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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 667 records · Page 37Linked to original sources
PubMed1990

Reversal of helpless behavior by serotonin uptake blockers in rats.

Serotonergic systems are thought to be involved in the mechanisms of action of antidepressants in humans. There is little evidence, however, to suggest that serotonin uptake blockers are efficacious in animal models of depression. To further explore the antidepressant activity of these drugs, four compounds from this class (citalopram, fluvoxamine, indalpine or zimelidine) were tested in rats subjected to helplessness training. Rats were first exposed to inescapable shocks and 48 h later, shuttle-box training was initiated to evaluate escape learning. Twice-daily IP injections of citalopram (1 mg/kg), fluvoxamine (4 mg/kg), indalpine (1 and 2 mg/kg) and zimelidine (1 and 2 mg/kg) reduced escape deficits in a manner similar to that produced by the tricyclic antidepressants desipramine and clomipramine. Reversal of escape deficit by serotonin uptake blockers was observed only when the drugs were administered after the shuttlebox sessions. At higher doses, the four serotonin uptake blockers were without effect. These data suggest that serotonin uptake blockers exert antidepressant-like effects in animals but only when they produce a moderate stimulation of serotonin neurotransmission.

Animals↗
PubMed1990

Effects of an extract of Ginkgo Biloba (EGB 761) on "learned helplessness" and other models of stress in rodents.

The effects of repeated oral administration of an extract of Ginkgo Biloba (EGB 761) on various behavioral models of stress in rodents were investigated. The models in rats included "learned helplessness," shock-suppressed licking (Vogel conflict test) and forced swimming-induced immobility ("behavioral despair"). The models in mice included shock-suppressed exploration (four plates test), spontaneous exploration (staircase test) and food consumption in a novel situation (emotional hypophagia). Further tests in rats examined the effects of EGB 761 on memory (passive avoidance test) and responsiveness to shock to determine whether the preventive effects observed with EGB 761 in the learned helplessness procedure were due either to drug-induced impairment of memory or to reduced shock sensitivity. In all experiments EGB 761 was administered over 5 days at daily doses of 50 and 100 mg/kg PO. In some experiments (Vogel test, four plates test, staircase test, emotional hypophagia) the effects of acute administration were also investigated. The results showed that repeated administration of EGB 761 (50 and 100 mg/kg/day) before exposure to unavoidable shock (preventive treatment) clearly reduced the subsequent avoidance deficits in the learned helplessness procedure but was less effective when first administered after "helplessness" induction (curative treatment). EGB 761 did not affect performance in the passive avoidance task or alter the animals' response to electric shock, suggesting that the effects observed in the learned helplessness procedure were not due to impaired memory or reduced shock sensitivity. Anxiolytic-like activity was also seen in the emotional hypophagia test in mice where repeated administration of EGB 761 increased the amount of food consumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

A randomized, double-blind, placebo-controlled trial of recombinant human alpha-interferon therapy for chronic non-A, non-B (type C) hepatitis.

The effects of alpha-interferon therapy were evaluated in a prospective, randomized, double-blind, controlled trial of recombinant human interferon alfa-2b versus placebo in patients with well-documented chronic non-A, non-B hepatitis (type C). Forty-one patients, of whom 37 (90%) had hepatitis C virus antibodies in their serum, were enrolled in the trial. Twenty-one patients received interferon (2 million units) and 20 received placebo as subcutaneous injections three times weekly for 6 months. Mean serum aminotransferase activities and liver histology improved significantly in interferon-treated patients but not in placebo recipients. Ten interferon-treated patients (48%) had a complete response to therapy as shown by a reduction of mean serum aminotransferase activities into the normal range during therapy; three more patients had a partial response with aminotransferase activities decreasing by more than 50% on average. In follow up, however, serum aminotransferase levels usually returned to pre-treatment levels; at 6 to 12 months after stopping interferon, only two (10%) patients still had normal aminotransferase activity. These results indicate that alpha-interferon therapy is beneficial in reducing the disease activity in chronic hepatitis C. Only a minority of patients, however, appear to have a long-term response. In this study, interferon was generally well tolerated, with only one patient discontinuing therapy because of adverse effects.

