Alterations in erythrocyte Na+,K+-cotransport in normal and hypertensive human pregnancy

Many physiological variables known or thought to affect erythrocyte Na+,K+-cotransport are altered in pregnancy. The interrelationships of Na+,K+-cotransport and pregnancy were therefore examined. Values were elevated by more than 30% in both second and third trimesters with a return towards non-pregnant levels in the postpartum period. Although pregnancy was also associated with elevated plasma cholesterol, renin activity and aldosterone, there was no significant relationship within the pregnant group between Na+,K+-cotransport and any of these factors. No change could be demonstrated in Na+,K+-cotransport values after 7 days of either high (greater than 250 mmol/day) or low (less than 50 mmol/day) sodium intake and values for those who developed pregnancy-associated hypertension (PAH, pre-eclampsia) were not significantly different from those in continuously normotensive women in either the second or the third trimesters of pregnancy.     

Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.

The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of micro-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in delta-receptor binding. In contrast to the NACC, substantially lower levels of micro-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH- and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the micro-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 microg) or bilateral (0.5-10 microg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 microg) and bilateral (10 microg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 microg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH- and saccharin-maintained responding over a range of doses (1-20 microg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.     

Change in the oestrogen receptor status of breast cancer with age--comparison of two types of assay.

The oestrogen receptor (ER) is considered to be an essential component of the mechanism of response of a breast tumour to endocrine therapy, but ER measurements have proved to have only modest predictive value. In the present study, we have examined ER status by both immunocytochemical assay (ER-ICA) on a fine needle aspirate and by radioligand-binding assay (DCC) on an excised portion of tumour. There was a correlation between the ER level detected by the two assays (Spearman's r = 0.77 for DCC versus ER-ICA staining intensity, r = 0.70 for DCC versus ER-ICA percentage of cells stained, P < 0.0001, n = 137 in each case). Each assay showed an increasing proportion of ER+ve results with increasing patient age. In the case of ER+ve tissues only, while ER concentration by DCC assay increased steadily with age (r = 0.39, P < 0.0001, n = 108), the ER-ICA assay revealed that, staining intensity increased with age (r = 0.26, P = 0.001, n = 149) but the percentage of cells stained did not (r = 0.08, P = NS, n = 149). It is concluded that increasing endocrine responsiveness with advancing age could reflect the increasing proportion of ER+ve tumours with increased levels of ER per cell (as indicated by staining intensity) rather than increasing proportion of ER+ve cells.     

A PACU crisis: a case study on the development and management of methemoglobinemia.

The development of methemoglobinemia requires rapid recognition, confirmation, and treatment. This case study describes the development, diagnosis, and management of a 63-year-old male scheduled for a laparoscopic cholecystectomy with an intraoperative cholangiogram who developed methemoglobinemia after benzocaine was given for intubation.     

Mediastinitis in heart transplantation.

Between March 1985 and December 1991, mediastinitis developed in 12 of 420 cardiac transplantation patients (2.8%). The mortality rate in this group of patients was 8.3% (1/12). Actuarial survival (1 year, 75%; and 5 years, 65%) was not significantly different from that of the group without mediastinitis (1 year, 88%; and 5 years, 75%). A higher percentage of the patients in the group with mediastinitis were listed as UNOS status 1 (50% versus 35%) and had a history of previous sternotomies (58% versus 44%). The presentation of mediastinitis was typical. Computed tomographic scanning with or without aspiration was a valuable adjunct in the diagnosis of mediastinitis. Induction immunotherapy with minimal steroids in the perioperative period was used in all patients. This may contribute to the patients' ability to mount an appropriate and effective response to infection, permitting earlier diagnosis. The debridement irrigation technique used in 8 of 12 patients had a low success rate of 33%, whereas the debridement muscle flap technique used in 4 of 12 was 100% successful in eliminating infection.     

Single-scan Bayes estimation of cerebral glucose metabolic rate: comparison with non-Bayes single-scan methods using FDG PET scans in stroke

Three single-scan (SS) methods are currently available for estimating the local cerebral metabolic rate of glucose (LCMRG) from F-18 deoxyglucose (FDG) positron emission tomography (PET) scan data: SS(SPH), named for Sokoloff, Phelps, and Huang; SS(B), named for Brooks; and SS(H), named for Hutchins and Holden et al. All three of these SS methods make use of prior information in the form of mean values of rate constants from the normal population. We have developed a Bayes estimation (BE) method that uses prior information in the form of rate constant means, variances, and correlations in both the normal and ischemic tissue populations. The BE method selects, based only on the data, whether the LCMRG estimate should be computed using prior information from normal or ischemic tissue. The ability of BE to make this selection gives it an advantage over the other methods. The BE method can be used as a SS method or can use any number of PET scans. We conducted Monte Carlo studies comparing BE as a SS method with the other SS methods, all using a single scan at 60 min. We found SS(H) to be strongly superior to SS(SPH) and SS(B), and we found BE to be definitely superior to SS(H).     

Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.     

Impact of restricting paracetamol pack sizes on paracetamol poisoning in the United Kingdom: a review of the literature.

Paracetamol (acetaminophen) is the most common drug taken in overdose in the UK, accounting for 48% of poisoning admissions to hospital and being involved in an estimated 100-200 deaths per year. In 1998, the UK government introduced legislation that reduced the maximum pack size of all non-effervescent tablets and capsules containing aspirin (acetylsalicylic acid) or paracetamol that can be sold or supplied from outlets other than registered pharmacies from 25 to 16 tablets or capsules. This article reviews the literature to determine the effectiveness of the legislation, focusing specifically on paracetamol poisoning. Seventeen studies on this subject were identified. Three studies found reductions in mortality rates; one study found an increase in mortality rates, while one found an initial reduction followed by an eventual increase; three found no significant difference in mortality rates before and after introduction of the legislation. Five studies found reductions in admissions to liver units, three of these finding a reduction in liver transplantation rates; two further studies found no change in liver function tests and rates of paracetamol-induced acute liver injury or failure. Four studies found a sustained decrease in hospital admissions, while two found an initial decrease followed by an eventual increase. One study found a decline in admissions for paracetamol poisoning and an increase in admissions for non-paracetamol poisoning. Sales data are conflicting, with two studies finding no significant difference in paracetamol sales before and after the introduction of the legislation and one reporting a decline. The severity of overdose appears to have decreased since the maximum permitted packet size was reduced, with five studies reporting a reduction in the number of severe overdoses (measured by numbers of tablets ingested, serum paracetamol concentrations and usage of antidotes). Only two studies reported an increase in the number of severe overdoses.Paracetamol-associated mortality rates, admissions to liver units/liver transplants, hospital admissions and the severity of paracetamol overdose appear to have been decreasing since 1998. However, one study showed that the reductions in mortality and hospital admissions began in 1997; therefore, the contribution of the 1998 legislation to the observed changes is unclear. Most of the studies are based on short-term follow-up so it is difficult to draw any conclusions regarding long-term trends. Many of the studies were also restricted to relatively small areas of the UK; this, combined with a variety of outcome measures, makes it difficult to distinguish any conclusive trends. The studies also suffer from a lack of comparison and control groups. Some studies do not clearly differentiate between the paracetamol preparations covered by the legislation and those not.The limited number of studies to date, combined with a variety of outcome measures, make it difficult to determine with accuracy whether or not the legislation has been a success. More long-term studies are needed to fully assess the impact of the legislation.