Neuronal nitric oxide synthase: its role and regulation in macula densa cells

Macula densa (MD) cells detect changes in distal tubular sodium chloride concentration ([NaCl](L)), at least in part, through an apical Na:2Cl:K co-transporter. This co-transporter may be a site for regulation of tubuloglomerular feedback (TGF), and recently angiotensin II (Ang II) was shown to regulate the MD Na:2Cl:K co-transporter. In addition, nitric oxide (NO) produced via neuronal NO synthase (nNOS) in MD cells attenuates MD-TGF signaling. This study investigated [NaCl](L)-dependent MD-NO production, the regulation of co-transporter activity by NO, and the possible interaction of NO with Ang II. MD cell Na(+) concentration ([Na(+)](i)) and NO production were measured using sodium-binding benzofuran isophthalate and 4-amino-5-methylamino-2',7'-difluorescein diacetate, respectively, using fluorescence microscopy. Na:2Cl:K co-transport activity was assessed as the initial rate of increase in [Na(+)](i) when [NaCl](L) was elevated from 25 to 150 mM. 10(-4) M 7-nitroindazole, a specific nNOS blocker, significantly increased by twofold the initial rate of rise in [Na(+)](i) when [NaCl](L) was increased from 25 to 150 mM, indicating co-transporter stimulation. There was no evidence for an interaction between the stimulatory effect of Ang II and the inhibitory effect of NO on co-transport activity, and, furthermore, Ang II failed to alter MD-NO production. NO production was sensitive to [NaCl](L) but increased only when [NaCl](L) was elevated from 60 to 150 mM. These studies indicate that MD-NO directly inhibits Na:2Cl:K co-transport and that NO and Ang II independently alter co-transporter activity. In addition, generation of MD-NO seems to occur only at markedly elevated [NaCl](L), suggesting that NO may serve as a buffer against high rates of MD cell transport and excessive TGF-mediated vasoconstriction.     

The subjective and objective benefits of a remote-controlled intraurethral device for managing the female acontractile bladder

OBJECTIVE: To determine the subjective and objective benefits of the Inflow (SRS Medical Systems, N. Billerica, MA, USA) intraurethral device for managing acontractile bladders in women. PATIENTS AND METHODS: Twenty women with acontractile bladders who had been managed unsuccessfully by the usual methods were recruited. All patients were asked to complete a quality-of-life (QoL) questionnaire and were assessed with urine flowmetry and urine culture; to measure the postvoid residual urine (PVR) in the bladder, ultrasonography was used after activating the device. RESULTS: There was a decrease in the QoL score from a mean of 59.6 before insertion to means of 11.2, 8.8, 6.3 and 5.0 at 1, 3, 6 and 12 months afterward. The mean (range) urinary flow rate was 10.7 (9-16) mL/s and the PVR 3 (0-17) mL. Three patients had temporary asymptomatic bacteriuria and two a single infection after the device was inserted that settled readily with antibiotics. CONCLUSION: This study shows that the Inflow device provides an effective method of bladder drainage, with few side-effects and a significant improvement in QoL.     

The effects of hormone replacement therapy on cortical bone in postmenopausal women. A histomorphometric study

Investigations of the actions of estrogen on the skeleton have mainly focused on cancellous bone and there are no reported histomorphometric studies of the effects of oestrogen on cortical bone in humans. The aim of this study was to investigate the effects of both conventional hormone replacement therapy (HRT) and high-dose oestradiol on cortical bone in postmenopausal women. Transiliac biopsies were obtained from nine postmenopausal women aged 54-71 yr before and after 2 yr (mean, 23.5 months) of conventional HRT and in seven postmenopausal women aged 52-67 yr after long-term, high-dose oestradiol implant therapy (at least 14 yr). Indices of bone turnover, remodeling, and cortical structure were assessed by image analysis. Cortical width was highest in the women treated with high-dose oestrogen therapy (2.29 +/- 0.78 mm; mean +/- SD) and lowest in untreated women (1.36 +/- 0.60 mm; P=0.014). The proportion of canals with an eroded surface was significantly lower in the high-dose oestrogen group than in women before or after conventional HRT (3.03 +/- 3.7% vs. 11.1 +/- 7.1% and 10.5 +/- 8.6%; P=0.017 and 0.05, respectively). Bone formation rate (microm2/microm/day) in untreated women was significantly higher than in the high-dose oestrogen group (0.121 +/- 0.072 vs. 0.066 +/- 0.045, respectively; P=0.05), values in women treated with conventional HRT being intermediate. Our results provide the first histomorphometric evidence in postmenopausal women of dose-dependent oestrogen-induced suppression of bone turnover in iliac crest cortical bone. There was also a trend toward higher wall width with increasing dose of oestrogen, consistent with the previously reported anabolic effect in cancellous bone.     

Progressive neocortical damage in epilepsy

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow-up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions.     

