A randomized, placebo-controlled trial of melatonin on breast cancer survivors: impact on sleep, mood, and hot flashes.

The purpose is to examine the effects of melatonin supplementation on sleep, mood, and hot flashes in postmenopausal breast cancer survivors. In a randomized, double-blind, placebo-controlled study, 95 postmenopausal women with a prior history of stage 0-III breast cancer, who had completed active cancer treatment (including hormonal therapy) were randomly assigned 1:1 to either 3 mg oral melatonin (n = 48) or placebo daily (n = 47) for 4 months. Sleep, mood, and hot flashes were assessed at baseline and 4 months via self-administered questionnaire using the Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiologic Studies-Depression (CES-D), and the North Central Cancer Treatment Group (NCCTG) hot flash diary, respectively. Eighty-six women (91 %) completed the study and provided pre- and post-questionnaires. At baseline, 52 % of participants reported poor sleep in the month prior to enrollment. Compared to subjects on placebo, subjects randomized to melatonin experienced significantly greater improvements in subjective sleep quality as measured by the PSQI, including domains on sleep quality, daytime dysfunction and total score. For example, the mean change in PSQI score was -0.1 in the placebo group compared to -1.9 in the melatonin group (p < 0.001). There were no significant differences in measures of depression or hot flashes. Sleep disturbances are common among breast cancer survivors, even after completion of active cancer treatment. This is the first randomized placebo-controlled study among breast cancer survivors to demonstrate that melatonin was associated with an improvement in subjective sleep quality, without any significant adverse effects.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

[Central-medullary nailing of proximal humerus fractures using T2 nails. A retrospective study of 38 cases]. / Enclouage centromédullaire des fractures de l'extrémité proximale de l'humérus par clou T2. Etude rétrospective de 38 cas.

The intramedullary nailing of humerus has emerged as one of the treatments of reference for proximal fractures. We have reviewed 38 patients aged 64.2 on average with a mean follow of 18 months. The functional scores used were the Constant and Murley's score as well as the DASH self-administered quality of life questionnaire. Radiological criteria have been analyzed, namely the cephalic angle noted alphaF and the presence of any osteolysis of the major tuberosity. Patients were grouped by type of fracture, according to Neer's classification, with nine cases in Neer 2 group, 19 in Neer 3 group, and ten in Neer 4 group. The unrefined Constant score was 53.4 points on average, balanced to 71.6%. The joint mobilities were an average forward elevation of 108 degrees, an average abduction of 100 degrees and an external rotation of 27 degrees. These scores were even worse than the fracture was comminuted. It was not found a radioclinical correlation between value of the angle alphaF and clinical outcome, but the presence of osteolysis of the major tuberosity was significantly associated with poor late functional results. Five cases of osteonecrosis have been counted, divided with 10.5% in the Neer stage 3, and 30% in the Neer stage 4. The average unrefined Constant score from these patients was 38.5 points on average, balanced to 57.7%. Intramedullary nailing allows fixation of comminuted fractures with three or four fragments, but control of fixing and strength of assembly were not always practiced. In young patients, where tuberosities consolidation is essential, screwed plates seem to be a favorable alternative. Moreover, total reverse prosthesis seems to have more and more arguments to impose itself like the preferred treatment towards fractures in four fragments in people aged over 75 years.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and therapies are empirical and mostly untested. Antimicrobial agents and alpha-adrenergic receptor blockers are frequently used. OBJECTIVE: To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS. DESIGN: Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo. SETTING: Urology outpatient clinics at 10 tertiary care medical centers in North America. PATIENTS: Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment. MEASUREMENTS: The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events. INTERVENTIONS: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo. RESULTS: The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes. LIMITATIONS: Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently. CONCLUSION: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.

Transdermal permeation of neutral molecules by skin electroporation.

Electroporation of skin has recently been shown to enhance transport of charged molecules across skin by up to four orders of magnitude. This study demonstrates that high-voltage pulses can also increase transdermal permeation of two neutral model solutes, i.e. mannitol and water, up to 100-fold. The elevated flux results from the persistent increase in skin permeability following electroporation, rather than from electro-osmosis during pulsing. Control on transport was achieved by controlling the electrical parameters of the pulse, i.e. the pulse voltage, time constant and number.

