Oral paracetamol and/or ibuprofen for treating pain after soft tissue injuries: Single centre double-blind, randomised controlled clinical trial.

BACKGROUND: Soft tissue injuries commonly present to the emergency department (ED), often with acute pain. They cause significant suffering and morbidity if not adequately treated. Paracetamol and ibuprofen are commonly used analgesics, but it remains unknown if either one or the combination of both is superior for pain control. OBJECTIVES: To investigate the analgesic effect of paracetamol, ibuprofen and the combination of both in the treatment of soft tissue injury in an ED, and the side effect profile of these drugs. METHODS: Double-blind, double dummy, placebo-controlled randomised controlled trial. 782 adult patients presenting with soft tissue injury without obvious fractures attending the ED of a university hospital in the New Territories of Hong Kong were recruited. Patients were randomised using a random number table into three parallel arms of paracetamol only, ibuprofen only and a combination of paracetamol and ibuprofen in a 1:1:1 ratio. The primary outcome measure was pain score at rest and on activity in the first 2 hours and first 3 days. Data was analysed on an intention to treat basis. RESULTS: There was no statistically significant difference in pain score in the initial two hours between the three groups, and no clinically significant difference in pain score in the first three days. CONCLUSION: There was no difference in analgesic effects or side effects observed using oral paracetamol, ibuprofen or a combination of both in patients with mild to moderate pain after soft tissue injuries attending the ED. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (no. NCT00528658).

Disease severity prediction for nursing home-acquired pneumonia in the emergency department.

BACKGROUND: Prediction rules exist for the assessment of community-acquired pneumonia but their use in nursing home-acquired pneumonia (NHAP) remains undefined. The objectives of this study were to compare the prognostic ability for severe NHAP of five prediction rules (PSI, CURB-65, M-ATS, R-ATS, España rule), and to evaluate their usefulness to identify patients with less severe disease in the emergency department for outpatient care. METHODS: A prospective observational study of consecutive NHAP patients was conducted at a university teaching hospital emergency department in Hong Kong between January 2004 and June 2005. The primary outcome was severe pneumonia (defined as combined 30-day mortality and/or intensive care unit (ICU) admission). RESULTS: 767 consecutive NHAP patients were included. Mean (SD) age was 83.4 (9.0) years; 350 (45.6%) were male and 644 (84.0%) had coexisting illness. 95 patients died within 30 days (12.4%), five patients were admitted to the ICU (0.7%) and 98 patients had severe pneumonia (12.8%). Sensitivity and specificity of each decision rule ranged from 37.8% to 95.9% and 15.1% to 87.6% respectively. The overall predictive performance of each rule was between 0.627 and 0.712. The negative likelihood ratios of PSI (0.27) and CURB-65 (0.23) were lower than M-ATS (0.71), R-ATS (0.45) and España (0.39). After excluding 204 patients with either poor functional status or those >90 years of age, sensitivities of M-ATS (96.0%) and R-ATS (100%) improved greatly with negative likelihood ratios of <0.1. CONCLUSION: PSI and CURB-65 are useful for identification of patients with less severe NHAP.

Cost-consequence analysis comparing 2-octyl cyanoacrylate tissue adhesive and suture for closure of simple lacerations: a randomized controlled trial.

