A comparative study of transcutaneous electrical nerve stimulation (TENS), entonox, pethidine + promazine and lumbar epidural for pain relief in labor

Analgesic effect, labor outcome, safety and consumer satisfaction were compared in 170 primigravid women; 50 using TENS initially for pain relief, 20 using entonox, 50 pethidine + promazine and 50 lumbar epidural. 88% choosing epidural related it fully effective. 90% using entonox, 96% using TENS and 54% given pethidine + promazine found partial relief. 82% of patients given TENS and 80% given pethidine + promazine required additional analgesia. This was also needed by one of the 20 patients choosing entonox. Women using entonox alone had the shortest labors and women using lumbar epidural, the longest. Operative delivery was significantly more common in women receiving lumbar epidural. No significant inter-group differences were noted in cord pH or Apgar scores. Parturients and midwives both gave high consumer satisfaction ratings to all methods--except for pethidine + promazine, whose use must therefore be questioned. The analgesic efficacy of lumbar epidural outweighs any possible side effects. Entonox appears suited to those able to cope with the earlier part of labor, drug-free. Realization of the potential of TENS requires the design of machines specifically to cope with the quality of the pain of labor.     

Examination of different pointwise linear regression methods for determining visual field progression

PURPOSE: To compare the specificity and sensitivity of several different methods for using pointwise linear regression (PLR) to detect progression (deterioration) in visual fields. METHODS: First, theoretical results were derived to predict which of the considered PLR methods would be the most specific and hence the least sensitive. Then, a "Virtual Eye" simulation model was developed that simulates series of sensitivity readings for a point over time. The model adds normally distributed noise (estimated from published results) to the sensitivity at each point to produce a series of fields to be analyzed using each method. Stable and deteriorating eyes were simulated, with the latter defined to have a noise-free loss of 2 dB/y at a significant cluster of points over the series. RESULTS: The most sensitive method tested was to flag a visual field as progressing if it had a point that exhibited a statistically significant slope (at the 1% level) of at least -1 dB/y in the sensitivity. The most specific was a new "Three-Omitting" method that is being proposed, using two confirmation fields in a novel way. Current methods of using confirmation fields to verify a significant slope incorrectly flagged up to twice as many stable eyes as having progressing fields as did our new method. CONCLUSIONS: Using the new proposed PLR method is recommended in preference to current PLR methods in any applications when a high degree of specificity is the main priority.     

Assessment of bioaccumulation,neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P < 0.05) while for the caudate/putamen, Mn concentrations were 1.06 vs 0.73 vs 0.62 vs 0.47 ppm (P < 0.05). The Mn concentrations in lung were also dose-dependent (10.30 vs 1.40 vs 0.42 vs 0.17 ppm; P < 0.05). No statistical difference was observed for loss of neurons in caudate/putamen and globus pallidus. Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.     

Influence of the CB(1) receptor antagonist,AM 251, on the regional haemodynamic effects of WIN-55212-2 or HU 210 in conscious rats

In conscious, freely-moving, male, Sprague-Dawley rats, the regional haemodynamic responses to the synthetic cannabinoids, WIN-55212-2 and HU 210, were compared. The possible involvement of cannabinoid, CB(1)-receptors, or beta(2)-adrenoceptors in the responses to WIN-55212-2 and HU 210 were investigated using the CB(1)-receptor antagonist, AM 251, or the beta(2)-adrenoceptor antagonist, ICI 118551, respectively. Both WIN-55212-2 (150 microg kg(-1)) and HU 210 (100 microg kg(-1)) had pressor, renal, and mesenteric vasoconstrictor and hindquarters vasodilator actions, although the effects of HU 210 were much more sustained than those of WIN-55212-2. Lower doses of the cannabinoids (WIN-55212-2, 50 microg kg(-1), HU 210, 10 microg kg(-1)) had less consistent actions. All the significant cardiovascular effects of WIN-55212-2 and HU 210 were antagonized by pretreatment with AM 251 (3 mg kg(-1)). Furthermore, pretreatment with the beta(2)-adrenoceptor antagonist, ICI 118551, inhibited the hindquarters vasodilator effects of WIN-55212-2 and of HU 210. On the basis of the present findings, and our earlier work, it is suggested that, in conscious rats, the pressor and vasoconstrictor effects of HU 210 and WIN-55212-2 involve cannabinoid-receptor-mediated increases in sympathetic activity. The accompanying hindquarters vasodilator actions of these agonists are cannabinoid receptor-mediated and appear to involve beta(2)-adrenoceptors.     

