Mechanism of action of sodium cyanide on rat diaphragm muscle.

The effects of sodium cyanide (NaCN) were investigated on the contractile and electrophysiological properties of rat diaphragm muscles in vitro. Sodium cyanide (0.1-1.0 mM) produced an initial potentiation of directly elicited twitch tensions, followed by a slow progressive depression. The potentiation and depression were both dependent on the NaCN concentration and stimulation frequency. Muscles exposed to NaCN exhibited marked reductions of creatine phosphate concentration, but ATP levels were not significantly lowered. Sodium cyanide had no effect on the resting potential, input resistance or action potential, indicating that the toxicity of the metabolic inhibitor is not mediated by alterations of membrane excitability or passive electrical properties. Sodium cyanide reduced the amplitude of contractures elicited by 70 mM K(2)SO(4), suggesting that the actions of NaCN cannot be explained by a failure of action potentials to propagate across the muscle surface or within t-tubular membranes. Sodium cyanide suppressed the first phase of the caffeine contracture, an observation consistent with an impaired release of, or reduced sensitivity to, sarcoplasmic reticular Ca(2+), but did not alter the amplitude of the second phase, which represents rigor following ATP depletion. These results, in conjunction with those of previous studies, suggest that the depression in muscle tension following exposure to NaCN may result from alterations in Ca(2+) homeostasis, intracellular acidosis or from accumulation of one or more products of phosphocreatine breakdown.     

Effect of age on ibuprofen pharmacokinetics and antipyretic response.

The effect of age on ibuprofen pharmacokinetics and antipyretic effect was studied in 49 infants and children aged 3 months to 10.4 years. The relationship of plasma concentration to antipyretic effect was examined in 38 of the children by using an iterative least squares technique that allows estimation of drug concentration with time in a theoretical effect compartment and rate constant for elimination of drug from the effect compartment. There was a delay of 1 to 3 hours between peak ibuprofen plasma concentration and peak temperature decrement. The mean elimination rate constant from the effect compartment was 0.6 hour-1, corresponding to a half-life of drug in the effect compartment of 1.1 hours. The mean slope of the effect compartment concentration versus temperature regression line was -0.242 degrees C/mg per liter. Age did not significantly influence the rate of absorption of ibuprofen, its plasma concentration, its rate of elimination, or the time course of ibuprofen concentration in the effect compartment. However, in younger children the onset of antipyresis was earlier, maximum antipyretic effect was greater, and the area under the curve of the percentage of change in temperature from baseline versus time was greater than in older children. We conclude that the greater relative body surface area in younger children may allow more efficient dissipation of heat in response to antipyretic-induced lowering of the temperature "set point" in the hypothalamus.     

Bilateral pheochromocytoma and islet cell adenoma of the pancreas

An 18-year-old woman with bilateral pheochromocytomas and an asymptomatic islet cell adenoma of the pancreas represents the 11th patient to be described with this combination of endocrine tumors. No other components of any multiple endocrine adenomatosis (MEA) syndromes were present. Because of this "overlap syndrome," in which tumors that have traditionally been considered to be components of separate and mutually exclusive MEA syndromes have occurred concomitantly in the same patient, a question is raised regarding the validity of a rigid classification of these various MEA syndromes. The possibility of a pancreatic tumor should be kept in mind in any patient with a pheochromocytoma, especially if it is bilateral of multicentric in origin.     

Postoperative synergistic gangrene after spinal fusion

STUDY DESIGN: A case of synergistic necrotizing gangrenous fasciitis after spinal surgery is reported. OBJECTIVES: To describe this unusual complication, explain the rationale of treatment, and increase awareness of this serious postoperative complication. SUMMARY OF BACKGROUND DATA: Although several cases of postoperative synergistic necrotizing fasciitis have been reported, there are no previously reported cases of this condition after spinal surgery. METHODS: A rapidly progressive necrotizing spinal wound infection after fusion for degenerative disc disease was treated in a 39-year-old man. RESULTS: The infection was successfully treated with serial debridements, appropriate antibiotics, and hyperbaric wound oxygenation. CONCLUSIONS: The authors suggest adherence to the fundamental principles of treatment including radical surgical debridement and appropriate antibiosis for necrotizing gangrene after spinal surgery. In evaluation of aggressive spinal wound infections, diagnosis of synergistic necrotizing fasciitis should be kept in mind. Although hyperbaric wound oxygenation was implemented as an adjunct and appeared to aid in controlling the infection, its effect on outcome is not clear.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

