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Biomedical subjects

A Horton

Publications and source records attributed to A Horton.

At least 19 recordsLinked to original sources
PubMed2000

Immunoplatelet counting: a proposed new reference procedure.

Given the high degree of interoperator error and poor precision of manual platelet counting, it has recently been proposed that an immunoplatelet counting method could become the new reference procedure. Platelets are identified immunologically with a suitable monoclonal antibody, and the platelet count is derived from the ratio of fluorescent platelet events to collected red blood cell (RBC) events that are also counted by a reliable and calibrated standard impedance counter (RBC ratio). In this study, we have set up a rapid and simple method for immunoplatelet counting and simultaneously compared the RBC ratio with the bead ratio derived from two different preparations of commercial calibration beads (Trucount and FlowCount beads). Comparison of the level of imprecision of the RBC ratio with either the manual count or bead ratios revealed a superior coefficient of variation of < 5% even in samples with a platelet count < 20 x 10(9)/l. The RBC ratio correlated extremely well with the existing manual phase reference method (r2 = 0.93) and especially well with three different commercial impedance counters and a dual-angle optical counter (r2 = 0.98-0.99). However, at < 100 x 10(9)/l, the correlation of the RBC ratio with the dual-angle optical count (ADVIA 120) (r2 = 0.96) was superior to all impedance counters. This suggests that automated optical counting methods may be more accurate at determining platelet counts in thrombocytopenic samples. As the RBC ratio is rapid, cheap and relatively easy to perform, we propose that this method could replace the manual count as a new international reference method.

Calibration↗
PubMed1998

Assessing metered-dose inhaler technique: comparison of observation vs. patient self-report.

The purpose of this study was to develop and determine the validity of a patient-completed questionnaire that assesses metered-dose inhaler (MDI) technique. Self-reported MDI technique was compared to observed technique. The questionnaire included nine steps for MDI use, with two to three response choices for each step. A total of 159 patients were studied. Direct observation revealed that greater than 82% of patients exhibited inadequate technique (more than two out of nine steps incorrect). The mean percentage agreement between the questionnaire and observation was 77.4%. Questionnaire results where in higher agreement with observation when patients performed correct MDI technique.

Adolescent↗
PubMed1997

Efficacy of danazol in a patient with congenital protein-S deficiency: paradoxical evidence for decreased platelet activation with increased thrombin generation.

Danazol, a synthetic attenuated anabolic steroid, has been administered for 36 months to a 32 year old male with hereditary Protein S (PS) deficiency who had become non-compliant for warfarin therapy. The patient has an eleven year history of venous thrombosis. Since danazol therapy was initiated, the patient has not experienced a thrombotic event or adverse side-effects. Levels of PS, other inhibitors, fibrinolytic components, and markers for thrombin and platelet activation were measured prior and subsequent to therapy. Following danazol administration, marked and sustained increases were noted in Free Protein S, Antithrombin, and Protein C. Platelet CD62 (P-selectin) positivity which was elevated before therapy, decreased to assay threshold limits within five weeks. Both Prothrombin Fragment 1.2 and thrombin-antithrombin complexes were elevated post danazol therapy indicating continued clearance of generated thrombin. These data suggest that the protective effect provided by danazol in this patient with hereditary PS deficiency, may in large part be due to suppression of platelet activation by thrombin inhibition than simply through elevation of PS.

Adult↗
PubMed1997

Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase.

Neurturin (NTN) is a recently identified homologue of glial-cell-line-derived neurotrophic factor (GDNF). Both factors promote the survival of a variety of neurons, and GDNF is required for the development of the enteric nervous system and kidney. GDNF signals through a receptor complex consisting of the receptor tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor termed GDNFR-alpha. Here we report the cloning of a new GPI-linked receptor termed NTNR-alpha that is homologous with GDNFR-alpha and is widely expressed in the nervous system and other tissues. By using microinjection to introduce expression plasmids into neurons, we show that coexpression of NTNR-alpha with Ret confers a survival response to neurturin but not GDNF, and that coexpression of GDNFR-alpha with Ret confers a survival response to GDNF but not neurturin. Our findings indicate that GDNF and neurturin promote neuronal survival by signalling through similar multicomponent receptors that consist of a common receptor tyrosine kinase and a member of a GPI-linked family of receptors that determines ligand specificity.

Amino Acid Sequence↗
PubMed1997

NGF binding to p75 enhances the sensitivity of sensory and sympathetic neurons to NGF at different stages of development.

