Ocular autonomic function in progressive autonomic failure

Ocular autonomic function was assessed in 4 patients with progressive autonomic failure (PAF) and age-matched control subjects, by measurement of the pupil cycle time, and determination of autonomic denervation hypersensitivity of the iris. Pupil cycle time was abnormal in all patients with PAF; sustained pupil cycling was absent in 5 of the 8 eyes tested of the PAF patients, compared with only 16 eyes from 70 control subjects. Pupil constriction in response to 2.5% methacholine, indicative of parasympathetic denervation hypersensitivity, was significantly increased in patients with PAF (p < 0.001), whilst pupil dilation in response to 0.5% phenylephrine, indicative of sympathetic denervation hypersensitivity, was also significantly higher in the PAF patients (p < 0.001). The results suggest that ocular autonomic function may provide a sensitive early indicator of generalised autonomic dysfunction.     

Laparoscopic Medial-to-lateral Colon Dissection: How and Why

Laparoscopic colectomy is a difficult procedure with a long learning curve. We describe in this study our technique for right- and left-sided laparoscopic medial-to-lateral colectomy. The medial approach involves division of the vascular pedicle first, followed by mobilization of the mesentery toward the abdominal wall, and finally freeing of the colon along the white line of Toldt. This approach allows immediate identification of the plane between the mesocolon and the retroperitoneum and renders the dissection fast and safe. Our series of 50 consecutive laparoscopic colectomies supports this concept. We believe that surgeons familiar with this technique will have an important tool in their armamentarium to circumvent some of the challenges of laparoscopic colectomy.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Does ethane 1,2-dimethanesulphonate (EDS) have a direct cytotoxic effect on the seminiferous epithelium of the rat testis?

The authors examined the possibility that ethane 1,2-dimethanesulphonate (EDS) has a cytotoxic effect on spermatogenesis that is not secondary to androgen withdrawal resulting from the well known cytotoxic effect of EDS on Leydig cells. Adult male rats were implanted with polydimethylsiloxane (PDS) capsules containing testosterone (T) and estradiol (E), and were simultaneously injected with EDS. The PDS-TE implants, by inhibiting luteinizing hormone (LH) production, prevented Leydig cells from repopulating the testis and clamped testosterone within the seminiferous tubules at increasing concentrations relative to implant size. In rats that received EDS alone, the number of advanced spermatids per testis was significantly reduced by 2 weeks, but within 8 weeks returned to the numbers maintained in vehicle-injected control rats or in vehicle-injected rats that received testosterone- and estradiol-filled capsules of 24 cm and 0.1 cm, respectively (PDS-24TE). Surprisingly, in rats that received an EDS injection plus PDS-24TE implants, the number of advanced spermatids per testis was significantly reduced at 8 weeks and severe seminiferous tubule atrophy occurred despite the fact that the testosterone concentration was sufficient to quantitatively maintain spermatogenesis in vehicle-injected rats. In rats injected with EDS and implanted with 24 cm testosterone but not estradiol-filled capsules (PDS-24T), the advanced spermatid number per testis was significantly higher than that in the EDS plus PDS-24TE rats, but significantly lower than that in control rats. These results suggest that EDS may have a cytotoxic effect on the seminiferous epithelium that is independent of the elimination of Leydig cells, and the EDS and estradiol act synergistically to exert a profound toxic effect on spermatogenesis.     

Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.     

The effect of maternal fluid intake on breast milk supply: a pilot study.

To examine the effect of increased and decreased fluids on breast milk supply, a pilot study using a cross-over design with 10 mother-infant pairs was completed. Baseline measures of milk supply were determined over a 3-day period of normal fluid intake based on body weight. Subjects were studied over 3-day periods when fluid intake was alternately 50% more and 50% less than normal level. Milk supply was calculated by averaging breast milk intake, determined by test weighing the infants with electronic scales, and milk yield, measured either by total breast expression with an electric breast pump or a combination of expression and test weighing. Although milk supply decreased with decreased fluids and increased with increased fluids, this change was not statistically significant. Recommendations for further research include replication using subjects' usual fluid intake as a baseline and replication using mothers suspected of insufficient milk syndrome.     

Suramin inhibits bone resorption and reduces osteoblast number in a neonatal mouse calvarial bone resorption assay.

The antineoplastic properties of suramin, a polyanionic agent with demonstrated antigrowth factor activity, are under evaluation in vitro, in vivo, and in clinical trials. Suramin has been shown to have antitumor activity in patients with advanced, hormone refractory prostate cancer. During these trials, significant resolution of osseous pain was observed in nearly three quarters of the patients treated with suramin. To evaluate the effect of suramin on bone cells, we studied the effect of suramin on bone resorption in a neonatal mouse calvarial assay. Suramin inhibited bone-resorbing activity in a dose-related fashion and had an additive effect with calcitonin. Calvaria pretreated with suramin had less bone-resorbing activity, fewer attached osteoblasts, and less medium alkaline phosphatase activity than control calvaria. Suramin also inhibited osteoclastic release of tritiated proline from labeled bone in a dose-dependent fashion. The effect of metastatic prostate carcinoma on bone is incompletely understood, but may be moderated by tumor-produced factors and/or cytokines. The effects of several such agents, therefore, were examined in combination with suramin. Bone resorption induced by PTH, epidermal growth factor, tumor necrosis factor, and a tumor-produced factor, PTH related-protein, was blocked by suramin. The ability of suramin to inhibit the bone-resorbing effects of several cytokines suggests that its mechanism may involve direct action on bone metabolism. Autoradiography performed on calvaria treated with labeled suramin demonstrated heavy deposition of suramin on the outer surface of the matrix, adjacent to osteoblasts and osteoclasts lining the outer table, suggesting that bone cells may be subject to high local concentrations of the drug, in keeping with this hypothesis.     

Visual assessment of urethrovesical junction mobility

The aim of the study was to compare visual assessment of anterior vaginal wall descent with the Q-tip test in evaluating urethrovesical junction mobility. One hundred and eleven patients with prolapse and/or urinary incontinence were examined in the supine lithotomy position with an empty bladder. Maximum straining Q-tip tests and maximum descent of the anterior vaginal wall were measured. Using each centimeter of descent as a cutoff value, the sensitivities, specificities and positive and negative predictive values were compared to those of the Q-tip test. As the cutt-off points were moved distally, specificity increased at the expense of sensitivity. There was no single cut-off point that provided adequate sensitivity and specificity to be clinically useful to replace the Q-tip test. It was concluded that visual assessment of anterior vaginal wall descent does not provide diagnostic accuracy and acceptable sensitivity and specificity to determine urethrovesical junction mobility. Other methods should be employed to assess support.Editorial Comment: Many clinicians claim that they can assess urethrovesical junction mobility visually and thus avoid employing other means, such as the Q-tip test, ultrasonography, bead-chain cystography or fluoroscopy. Montella et al. evaluate a technique of visual assessment of urethrovesical junction mobility based on the International Continence Society's Standardization of Terminology of Female Organ Prolapse and Pelvic Floor Dysfunction as compared to evaluation with the Q-tip test. Their results clearly indicate that this technique (measurement of the descent of point Aa) does not provide adequate sensitivity or specificity in determining urethrovesical junction descent compared to the Q-tip test. Although this technique was only compared to the Q-tip test and not all other modalities available, it is doubtful that visual assessment of anterior wall descent at any level would correspond to urethrovesical junction mobility, as is discussed very succinctly by the authors.