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Biomedical subjects

C McKay

Publications and source records attributed to C McKay.

At least 37 records · Page 2Linked to original sources

Impact of assertive community treatment on homeless persons with co-occurring severe psychiatric and substance use disorders.

This study evaluated the impact of an integrated (mental health/substance abuse) assertive community treatment program on homeless persons with serious mental and substance use disorders. High rates of retention in treatment, housing stability, and community tenure were attained, and all but the most severe substance users appeared to gain these benefits. While the intervention appears to be an effective means of retaining in services and monitoring such difficult-to-treat and costly populations, it did not yield high rates of abstinence and social benefits in severe users.

Adult↗

A preliminary investigation into resistance to synthetic pyrethroids by the sheep biting louse (Bovicola ovis) in New Zealand.

Increasing reports of failure of synthetic pyrethroids for the control of Bovicola ovis on sheep lead to a preliminary investigation into the insecticide resistance status of this pest during 1994. Eighteen strains of lice from North and South Island flocks experiencing failure of synthetic pyrethroid treatments to control lice were exposed to cypermethrin (high-cis) in a treated surface (contact) bioassay. Lice from a group of hermit sheep were chosen as a reference susceptible strain against which resistance of field strains was measured and resistance factors (RFs) calculated. Low to moderate resistance to cypermethrin (high-cis) was demonstrated, with RFs ranging from 1.0 to 12.4.

Journal Article↗

(1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol as an inhibitor of ceramidase.

In this study, we have examined the cellular and biochemical activities of the ceramide analog (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (D-erythro-MAPP). Addition of 5 microM D-e-MAPP to HL-60 human promyelocytic leukemia cells resulted in a concentration- and time-dependent growth suppression accompanied by an arrest in the G0/G1 phase of the cell cycle; thus mimicking the action of exogenous ceramides. Its enantiomer L-e-MAPP was without effect. Two lines of evidence suggested that D-e-MAPP may not function as a direct analog of ceramide. First, D-e-MAPP possesses a stereochemical configuration opposite to that of D-erythro-ceramide. Second, D-e-MAPP failed to activate ceramide-activated protein phosphatase in vitro. Therefore, we examined if D-e-MAPP functioned indirectly by modulating endogenous ceramide levels. The addition of D-e-MAPP to cells, but not L-e-MAPP, caused a time- and concentration-dependent elevation in endogenous ceramide levels reaching greater than 3-fold over baseline following 24 h of treatment. Both D-e-MAPP and L-e-MAPP underwent similar uptake by HL-60 cells. D-e-MAPP was poorly metabolized, and remained intact in cells, whereas L-e-MAPP underwent a time- and concentration-dependent metabolism; primarily through N-deacylation. In vitro, L-e-MAPP was metabolized by alkaline ceremidase to an extent similar to that seen with C16-ceramide. D-e-MAPP was not metabolized. Instead, D-e-MAPP inhibited alkaline ceramidase activity in vitro with an IC50 of 1-5 microM. D-e-MAPP did not modulate the activity of other ceramide metabolizing enzymes in vitro or in cells, and it was a poor inhibitor of acid ceramidase (IC50>500 microM). Finally, D-e-MAPP inhibited the metabolism of L-e-MAPP in cells. These studies demonstrate that D-e-MAPP functions as an inhibitor of alkaline ceramidase in vitro and in cells resulting in elevation in endogenous levels of ceramide with the consequent biologic effects of growth suppression and cell cycle arrest. These studies point to an important role for ceramidases in the regulation of endogenous levels of ceramide.

Acid Ceramidase↗

The use of lexipafant in the treatment of acute pancreatitis.

The pathophysiology of systemic organ failure in acute pancreatitis has been the subject of debate for many years but there is growing evidence that increase production of pro-inflammatory cytokines plays an important role. from this work and from the results of studies in experimental pancreatitis there exists a rationale for the use of PAF antagonists in the treatment of acute pancreatitis. Two pilot studies have now demonstrated a beneficial effect of the PAF antagonist Lexipafant on acute pancreatitis which may lead to an important advance in the treatment of these patients. A multicentre trial aiming to recruit 300 patients with severe acute pancreatitis is now underway in the UK, the results of which will be awaited with interest.

Acute Disease↗

Homochirality as the signature of life: the SETH Cigar.

A characteristic hallmark of life is its homochirality: all biomolecules are usually of one hand, e.g. on Earth life uses only L-amino acids for protein synthesis and not their D mirror images. It is therefore suggested that a search for extra-terrestrial life can be approached as a Search for Extra-Terrestrial Homochirality (SETH). A novel miniaturized space polarimeter, called the SETH Cigar, is described which could he used to detect optical rotation as the homochiral signature of life on other planets. Moving parts are avoided by replacing the normal rotating polarizer by multiple fixed polarizers at different angles as in the eye of the bee. It is believed that homochirality will be found in the subsurface layers on Mars as a relic of extinct life.

Astronomy↗

Relationship among cellular diacylglycerol, sphingosine formation, protein kinase C activity, and parathyroid hormone secretion from dispersed bovine parathyroid cells.