Adult↗
PubMed1990

Therapy of chronic delta hepatitis with interferon alfa-2b.

In this pilot study, 12 patients with chronic delta hepatitis were studied. The diagnosis was based on the presence of antibodies to the hepatitis delta antigen in the serum and hepatitis delta virus RNA and hepatitis delta antigen in the serum and liver. All patients were also positive for hepatitis B surface antigen. The infection was presumed to have been transmitted by intravenous drug abuse in six of the patients, blood transfusion in one and by sexual contact in four (two had antibodies to human immunodeficiency virus in their serum, but did not show signs of acquired immunodeficiency syndrome). In one further patient, the source of infection was unknown. Interferon alfa-2b (INTRON A, Schering-Plough Corporation) was initiated at 5 million units per day subcutaneously for at least 4 months, being reduced by half if side effects occurred. Serum alanine aminotransferase levels, hepatitis delta virus RNA and hepatitis delta antigen were measured at monthly intervals for up to 12 months in some patients. Interferon therapy resulted in decreased serum levels of these three markers. On cessation of therapy, most patients experienced a relapse over 6 months, but alanine amino transferase levels could be normalized once more by restarting interferon therapy. In conclusion, interferon decreased hepatic inflammation by the inhibition of hepatitis delta virus replication, although relapse occurred when interferon was stopped and long-term therapy is required to achieve permanent control of the disease. Care will be required when treating patients with advanced or decompensated liver disease.

Adult↗
PubMed1990

Antidepressant profile of bupropion and three metabolites in mice.

Bupropion is a novel antidepressant, distinct from tricyclic antidepressants both neurochemically and behaviorally. Bupropion forms several metabolites in both rodents and humans. Three chemically different molecules - BW 306, BW 494, and BW 287 - were selected. Comparative assessment of antidepressant activity of bupropion and its metabolites in mice, and pharmacological analysis of possible mechanisms of action of the parent drug and its metabolites (using interaction studies with pimozide, D,L-propranolol, and prazosin) were carried out. The results obtained show that: bupropion has a pharmacological spectrum in various animal models which predicts both antidepressant and stimulatory activity in man. BW 306 is the most active of the metabolites studied and, compared to bupropion, seems more "antidepressant" and less stimulant. BW 494, compared to bupropion or BW 306, has a lower degree of activity in various tests used to evaluate antidepressants. BW 287 has no effect in any of the tests used in this study. The interaction studies with pimozide, D,L-propranolol, and prazosin in the various tests have shown that: the stimulatory effect of bupropion, BW 306, and BW 494 is antagonized by both pimozide and prazosin. in the behavioral despair test, the reduction in the duration of immobility by bupropion and BW 494 is antagonized by pimozide, but not by prazosin or D,L-propranolol. the antagonism of reserpine-induced hypothermia by bupropion and BW 306 is significantly decreased by prazosin and D,L-propranolol, but not by pimozide. These data suggest that the clinical antidepressant profile (without a major stimulatory effect) observed in man after administration of bupropion is related to metabolite BW 306 and possibly to BW 494, rather than to bupropion itself.

Animals↗
PubMed1990

Restriction fragment length polymorphism identification of goat alpha s1-casein alleles: a potential tool in selection of individuals carrying alleles associated with a high level protein synthesis.

The extensive polymorphism of caprine alpha s1-casein, which is controlled by at least seven autosomal alleles segregating in a Mendelian fashion, was investigated by RFLP analysis. Genomic DNA from 77 lactating goats, whose genotypes had been previously determined by electrophoretic analysis of milk proteins, was digested with 11 restriction endonucleases and Southern blots were probed with a radiolabelled ovine alpha s1-casein cDNA. Three enzymes, PstI, TaqI and Rsa I, allowed the unambiguous identification of known alleles alpha s1-CnA, E and O and of the allelic pairs [alpha s1-CnD and F] and [alpha s1-CnB and C]. Evidence for a second null allele, termed alpha s1-CnO', and for an additional allele, designated alpha s1-CnF', was provided, which leads to the identification of nine alleles at the alpha s1-Cn locus, in this species. Although only 15 out of the 45 expected genotypes could be fully ascertained, this procedure allows the identification at birth of animals carrying the alpha s1-CnA, B or C alleles associated with a high alpha s1- and whole-casein content.

