Comparison of the mouse spleen cell assay and a radioimmunoassay for the measurement of serum erythropoietin

The mouse spleen cell assay (MSCA) has been compared with a radioimmunoassay for the measurement of serum erythropoietin (Ep). In 20 normal subjects the serum values ranged from 15 to 73 mU/ml for the MSCA compared with 5-30 mU/ml for the RIA. For normal sera there was no correlation between the results of the two assays. In 37 patients with anaemias of differing aetiologies and at various stages of treatment values ranged from 10 to 3645 mU/ml for the MSCA and 13-10,000 mU/ml for the RIA. Although patient values from the two assays were highly correlated (r = 0.98, P less than 0.001), the MSCA results were generally lower. These discrepancies can be largely accounted for by two factors. Firstly the MSCA is sensitive to non-specific matrix effects. Secondly, heat inactivation of serum, a prerequisite for the MSCA, but not for the RIA, destroys a variable and unpredictable proportion of the Ep in the test sera leading to an underestimation of Ep in the MSCA. We conclude that the RIA is more reliable than the MSCA which, in its present form, cannot be recommended for the accurate measurement of serum erythropoietin.     

A test of the chromosomal theory of ecotypic speciation in Anopheles gambiae

The role of chromosomal inversions in speciation has long been of interest to evolutionists. Recent quantitative modeling has stimulated reconsideration of previous conceptual models for chromosomal speciation. Anopheles gambiae, the most important vector of human malaria, carries abundant chromosomal inversion polymorphism nonrandomly associated with ecotypes that mate assortatively. Here, we consider the potential role of paracentric inversions in promoting speciation in A. gambiae via "ecotypification," a term that refers to differentiation arising from local adaptation. In particular, we focus on the Bamako form, an ecotype characterized by low inversion polymorphism and fixation of an inversion, 2Rj, that is very rare or absent in all other forms of A. gambiae. The Bamako form has a restricted distribution by the upper Niger River and its tributaries that is associated with a distinctive type of larval habitat, laterite rock pools, hypothesized to be its optimal breeding site. We first present computer simulations to investigate whether the population dynamics of A. gambiae are consistent with chromosomal speciation by ecotypification. The models are parameterized using field observations on the various forms of A. gambiae that exist in Mali, West Africa. We then report on the distribution of larvae of this species collected from rock pools and more characteristic breeding sites nearby. Both the simulations and field observations support the thesis that speciation by ecotypification is occurring, or has occurred, prompting consideration of Bamako as an independent species.     

Maternal Physical Activity Is Associated With Improved Blood Pressure Regulation During Late Pregnancy

Background

Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy.

Liver dysfunction in Pennsylvania's multitransfused hemophiliacs

Transaminase values [alanine amino transferase (ALT) and aspartate amino transferase (AST)] and markers for hepatitis B were serially determined in 558 hemophiliacs exposed to blood products. Hepatitis B surface antigen (HB_sAg) persistent for over 12 months was present in 6% of the patients. Antibody to hepatitis B surface antigen (anti-HBs) was noted in 90% of the 259 patients treated with factor VIII or IX concentrates but in only 49% of the 43 patients treated with fresh frozen plasma (FFP) or cryoprecipitate. Persistently abnormal transaminase values were noted in 31% of the patients treated with commercial concentrates but in only one (2%) of the patients exposed to cryoprecipitate or FFP. This difference continued even when the two groups of patients were matched for the amount of blood products, up to 50, 000 units, which they had received in the study period. In the concentrate-treated patients, no correlation could be found between transaminase values and the number of units of factor VIII or IX they had received during the six years of the study (1973–1978).Supported in part by the Pennsylvania Hemophilia Centers and the Pennsylvania State-Wide Hemophilia Program.     

Digital communication between clinician and patient and the impact on marginalised groups: a realist review in general practice

Background

Increasingly, the NHS is embracing the use of digital communication technology for communication between clinicians and patients. Policymakers deem digital clinical communication as presenting a solution to the capacity issues currently faced by general practice. There is some concern that these technologies may exacerbate existing inequalities in accessing health care. It is not known what impact they may have on groups who are already marginalised in their ability to access general practice.

