Regional quality control.

Methods of quality control of some major haematological techniques are described. These methods have been applied in haematology laboratories serving a population of 2 million using existing facilities for preparation and transport of the necessary materials.     

Coronary artery distribution in bonnet monkeys (Macaca radiata)

Full use of nonhuman primates as a model for coronary vascular disease has been hampered by several factors, including the limited availability of detailed coronary anatomic data. This study was undertaken to identify the gross coronary arterial anatomy of the Bonnet monkey (Macaca radiata). The hearts of sixteen adult male Bonnet monkeys were subjected to postmortem coronary angiography and gross morphological examination. The main left coronary artery divided into the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCA). The posterior descending coronary artery (PDCA) arose from the LCA in 31% of the cases and from the right coronary artery (RCA) in 56% of the hearts. Hearts from two animals (13%) had paired arteries, arising from the LCA and RCA, located in the posterior interventricular groove. The arterial supply to the sinoatrial node originated from the LCA in 69% of the animals and from the RCA in the remainder. The atrioventricular node was supplied by a branch of the RCA in 69% of the animals and from the LCA in the remainder. The coronary anatomy of the bonnet monkey resembles that of man more closely than does the dog in terms of origin of the PDCA, supply of the sinoatrial and atrioventricular nodes, and perfusion of the interventricular septum. The Bonnet monkey may therefore be a useful model for certain specific pathophysiological studies on the coronary circulation.     

The sectorial loop-gap resonator for 31P NMR of the adult human liver at 1.5 T with surface tissue suppression

A new type of loop-gap resonator, which because of its topology is called a "sectorial resonator," is described in considerable analytical detail. It was used for 31P NMR of the livers of two human adult normal volunteers. An effective strategy for suppression of signals from surface tissue was developed. Depth selection was achieved using a separate excitation coil, permitting a reasonable degree of control of the shape of the sensitive region by adjustment of the dimensions of the excitation coil and of the type of pulse delivered. In addition a new principle for cancellation is described: the topology of the sectorial resonator leads to cancellation signals from tissue masses at the two openings of the structure. Using a phase-alternated repeated 90 degrees FID pulse sequence, good spectra were achieved in 2.5 min that are free from contamination by the phosphocreatine peak.     

Sciatic artery aneurysms: report of three cases and review of the literature

Sciatic artery aneurysms (SAAs) develop in a persistent sciatic artery, which is a congenital anomalous continuation of the internal iliac artery and may be the major blood supply to the lower extremity. SAAs may appear clinically with rupture, thrombosis, distal embolization, or compression of the sciatic nerve. We have reviewed our three cases and the literature to delineate those factors that permit correct preoperative diagnosis and appropriate surgical intervention. Our three patients (aged 54 to 82 years) appeared with severe ischemia that resulted in above-knee amputations. The literature reveals 21 patients ranging in age from 35 to 84 years (58% were women). Twenty of those patients had operations, one of which resulted in death, and five in above-knee amputations. Unexplained sciatic or buttock pain, or a palpable "pulsating" buttock mass, suggests an SAA. The diagnosis is confirmed by angiography. The recommended treatment is femoropopliteal bypass grafting followed by ligature or percutaneous endovascular thrombosis of the aneurysm. Early diagnosis and correct surgical therapy are the keys to successful management of SAA.     

Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults

Ketogenic diets (KDs) often contain high levels of saturated fat, which may increase liver fat, but the lower carbohydrate intake may have the opposite effect. Using a controlled feeding design, we compared liver fat responses to a hypocaloric KD with a placebo (PL) versus an energy-matched low-fat diet (LFD) in overweight adults. We also examined the added effect of a ketone supplement (KS). Overweight adults were randomized to a 6-week KD (KD + PL) or a KD with KS (KD + KS); an LFD group was recruited separately. All diets were estimated to provide 75% of energy expenditure. Weight loss was similar between groups (p > 0.05). Liver fat assessed by magnetic resonance imaging decreased after 6 week (p = 0.004) with no group differences (p > 0.05). A subset with nonalcoholic fatty liver disease (NAFLD) (liver fat > 5%, n = 12) showed a greater reduction in liver fat, but no group differences. In KD participants with NAFLD, 92% of the variability in change in liver fat was explained by baseline liver fat (p < 0.001). A short-term hypocaloric KD high in saturated fat does not adversely impact liver health and is not impacted by exogenous ketones. Hypocaloric low-fat and KDs can both be used in the short-term to significantly reduce liver fat in individuals with NAFLD.     