Development of the Proteasome Inhibitor Velcade™ (Bortezomib)

The dipeptide boronic acid analogue VELCADE™ (Bortezomib; formerly known as PS-341, LDP-341 and MLM341) is a potent and selective inhibitor of the proteasome, a multicatalytic enzyme that mediates many cellular regulatory signals by degrading regulatory proteins or their inhibitors. The proteasome is, thus, a potential target for pharmacological agents. Bortezomib, the first proteasome inhibitor to reach clinical trials, has shown in vitro and in vivo activity against a variety of malignancies, including myeloma, chronic lymphocytic leukemia, prostate cancer, pancreatic cancer, and colon cancer. The drug is rapidly cleared from the vascular compartment, but a novel pharmacodynamic assay has shown that bortezomib-mediated proteasome blockade is dose-dependent and reversible. Based on phase I studies demonstrating that bortezomib has manageable toxicities in patients with advanced cancers, phase II trials have been initiated for both solid and hematological malignancies.     

CT-Cephalometry—A study in Indian population

Determination of obstructive site in obstructive sleep apnoea (OSA) is of paramount importance is planning the management. Cephalometric evaluation of lateral X-rays when combined with clinical assessment and fibreoptic examination of the airway helps in locating the site of obstruction. The usual technique of cephalometry has been modified so as to give a better delineation of the soft tissues. Holding a 2mm card board in the mouth and using barium paste helped in more accurate calculations. Using our technique, various parameters have been quantified and a number of controls were studied and normal range derived. Further improvement in cephalometry has been done by using C.T. cephlometry topogram technique. A topogram is a scan done on a running table top cranio-caudally. Using the topogram technique 38 OSA patients were evaluated for all the parameters. The technique, its advantages over traditional cephalometry and the values obtained in the study are discussed in this paper.     

TMD before and after correction of dentofacial deformities by orthodontic and orthognathic treatment

The aims of the study were to investigate the alteration of temporomandibular disorders (TMD) after correction of dentofacial deformities by orthodontic treatment in conjunction with orthognathic surgery; and to compare the frequency of TMD in patients with dentofacial deformities with an age and gender matched control group. TMD were evaluated in 121 consecutive patients (treatment group), referred for orthognathic surgery, by a questionnaire and a clinical examination. 18 months after treatment, 81% of the patients completed a follow-up examination. The control group comprised 56 age and gender matched subjects, of whom 68% presented for follow-up examination. TMD were diagnosed according to research diagnostic criteria for TMD. At baseline examination, the treatment group had a higher frequency of myofascial pain (P = .035) and arthralgia (P = .040) than the control group. At follow-up, the frequencies of myofascial pain, arthralgia and disc displacement had decreased in the treatment group (P = .050, P = .004, P = .041, respectively). The frequency of TMD was comparable in the two groups at follow-up. Patients with dentofacial deformities, corrected by orthodontic treatment in conjunction with orthognathic surgery, seem to have a positive treatment outcome in respect of TMD pain.     

A Weight-Loss Intervention Program Designed for Mexican–American Women: Cultural Adaptations and Results

This study assessed the feasibility of a culturally-appropriate weight-loss intervention targeting obese Spanish-speaking Mexican women. This 12-month weight-loss program was based on behavioral interventions previously used successfully with English-speaking participants. Cultural adaptations included: female interventionists, minimal written materials, emphasis on group activities, focus on Mexican traditions and beliefs, and skill-building approach to food measurement. All sessions were conducted in Spanish. The study had few exclusionary criteria, which allowed participation of women with a wide range of literacy levels. Recruitment exceeded expectations, with 47 participants enrolling in the program. Not counting participants who became pregnant during the study, attendance at 6 and 12?months was 62 and 50?% respectively. Mean weight loss at 6 and 12?months was 5.3 and 7.2?kg, respectively, with a mean reduction in BMI of 4.0 and 5.5?kg/m² from baseline to 6 and 12?months, respectively. This pilot study shows that it is feasible to develop and implement culturally-appropriate behavioral lifestyle interventions for obesity treatment in Mexican–American women.