To separate the role of changes in parathyroid diacylglycerol (DG) from other effects of extracellular calcium, we studied the effect of inhibition of DG metabolism on PTH secretion and cellular DG content in acutely dispersed bovine parathyroid cells. R 59 022, an inhibitor of DG kinase, increased cellular DG, but significantly decreased PTH secretion. Particulate protein kinase C (PKC) activity decreased in bovine parathyroid cells incubated at high extracellular calcium or in the presence of R 59 022, which is the opposite of what was observed in the presence of the phorbol ester, phorbol myristate acetate. Sphinganine, a normal cellular product that is a known inhibitor of PKC, significantly inhibited PTH secretion at low extracellular calcium, but had no significant effect at normal or high extracellular calcium. We then measured sphingosine in bovine parathyroid cells incubated with high extracellular calcium or R 59 022. Both conditions were associated with significant elevations of cellular sphingosine. These studies suggest that inhibition of PTH secretion and PKC activity by enhanced cellular DG may result from the activation of an inhibitory second messenger pathway involving the sphingoid lipids.

Animals↗

Mononuclear phagocyte activation and acute pancreatitis.

Severe, acute pancreatitis is commonly associated with a systemic illness which may result in multiple organ failure. There is evidence that an aberrant immune response, involving increased secretion of proinflammatory cytokines from activated monocytes and mononuclear phagocytes, is responsible for another systemic illness--septic shock. Previous studies have investigated whether there is a correlation between plasma cytokine levels and severity of pancreatitis. However, these results may not reflect mononuclear phagocyte activation. In this paper, monocytes (collected from patients with severe pancreatitis) were cultured in vitro and secreted cytokine levels measured after 24 hours by ELISA. Secretion of tumour necrosis factor alpha, interleukin-6 and interleukin-8 was higher in cells taken from patients who later developed systemic complications. There was no difference in the secretion of interleukin-1 beta. The mechanism by which mononuclear phagocytes are activated in acute pancreatitis, and the role of genetic predisposition, are discussed.

Acute Disease↗

The safety of manipulative treatment: review of the literature from 1925 to 1993.

Many osteopathic medical students and physicians have an inherent fear of injuring patients when they perform osteopathic manipulative treatment (OMT). Based on the estimated several hundred million treatments performed each year in the United States as well as a review of the literature over the past six decades, only 185 reports of injury were found. However, besides good training in these techniques, the key to the safety of OMT is the taking of a thorough patient history and performing a thorough physical examination before the application of any manipulative procedure.

Adult↗

Advances in poison management.

This article advances the most current concepts in the management of poisoned patients including the use of ipecac, lavage, activated charcoal, whole-bowel irrigation, and specific antidotes. The benefits vs the risks of each of these procedures are reviewed.

Antidotes↗

Screening for tuberculosis infection among secondary school students in Minneapolis-St. Paul: policy implications.

Three students in the St. Paul Public Schools were diagnosed with active tuberculosis (TB) in late 1991 and early 1992. To define the prevalence of TB infection in St. Paul and Minneapolis, we conducted school-based screening projects in the St. Paul and Minneapolis public schools during 1992 and 1993. In St. Paul, 7,596 (74.8%) students in grades six through 12 received Mantoux tests; 268 (3.5%) were reactive. Infection rates varied significantly by country of birth, with students born outside the United States more likely to be Mantoux reactors than U.S.-born students (RR = 20.2; 95% CI = 14.9-27.3; p < 0.001). In Minneapolis, 752 (47.2%) eighth-grade students received Mantoux tests; 23 (3.1%) were reactive. As in St. Paul, infection rates varied by country of birth; students born outside the United States were more likely to have reactive Mantoux tests than students born in this country (RR = 13.2; 95% CI = 5.6-31.4; p < 0.001). We conclude that routine TB screening of school students is not warranted in Minnesota, although school-based screening targeted at the highest risk students, particularly those born outside the United States, may be a beneficial prevention strategy.

Adolescent↗

Definitive identification of an exceptionally high methanol concentration in an intoxication of a surviving infant: methanol metabolism by first-order elimination kinetics.

Intoxication by methanol was identified in a five-week-old infant suffering from moderate metabolic acidosis. The initial serum methanol at admission was 1148 mg/dL as measured by gas chromatography. The osmolal gap and formic acid concentrations were consistent with methanol intoxication. The child was treated with folic acid and a continuous ethanol infusion and survived without any apparent permanent problems. Because expected toxic symptoms did not develop in this case, and the methanol concentrations were at levels that might be deemed to be incompatible with life, blood and urine samples were assayed by a specific enzymatic assay, and by gas chromatography/mass spectrometry (GC/MS). Positive results definitively confirmed the presence of methanol. In contrast to previous reports, the elimination of methanol in this case appeared to following first-order kinetics. If hepatic ADH activity is low in neonates and young infants, another enzyme system such as catalase may be involved to explain this data. The lack of formic acid accumulation may have been due to folic acid therapy.

Acidosis↗

Laparoscopic subtotal cholecystectomy.