Effects of Palm Stearin versus Butter in the Context of Low-Carbohydrate/High-Fat and High-Carbohydrate/Low-Fat Diets on Circulating Lipids in a Controlled Feeding Study in Healthy Humans

Background. Foods rich in saturated fatty acids (SFAs) have been discouraged by virtue of their cholesterol-raising potential, but this effect is modulated by the food source and background level of carbohydrate. Objective. We aimed to compare the consumption of palm stearin (PS) versus butter on circulating cholesterol responses in the setting of both a low-carbohydrate/high-fat (LC/HF) and high-carbohydrate/low-fat (HC/LF) diet in healthy subjects. We also explored effects on plasma lipoprotein particle distribution and fatty acid composition. Methods. We performed a randomized, controlled-feeding, cross-over study that compared a PS- versus a Butter-based diet in a group of normocholesterolemic, non-obese adults. A controlled canola oil-based ‘Run-In’ diet preceded the experimental PS and Butter diets. All diets were eucaloric, provided for 3-weeks, and had the same macronutrient distribution but varied in primary fat source (40% of the total fat). The same Run-In and cross-over experiments were done in two separate groups who self-selected to either a LC/HF (n = 12) or a HC/LF (n = 12) diet track. The primary outcomes were low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL)-C, triglycerides, and LDL particle distribution. Results. Compared to PS, Butter resulted in higher LDL-C in both the LC/HF (13.4%, p = 0.003) and HC/LF (10.8%, p = 0.002) groups, which was primarily attributed to large LDL I and LDL IIa particles. There were no differences between PS and Butter in HDL-C, triglycerides, or small LDL particles. Oxidized LDL was lower after PS than Butter in LC/HF (p = 0.011), but not the HC/LF group. Conclusions. These results demonstrate that Butter raises LDL-C relative to PS in healthy normocholesterolemic adults regardless of background variations in carbohydrate and fat, an effect primarily attributed to larger cholesterol-rich LDL particles.     

A bifunctional dihydrofolate synthetase--folylpolyglutamate synthetase in Plasmodium falciparum identified by functional complementation in yeast and bacteria

Folate metabolism in the human malaria parasite Plasmodium falciparum is an essential activity for cell growth and replication, and the target of an important class of therapeutic agents in widespread use. However, resistance to antifolate drugs is a major health problem in the developing world. To date, only two activities in this complex pathway have been targeted by antimalarials. To more fully understand the mechanisms of antifolate resistance and to identify promising targets for new chemotherapies, we have cloned genes encoding as yet uncharacterised enzymes in this pathway. By means of complementation experiments using 1-carbon metabolism mutants of both Escherichia coli and Saccharomyces cerevisiae, we demonstrate here that one of these parasite genes encodes both dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS) activities, which catalyse the synthesis and polyglutamation of folate derivatives, respectively. The malaria parasite is the first known example of a eukaryote encoding both DHFS and FPGS activities in a single gene. DNA sequencing of this gene in antifolate-resistant strains of P. falciparum, as well as drug-inhibition assays performed on yeast and bacteria expressing PfDHFS--FPGS, indicate that current antifolate regimes do not target this enzyme. As PfDHFS--FPGS harbours two activities critical to folate metabolism, one of which has no human counterpart, this gene product offers a novel chemotherapeutic target with the potential to deliver a powerful blockage to parasite growth.