Sickle cell trait and stroke in the young adult

Two young patients with sickle cell trait (AS haemaglobinopathy) and ischaemic stroke are reported. The stroke involved the internal carotid artery territory in one and the brainstem in the other. A review of the literature is presented to suggest that the association of sickle cell trait and cerebral infarction is more than coincidental. Haemoglobin electrophoresis should be undertaken routinely in young subjects with ischaemic stroke.     

White matter lesions account for all age-related declines in speed but not in intelligence

MRI scans measured white matter lesion prevalence (WMLP) in 65 people ages 65-84 years who also took 17 cognitive tests: 3 tests of general fluid intelligence, 3 of vocabulary, 2 of episodic and 3 of working memory, 2 of processing speed, and 4 of frontal and executive function. Entry of age with WMLP into regression equations as predictors of test scores showed that inferences about the functional relationships between markers of brain aging and cognitive impairments are seriously misleading if they are based on simple correlations alone. A new finding that WMLP accounts for all of the age-related variance between individuals in tests of speed and executive ability but for none of the age-related variance in intelligence revises current hypotheses that gross brain changes affect general fluid intelligence and other mental abilities solely through their effects on information-processing speed.     

Paediatric palliative care: a lack of research-based evidence

Providing the best possible care for the child and family is paramount to health professionals working in paediatric palliative care. However, there is little research which enables practitioners to question their current practice. There are concerns about conducting research on children receiving palliative care at such a sensitive time for the child and his/her family. These concerns must be considered against the growing demand for clear standards and guidelines for practice within health care. According to the Department of Health (DoH) there is no place within the modern healthcare system for the adoption of unproven theories or outdated care (DoH, 1998). While no-one would question the dedication and care being delivered to children and their families by well-trained staff, the lack of research is a cause for concern. A group of students undertaking a degree module in paediatric palliative care identified the lack of literature and research in this area and have undertaken a review of the available literature.     

Four serogroups of Legionnaires' disease bacteria defined by direct immunofluorescence.

Thirty-five strains of Legionnaires' disease bacteria were shown to belong in four distinct serologic groups on the basis of findings obtained with direct fluorescent antibody testing. Thirty of the strains were placed in group 1, three in group 2, one in group 3, and one in group 4. Immunoelectrophoretic studies showed both unique and common antigens among the representative strains of the four serogroups.     

An Israeli Arab patient with a de novo TNFRSF1A mutation causing tumor necrosis factor receptor-associated periodic syndrome

OBJECTIVE: To investigate genetic susceptibility to recurrent fevers, generalized severe myalgia, and migratory erythema in an Israeli Arab child with no family history of similar disease. METHODS: DNA sequencing of exons 1-6 of the TNFRSF1A gene (formerly TNFR1) was performed in the patient and his parents to determine the presence of the autosomal-dominant tumor necrosis factor receptor-associated periodic syndrome (TRAPS); informative markers spanning the TNFRSF1A locus were used to genotype all available members of the patient's family. The TNFRSF1A gene was subsequently screened in 69 healthy Arab controls and 96 Caucasian controls. Formal forensic paternity testing was performed on the child. RESULTS: We found a de novo missense mutation in exon 3 of the TNFRSF1A gene, involving a novel C-->T transition encoding a Cys70Arg (C70R) variant, in the Israeli Arab patient. Eight of the common familial Mediterranean fever (FMF) gene MEFV mutations were excluded. This mutation was not present in the parents or siblings, or among the 69 healthy Arab controls. However, another TNFRSF1A variant, Pro46Lys (P46L), was present in 1 of the Arab controls. CONCLUSION: We have identified a TNFRSF1A mutation associated with periodic fever in an Arab patient, and a TNFRSF1A variant, which is variably pathogenic in Caucasians, in an Arab control. This is the first report of a de novo mutation in periodic fevers in general, and also of TRAPS in the Arab population. These findings demonstrate the need to include TRAPS in the differential diagnosis of recurrent fevers in this population.     