Alleles↗
PubMed1990

Increased urinary excretion of transferrin in children with type 1 diabetes mellitus.

Urinary transferrin excretion was measured by radioimmunoassay in 74 children with Type 1 diabetes mellitus and in 40 normal children, and compared with urinary excretion of albumin, alpha-1-microglobulin, and N-acetyl-beta-D-glucosaminidase. Urinary transferrin excretion was significantly elevated in diabetic (median (range) 186 (18-1671) mg mol-creatinine-1) compared with normal (85 (27-668) mg mol-creatinine-1) children (p less than 0.001). Seventeen diabetic children had transferrin excretion above the 95th centile for normal children. In contrast there was no significant increase in urinary albumin excretion in the diabetic children although 8 had urinary albumin excretion which exceeded the 95th centile for normal children (6 of these 8 patients having coexistent urinary hyperexcretion of transferrin). Urinary transferrin excretion correlated significantly with urinary albumin excretion in both normal (rs = 0.62, p less than 0.001) and diabetic (rs = 0.61, p less than 0.001) children. The indices of proximal renal tubular function (urinary excretion of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase) correlated significantly with transferrin excretion in both diabetic (rs = 0.43 and rs = 0.41, p less than 0.001) and normal (rs = 0.40, p less than 0.02 and rs = 0.53, p less than 0.001) children, but not with albumin excretion (rs = 0.20, p greater than 0.05 and rs = 0.22, p greater than 0.05). In addition urinary transferrin excretion significantly correlated with urinary glucose concentration (rs = 0.34, p less than 0.007) in Type 1 diabetic children. The discrepancy in urinary excretion of transferrin and albumin may reflect impaired proximal renal tubular reabsorption of transferrin and/or altered glomerular basement membrane selectivity for the two proteins.

Acetylglucosaminidase↗
PubMed1990

Microproteinuria in type 2 diabetes mellitus from diagnosis.

Glomerular and tubular microproteinuria precede the development of overt nephropathy in Type 1 diabetes mellitus. However, in Type 2 diabetes urinary protein excretion and its relationship to diabetic nephropathy has not been clearly characterized. Twenty consecutive, newly diagnosed patients with Type 2 diabetes, whose urine was Albustix-negative and sterile on culture, were studied. Two timed overnight urine samples were collected at diagnosis, and after 2 months and 2 years, and excretion rates of albumin, alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase were calculated. HbA1c fell from 12.1 +/- 2.4% at diagnosis to 9.5 +/- 1.5% at 2 months and 9.6 +/- 2.2% at 2 years. Albumin excretion rate fell marginally from 6.5 (2.1-242.5) micrograms min-1 at diagnosis to 5.5 (1.7-274.0) micrograms min-1 at 2 months (p less than 0.05) rising again to 6.1 (1.9-201.7) micrograms min-1 at 2 years. alpha-1-Microglobulin excretion rate fell from 13.5 (3.6-59.9) micrograms min-1 at diagnosis to 8.4 (2.9-16.1) micrograms min-1 at 2 months and 8.8 (1.8-54.1) micrograms min-1 at 2 years (both p less than 0.05). Albumin excretion rate was found to correlate significantly with creatinine clearance at diagnosis (rs = 0.61, p less than 0.005), though not subsequently. In contrast, excretion rates of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase correlated with HbA1c (rs = 0.68 and 0.66, respectively, p less than 0.005 at diagnosis and rs = 0.57 and 0.53, p less than 0.05 subsequently in both cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1990

Effects of calcium channel antagonists on the vagally mediated cardiac chronotropic response in dogs.