To clarify the role of the common neurotrophin receptor p75 in modulating the survival response of sensory and sympathetic neurons to NGF at different stages of development, we compared the actions of wild-type NGF with a mutated NGF protein that binds normally to TrkA, the NGF receptor tyrosine kinase, but has greatly reduced binding to p75. At saturating concentrations, the NGF mutant promoted the survival of similar numbers of trigeminal sensory and sympathetic neurons as NGF. At subsaturating concentrations, the NGF mutant was less effective than wild-type NGF in promoting the survival of embryonic sensory neurons and postnatal sympathetic neurons but was equally effective as wild-type NGF in promoting the survival of embryonic sympathetic neurons. Whereas the levels of trkA and p75 were similar in embryonic sensory neurons and postnatal sympathetic neurons, the level of p75 was significantly lower than that of trkA in embryonic sympathetic neurons. These results indicate that binding of NGF to p75 enhances the sensitivity of NGF-dependent neurons to NGF at stages in their development when the levels of p75 and TrkA are similar.

Animals↗
PubMed1996

Distal mucus fistula following resection for perforated sigmoid diverticular disease.

A retrospective study of 62 consecutive patients undergoing resection of perforated diverticular disease was undertaken to assess influence of distal stump closure (DSC) or creating a distal mucus fistula (DMF) on subsequent restoration of bowel continuity. Forty-one patients underwent DSC and 21 DMF. Mean operating time and hospital stay were 164 min and 30 days for patients undergoing DSC compared with 142 min and 18 days for those undergoing DMF. Of the 54 survivors, 44 underwent reversal (25/35; DSC, 19/19; DMF). Mean operative time and hospital stay was 208 min and 17 days for DSC compared to 143 min and 10 days for DMF (P = 0.0003). Overall mortality and morbidity of either groups were comparable. Distal mucus fistula can often be safely created following resection of perforated sigmoid diverticulitis. This may result in higher reversal rates and significantly reduces the operating time and hospital stay without compromising the outcome.

Aged↗
PubMed1995

GDNF is an age-specific survival factor for sensory and autonomic neurons.

Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of two populations of CNS neurons: motoneurons and midbrain dopaminergic neurons. To see whether GDNF promotes the survival of PNS neurons, we studied embryonic chicken autonomic and sensory neurons in culture. We show that GDNF promotes the survival of sympathetic, parasympathetic, proprioceptive, enteroceptive, and small and large cutaneous sensory neurons. Whereas sympathetic, parasympathetic, and proprioceptive neurons become less responsive to GDNF with age, enteroceptive and cutaneous sensory neurons become more responsive. GDNF mRNA is expressed in the tissues innervated by these neurons, and developmental changes in its expression in several tissues mirror the changing responses of the innervating neurons to GDNF. These results show that GDNF promotes the survival of multiple PNS and CNS neurons and suggest that GDNF may be important for regulating the survival of various populations of neurons at different stages of their development.

Animals↗
PubMed1993

Granisetron and ondansetron: effects on the ileal brake mechanism in the rat.

Studies were carried out on 20 male adult rats to investigate how the action of the selective 5-HT3-receptor antagonists, granisetron and ondansetron, influence gastrointestinal transit under control conditions and when stomach-to-caecum transit was delayed by ileal infusion of lipid. Stomach-to-caecum transit time (SCTT) was measured using environmental hydrogen analysis. Subcutaneous administration of granisetron (BRL 43694, 40, 80 or 150 micrograms kg-1) significantly delayed the passage of the head of the baked bean meal through the stomach and the small intestine under control conditions (P < 0.05). Similarly, subcutaneous administration of ondansetron (GR 38032F, 80 or 150 micrograms kg-1) delayed control SCTT of the head of the meal but this did not reach statistical significance. In contrast, granisetron significantly reversed the delay in SCTT induced by ileal infusion of lipid at 40 (P < 0.001), 80 (P < 0.01) and 150 micrograms kg-1 (P < 0.05). Ondansetron also reversed the lipid-induced delay at 40 (P < 0.01), 80 (P < 0.001) and 150 micrograms kg-1 (P < 0.001). These apparently conflicting results may be rationalized by postulating the presence of 5-HT3 receptors on afferent nerves which, when inhibited by the specific antagonists, initiate reflexes that both accelerate and delay transit.

Animals↗
PubMed1993

Neurotrophin-4/5 is a mammalian-specific survival factor for distinct populations of sensory neurons.