STUDY OBJECTIVE: We investigate the cost difference between conventional suture and tissue adhesive methods in simple wound closure. METHODS: A cost-consequence analysis was conducted alongside a nonblinded randomized controlled trial comparing 2-octyl cyanoacrylate tissue adhesive with conventional suture in simple lacerations closure in emergency departments (EDs) of a university teaching hospital and a major regional hospital in Hong Kong. One hundred eighty-six adult patients with simple lacerations of length within 8 cm were randomized to receive tissue adhesive (93 patients) or conventional suture (93 patients) for wound closure. The primary outcome measures were the costs to the Hospital Authority and the charges on participants incurred in each treatment method. The secondary outcome measures included the cosmetic visual analog scale, visual analog scale, Wound Evaluation Score, total time spent in each closure method, and the overall patients' satisfaction on the whole process of wound management. RESULTS: The 2 groups had similar baseline characteristics. The tissue adhesive method incurred a higher cost to the Hospital Authority (216.12 [US $27.70] versus 171.33 [US $21.96]; absolute difference 44.79 [US $5.74] [95% confidence interval (CI) 32.76 to 55.95 [US $4.20 to 7.14]]) but a lower charge to patients (109.68 [US $14.06] versus 156.96 [US $20.12]; absolute difference 47.28 [US $6.06] [95% CI, 35.58 to 58.98 [US $4.56 to 7.56]) than the conventional suture method. The mean cosmetic visual analog scale score, visual analog scale score, and Wound Evaluation Score of the 2 groups were similar at various intervals within 3 months after wound closure. Compared with the suture group, the tissue adhesive group had a shorter median procedure time, fewer patients had wound erythema or swelling after wound closure, fewer patients required analgesics on discharge at ED, and there was a higher overall patient satisfaction score. CONCLUSION: Simple wounds closed by tissue adhesives incur a higher cost to the Hospital Authority than the conventional suture but may be favored by patients because of lower personal charge.

Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients.

BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by the association of skin lesions, hearing loss and vascularizing keratitis. KID syndrome is caused by autosomal dominant mutations in the connexin 26 gene (GJB2). OBJECTIVES: To establish whether there is a correlation between genotype and phenotype in KID syndrome. METHODS: Clinical examination and molecular analysis of GJB2 were performed in a cohort of 14 patients with KID syndrome originating from 11 families. We also reviewed the 23 cases with molecular analysis previously reported in the literature. RESULTS: The patients displayed the classical signs of KID syndrome with the additional finding of inflammatory nodules in six patients (43%); this clinical finding has not been described previously in the literature. One patient presented at the age of 18 years with a fatal carcinoma of the tongue, an extremely rare reported complication. For seven of the 11 families (64%) the disease was sporadic, whereas it was familial in the remaining four families (36%). Twelve patients (86%) were heterozygous for the p.Asp50Asn mutation and two patients (14%) were heterozygous for the p.Ser17Phe mutation. Surprisingly, a family in which we personally examined the healthy parents had two affected children heterozygous for the p.Asp50Asn mutation, suggesting germinal mosaicism. Compared with patients with the p.Asp50Asn mutation, the two patients with the p.Ser17Phe mutation had more severe skin involvement. One of these two patients experienced a carcinoma of the tongue. CONCLUSIONS: Familial cases appear to be more frequent than reported in the literature. The possibility of germinal mosaicism must be taken into account for genetic counselling. This study also suggests that patients with the p.Ser17Phe mutation may have a more severe phenotype and could be at higher risk for tongue carcinoma.

A novel, high stringency selection system allows screening of few clones for high protein expression.

To obtain highly productive mammalian cell lines, often large numbers of clones need to be screened. This is largely due to low selection stringencies, creating many, but low protein producing clones. To remedy this problem, a novel, very stringent selection system was designed, to create few, but high protein producing clones. In essence, a selection marker with a startcodon that confers attenuated translation initiation frequency was placed upstream of the gene of interest with a startcodon that confers optimal translation initiation. From the transcribed bicistronic mRNA, the selection marker is translated at a low frequency, and the protein of interest at a high frequency. This selection system is so stringent that clones form only rarely. However, application of anti-repressor elements, which increase promoter activity, did induce the formation of clones that expressed proteins at high levels. When combined with anti-repressor elements, this novel selection system can be a valuable tool to rapidly create few, but highly productive mammalian cell lines.

Signal transduction in the ductuli efferentes testis of the rat: inhibition of fluid reabsorption by cyclic adenosine 3', 5'-monophosphate.