A brief electrical stimulation of the vagus nerve may elicit a triphasic response comprising (i) an initial prolongation of the same or the next cardiac cycle, (ii) a return of the subsequent cardiac cycle to about the level prior to vagal stimulation, and (iii) a secondary prolongation of cardiac cycle length that lasts several beats. We compared the effects of two calcium channel antagonists, verapamil and nifedipine, on this triphasic response to vagal stimulation in chloralose-anesthetized, open-chest dogs. In the absence of vagal stimulation, nifedipine (doses of 10, 40, and 50 micrograms/kg for a total dose of 100 micrograms/kg, i.v.) and verapamil (two doses of 100 micrograms/kg each, i.v.) increased the cardiac cycle length (A-A interval) by 16% (429 +/- 20 to 496 +/- 21 ms) and 29% (470 +/- 33 to 605 +/- 54 ms), respectively. Nifedipine (100 micrograms/kg total) attenuated the initial vagally mediated prolongation of the A-A interval, from 474 +/- 19 to 369 +/- 42 ms above the basal A-A interval. Following the initial prolongation of the vagal effect, other A-A intervals were not affected. In contrast, verapamil potentiated the vagally mediated initial prolongation in cardiac cycle length at the first dose administered (100 micrograms/kg) from 492 +/- 17 to 561 +/- 14 ms, but other increases in dosages had no further effect. Thus these two calcium channel antagonists have different effects on the sinoatrial chronotropic responses caused by brief vagal stimulation.

Animals↗
PubMed1990

AV junctional rhythm induced by sympathetic-parasympathetic imbalance in dog hearts.

We studied the atrioventricular (AV) junctional rhythm induced by stimulation of discrete autonomic nerves to the AV nodal area in spontaneously beating hearts of anesthetized dogs where all central autonomic connections to the heart had been cut. Simultaneous stimulation of intracardiac sympathetic and parasympathetic nerves to the AV nodal area (AVSP stimulation, at the junction of the inferior vena cava and left atrium) initially increased and then decreased the AV interval. During such stimuli no AV junctional rhythm was observed; however, after cessation of stimulation, an AV junctional rhythm then appeared in 6 of 12 dogs. Because norepinephrine (NE) persists much longer than acetylcholine in cardiac tissues, we postulated that the junctional rhythm was ascribable to the residual NE that had been released during stimulation. After the animals had been given atropine, an AV junctional rhythm was induced in all animals during AVSP stimulation. These junctional rhythms were suppressed by propranolol or by pacing the atria at a rate faster than the rate of the junctional rhythm. These results suggest that a regional sympathetic-parasympathetic imbalance may unmask subsidiary pacemaking activity, such as an AV junctional rhythm.

Animals↗
PubMed1990

The experience of micro- and macroevents. A life span analysis.

This study investigated how individuals retrospectively construe their lives in terms of major life events. Ninety-nine participants sorted a set of personal and historical events in terms of perceived importance for their lives. Analyses of variance with repeated measures and rank comparisons were computed. Overall findings revealed no cohort differences with regard to the perception of life events. However, within-cohort differences were found, indicating that more life events were recalled from the young adult years. Those experiences were also perceived as having been more important in the participants' lives than events from other age segments. With regard to historical events, war-related experiences were among the highest ranked. Analyses of variance revealed intracohort differences but not intercohort differences, indicating higher scores for the time between 1930 and 1948 relative to other historical periods.

Adolescent↗
PubMed1990

Antibody activity against lipopolysaccharides, lipid A and proteins from Enterobacteriaceae in patients with chronic inflammatory liver diseases.