Gender differences in religiosity and functional health in the elderly

This secondary analysis of a random, community survey of 271 people over 65 years old examined gender differences in religious coping, importance of faith, and frequency of prayer for their relationship on eight categories of functional physical and mental health, as measured by the Medical Outcomes Study Health Survey Short-Form 36. Mental health was the only outcome related to the spiritual indices for both genders but used differently. Frequency of prayer, a behavioral indicator, was positively related to mental health for men. Reliance on religious coping and a high importance of one's faith were positively related to mental health for women. The results indicated that cognitive coping responses were associated with lower anxiety and depression for women, whereas behavioral spiritual responses were the relevant variables for male mental health in this sample of elders.     

Delivery of an adenoviral vector to the crushed recurrent laryngeal nerve

OBJECTIVES: Objectives were to create a model of recurrent laryngeal nerve injury for testing the efficacy of potential therapeutic viral gene therapy vectors and to demonstrate that remote injection of a viral vector does not cause significant additional neuronal injury. STUDY DESIGN: Animal model. METHODS: Rats were randomly assigned to three groups of 10 animals each. In group I, the recurrent laryngeal nerve was crushed. In group II, the nerve was crushed and then injected with an adenoviral vector containing no transgene. In group III, the nerve was identified but was not crushed. Rats were killed at 1 week, and their larynges and brainstems were cryosectioned in 15-microm sections. Laryngeal cryosections were processed for acetylcholine histochemical analysis (motor endplates) followed by neurofilament immunoperoxidase (nerve fibers). Percentage of nerve-endplate contact was determined and compared between groups. Fluorescent in situ hybridization was performed on brainstem sections from rats in group II to confirm the presence of virus. RESULTS: No significant difference in percentage of nerve-endplate contact exists between the two crushed-nerve groups (groups I and II) (P =.88). The difference between both crushed-nerve groups and the group with noncrushed nerves (group III) was highly significant (P <.0001). The presence of virus was confirmed in group II rats. CONCLUSIONS: Crush provides a significant measurable injury to the recurrent laryngeal nerve and may be used as a model to explore therapeutic interventions for nerve injury. The remote injection of viral vector did not cause significant additional neuronal injury. Remote delivery of viral vectors to the central nervous system holds promise in the treatment of recurrent laryngeal nerve injury and central nervous system diseases.     

Should infants be screened for anaemia? A prospective study investigating the relation between haemoglobin at 8, 12, and 18 months and development at 18 months

AIMS—To investigate the relation between haemoglobin in children followed longitudinally from 8 to 18 months, and developmental outcome at 18months.
METHODS—The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) is a longitudinal survey of a geographically defined population of children born in 1991-92. In a randomly selected subsample, blood samples were assayed for Hb at 8, 12, and 18 months; a developmental assessment was carried out at 18 months on 1141 children using the Griffiths Scales of Mental Development.
RESULTS—There was a strong quadratic association between Hb at 8 months and performance on the locomotor subscale at 18 months. Average scores increased with increasing Hb up to 95 g/l; there was little additional developmental benefit in Hb levels beyond 95 g/l. Infants with Hb <95 g/l at 8 months of age scored on average 6 points lower on the locomotor subscale than infants with Hb ⩾ 95 g/l; infants with Hb <90 g/l at 8 months scored 12 points lower on the locomotor subscale than children with Hb ⩾ 90 g/l.
CONCLUSIONS—Low Hb concentrations (⩽ 95 g/l) in 8 month old children are associated with impaired motor development at 18 months. This cut off point corresponds to the 5th centile of Hb at 8 months. The results indicate that if there is an adverse effect of low Hb on developmental outcome, screening may be more effective at 8 months or earlier, rather than after this age. We propose to examine the importance of infant anaemia in relation to more accurate and detailed long term outcomes as the children get older.

     

The value of a screen and treat policy for Chlamydia trachomatis in women attending for termination of pregnancy

We aimed to assess the efficacy of a screen and treat policy for sexually transmitted infections in women requesting termination of pregnancy, with particular reference to Chlamydia trachomatis. A retrospective review of 100 consecutive cases of Chlamydia-positive women between December 1995 and February 1998, was performed. The referral rate to genitourinary medicine (GUM), the subsequent management, contact tracing and treatment of partners were assessed. Ninety-nine women were referred to the GUM department, of whom 72 (71.4%) attended. Eighteen (25%) required further treatment. Seventy-five women identified 89 potentially infected men, of whom 62 (69%) attended for treatment. Identification of positive cases with referral to GUM enabled tests of cure to be carried out, treatment of those reinfected and re-enforcement of behaviour modification, in addition to successful contact tracing. This policy may confer greater benefit for the patient herself and make a significant impact on the reservoir of infection in the community when compared to a policy of blanket prophylactic antibiotic treatment at the time of termination. The implications for future service provision are discussed.