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Biomedical subjects

A Young

Publications and source records attributed to A Young.

At least 235 records · Page 13Linked to original sources

Studies on central nervous system serotonin receptors in mood disorders.

The evidence from studies of central nervous system serotonin (5-HT) receptors is reviewed and the role of these in the pathogenesis of mood disorders is discussed. Clinical evidence indicates that 5-HT function is abnormal in mood disorders. 5-HT precursors and selective inhibitors of 5-HT uptake are effective antidepressives and inhibition of 5-HT synthesis can block the action of antidepressives. Studies of 5-HT in experimental animals after chronic administration of antidepressive treatments suggest that intact 5-HT neurons are necessary for the action of these treatments. Multiple 5-HT receptor subtypes have recently been identified and the effects of chronic antidepressive treatment on some receptor subtypes function in experimental animals have been established. The increasing availability of powerful new in vivo imaging techniques like single photon emission tomography (SPET), and positron emission tomography (PET) may make possible a more direct examination of 5-HT receptor function in patients suffering from mood disorders.

Animals↗

The Drug Advisory Service of England and Wales--the first 2 years.

An historical account is presented of the introduction and subsequent work of the Drug Advisory Service (DAS) of England and Wales since 1986. Data are presented from an analysis of the recommendations contained within the first 11 reports. The structural and operational strengths and weaknesses of the present approach are considered, and alternative approaches which might constitute constructive modifications or supplements to the present system are discussed.

Community Mental Health Services↗

Reflex actions of knee joint afferents during contraction of the human quadriceps.

(1) The spinal reflex actions of afferents stimulated by knee joint distension have been investigated in man. (2) Cannulation of the knee and infusion of saline raised intra-articular pressure, especially during quadriceps contraction. High pressures did not induce any sensation of pain. Pressure was taken as an index of joint proprioceptor activation. (3) Increased pressure progressively depressed the quadriceps H-reflex, both at rest and during quadriceps contraction. There was no indication of a threshold pressure for this inhibitory action. (4) It is concluded that joint distension inhibits quadriceps motoneurons through spinal pathways that still operate during voluntary contraction. These pathways could thus contribute to pathological weakness after joint injury. (5) Joint distension produced spatial facilitation of non-reciprocal inhibition of quadriceps H-reflexes from afferents in the tibial nerve.

Adult↗

Evaluation of a nonisotopic probe for detection of Chlamydia trachomatis in endocervical specimens.

A nonisotopic probe (Gen-Probe PACE; Gen-Probe, Inc., San Diego, Calif.) for detection of Chlamydia trachomatis in endocervical specimens was evaluated in 344 women attending a dysplasia clinic or an obstetrics clinic and 158 women who visited an emergency room. For each patient, the probe, a tissue cell culture, and a direct immunofluorescent-antibody test (DFA; MicroTrak; Syva Co., Palo Alto, Calif.) were used. C. trachomatis was detected in 54 specimens by at least one method. Forty-four, 44, and 37 specimens were positive by culture, probe, and DFA, respectively, and 31 were positive by all three methods. Considering culture-positive plus both probe- and DFA-positive results as the "gold standard," we determined the overall sensitivity, specificity, and positive and negative predictive values of the probe to be 80, 98, 82, and 98%, respectively. These values were 94, 98, 84, and 99%, respectively, in emergency room patients and 71, 98, 80, and 97%, respectively, in clinic patients. The sensitivities, specificities, and negative predictive values of the DFA and probe were comparable. The positive predictive values of the DFA in all patients and in emergency room and clinic patients were 97, 100, and 95%, respectively. Given the number of probe-positive results that were not confirmed by culture, we do not recommend using the Gen-Probe PACE to screen for C. trachomatis in women with a low to moderate risk for infection.

Cervix Uteri↗

Diarrhoea of famine and malnutrition: investigations using a rat model. 1. Jejunal hypersecretion induced by starvation.

