i.v.) and 13.1% (oral). Effects were seen much sooner after intravenous (5-8 min) than after oral administration (86-146 min), but they lasted about twice as long after oral as after intravenous treatment.     

Sonographic patterns of Caroli's disease: report of 5 new cases.

We have reviewed 5 cases of Caroli's disease, studied from 1982 to 1987, in order to define the validity of its sonographic signs. The "intraluminal portal vein" sign, found in all the cases, is emphasized. This sign may be easily identified and it is never encountered in other diseases. Recessive polycystic kidney disease was present in 3 cases, and congenital hepatic fibrosis was demonstrated in the 2 cases studied by liver biopsy.     

Factor V Leiden and G20210A prothrombin mutation and the risk of subclavian vein thrombosis in patients with breast cancer and a central venous catheter.

BACKGROUND: To analyze the influence of the prothrombotic gene mutation factor V G1691A (factor V Leiden) and prothrombin G20210A on the risk of a first episode of catheter-related deep venous thrombosis (DVT) in a group of patients with breast cancer treated with chemotherapy. PATIENTS AND METHODS: Between January 1999 and February 2001, the occurrence of a first symptomatic DVT was investigated in a cohort of 300 consecutive patients with locally advanced or metastatic breast cancer treated at a single institution with fluorouracil-based chemotherapy, administered continuously through a totally implanted access port. A nested case-control study included 25 women (cases) with catheter-related DVT and 50 controls without DVT matched with cases for age, identical chemotherapy, stage of disease and prognostic features. The G1691A factor V and G20210A prothrombin mutation genotypes were analyzed. RESULTS: Five cases [20%; 95% confidence interval (CI) 9% to 39%)] and two controls (4%; 95% CI 1% to 14%) were heterozygous carriers of G1691A factor V (P = 0.04). The age-adjusted odds ratio for catheter-related DVT was 6.1 (95% CI 1.1-34.3). Only one patient (case) had the G20210A prothrombin gene mutation. Time from start of chemotherapy infusion to DVT was not significantly different between patients with (median 31 days) and without (median 43 days) G1691A factor V mutation (P = 0.6). CONCLUSIONS: Factor V Leiden carriers with locally advanced or metastatic breast cancer have an increased risk of developing catheter-related DVT during chemotherapy.     

Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

Enhancement of Radiation Response by Paclitaxel in Mice According to Different Treatment Schedules

Purpose: The aim of our study was to determine if paclitaxel could be used as a radiosensitizer in vivo.

Materials and methods: Paclitaxel was tested as a single agent and combined with an X-ray treatment. Paclitaxel was administered i.p. in doses from 30 to 120 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma. Tumor growth delay (TGD) or tumor control dose (TCD₅₀, radiation dose needed to induce local tumor control in 50% of irradiated animals) and moist desquamation dose (MDD₅₀, radiation dose needed to induce serious moist desquamation in 50% of the non-tumor-bearing feet) were the endpoints. DNA flow cytometric analysis was performed.

Results: DNA analysis demonstrated a G2/M block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h from paclitaxel administration. Administering paclitaxel, in graded doses, 15 min before a 10-Gy X-ray treatment resulted in a linear regression line, almost parallel to that with paclitaxel alone, with a growth delay of about 6 days. In contrast, varying the X-ray dose with a constant paclitaxel injection (45 mg/kg b.w.) treatment showed some degree of synergism as the linear regression curves diverged. Interval time and sequence between paclitaxel administration and a 10 Gy X-ray treatment did not influence TGD. Protocols with paclitaxel at 30, 45, or 60 mg/kg were combined with radiation treatments at various doses (from 10 to 65 Gy). Values of TCD50 varied from 50.8 Gy for X-ray alone to 31.8 Gy for paclitaxel 60 mg/kg + X-ray. No differences were observed among MDD of different protocols.

Conclusions: These results suggest that, under some conditions, paclitaxel combined with radiation can show superadditive effects and this result combined with the lack of severe normal tissue damage indicate that a favorable therapeutic gain can be obtained.     

Experience of spirituality, mental illness and occupation: A life-sustaining phenomenon

Background and Aim:  This article provides an overview of a phenomenological investigation of spirituality with six people who have experienced mental illness. The study aimed to gain a greater understanding of the phenomenon of spirituality and its relationships to occupation and the experience of mental illness.
Methods and Results:  Participants were interviewed and the interviews were audiotaped and transcribed verbatim. Findings emerged through multiple readings and gradually constructed meanings from the data. Spirituality was found to be: unique to each participant, a journey through life, vitally important to participants, manifested as 'spiritual occupations', the foundation of meaningful doing, important socially as well as individually, and was found to support participants in coping with mental illness. This article focuses on the 'meta', integrative theme of spirituality as life sustaining. It concludes with the notion that spirituality is essential to the participants and is a significant aspect of their occupational behaviour.
Conclusion:  It is recommended that occupational therapists give themselves a 'licence' to discuss spirituality in practice and that they commit to learning more about how spirituality is a part of the lives of their clients.     

Synthesis and Antimuscarinic Activity of Derivatives of 2-Substituted-1,3-Dioxolanes

Geometric cis, trans isomers, derivatives of 2-substituted-1,3-dioxanes were designed and studied as antimuscarinic agents. The synthesized compounds were evaluated as perchlorides and methiodides by functional tests with rabbit vas deferens (putative M₁), guinea-pig heart (M₂) and guinea-pig ileum (M₃). The effect of the replacement of a trimethylammonium group with a dimethysulfonium in the two rings was also evaluated. Pharmacological results indicate that the 1,3-dioxane nucleus shows the highest stereoselective values on the studied receptors.