Optokinetic and vestibulo-ocular reflex adjustment by GABA antagonists.

We determined if high and low doses of anti-GABAergic drugs have opposite effects on the visuo-vestibular activity in pigmented rats and examined a possible correlation with the level of GABA in the related structures. First, the horizontal optokinetic and vestibulo-ocular reflexes of most animals were depressed by high doses of anti-GABAergic drugs (10(-3) M purified picrotoxin or 10(-6) M picrotoxin in unpurified vegetal extract). Simultaneously, a drop in GABA level in the cerebellum and posterior brainstem was detected. Second, after a subsequent injection (1 ml) of the diluted extract (10(-13) M picrotoxin), the reflexes returned to normal despite the fact that no correlation with the GABA level was found. These results demonstrate that small doses of anti-GABAergic drugs reverse the depressive effect created by large doses of these drugs on the oculomotor system, and even adjust the reflexes to the stimulation. This adjustment, without correlation with the GABA level, suggest a powerful effect of very low dose of the drug to modulate either the activity of the cerebellar inhibiting input or of the vestibular nuclei neurons or to trigger the adaptation by other neurotransmitter systems involved in the performances of the reflexes.

Effect of manganese on the development of glial cells cultured from prenatally alcohol exposed rats.

Maternal alcohol abuse is known to produce retardation in brain maturation and brain functions. Using cultured glial cells as a model system to study these effects of alcohol we found an alcohol antagonizing property for manganese (Mn). Mn was added to the alcohol diet (MnCl2 25 mg/l of 20% v/v ethanol) of pregnant rats. Glial cells were cultured during 4 weeks from cortical brain cells of pups born to these mothers. Several biochemical parameters were examined: protein levels, enzymatic markers of glial cell maturation (enolase and glutamine synthetase), superoxide dismutase a scavenger of free radicals produced during alcohol degradation. The results were compared to appropriate controls. A beneficent effect of Mn was observed for the pups weight which was no more significantly different from the control values. Protein levels, enolase and glutamine synthetase activities were increased mainly during the proliferative period when Mn was added to the alcohol diet compared to the only alcohol treated animals. This Mn effect was not found for superoxide dismutase in cultured glial cells but exists in the total brain of the 2 week-old offspring. In the total 2 and 4 week-old brain the alcohol induced decrease of enolase and glutamine synthetase was also antagonized by the Mn supplementation. Our data suggest that Mn may act as a factor overcoming at least partially some aspects of alcohol induced retardation of nerve cell development.

[Critical analysis of 1000 systematic assays of serum levels of vitamin B12 and folates]. / Analyse critique de 1,000 dosages systématiques du taux sérique de vitamine B12 et des folates.

Between January 15 and April 30, 1988, one thousand assays of serum vitamin B12 and folates were performed, and the reasons why they were requested as well as their clinical usefulness are discussed. In 50 cases these assays were requested for a suspected myeloproliferative syndrome; in some of the patients with polycythaemia vera an excess of B12 was observed without hyperleukocytosis, an argument for keeping the B12 assay as an element of initial evaluation. In numerous cases the assays were performed for aetiological evaluation of a macrocytosis of suspected alcoholic origin in most patients; more than 50 per cent of the patient had folate deficiency and only a few had low B12 values. Folate levels were frequently low and B12 levels generally normal in patients with gastrointestinal disease, but many of them had been supplemented with folate and/or B12 prior to the assay. More than 20 per cent of the 1,000 assays were performed in patients aged 80 years or more, and more than 50 per cent of them had a low folate level; this has no consequences for individual subjects, but it may be of epidemiological or sociological interest. It must be mentioned that too many blood samples (more than 40 per cent) were sent to the laboratory without adequate information and after supplementation in 20 per cent of the cases. Very few patients with very low B12 levels were subjected to Schilling's test, so that the clinical usefulness of this assay, as currently utilized, is questionable in a large number of cases.