Activation of MAP kinase-activated protein kinase 2 in human neutrophils after phorbol ester or fMLP peptide stimulation

In response to extracellular stimulation, one of the earliest events in human neutrophils is protein phosphorylation, which mediates signal transduction and leads to the regulation of cellular functions. Mitogen- activated protein (MAP) kinases are rapidly activated by a variety of mitogens, cytokines, and stresses. The activated MAP kinases in turn regulate their substrate molecules by phosphorylation. MAP kinase- activated protein (MAPKAP) kinase 2, a Ser/Thr kinase, has been shown to be phosphorylated by p38 MAP kinase both in vivo and in vitro. Phosphorylation of the Thr-334 site of MAPKAP kinase 2 results in a conformational change with subsequent activation of the enzyme. To better define the role of MAPKAP kinase 2 in the activation of human neutrophils, its enzymatic activity was measured after stimulation by either a phorbol ester (phorbol myristate acetate [PMA]), a potent protein kinase C activator, or the tripeptide fMLP, which is a chemotactic factor. The in vitro kinase assays indicate that both PMA and fMLP stimulated a transient increase in the enzymatic activity of cellular MAPKAP kinase 2. The induced kinase activation was concentration-dependent and reached a maximum at 5 minutes for PMA and 1 minute for fMLP. To identify potential substrate molecules for MAPKAP kinase 2, a highly active kinase mutant was generated by mutating the MAP kinase phosphorylation site in the C-terminal region. The replacement of threonine 334 with alanine resulted in a marked augmentation of catalytic activity. Analysis of in vitro protein phosphorylation in the presence of the active kinase indicates that a 60-kD cytosolic protein (p60) was markedly phosphorylated and served as the major substrate for MAPKAP kinase 2 in human neutrophils. Based on the MAPKAP kinase 2 phosphorylation site of Hsp27, a competitive inhibitory peptide was synthesized. This competitive inhibitory peptide specifically inhibited MAPKAP kinase 2 enzymatic activity, as well as the in vitro and in vivo kinase-induced p60 phosphorylation. To assess the contribution of MAPKAP kinase 2 in neutrophil function, the oxidative burst response after manipulation of endogenous kinase activity was measured. Intracellular delivery of the competitive inhibitory peptide into human neutrophils reduced both PMA- and fMLP- stimulated superoxide anion production. Thus, the results strongly suggest that MAPKAP kinase 2 is involved in the activation of human neutrophils.     

Impact of Anemia on Surgical Outcomes: Innovative Interventions in Resource-poor Settings

Background

The aim of this work was to study the impact of anemia on surgical outcomes and the impact of instituting appropriate workup and treatment of anemia on surgical outcomes.

Methods

We conducted a case–control retrospective chart review of all hernia repair, hydrocele repair, and hysterectomy cases at the SEARCH Hospital in Gadchiroli, India, from January 2008 to April 2010, and included 340 male and 112 female surgical patients. We also performed a prospective assessment of the impact of the institution of appropriate workup and treatment of anemia on the surgical outcomes for all hernia repair, hydrocele repair, and hysterectomy cases at SEARCH from May 2010 to May 2011 and included 138 male and 76 female surgical patients.

Results

The retrospective arm of the study included 340 males and 112 females with a median age of 39 and 41?years, respectively. The mean hemoglobin values were 12.50 (range?=?8.8–15.4) for men and 10.39 (range?=?5.2–14.8) for women. Patients with anemia had (1) increased incidence of spinal headache after inguinal hernia repair (p?=?0.0266) and (2) increased incidence of fever after total hysterectomy (p?=?0.0070). There was no statistically significant correlation between anemia and other outcomes (all p?>?0.05). The prospective arm of the study included 138 males and 76 females with a median age of 35 and 40, respectively. The mean hemoglobin values were 11.8 (range?=?6.4–14.8) for men and 10.6 (range?=?6.9–12.8) for women. There was no statistically significant correlation between anemia and any surgical outcomes (p?>?0.05). The incidence of complications in both the retrospective and the prospective arm was compared according to increasing severity of anemia across genders. Overall, there was no statistically significant increase in complication rates with increasing severity of anemia (p?>?0.05).

Conclusions

In the retrospective arm of this study, anemia was associated with increased incidence of spinal headache and fever. In the prospective arm of this study, there was no statistically significant correlation between anemia and any surgical outcome. The incidence of complications did not increase with the severity of anemia in either arm of the study. Further investigation is needed into the optimal management and treatment of anemia prior to surgery in resource-poor settings.