We have studied the effect of human recombinant neurotrophin-4/5 (NT-4/5) on the survival of developing PNS neurons from embryonic mice and chickens. NT-4/5 transiently supported mouse NGF-dependent trigeminal and jugular neurons at early stages of target field innervation and mouse brain-derived neurotrophic factor (BDNF)-dependent no-dose neurons during the phase of naturally occurring cell death. NT-4/5 was as potent as BDNF in supporting the survival of these neuronal populations. Surprisingly, NT-4/5 was 3 orders of magnitude less potent than BDNF as a survival factor for early chick dorsomedial trigeminal sensory neurons and did not support the survival of chick BDNF-dependent trigeminal mesencephalic or ventrolateral trigeminal sensory neurons at any of the developmental stages tested. Thus, NT-4/5 is a survival factor for certain embryonic mouse cranial sensory neurons. It is the first species-specific neurotrophin to be identified and it can discriminate at high concentrations between different BDNF-responsive chick neurons.

Animals↗
PubMed1993

Placebo-controlled trial of lisinopril in normotensive diabetic patients with incipient nephropathy.

To study the effects of an angiotensin converting enzyme inhibitor, lisinopril, on renal function in incipient diabetic nephropathy, a prospective double-blind randomised placebo-controlled single centre study was set up at our outpatient diabetic-renal clinic. There were 27 patients with Type I and Type II diabetes with an albumin excretion rate of between 20 micrograms/min and 200 micrograms/min, respectively and no hypertension. Intervention treatment with placebo or low dose lisinopril was for 48 weeks. The main outcome changes were in urinary albumin excretion rate, urinary prostaglandin excretion, and glomerular filtration rate. Secondary outcome measures included changes in BP and heart rate. Of the 32 patients entered into the study, 27 completed 48 weeks treatment (12 lisinopril, 15 placebo). Mean (+/- SD) urinary albumin excretion rate fell from 57.6 (25.7) micrograms/min (n = 15) at visit 1 to 26.8 (26.7) micrograms/min (n = 12) at visit 7 after 48 weeks treatment in the lisinopril group but not in the placebo group: 119.2 (116.6) micrograms/min (n = 17) vs. 113.7 (77.0) micrograms/min (n = 15). There was a least squares mean treatment difference of -67.6 micrograms/min (95% confidence interval (CI), -115.0 to -20.2, P < 0.01) in favour of lisinopril compared with placebo. After 48 weeks treatment seven lisinopril treated patients were normoalbuminuric and five were microproteinuric; three placebo treated patients were normoalbuminuric, nine were microalbuminuric and three were macroproteinuric. Excretion of prostaglandin-F1 alpha (PGF1 alpha) and thromboxane-B2 (TXB2) fell in the lisinopril treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Comparison of the effects of an angiotensin converting enzyme inhibitor and a calcium antagonist in hypertensive, macroproteinuric diabetic patients: a randomised double-blind study.

The objective of this study was to compare the effects of an angiotensin converting enzyme inhibitor, lisinopril, with those of a calcium blocker, nifedipine, on BP control and renal function, in a prospective randomised double-blind, double-dummy trial lasting 19 weeks in patients with diabetic nephropathy. We enrolled 28 diabetic patients with hypertension and macroproteinuria from the out-patient diabetic-renal clinic. The antihypertensive treatment consisted of lisinopril or nifedipine, and their effect on arterial BP, urinary albumin excretion, glomerular filtration rate, and renal blood flow were measured. BPs at entry were 166/99 (SD 23/9) mmHg for the lisinopril group and 165/99(21/7) mmHg for the nifedipine group. BPs fell to 143/88 (17/13) mmHg for the lisinopril group and 148/85(25/10) mmHg for the nifedipine group at the end of the study. The albumin excretion rate fell in the lisinopril group from 738.7 (635.2) micrograms/min to 644.6 (965.2) micrograms/min and rose in the nifedipine group from 981.2 (1022.2) micrograms/min to 1072.5 (908.5) micrograms/min (P = NS). Glomerular filtration rates fell from 105.2 (57.5) ml/min per 1.73 m2 to 72.1 (39.4) ml/min per 1.73 m2 in the lisinopril group and from 109.9 (50.0) ml/min per 1.73 m2 to 82.9 (53.9) ml/min per 1.73 m2 in the nifedipine treated group. Renal blood flow fell from 446.8 (217.9) ml/min per 1.73 m2 to 435.1 (243.3) ml/min per 1.73 m2 for the lisinopril group and from 473.0 (216.4) ml/min per 1.73 m2 to 419.0 (278.6) ml/min per 1.73 m2 for the nifedipine group. Differences between the groups were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

ECMO in newborn infants: the Melbourne experience.