Laparoscopic subtotal cholecystectomy has been carried out on 5 patients during a 28-month period. The indications were severe inflammation/fibrosis in 3 patients, cirrhosis with mild portal hypertension in 1 patient and the Mirizzi syndrome in the last patient. There were no deaths and only minor in hospital morbidity. Subtotal cholecystectomy carried out laparoscopically is a safe procedure and can be used in selected patients in order to avoid conversion to an open operation.

Adult↗

Circulating intact parathyroid hormone levels in acute pancreatitis.

Serum levels of parathyroid hormone (PTH), calcium and albumin were measured daily for 5 days in 41 selected patients with moderate to severe acute pancreatitis. The PTH level was measured by means of a two-site immunoradiometric assay specific for the intact polypeptide. A rise in PTH level was observed more commonly in patients with a complicated or fatal outcome than in those with an uncomplicated course (14 of 16 versus six of 25 patients, P < 0.001). Although PTH levels were variable in the presence of hypocalcaemia, raised concentrations were found more frequently in patients with complications (seven of eight versus two of seven without complications, P = 0.035). This study confirms that an appropriate rise in PTH level occurs in response to the hypocalcaemic stimulus in patients with acute pancreatitis.

Acute Disease↗

Predictability of sacral base levelness based on iliac crest measurements.

A level sacral base plane is necessary to allow normalization of complex lumbosacral mechanics. Palpatory examinations are often used to evaluate for leg length discrepancy and pelvic obliquity despite improved accuracy and consistency of radiographic techniques. Treatment based on palpatory examinations suppose a direct and consistent relationship between the pelvic bones (innominates) and the sacral base. To evaluate the relationship between iliac crest levelness and sacral base levelness, a radiographic postural survey in the upright, weight-bearing position was performed on 358 men and women thought to have pelvic obliquity. Of these subjects, 293 demonstrated unlevel iliac crest heights or sacral base > or = 3/16 inch (4.76 mm), with iliac crest heights accurately predicting sacral base position 62% of the time. At > or = 3/8 inch (9.53 mm), 68% of the cases were accurately predicted. When the criterion for unlevelness was increased to > or = 1/2 inch (12.70 mm), the predictive accuracy improved to 83%. Radiographic findings in this study demonstrate a significant difference between iliac crest heights and sacral base position. In cases of mild to moderate short leg syndromes, the iliac crest height is an unreliable predictor of the direction or degree of sacral base levelness.

Adult↗

Hypercalcemia complicating childhood malignancies.

BACKGROUND: Hypercalcemia complicating malignancy is a frequent complication in adults, but little has been published about the pathogenesis or the true incidence of hypercalcemia in children with cancer. METHODS: Hypercalcemia developing in childhood malignancies was studied retrospectively at St. Jude Children's Research Hospital to determine its incidence, the timing of its presentation, and its response to therapy. RESULTS: Over a 29-year period, 25 children (median age, 9.5 years) had been diagnosed and treated for hypercalcemia that occurred during the course of their malignancy. These 25 represented 0.4% of the total number of children treated for cancer at the institution during that period. Their malignancies comprised acute leukemias (11; 0.6%), rhabdomyosarcoma (4; 1.2%), malignant rhabdoid tumor (2), Hodgkin disease (1), non-Hodgkin lymphoma (1), hepatoblastoma (2), neuroblastoma (1), brain tumor (1), angiosarcoma (1), and a solid malignant tumor of undetermined type. CONCLUSIONS: Patients with acute lymphoblastic leukemia were more likely to present with hypercalcemia at the time of their initial diagnosis and to achieve resolution of this complication, whereas patients with solid tumors presented with hypercalcemia later in the course of their disease and had hypercalcemia that was more resistant to therapy. In contrast to adults with cancer, hypercalcemia of malignancy is extremely rare in children.

Adolescent↗

Subtotal cholecystectomy.

Subtotal cholecystectomy has been carried out on 11 patients during a 5-year period, constituting 3.8 per cent of cholecystectomies performed during this time. The indications were severe inflammation/fibrosis in six patients, portal hypertension in three and the Mirizzi syndrome in two patients. There were no deaths and only minor in-hospital morbidity. One patient developed a common bile duct stone 21 months after the operation. None of the remaining patients has to date developed postcholecystectomy sequelae (mean follow-up period 29 (range 1-62) months). Subtotal cholecystectomy is a safe, straightforward and definitive operation in patients for whom standard cholecystectomy could be dangerous, and is a more attractive proposition than cholecystostomy.

Acute Disease↗

Catheter balloon valvuloplasty of stenotic porcine bioprosthetic valves: Part I: Anatomic considerations.

During the last several years, dilating balloons have been applied in the treatment of stenotic cardiac valves. This interest has recently been extended to stenotic porcine bioprosthetic valves. Part I of this review discusses the pathologic processes responsible for degeneration of porcine prostheses: intrinsic calcification (mineralization), cuspal tears and perforations, and cuspal thrombosis (non-infective). These changes form the basis of applied balloon valvuloplasty techniques.

Bioprosthesis↗