The effects of progressive starvation for up to three days on the secretory functions of the intestine were investigated using in vitro and in vivo preparations of rat jejunum and secretagogues whose action was either through cyclic AMP or Ca++. Initial starvation for 24 h (day 1) did not significantly alter the basal net electrogenic ion secretion measured in vitro as the short circuit current (Isc, muamps/cm2) or the change in electrogenic ion secretion (delta Isc) induced by the secretagogues. By day 2 of starvation, however, the maximum delta Isc transient induced by the cholinergic and other secretagogues (delta Isc = Isc max-basal Isc) was greatly increased (up to a maximum of 117%) compared with the fed controls on an area basis. The delta Isc were even greater on day 3 of starvation. If a tissue weight basis was used to normalise the data the increase became even more marked. The enhancement in secretion was not caused by a decrease in absorptive capacity as glucose, added mucosally, gave larger increases in absorptive currents in the starved than in the fed jejuna. Bethanecol dose-delta Isc response curves in fed and starved jejuna showed an increase in the maximum electrogenic secretion in the starved but no apparent change in the affinity of their cholinergic receptors mediating the enhanced secretion. The starvation-induced increase in secretion elicited by bethanecol was blocked by atropine, indicating that the receptors were muscarinic, but was unaffected by tetrodotoxin indicating that the enteric neural innervation was not essential for its expression. Noradrenaline released by tyramine was greater in the starved than the fed jejunum, suggesting that a decreased sympathetic tone was unlikely to be the major cause of the starvation induced secretory enhancement. Measurement of jejunal fluid movements in vivo showed that in fed controls and throughout the three days of starvation there was an unchanged net fluid absorption in the basal, unstimulated state. By day 2 and day 3 of starvation, however, bethanecol stimulated fluid secretion was very much greater than that of the fed controls. This increase in fluid secretion was concomitant with significant increases in the concentration of chloride in the lumenal fluid. Starvation thus appears to make the rat jejunum hypersensitive to cholinergic and other secretagogues, increasing the electrogenic secretion of chloride in vitro and that of chloride and fluid in vivo. These results obtained with the rat model give a new insight into possible mechanisms by which the diarrhoea of human famine and malnutrition may be expressed.

Animals↗

Diarrhoea of famine and malnutrition--investigations using a rat model. 2--Ileal hypersecretion induced by starvation.

The effects of progressive starvation for up to three days on the basal and secretagogue stimulated secretory functions of the rat ileum were investigated in vitro and in vivo. The secretagogues used included agents acting via cyclic AMP (dibutyryl cyclic AMP, theophylline, forskolin, and PGE2) and those acting via Ca++ (acetylcholine, bethanecol, carbachol, 5-hydroxytryptamine, and A23187). Starving rats for 24 h (day 1) had no effect on the basal electrogenic secretion (measured as the short circuit current, Isc muamps/cm2) or on the stimulated maximum electrogenic secretion (measured as the delta Isc where delta Isc = maxIsc-basal Isc). By day 2 of starvation, however, both the basal Isc and the delta Isc induced by all the secretagogues were significantly greater than in the fed and increased even more on day 3. Replacement of all the chloride ions and inhibition by furosemide indicated that the enhanced secretion was due mainly to chloride ions. Cholinergic stimulation was blocked by atropine, indicating the stimulation was via muscarinic receptors while cholinergic dose - delta Isc response curves for fed and starved ilea showed significantly increased maximum electrogenic secretory response in the latter but no evidence of any change in the affinity (ED50) of the receptors mediating the response. The basal secretion and the secretory response to acetylcholine in both fed and starved ilea was unaffected by tetrodotoxin, revealing that the enhanced secretory response could be expressed via the muscarinic receptors on the enterocytes without the enteric neural network. Measurement of ileal fluid movement in vivo showed that in fed and day 1 starved rats the basal, unstimulated 'tone' of the ileum was absorptive. On day 2, however, the basal 'tone' had reversed to one of secretion which increased further on day 3. Stimulation of fluid secretion in vivo by bethanecol, carbachol, or PGE2 induced larger increases in the starved ilea by day 2 which increased even further on day 3. Lumenal chloride and bicarbonate concentrations were greater in the starved ileal fluid than in the fed. The studies in rat ileum confirm and extend those on rat jejunum and indicate that starvation creates a hypersensitive small bowel that responds to secretagogues and cholinergic neurotransmitters with a greatly enhanced secretory response.

Acetylcholine↗

Digoxin-like immunoreactive substances in the plasma of intensive care unit patients: relationship to organ dysfunction.

