Transcutaneous mechanical nerve stimulation using perineal vibration: a novel method for the treatment of female stress urinary incontinence

PURPOSE: We defined basic guidelines for transcutaneous mechanical nerve stimulation in modifying pelvic floor responses in women and determined the efficacy of transcutaneous mechanical nerve stimulation in treating stress urinary incontinence. MATERIALS AND METHODS: Perineal and clitoral transcutaneous mechanical nerve stimulation was performed in healthy volunteers while measuring changes in peak urethral pressure to determine optimal vibration amplitude and site of stimulation. Perineal transcutaneous mechanical nerve stimulation was then performed weekly for 6 weeks in a cohort of women with stress urinary incontinence (33). Reduction in incontinence episodes and pad use on voiding diary were compared from baseline to 6 weeks. Global efficacy was determined at 6 weeks and 3 months after the completion of the program. RESULTS: In healthy subjects a vibration amplitude of 2.0 mm resulted in the highest urethral pressure increase. Although the increase with perineal transcutaneous mechanical nerve stimulation was lower than that seen with clitoral stimulation (80 vs 115 cm H(2)O), perineal transcutaneous mechanical nerve stimulation was more acceptable to the patient and resulted in a better subjective response. Urethral pressure increases with transcutaneous mechanical nerve stimulation at either site were greater than with voluntary contraction (60 cm H(2)O). After 6 weeks of transcutaneous mechanical nerve stimulation in the subjects with stress urinary incontinence, there was a significant reduction in daily incontinence episodes (2.6 +/- 1.1 vs 0.5 +/- 1.1, paired t test p <0.001) and pad use (3.5 +/- 0.9 vs 0.6 +/- 1.3, paired t test p <0.001). At 6 weeks the cure rate (no incontinence episodes) was 73%, with durability through 3 months with 67% still reporting persistent resolution. CONCLUSIONS: Perineal transcutaneous mechanical nerve stimulation has promise as a noninvasive and well tolerated method of treating stress urinary incontinence.     

Concentration of valproate during pregnancy, in the newborn and in breast milk

The serum-valproate level of four patients with epilepsy was followed during pregnancy. A decrease in serum level occurred late in pregnancy and was followed by a pronounced increase in the first week after delivery. The maternal serum concentration of valproate was compared to that of the umbilical cord. The level in cord blood was 145-219% higher than that in maternal blood. The concentration of valproate in breast milk was found to be 5-10% of the maternal serum concentration. The serum concentration was measured in one breastfed child. The level was 7.6% of the maternal serum concentration. All children were healthy without any signs of intoxication or malformation. Based on our experience, pregnant patients treated with valproate must be carefully controlled especially during the last month of pregnancy and in the first two weeks after delivery. The amount of valproate excreted into the breast milk was negligible and should not prevent breast feeding.     

Sexuality after total vs. subtotal hysterectomy

BACKGROUND: The effect of hysterectomy on sexuality is not fully elucidated and until recently total and subtotal hysterectomies have only been compared in observational studies. AIMS: To compare total abdominal hysterectomy (TAH) to subtotal abdominal hysterectomy (SAH) regarding effects on sexuality. METHODS: In a Danish multicenter trial 319 women were randomized to TAH (n = 158) or SAH (n = 161); 185 women had self-selected TAH (n = 80) or SAH (n = 105) in a simultaneously conducted observational study. Women were followed for 1 year by strict data collection procedures, including postal questionnaires. Results were analyzed by intention to treat (ITT) analyses. RESULTS: No significant differences were observed between TAH and SAH at 1-year follow-up in both the randomized trial and the observational study regarding women's desire for sex, frequency of intercourse, frequency of orgasm, quality of orgasm, localization of orgasm, satisfaction with sexual life, and dyspareunia. None of these sexual variables changed significantly from entry to the 1-year follow-up, apart from dyspareunia, which was significantly (p = 0.009) reduced in both intervention groups. Significant (p < 0.05) predictors for satisfaction with sexual life after hysterectomy were the preoperative satisfaction with sexual life [odds ratio (OR) 32, 95% confidence interval (CI) 10-125], good relationship with partner (OR 50, 95% CI 9-354), physical well-being (OR 0.30, 95% CI 0.09-0.88) and hormone replacement therapy (OR 0.23, 95% CI 0.06-0.78). CONCLUSIONS: Both TAH and SAH significantly reduce dyspareunia without having a negative effect on sexual function. The shift toward SAH seems unwarranted.     