It is important to identify the signal transduction pathway involved in the regulation of fluid reabsorption by the ductuli efferentes of the testis because they reabsorb most of the fluid leaving the testis and are essential for male fertility. Microperfusion studies of the ducts in vivo showed that 0.1 or 1.0 mM dibutyryl (db)-cGMP in the perfusate had no effect on fluid reabsorption, but 0.1 mM db-cAMP significantly reduced fluid reabsorption, 0.25 mM abolished reabsorption, and 0.5-1.0 mM caused secretion. The inhibitory effect of db-cAMP was reversible. Although the presence of db-cAMP in the perfusate did not affect the concentration of Na+ in the collectate, the concentrations of K(+) and Cl(-) increased, indicating that their transport is at least partly regulated by cAMP. Including the phosphodiesterase inhibitor pentoxifylline in the perfusate decreased fluid reabsorption by the ducts in a dose-dependent manner, and it also increased the concentration of cAMP (5.5-fold) in collectate. Pentoxifylline also increased the production of cAMP (4-fold) by ducts incubated in vitro. It is concluded that cAMP, but probably not cGMP, is an intracellular messenger regulating fluid reabsorption in the efferent ducts.

pH and bicarbonate in the ductuli efferentes testis of the rat.

The pH and bicarbonate concentrations of luminal fluids in the efferent ducts of the rat were estimated from pH measurements of samples in vitro under conditions of controlled temperature and carbon dioxide tension. The pH of scrotal blood was estimated to be more acidic than systemic blood (mean pH=7.44) at either of the putative scrotal carbon dioxide tensions (5% and 7%, pH, respectively,=7.42 and 7.28). For PCO2 tensions of 5% and 7%, respectively, the data indicated that the pH in the efferent ducts was significantly higher (distal initial zone pH=7.55 or 7.41; coni vasculosi pH=7.66 or 7.51; p < 0.01) than in fluid entering (rete testis fluid, pH=7.34 or 7.20) or leaving the ducts (zone 1a of the epididymal duct 7.26 or 7.11). Bicarbonate concentrations were also significantly higher (p < 0.01) in the efferent ducts (35.4 +/- 4.7 mM, distal initial zone; 45.2 +/- 7.6 mM, coni vasculosi) than in fluids entering (22.9 +/- 3.6 mM) or leaving (20.4 +/- 4.9 mM) the ducts. Estimates of the reabsorption of bicarbonate and fluid indicated that 96% of the testicular output of bicarbonate was reabsorbed in the efferent ducts, but there was also some secretion of bicarbonate into the ducts. It is concluded that luminal pH and bicarbonate levels in the efferent ducts of the rat are high relative to those found in the epididymis where low pH and bicarbonate contributes to sperm quiescence during storage. Nevertheless, the high rate of bicarbonate reabsorption in the efferent ducts is a major contributor to the establishment of the low pH and bicarbonate milieu of the epididymis.

Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum.

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

Fluid and electrolyte reabsorption in the ductuli efferentes testis.

The efferent ducts of mammals are a series of ducts that are arranged in parallel and reabsorb most of the fluid released with spermatozoa from the testis. This function is essential for spermatogenesis, and for sperm maturation and storage in the epididymis. There is evidence for the involvement of three major transport processes in the bulk reabsorption of water and low molecular weight solutes from the ducts: active solute transport, passive (presumably paracellular) diffusion and fluid phase endocytosis. A small back-flux into the ducts via anion secretion also appears to occur. Control of fluid reabsorption by the efferent ducts is emerging as a complex process with multiple components. Reabsorption is flow dependent which provides local control of reabsorption with a rapid response to changes in luminal conditions. Sex steroids (oestrogen as well as androgen), but not mineralocorticosteroids, are involved in the chronic control of reabsorption in the ducts. Control of epithelial transport in the efferent ducts appears to be mediated by cAMP and probably other signal transduction systems.

Adrenal independence of fluid and electrolyte reabsorption in the ductuli efferentes testis of the rat.