Patients' and carers' preferences in two models of care for acute exacerbations of COPD: results of a randomised controlled trial

BACKGROUND: Patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) were randomised to either hospital at home (HaH) or inpatient management, and patient and carer preferred site of management and satisfaction with care received in the two arms was determined. METHODS: Emergency admissions with an acute exacerbation of COPD were randomised to inpatient care or HaH care. After discharge an independent observer administered a questionnaire to both patients and carers on the preferred site of care and scored satisfaction with the care received. RESULTS: Of 60 patients recruited, 30 were randomised to receive HaH care. Retrospective patient preference for HaH care was 96.3% in the domiciliary arm and 59.3% in the conventional arm; carer preference figures were 85.7% and 42.9%, respectively. There was a higher preference for domiciliary care by both patients and carers in the HaH arm than in the inpatient arm (p=0.001 and p=0.01, respectively). Patients recorded equal satisfaction with care in the two arms (88.1% in the conventional arm, 91.7% in the domiciliary arm); carer scores were 91.3% and 91.9%, respectively. CONCLUSIONS: The results of this study show that both patients and carers were significantly more likely to prefer domiciliary care if they were in the HaH arm. Since patients had to be willing to be looked after at home, both patients' and carers' perceptions of the benefits of HaH care were reinforced by their experience. HaH care of acute exacerbations of COPD is the preferred option in suitable patients.     

Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients

PURPOSE: The primary objective of this study was to investigate the influence of renal impairment on the pharmacokinetics of capecitabine and its metabolites in cancer patients. Capecitabine (Xeloda) is an orally administered precursor of 5'-deoxy-5-fluorouridine (5'-DFUR), which is preferentially activated to 5-fluorouracil (5-FU) in tumors. METHODS: A total of 27 patients were enrolled, of whom 24 were evaluable for pharmacokinetics (6 with normal renal function, 8 with mild, 6 with moderate, and 4 with severe renal impairment at baseline). Patients received capecitabine orally at the standard dosing regimen (1250 mg/m(2) capecitabine twice daily for 2 weeks followed by a 1-week rest period). On study days 1 and 14, blood samples were collected to evaluate the pharmacokinetics of capecitabine and its metabolites. The relationship between the area under the plasma concentration-time curve (AUC) and creatinine clearance (CL(CR)) was assessed by log-linear regression analysis. RESULTS: The primary pharmacokinetic parameter with respect to the effect of renal dysfunction was systemic exposure to 5'-DFUR, 5-FU and FBAL determined on study day 14. Renal impairment led to an increase in the systemic exposure to 5'-DFUR and FBAL (23% and 109% increase in AUC, respectively) for a 50% reduction in CL(CR). By contrast, renal impairment may lead to decreased exposure to 5'-DFCR. There was no evidence for an effect of renal impairment on systemic exposure to 5-FU or capecitabine. Renal impairment did not have a major effect on peak concentration (C(max)) or elimination half-life (t(1/2)) of capecitabine, 5'-DFCR, 5'-DFUR, and 5-FU. However, in the case of FBAL, moderate or severe renal impairment caused up to a twofold increase in C(max) and prolongation of t(1/2). All patients with severe renal impairment (four patients) had drug-related grade 3 or 4 adverse-events (AEs) and serious AEs. Patients with moderate renal impairment experienced a similar number of grade 3 or 4 AEs (six of nine patients) but had a higher incidence of serious AEs (three of nine patients) when compared with those with normal renal function (four of six patients and one of six patients, respectively). A similar effect was seen in patients with mild renal dysfunction (grade 3 or 4 AEs in four of eight patients; serious AEs in three of eight patients). The relationship between systemic exposure to capecitabine or its metabolites and safety was investigated using logistic regression. This exploratory analysis showed a strong positive relationship between AUC of 5'-DFUR and treatment-related grade 3 or 4 AEs, whereas there was no relationship with exposure to capecitabine, 5'-DFCR, 5-FU or FBAL. CONCLUSIONS: Renal impairment has no effect on the pharmacokinetics of capecitabine or 5-FU, but leads to an increase in the systemic exposure to 5'-DFUR and FBAL. However, only the AUC of 5'-DFUR is correlated with safety. Based on the safety results in patients with severe renal impairment, a dose modification cannot be recommended for these patients and they should not be treated with capecitabine. Additional data from the clinical safety database and pharmacokinetic results from the present study support the recommendation that patients with moderate renal impairment should be treated with 75% of the recommended standard starting dose to achieve systemic exposure comparable to that in patients with normal renal function.