Digoxin-like immunoreactive substances are an endogenous group of compounds that cross-react in conventional immunoassays for digoxin. Plasma digoxin-like immunoreactive substance concentrations were estimated using the Abbott TDxll fluorescence polarisation immunoassay kit for digoxin. Digoxin-like immunoreactive substances were measured in one hundred consecutive Intensive Care Unit (ICU) patients who were not treated with digoxin. One hundred healthy blood donors were used as controls. Thirty of the ICU patients had plasma digoxin-like immunoreactive substance concentrations greater than or equal to the greatest value found in the control group (0.22 nmol/l). In the ICU group the median value was 0.17 nmol/l and the range zero to 1.69 nmol/l. In the control group the median was less than the limit of detection of the assay, and the range zero to 0.22 nmol/l. Sixteen ICU patients had coexisting renal and hepatic dysfunction and this group had a median digoxin-like immunoreactive substance concentration of 0.21 nmol/l (range zero to 1.69 nmol/l), while 38 patients with hepatic dysfunction and normal renal function had a median concentration of 0.17 nmol/l (range zero to 0.77 nmol/l). In contrast four patients with renal dysfunction only had a median concentration of 0.05 nmol/l (range zero to 0.34 nmol/l). The remaining forty-two patients had neither hepatic nor renal dysfunction and this group had a median concentration of 0.15 nmol/l (range zero to 0.36 nmol/l). This study has identified the critically ill as a group of patients who exhibit measurable plasma digoxin-like immunoreactive substances using the most commonly used kit for analysis of digoxin.

Adolescent↗

Cloning and expression of a trypomastigote-specific 85-kilodalton surface antigen gene from Trypanosoma cruzi.

An 85-kDa trypomastigote-specific surface antigen gene from Trypanosoma cruzi has been identified by screening a genomic library in lambda gt10 with trypomastigote and epimastigote cDNA. The 1.3-kb genomic clone (pTt34) hybridizes to a single trypomastigote mRNA of 3.7 kb and to multiple bands in genomic Southern blots. Dot-blot experiments show that there are 5-10 copies of this sequence per haploid genome, and these are arranged in a non-tandem manner. pTt34 has been expressed as an anthranilate synthetase fusion protein in Escherichia coli, and inclusion bodies have been used to raise antiserum in rabbits. This antiserum immunoprecipitates a cell surface trypomastigote-specific protein of 85 kDa. The DNA and predicted amino acid sequences of pTt34 are given. Four further clones obtained from a PvuII/HpaI partial genomic library in pUC13 have extended the sequence of the 3' end of pTt34; each of these clones has regions of sequence divergence and each could represent a different member of the gene family.

Amino Acid Sequence↗

The relationship of cerebral atrophy and T1 in alcoholics: an MRI study.

There was a significant correlation between two measures of cerebral atrophy (the ventricle to brain ratio and the relative cerebral volume) and T1 in 19 detoxified alcoholics. This provides further evidence that T1 is a marker of structural damage in alcoholics although the partial volume effect of CSF may contribute to this finding. This has implications for studies comparing alcoholics to normal controls and suggests that better ways of excluding CSF need to be found.

Adult↗

Fluid balance, vasopressin and withdrawal symptoms during detoxification from alcohol.

Nineteen patients were studied during the first 4 days after withdrawal from alcohol. Plasma vasopressin was raised (P less than 0.05) and fluid retention occurred (P less than 0.05), with falls in haematocrit (P less than 0.01) and calculated plasma osmolality (P less than 0.02), which were consistent with expansion of plasma volume. Despite these changes mean total body water was within normal limits although there were substantial inter-individual variations. There was no correlation between any measure of fluid balance and the severity of withdrawal symptoms.

Adult↗

Focal retrograde amnesia: a long term clinical and neuropsychological follow-up.

A patient (E.D.) who had displayed a selective retrograde amnesia in association with transient amnesic episodes (Kapur et al., 1986) was reexamined five years after initial assessment. At the clinical level, his transient amnesic attacks continued, but some of these had clear epileptic features. In addition, EEG investigation indicated temporal lobe abnormality, more prominent in the left temporal region, and supported a clinical diagnosis of temporal lobe epilepsy. Both CT scanning and magnetic resonance imaging were unable to detect the presence of any structural lesion. At the neuropsychological level, there was no evidence of dementia in the form of generalized cognitive dysfunction nor significant deterioration in cognitive functioning since the earlier assessment. Our patient continued to show marked memory loss for public events over the past 20-30 years, in the context of normal or near normal performance on most tests of anterograde memory functioning. While memory for famous scenes and famous faces was markedly impaired, our patient's memory for famous cars was within normal limits and his memory for autobiographical events showed only patchy impairment. Although E.D. performed at an average or above average level on most standard tests of anterograde memory functioning, our patient did show evidence of significant memory loss for public events which had occurred over the past ten years (i.e. since the onset of his illness). The possibility is raised that E.D.'s memory disorder may represent a form of disconnection syndrome.

Aged↗