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Biomedical subjects

M Sumner

Publications and source records attributed to M Sumner.

9 recordsLinked to original sources
PubMed2004

Type 3 von Willebrand disease: assessment of complications and approaches to treatment -- results of a patient and Hemophilia Treatment Center Survey in the United States.

It has been reported many times that the optimal treatment of patients with von Willebrand disease (VWD) has yet to be determined. To assist in achieving this goal, the aim of this survey was as follows: to collect information on current treatment practices; to determine the impact of the disease in type 3 VWD patients in the USA and to gain insight into the perceived and actual role that prophylaxis therapy plays in patient management. Nurse coordinators of the 146 federally funded Hemophilia Treatment Centers (HTCs) in the USA were contacted and informed of the survey and its goals. Those caring for type 3 VWD patients and willing to participate in the survey were mailed two questionnaires. The first questionnaire addressed the overall VWD patient population at their centre and asked questions relating to treatment practices. The second questionnaire focused on the impact that type 3 VWD has upon a patient's life. Thirty-four centres responded to the survey, providing a 48% response rate within the available pool of those centres treating type 3 VWD patients. Seventy-nine patients, with a mean age of 24.2 years, reported their primary causes of bleeding as; epistaxis (53.9%); joint bleeds (40.9%); dental bleeds (27.6%) and heavy menstrual bleeding (23.7%). There were a mean number of 9.2 reported non-life-threatening bleeds per year and a mean of 0.7 reported life-threatening bleeds per year. Forty percent reported lost days from school or work, caused by bleeds or other VWD complications. Sixty-two percent reported no joint damage. Regarding current treatment practices, 88.6% of respondents stated that their centre treated on demand and 13.9% used a prophylactic treatment regimen. Seventy-three percent of respondents felt that prophylaxis was either very or extremely helpful. This survey helps to document current treatment practices and morbidity exhibited by type 3 VWD patients. The results highlight the discrepancy between the use of prophylactic therapy, its perceived value and the level of joint damage and other morbidity experienced in this population.

Adolescent↗
PubMed2001

alpha(1)-adrenergic receptors mediate LH-releasing hormone secretion through phospholipases C and A(2) in immortalized hypothalamic neurons.

Norepinephrine has long been known to stimulate the pulsatile and preovulatory release of LH-releasing hormone (LHRH). In vivo and in vitro studies indicate that these effects are mediated primarily through alpha(1)-adrenergic receptors (alpha(1)-ARs). With the immortalized hypothalamic LHRH neurons, we have found that alpha(1)-adrenergic agents directly stimulate the secretion of LHRH in a dose-dependent manner. Ligand binding and RNA studies demonstrate that the GT1 cells contain both alpha(1A)- and alpha(1B)-ARs. Competition binding experiments show that approximately 75% of the binding is due to alpha(1B)-ARs; the remainder is made up of alpha(1A)-ARs. Receptor activation leads to stimulation of PLC. PLC beta 1 and PLC beta 3 are expressed in GT1 neurons, and these PLCs are probably responsible for the release of diacylglycerol and IP as well as the increase in intracellular calcium. The mobilization of cytoplasmic calcium is sufficient to stimulate cytosolic PLA(2) (cPLA(2)) and release arachidonic acid. A dissection of the contributions of the phospholipases to LHRH secretion suggests that cPLA(2) acts downstream of PLC and that it significantly augments the PLC-stimulated LHRH secretory response. Inasmuch as the alpha(1)-ARs are known to play a critical role in LHRH physiology, we propose that both PLC and cPLA(2) are critical in regulating and amplifying LHRH release.

Arachidonic Acid↗
PubMed1998

Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability.

OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.

Adolescent↗
PubMed1995

Effects of aluminium on the hepatic inositol polyphosphate phosphatase.

There is speculation that some of the toxic effects of Al3+ may originate from it perturbing inositol phosphate/Ca2+ signalling. For example, in permeabilized L1210 mouse lymphoma cells, 10-50 microM Al3+ activated Ins(1,3,4,5)P4-dependent Ca2+ mobilization and Ins(1,3,4,5)P4 3-phosphatase activity [Loomis-Husselbee, Cullen, Irvine and Dawson (1991) Biochem. J. 277, 883-885]. Ins(1,3,4,5)P4 3-phosphatase activity is performed by a multiple inositol polyphosphate phosphatase (MIPP) that also attacks Ins(1,3,4,5,6)P5 and InsP6 [Craxton, Ali and Shears (1995) Biochem. J. 305, 491-498]: 5-50 microM Al3+ increased MIPP activity towards both Ins(1,3,4,5)P4 (by 30%) and Ins(1,3,4,5,6)P5 (by up to 500%), without affecting metabolism of InsP6. Higher concentrations of Al3+ inhibited metabolism of all three substrates, and in the case of InsP6, Al3+ altered the pattern of accumulating products. When 1-50 microM Al3+ was present, InsP6 became a less effective inhibitor of Ins(1,3,4,5)P4 3-phosphatase activity; this effect did not depend on the presence of cellular membranes, contrary to a previous proposal. The latter phenomenon largely explains how, in a cell-free system where Ins(1,3,4,5)P4 3-phosphatase is inhibited by endogenous InsP6, the addition of Al3+ can apparently increase the enzyme activity. However, there was no effect of either 10 or 25 microM Al3+ (in either the presence or absence of apotransferrin) on inositol phosphate profiles in either Jurkat E6-1 lymphoma cells or AR4-2J pancreatoma cells.

Aluminum↗