Enzymatic modification of plasma low density lipoproteins in rabbits: a potential treatment for hypercholesterolemia.

Phospholipase A2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.     

Endoscopic ultrasound for localisation of islet cell tumours.

In a prospective study endoscopic ultrasound localisation of pancreatic endocrine tumours was attempted in 21 patients with clinically suspected islet cell tumours. Most patients were referred after the failure of conventional imaging methods. Endoscopic ultrasound correctly identified the site of 12 of 15 insulinomas, one glucagonoma, and a diffuse pancreatic abnormality in a patient with multiple endocrine adenopathy. There were two true negative examinations and one technical failure. The sensitivity of endoscopic ultrasound was much greater than that of computed tomography or conventional transabdominal ultrasonography.     

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure

Angiotensin-converting enzyme (ACE) inhibitors improve survival in heart failure and delay progression to clinical heart failure in patients with left ventricular dysfunction after myocardial infarction. Increasing numbers of older patients are being considered for such treatment. However, there are reports of excessive and prolonged decreases in blood pressure (BP) after the first dose of some ACE inhibitors. We have studied the hemodynamics, pharmacokinetics, and neurohumoral responses to the first dose of oral captopril 6.25 mg, enalapril 2.5 mg, perindopril 2.0 mg, intravenous enalaprilat 1.5 mg, and perindoprilat 1.0 mg, compared with oral or intravenous placebo in 6 parallel groups of 12 elderly patients each with moderate-to-severe (New York Heart Association classes II-IV) heart failure. Oral dosing with active drugs led to different temporal responses. After captopril, there was an early short-lived decrease in BP. Enalapril led to a later long-lasting decrease, but perindopril was not different from placebo. Intravenous enalaprilat and intravenous perindoprilat each lowered BP to a similar extent. The doses of drugs used appeared to be comparable because plasma ACE inhibition was similar following perindopril or enalapril and also comparing perindoprilat and enalaprilat. These studies indicate that oral ACE inhibitors have different profiles of acute BP changes after the first dose. The explanation is not clear, but could include physicochemical differences in the interaction between prodrug ester and diacid metabolites leading to differences in tissue distribution and local enzyme inhibition.     

Visual search for features and conjunctions following declines in the useful field of view

Background/Study Context: Typical measures for assessing the useful field (UFOV) of view involve many components of attention. The objective of the current experiment was to examine differences in visual search efficiency for older individuals with and without UFOV impairment. Methods: The authors used a computerized screening instrument to assess the useful field of view and to characterize participants as having an impaired or normal UFOV. Participants also performed two visual search tasks, a feature search (e.g., search for a green target among red distractors) or a conjunction search (e.g., a green target with a gap on its left or right side among red distractors with gaps on the left or right and green distractors with gaps on the top or bottom). Results: Visual search performance did not differ between UFOV impaired and unimpaired individuals when searching for a basic feature. However, search efficiency was lower for impaired individuals than unimpaired individuals when searching for a conjunction of features. Conclusion: The results suggest that UFOV decline in normal aging is associated with conjunction search. This finding suggests that the underlying cause of UFOV decline may arise from an overall decline in attentional efficiency. Because the useful field of view is a reliable predictor of driving safety, the results suggest that decline in the everyday visual behavior of older adults might arise from attentional declines.     

Cemented hemiarthroplasty or hip replacement for intracapsular neck of femur fracture? A comparison of 7732 matched patients using national data

Background

The treatment of choice for intracapsular neck of femur (NOF) fractures in younger, more active patients remains unknown. Some surgeons advocate total hip replacement (THR).

Aim

This study aimed to compare complications following THR and hemiarthroplasty using the Hospital Episode Statistics (HES) database in England.

Method

Dislocation and revision rates were extracted for all patients with NOF fracture who underwent either cemented hemiarthroplasty or cemented THR between January 2005 and December 2008. To make a ‘like for like’ comparison all 3866 THR patients were matched to 3866 hemiarthroplasty patients (from a total of 41,343) in terms of age, sex and Charlson score.

Results and conclusion

Eighteen-month dislocation was significantly higher in the THR group (2.4% vs. 0.5%, odds ratio (OR) 3.90 (2.99–5.05), p < 0.001). This difference was sustained at the 4-year stage (2.9% vs. 0.9%, OR 3.18 (1.58–6.94), p = 0.001) in a subset of patients with longer follow-up. There was no significant difference in revision rate up to 4 years (1.8% vs. 2.1%, OR 0.85 (0.46–1.55), p = 0.666). In this national analysis of matched patients short- and medium-term dislocation rates following THR were significantly higher than following cemented hemiarthroplasty, without any difference in revision rates at 4 years. The low risk of dislocation may be acceptable in order to experience the apparent functional benefits of THR.     

α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy?

We report a British family with young-onset Parkinson’s disease (PD) and a G51D SNCA mutation that segregates with the disease. Family history was consistent with autosomal dominant inheritance as both the father and sister of the proband developed levodopa-responsive parkinsonism with onset in their late thirties. Clinical features show similarity to those seen in families with SNCA triplication and to cases of A53T SNCA mutation. Post-mortem brain examination of the proband revealed atrophy affecting frontal and temporal lobes in addition to the caudate, putamen, globus pallidus and amygdala. There was severe loss of pigmentation in the substantia nigra and pallor of the locus coeruleus. Neuronal loss was most marked in frontal and temporal cortices, hippocampal CA2/3 subregions, substantia nigra, locus coeruleus and dorsal motor nucleus of the vagus. The cellular pathology included widespread and frequent neuronal α-synuclein immunoreactive inclusions of variable morphology and oligodendroglial inclusions similar to the glial cytoplasmic inclusions of multiple system atrophy (MSA). Both inclusion types were ubiquitin and p62 positive and were labelled with phosphorylation-dependent anti-α-synuclein antibodies In addition, TDP-43 immunoreactive inclusions were observed in limbic regions and in the striatum. Together the data show clinical and neuropathological similarities to both the A53T SNCA mutation and multiplication cases. The cellular neuropathological features of this case share some characteristics of both PD and MSA with additional unique striatal and neocortical pathology. Greater understanding of the disease mechanism underlying the G51D mutation could aid in understanding of α-synuclein biology and its impact on disease phenotype.