[Disorders of plasma trace elements in diabetes. Relation to blood glucose equilibrium]. / Perturbation des oligoéléments plasmatiques dans le diabète. Relation avec l'équilibre glycémique.

The influence of glycaemic control and diabetes characteristics on plasma concentrations of magnesium, zinc, copper, selenium, rubidium and bromine has been evaluated in 44 diabetics (30 insulin-dependent, 14 non insulin-dependent), and the results obtained were compared to those of 309 control subjects of the same mean age. Diabetics had reduced plasma magnesium concentrations (P less than 0.01) but normal erythrocyte magnesium levels. Plasma zinc and selenium concentrations were reduced, whereas those of copper were increased and those of bromine and rubidium were normal. Correlation between glycaemic control, evaluated by measurement of glycosylated haemoglobin levels, and each of the parameters studied was only demonstrated with magnesium in insulin-dependent diabetics (r = -0.561; P less than 0.02). No correlation was found with the other clinical or anthropometric characteristics of the diabetic patients studied. Diabetes seems to be associated with numerous abnormalities of plasma trace elements and magnesium, but the mechanism of these abnormalities has not yet been elucidated. A decrease in zinc and selenium concentrations and an increase in copper concentrations might be additional factors of atherogenicity.

Acute mercury chloride intoxication. Effects of hemodialysis and plasma exchange on mercury kinetic.

A 27 year-old man developed after ingestion of mercury chloride, 6 g, a hypovolemic shock, an acute renal failure and a necrosis of the stomach which required a total gastrectomy. The anuria did not improve and required 42 hemodialyses. Subsequent evolution showed numerous complications and the patient died on the 91st day. On admission mercury plasma concentration was 5 mg/L and decreased slowly with an apparent half-life of 226 hours. Hemodialyses were ineffective for mercury elimination: mercury clearances varied between -10 and + 1.5 ml/min. Seventeen mg of mercury were removed by six plasma exchanges: the mercury clearance was mean 17.3 ml/min. Among the extracorporeal elimination methods, plasma exchange appears to be the most efficient for inorganic mercury and it could be usefull in association with chelation therapy at the early phase of the intoxication.

Effects of a low dose of pancuronium on oxygen consumption during sustained muscular exercise.

The effects of a low dose of pancuronium on muscular performance were studied in six healthy volunteers. Three dynamic exercise tests at increasing levels of power were performed by each subject on two consecutive days using an ergometric bicycle. To assess muscular function, oxygen consumption was measured in a steady state at each level of power output. Pancuronium 6-8 micrograms kg-1 or placebo was administered i.v. in a double-blind fashion before the second test each day. Plasma pancuronium levels were measured 8 min after administration but even with pancuronium clearly detectable in the plasma no significant differences were found either in oxygen consumption or in the haemodynamic measurements made. The authors conclude that such doses of non-depolarizing neuromuscular blocking agents do not disturb oxygen consumption during dynamic muscular exercise and are therefore unlikely to have a significant effect on muscular function.

Procedures for handling antineoplastic injections in comprehensive cancer centers.

The procedures for handling injectable antineoplastic drugs in comprehensive cancer centers in the U.S. are summarized. In May 1982, a survey was sent to directors of pharmacy at 27 institutions designated as comprehensive cancer centers. Some questions duplicated a 1979 survey, while others addressed points in recently published guidelines on handling antineoplastic medications. Representatives of 21 institutions responded. These institutions represented 13,638 beds, 1,848 of which were oncology beds. Seventeen institutions had written policies for the preparation of antineoplastics, but only nine had a training program. The pharmacist or pharmacy technician prepared these medications in 12 institutions. Ten institutions prepared antineoplastics in a vertical laminar-flow hood. Gloves and masks were worn by employees in 20 and 13 of the institutions, respectively. Six institutions in some way assessed the health of employees handling antineoplastics. Eleven institutions had written policies on disposal of antineoplastics; 13 institutions disposed of this waste separately. Ten institutions had a training program for administration of antineoplastics. Compared with 1979, the trend is toward increased protection of persons handling injectable antineoplastic agents, but the procedures used at comprehensive cancer centers are not uniform.