The ductuli efferentes testis (efferent ducts) of the rat were studied to determine whether fluid and electrolyte reabsorption by the ducts is under the control of adrenal mineralocorticoids. Testicular fluid output and the rate of fluid reabsorption by the ducts were determined in sham-operated controls and in rats which had been adrenalectomized 10 days previously, adrenalectomized 10 days previously and given aldosterone therapy (75 micrograms kg-1 day-1 S.C.) from day 3 to day 10 post adrenalectomy, and in rats given injections of the aldosterone antagonist, spironolactone, for 10 days (10 mg kg-1 day-1 S.C.). The values for testicular fluid output and fluid flow from the efferent ducts (means +/- S.E.M.) in the sham-operated rats were 36.0 +/- 7.8 and 1.23 +/- 0.12 microliters h-1, respectively, resulting in an estimate of fluid reabsorption by the efferent ducts of 94.8 +/- 1.6% of the testicular fluid output. None of the treatments resulted in a significant change in testicular fluid output or in fluid reabsorption from the efferent ducts. Similarly, the treatments did not significantly alter the osmolality or electrolyte concentrations in fluid samples from the rete testis or the distal end of the efferent ducts (sham-operated values for rete testis and efferent duct fluid, respectively, were: osmolality, 311.2 +/- 1.7 and 302.7 +/- 5.7 mosmol kg-1; [Na+], 151.2 +/- 5.6 and 150.8 +/- 8.1 mmol l-1; [Cl-], 147.9 +/- 6.6 and 126.7 +/- 2.2 mmol l-1; [K+], 15.2 +/- 0.7 and 13.5 +/- 2.4 mmol l-1). It is concluded that, like the homologous proximal tubule of the metanephric kidney, fluid reabsorption from the efferent ducts is independent of adrenal mineralocorticoid control.

Age-related changes in the contents of neuropeptides in the rat brain and pituitary.

beta-Endorphin, Leu-enkephalin, Met-enkephalin, substance P, somatostatin, and cholecystokinin were measured in the brain and the pituitary of male Sprague-Dawley rats aged 3 months, 12 months, and 22 months. beta-Endorphin, Met-enkephalin and Leu-enkephalin contents in the neurointermediate lobe, and the enkephalin levels in the anterior lobe of the pituitary increased with age. The increases in contents were both in the day and at night for beta-endorphin and Met-enkephalin. However, the increase for Leu-enkephalin content was in the day only. Hypothalamic beta-endorphin content decreased with age only in the day. beta-Endorphin and Leu-enkephalin contents in the brain stem, and Leu-enkephalin levels contents in the cortex decreased with age at night. Leu-enkephalin in the striatum decreased with age in the day. There was also an age-related decrease for somatostatin and substance P contents in the striatum and the hypothalamus in the day, and in cholecystokinin levels in the hippocampus, and the hypothalamus at night. It is concluded that there are age differences in neuropeptide levels, and that these changes may differ according to diurnal rhythms.

T3 reverses the changes in met-enkephalin and beta-endorphin contents in the anterior lobe, but not the neuro-intermediate lobe of the pituitary of rats rendered hypothyroid by PTU-treatment.

The changes in met-enkephalin and beta-endorphin contents in the pituitary in PTU-induced hypothyroidism were studied in the rat. After 2 weeks of PTU-treatment, both IR-met-enkephalin and IR-beta-endorphin contents in the pituitary were significantly reduced. Gel filtration chromatography followed by radioimmunoassay showed that the immunoactivities in the peaks of precursors, met-enkephalin, beta-lipotropin and beta-endorphin were all lower in the pituitaries from the PTU-treated rats. In another experiment, some of the PTU-treated rats were injected daily with 500 micrograms T3/kg b.w. In the hypothyroid rats, IR-met-enkephalin and IR-beta-endorphin contents were decreased in both the anterior and neurointermediate lobes. Only the changes in the anterior lobe were reversed by T3 treatment. In conclusion, while the effects on the anterior lobe are probably due to a deficiency in thyroid hormones, the mechanism for the decrease of opioid peptide contents in the neurointermediate lobe is still unclear.

Hypothyroidism and pituitary contents of immunoactive met-enkephalin and beta-endorphin in male rats of different ages.

A comparison of the effect of PTU-induced hypothyroidism on the contents of immunoactive met-enkephalin and beta-endorphin in the pituitaries from rats aged 2 1/2, 12, and 18 months was made. In all ages, there was significant reduction of IR-met-enkephalin content in the anterior lobe and IR-beta-endorphin content in the neuro-intermediate lobe after PTU treatment. There was a significant age-related decrease in IR-beta-endorphin content in the anterior lobe. Rats of all three ages responded to PTU treatment with an increase in serum TSH level and a drastic reduction in serum T3 and T4 levels. The results indicate that there was no age-related difference in the change of pituitary opioid peptide contents in response to hypothyroidism.