Evaluation of pentitol metabolism in mammalian tissues provides new insight into disorders of human sugar metabolism

To more completely elucidate the pathways of sugar metabolism in human, we have evaluated the formation and degradation of pentitols in human fibroblasts and erythrocytes. Cultured human fibroblasts were incubated with d-arabinose, d-ribose, d-ribulose, and d-xylulose. Formation of arabitol and ribitol was analyzed by gas chromatography of the incubation medium and cell homogenate. We found that the pentoses d-arabinose and d-ribose could cross cell membranes, which indicate possible pentitol formation from extracellular pentoses. Fibroblasts formed 17+/-4 nmol arabitol/4 days/mg protein from d-arabinose and ribitol production rates of 70+/-15 nmol/4 days/mg protein were found after d-ribose incubation. Following d-ribulose incubation 13 nmol ribitol/4 days/mg protein was found. Human cultured fibroblasts were also incubated with d-arabitol, ribitol, and xylitol. Analyzing the incubation medium and cell homogenate revealed an absence of pentose formation. However, export of the pentitols arabitol and ribitol across the cell membrane was demonstrated, indicating that pentitols can be cleared from the body without metabolic conversion. Finally, human erythrocytes were incubated with d-/l-arabitol, ribitol, sorbitol, and xylitol. Activities of potential pentitol dehydrogenases were evaluated by a fluorometric assay. No evidence for ribitol and arabitol degradation was observed in human erythrocytes, as compared to polyol dehydrogenase activities ranging from 1.3 to 6.1 pmol NADH/min/microl erythrocytes observed using sorbitol and xylitol. Our results indicate that ribitol and arabitol are metabolic end products in humans.     

Fish intake is positively associated with breast cancer incidence rate

Animal studies have, in general, been supportive of a protective effect of fish and fish (n-3) PUFA against breast cancer risk; but the epidemiologic evidence of such a relationship is limited. Case-control and cohort studies have rarely shown significant associations. The association between total fish intake and the effect of fat content and preparation method of the fish, in relation to the incidence rate ratios of breast cancer, were investigated among postmenopausal women. We also investigated the effect of fish intake with respect to estrogen receptor expression of breast cancer tumors. A total of 23,693 postmenopausal women from the prospective study "Diet, Cancer and Health" were included in the study. During follow-up, 424 women were diagnosed with breast cancer. The incidence rate ratio (IRR) and 95% CI per each additional 25 g of mean daily intake of fish were 1.13 (CI, 1.03-1.23). Analysis of fatty fish gave IRR of 1.11 (CI, 0.91-1.34), and the result for lean fish was 1.13 (CI, 0.99-1.29). When fish intake was stratified into three types of preparation methods, the IRR for fried fish was 1.09 (CI, 0.95-1.25), for boiled fish 1.09 (CI, 0.85-1.42), and for processed fish 1.12 (CI, 0.93-1.34). The IRR per additional 25 g of mean daily intake of fish was 1.14 (CI, 1.03-1.26) for estrogen receptor-positive (ER+) and 1.00 (CI, 0.81-1.24) for estrogen receptor-negative (ER-) breast cancer. In conclusion, this study showed that higher intakes of fish were significantly associated with higher incidence rates of breast cancer. The association was present only for development of ER+ breast cancer.     