Aim

To assess the potential impact of the availability of digital clinician–patient communication on marginalised groups’ access to general practice in the UK.

Design and setting

Realist review in general practice.

Method

A four-step realist review process was used: to define the scope of the review; to search for and scrutinise evidence; to extract and synthesise evidence; and to develop a narrative, including hypotheses.

Results

Digital communication has the potential to overcome the following barriers for marginalised groups: practical access issues, previous negative experiences with healthcare service/staff, and stigmatising reactions from staff and other patients. It may reduce patient-related barriers by offering anonymity and offers advantages to patients who require an interpreter. It does not impact on inability to communicate with healthcare professionals or on a lack of candidacy. It is likely to work best in the context of a pre-existing clinician–patient relationship.

Conclusion

Digital communication technology offers increased opportunities for marginalised groups to access health care. However, it cannot remove all barriers to care for these groups. It is likely that they will remain disadvantaged relative to other population groups after their introduction.     

Family history of alcoholism and response to amphetamine: sex differences in the effect of risk

BACKGROUND: Individuals at risk for alcoholism exhibit an enhanced stimulant response to alcohol. It is not known whether individuals at risk also exhibit a heightened sensitivity to other drugs with stimulant properties. METHODS: Healthy young men and women each received, in separate sessions, placebo and 10 mg of d-amphetamine in counterbalanced order. Stimulant and sedative subjective effects were recorded before and three times after capsule administration using the Biphasic Alcohol Effects Scale. The sample comprised 19 family-history-positive (FHP; 58% women) and 53 family-history-negative (FHN; 51% women) participants. RESULTS: As compared with placebo, amphetamine increased ratings of stimulation in the sample as a whole. In addition, the ratings revealed an enhanced, as well as a protracted, stimulant response to amphetamine among FHP men, as compared with FHN men: for FHP men, ratings of stimulation made 3 and 6 hr after amphetamine administration were greater than baseline ratings. Moreover, in FHP men, the effect of amphetamine, as compared with placebo, was most evident 6 hr after capsule administration. In contrast, despite a dose x hour interaction in FHN men, post hoc comparisons revealed no differences between the baseline and any of the postamphetamine measurements or between amphetamine and placebo ratings at any of the time points. Among women, the drug effect did not differentiate the family-history groups. CONCLUSIONS: Consistent with previous research on alcohol, high-risk men exhibited a heightened stimulant response to amphetamine. Thus, for men, sensitivity to the stimulant properties of drugs may be an endophenotype for alcoholism. Whereas the present results suggest that women at risk do not exhibit an enhanced stimulant response to amphetamine, further study is needed, including evaluation at various points in the menstrual cycle.     

Focus on Kir6.2: a key component of the ATP-sensitive potassium channel

ATP-sensitive potassium (K(ATP)) channels are found in a wide variety of cell types where they couple cell metabolism to electrical activity. In glucose-sensing tissues, these channels respond to fluctuating changes in blood glucose concentration, but in other tissues they are activated only under ischemic conditions or in response to hormonal stimulation. Although K(ATP) channels in different tissues have different regulatory subunits, in almost all cases (except vascular smooth muscle) the pore-forming subunit is the inwardly rectifying K(+) channel Kir6.2. This article reviews recent studies of Kir6.2, focussing on the relation between channel structure and function, and on naturally occurring mutations in Kir6.2 that lead to human disease. New insights into the location of the ATP-binding site, the permeation pathway for K(+), and the gating of the pore provided by homology modelling are discussed in relation to functional studies. Gain-of-function mutations in Kir6.2 cause permanent neonatal diabetes mellitus (PNDM) by reducing the ATP sensitivity of the K(ATP) channel and increasing the K(ATP) current, which is predicted to inhibit beta-cell electrical activity and insulin secretion. Mutations at specific residues, that cause a greater decrease in ATP sensitivity, are associated with additional neurological symptoms. The molecular mechanism underlying the differences in ATP sensitivity produced by these two classes of mutations is discussed. We speculate on how some mutations lead to neurological disease and why no obvious cardiac symptoms are observed. We also consider the implications of these studies for type-2 diabetes.