These studies are concerned with detection of circulating antibodies against various defined enterobacterial antigens in patients with chronic inflammatory liver diseases such as chronic hepatitis type B (n = 46), chronic active hepatitis (CAH) of autoimmune type (n = 10), alcoholic cirrhosis (n = 24) and primary biliary cirrhosis (PBC) (n = 24) as well as in healthy individuals (n = 39). Anti-LPS and anti-lipid A were determined by hemolytic and hemagglutination assay. Immunoblot technique was used to investigate the antibody activity against plasmid encoded proteins from Yersinia enterocolitica. Persistent titers of anti-LPS up to serum dilution 1:32.768 were found with hemolytic and hemagglutination assay in patients with alcoholic cirrhosis or PBC and in healthy control. In contrast nearly 50% of patients with chronic hepatitis B had no hemolytic antibodies against the two LPS E. coli serotypes at the time of liver biopsy. Anti-lipid A was detectable in 58% of patients with alcoholic cirrhosis but in low titers in less than 10% in the other groups (p less than 0.001). Alcoholic cirrhosis was also associated with a high frequency of IgG and IgA antibodies against plasmid encoded proteins from Yersinia enterocolitica. The data indicate that the O-polysaccharides as strong antigens are physiologically exposed to the immune system while lipid A and enterobacterial proteins are solely immunogenic under abnormal conditions.

Adult↗
PubMed1990

Tissue patterning in the developing mouse limb.

The developing mouse fore- and hindlimbs begin as bumps on the flank of the embryo and grow out to form miniature models of the adult limb during a five day period from E9.5 to E14.5. In this paper I show a series of embryos taken at half-day intervals during limb development and outline the timetable of patterning for each of the component tissues of a limb: epidermis, connective tissues, muscle, nerves and blood vessels. Scanning electron micrographs, supplemented by histological sections, are presented to define a set of standard stages for the description of mouse limb development. I discuss my observations of the mouse limb in the light of current theories of vertebrate limb development, which are based on classic manipulation experiments in the chick as well as more recent molecular data from the mouse system. The limb skeletal pattern in a mouse is laid down in a proximodistal direction, as it is in a bird: the E11.5 forelimb reveals the first signs of a humerus and by E14.5 even the most distal phalanges of the hand are formed. At this late stage ossification sleeves are seen around the proximal limb elements as the cartilage template begins to be converted to a bony skeleton. Myogenic cells stainable with the MF20 antibody against early muscle myosin heavy chain are first seen in the mouse forelimb at E11.5, which is also when the first nerve fascicles begin to enter the limb. From E11.5 to E14.5 both muscle and nerve patterns mature to give distinct muscles at all proximodistal levels of the limb, each muscle with its own nerve branch, and a cutaneous nerve plexus that extends to the fingertips. The developing skin of the mouse limb matures from a bi-layered epidermis overlying an avascular, but otherwise nondescript, prospective dermal layer of mesenchyme at E9.5, to a 4- or 5-layered epidermis with early hair placodes and the first signs of a distinct dermal layer at E14.5. Notable differences between mouse and chick limb development lie in the relatively late formation of the apical ectodermal ridge in the mouse and its unexpectedly close relations with blood vessels, in the absence of anterior and posterior necrotic zones and, possibly, in a late migration of myogenic cells into the mouse limb bud.

Animals↗
PubMed1990

[Nondilated obstructive anuria complicating urethrocystopexy].

Anuria complicating urethrocystopexy is generally an obstructive uropathy. No urinary tract dilatation had been observed in these two following cases. The rupture of the collecting system, with urinary extravasation, is due to acute ureteral obstruction and furosemide associated. The first exam to be done is the ultrasonography. However, this exploration can fail to demonstrate obstruction. Urgent percutaneous nephrostomy appears to be the best curative method. Surgical liberation of the trapped ureters is almost necessary.

Aged↗
PubMed1990

Use of international data communications standards in hospital laboratories.

The National Health Service is committed to the use of Open Systems Interconnection (OSI) data communications standards. In this paper we describe a project aimed at demonstrating the use of OSI standards in practice. The Pathology Laboratory at Northampton General Hospital is involved in this major project to link its laboratory computer systems with hospital and GP computer systems. The data will be transferred using X.400 messaging standards over an X.25 Wide Area Network. Abstract Syntax Notation One (ASN.1) will be used to encode data being exchanged between laboratory, hospital and GP computer applications.

Computer Communication Networks↗