At the Royal Children's Hospital, Melbourne, extracorporeal membrane oxygenation (ECMO) has been used in the treatment of newborn infants with life-threatening respiratory or cardiac failure since May 1989. The main indications for the use of ECMO are that the disease is reversible, the surviving infant is likely to be normal and there is an 80% likelihood of death without ECMO. Sixteen of 22 (73%) newborn infants have survived at least 6 months after ECMO. Fourteen of 16 (87.5%) infants receiving ECMO (who did not have a congenital diaphragmatic hernia) were functionally normal survivors; the other two infants died. Two of six infants with congenital diaphragmatic hernia who received ECMO were discharged and survived to have normal neurological and respiratory function at 6 month follow up. These results are similar to results from other centres internationally. It would appear that ECMO is a useful therapy for near-term newborn infants with otherwise fatal cardiorespiratory failure.

Australia↗
PubMed1992

Irish brogue after stroke.

BACKGROUND: We describe a patient who presented a unique variation of the previously described acquired foreign accent syndrome. CASE DESCRIPTION: A 65-year-old women developed an Irish brogue immediately after a deep left hemisphere stroke. The newly accented speech possibly represented a previously learned speech pattern. CONCLUSIONS: Suppressed prosodic speech patterns may reemerge in the setting of brain injury.

Aged↗
PubMed1992

Experience with extracorporeal membrane oxygenation in children more than one month old.

Extracorporeal membrane oxygenation (ECMO) has been used at the Royal Children's Hospital, Melbourne, in the treatment of children with life-threatening respiratory or cardiac failure since May 1988. The main indications for its use are, first, the disease is thought to be reversible, second, the child will survive with an acceptable quality of life and, third, the child has an 80% chance of dying without ECMO. Seven of eighteen children receiving ECMO have survived to leave hospital, and all are functionally normal: these results are similar to international results. It would appear that ECMO is a useful therapy for some children with otherwise fatal cardiorespiratory failure.

Adolescent↗
PubMed1991

How can we combat excess mortality in Harlem: a one day survey of substance abuse in adult general care.

Our hypothesis was that a one-day survey of all patients hospitalized on Adult General Care would demonstrate a need for expanded addiction services in a municipal teaching hospital in East Harlem. We interviewed 276 patients in Adult General Care on February 16, 1990 to assess whether they abused drugs or alcohol or were hospitalized for reasons related to substance use. Of the 276 patients interviewed, 18 percent used alcohol alone, 14 percent used drugs alone, 17 percent used both drugs and alcohol and 2 percent were hospitalized for reasons related to substance use. One hundred forty or 51 percent of all patients were admitted because of substance use and its sequelae or as a result of violence associated with the buying or selling of drugs. The percentage was highest on one medical floor where 89 percent of the patients were substance users and on medical floors in general where the average was 60 percent. Forty patients or 14 percent were known to be HIV seropositive. Given the high mortality in Harlem, the results of our one-day survey indicate a need for expanded addiction services.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Severe head injury hastens age of onset of Alzheimer's disease.

Head trauma has been found with greater frequency in the histories of Alzheimer patients than age-matched controls in some studies, but not in others. We hypothesized that events that accelerate neuron loss, such as significant head trauma, hasten the onset of symptoms of Alzheimer's disease in persons vulnerable to the disorder. Retrospective data on 148 probable Alzheimer patients and 33 demented controls were examined. Alzheimer patients with severe head injury before the age of 65 showed onset of symptoms at an earlier age than Alzheimer patients without head trauma.

Age Factors↗
PubMed1988

Electrophoretic mobility studies on doxorubicin-resistant and -sensitive murine P388 leukemic cells.

The electrokinetic properties of doxorubicin (DOX)-resistant (P388/R) and -sensitive (P388/S) murine leukemic cells were studied in a free-flow electrophoresis (FFE) system. The electrophoretic mobilities (EM) of P388/S and P388/R cells were 1.07 and 1.35 x 10(-4) cm2 V-1 s-1, respectively, suggesting a higher net negative charge on the P388/R cells. Neuraminidase treatment decreased the EM of both the P388/S and P388/R cells by 15-20% but had no effect on cellular doxorubicin retention. Total and cell surface sialic acid contents were similar in both the cell lines. Our studies show that no direct correlations may exist among surface charge, cell surface sialic acid content, and doxorubicin retention in DOX-resistant and -sensitive P388 cells; however, differences in cell surface charge between these cell types were used to separate them by preparative FFE.

Animals↗