Assay of Adenylate Cyclase in Rat Brain Homogenates and Lysed Turkey Erythrocytes: Two Different Methods give Different Results with Brain but not with Erythrocytes

Abstract: Experiments showed that the cyclic AMP (cAMP) fraction isolated by alumina or Dowex 50/ alumina chromatography from brain adenylate cyclase reaction mixtures contained “P radioactivity 10–12 times in excess of that which could be accounted for by determination of cAMP using binding assays. No such discrepancy was found when lysed turkey erythrocytes were assayed. This indicated that special precautions must be taken for the purification of ³²PcAMP from brain adenylate cyclase assays due to the formation of ³²P-labelled contaminants.     

Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine

The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or IgA-antibodies on 3 mm blood spots collected from phenylketonuria [PKU cards (Guthrie cards)]. Toxoplasma-infected children received 3 months continuous treatment with 50–100 mg/kg per day sulfadiazine in two separate administrations and 1 mg/kg per day pyrimethamine after a 1-day loading dose of 2 mg/kg, and folinic acid 7.5 mg was administered twice weekly. Blood cell counts and body weight were recorded during follow-up. The plasma concentrations of pyrimethamine and sulfadiazine were analysed in a subgroup of seven children, using high performance liquid chromatography with ultraviolet and mass spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5×10⁹/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was 0.5×10⁹/l or lower in 4/29 (13.8%). None of the children had anaemia or thrombocytopenia. The drugs did not affect weight gain. Mean plasma drug concentrations varied between 1.3 g/ml and 2.2 g/ml for pyrimethamine and between 60 g/ml and 86 g/ml for sulfadiazine. Treatment efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits.     

Changes in neural network homeostasis trigger neuropsychiatric symptoms

The mechanisms that regulate the strength of synaptic transmission and intrinsic neuronal excitability are well characterized; however, the mechanisms that promote disease-causing neural network dysfunction are poorly defined. We generated mice with targeted neuron type–specific expression of a gain-of-function variant of the neurotransmitter receptor for glycine (GlyR) that is found in hippocampectomies from patients with temporal lobe epilepsy. In this mouse model, targeted expression of gain-of-function GlyR in terminals of glutamatergic cells or in parvalbumin-positive interneurons persistently altered neural network excitability. The increased network excitability associated with gain-of-function GlyR expression in glutamatergic neurons resulted in recurrent epileptiform discharge, which provoked cognitive dysfunction and memory deficits without affecting bidirectional synaptic plasticity. In contrast, decreased network excitability due to gain-of-function GlyR expression in parvalbumin-positive interneurons resulted in an anxiety phenotype, but did not affect cognitive performance or discriminative associative memory. Our animal model unveils neuron type–specific effects on cognition, formation of discriminative associative memory, and emotional behavior in vivo. Furthermore, our data identify a presynaptic disease–causing molecular mechanism that impairs homeostatic regulation of neural network excitability and triggers neuropsychiatric symptoms.     

Interobserver agreement in fusion status assessment after instrumental desis of the lower lumbar spine using 64-slice multidetector computed tomography: impact of observer experience

Purpose

Persistent lower back pain after instrumental posterolateral desis may arise from incomplete fusion. We investigate the impact of experience on interobserver agreement in fusion estimation.

Methods

Four independent observers, two residents and two musculoskeletal radiologists, reviewed dedicated lumbar 64-MDCT scans and scored vertebral levels 1–5 after Glassman’s grades, 1: solid bilateral fusion, 2: solid unilateral fusion, 3: partial bilateral fusion, 4: partial unilateral fusion, 5: non-fusion. We investigated two simplifying dichotomizations, solid bilateral fusion (Glassman 1) versus all others and uni- or bilateral fusion (Glassman 1–2) versus partial or non-fusion.

Results

Thirty-six patients with 61 operated lumbar levels were included. Interobserver agreement rates for four observers using Glassman’s system were fair (kappa 0.32), either dichotomization showed moderate agreement (kappa 0.53 and 0.59). Observer pairs had comparable prevalence adjusted interobserver agreement rates (residents: PABAK 0.67 and 0.54; consultants: PABAK 0.57 and 0.71).

Conclusions

Difference in observer experience seems of minor impact.