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Biomedical subjects

R J Porter

Publications and source records attributed to R J Porter.

At least 19 recordsLinked to original sources
PubMed2003

Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly.

BACKGROUND: The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects. METHOD: Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions. RESULTS: Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group. CONCLUSION: Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.

Affect↗
PubMed2001

Basal activity of the hypothalamic-pituitary-adrenal axis in patients with depersonalization disorder.

Depersonalisation disorder may occur during severe anxiety or following a traumatic event, suggesting a possible role of stress hormones. This study investigated basal activity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with depersonalisation disorder. Salivary cortisol levels were measured at four time points over 12 h in patients with depersonalisation disorder (N=13), major depressive disorder (MDD, N=14) and healthy controls (N=13). Beck Depression Inventory scores were significantly higher in depersonalised subjects than controls, while MDD subjects demonstrated higher scores than both groups. Basal cortisol levels of depersonalised subjects were significantly lower than those of MDD subjects but not healthy controls. These results point to reduced basal activity of the HPA axis in depersonalisation disorder. This pilot study supports the distinction between depersonalisation disorder and major depressive disorder which should be examined in a larger sample.

Adult↗
PubMed2000

Effect of hydrocortisone on the pituitary response to growth hormone releasing hormone.

RATIONALE: In depression, the growth hormone (GH) response to clonidine and L-tryptophan (L-TRP) is reduced, suggesting reduced alpha2-adrenergic and serotonin (5-HT)1A receptor function. Pretreatment with hydrocortisone (100 mg, orally 11 h before) also blunts the GH response to L-TRP. This effect may be mediated at the hypothalamic level via reduced 5-HT1A receptor function or at the pituitary level, either by a direct effect on somatotrope cells or via enhanced insulin-like growth factor-1 (IGF-1) or somatostatin (SS) release. OBJECTIVES: To examine the effects of acute and chronic exposure to hydrocortisone on baseline and stimulated GH release from the pituitary. METHODS: Twelve healthy male volunteers received pretreatment with acute hydrocortisone (100 mg, 11 h before), chronic hydrocortisone (20 mg twice a day for 1 week) and placebo in a double blind, balanced order, crossover design. Serial measurements of plasma GH, IGF-1 and thyroid stimulating hormone (TSH) levels were made at baseline and following intravenous administration of 1 mcg/kg GHRH. RESULTS: The GH response to growth hormone releasing hormone (GHRH) was significantly blunted by pretreatment with both acute and chronic hydrocortisone. Baseline IGF-1 levels were significantly lower at baseline after chronic hydrocortisone compared with placebo. Baseline TSH levels were significantly lower after acute hydrocortisone compared with placebo, suggesting an increase in somatostatin levels. CONCLUSIONS: These data suggest that hydrocortisone acts at the pituitary level to reduce GH release. The TSH and IGF-1 data support the hypothesis that hydrocortisone reduces GH release by enhancing somatostatin and IGF-1 release.

Adult↗
PubMed2000

Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease.

OBJECTIVE: The study assessed the effects on global cognitive function and mood of a reduction of brain serotonin by means of acute tryptophan depletion in 16 patients with dementia of the Alzheimer type and in 16 cognitively intact comparison subjects. METHOD: In a double-blind, crossover design, subjects received a tryptophan-free amino acid drink to induce acute tryptophan depletion and, on a separate occasion, a placebo drink containing a balanced mixture of amino acids. On each occasion, ratings of depressed mood were made at baseline and 4 and 7 hours later, and the Modified Mini-Mental State was administered at baseline and 4 hours later. RESULTS: Patients with dementia of the Alzheimer type had a significantly lower mean score on the Modified Mini-Mental State after acute tryptophan depletion than after receiving placebo. The comparison group showed no difference in mean score on the Modified Mini-Mental State after acute tryptophan depletion and after receiving placebo. No significant changes in mood were found in either group. CONCLUSIONS: Acute tryptophan depletion significantly impaired cognitive function in patients with dementia of the Alzheimer type. Compromised serotonergic function, in combination with cholinergic deficit, may make an important contribution to cognitive decline in dementia of the Alzheimer type.

Aged↗
PubMed1999

Effects of dexamethasone on neuroendocrine and psychological responses to L-tryptophan infusion.

UNLABELLED: 5-Hydroxytryptamine1A (5-HT1A) receptors have been shown to be suppressed by corticosteroid hormones in a variety of animal experimental paradigms. This effect may be central to the pathophysiology of severe clinical depressive illness, a condition in which 5-HT1A receptor function is reduced and corticosteroid hormones are elevated. Evidence suggests that the growth hormone (GH) response to L-tryptophan (L-TRP) is mediated by 5-HT1A receptors. This response has been shown to be reduced following acute administration of hydrocortisone. The purpose of this study was to examine the effects of acute administration of dexamethasone, in normal volunteers, on hormonal and psychological responses to L-TRP infusion. METHODS: Sixteen healthy male volunteers took part in a random order, double blind study, in which 5 mg dexamethasone or placebo was administered 11 h before infusion of L-TRP. RESULTS: Pretreatment with dexamethasone had no effect on the GH response to the infusion. However, baseline prolactin (PRL) was significantly reduced, as was the prolactin response to the infusion. CONCLUSIONS: These data contrast with a previous study using hydrocortisone in the same paradigm and demonstrate important functional differences between dexamethasone and hydrocortisone.

Adolescent↗
PubMed1999

Acute effects of venlafaxine and paroxetine on serotonergic transmission in human volunteers.

RATIONALE: Antidepressant drugs are thought to enhance serotonergic neurotransmission through postsynaptic 5-HT(1A) receptors. This effect is delayed in animals and may be paralleled by a delay in the onset of a clinical response in humans. In humans, the growth hormone (GH) response to intravenous l-tryptophan (IV l-TRP) is blocked by the 5-HT(1A) antagonist pindolol and the prolactin response is blunted. Both are therefore thought to be a useful measure of 5-HT(1A) receptor function. Clomipramine has previously been found to enhance the GH and prolactin responses to IV l-TRP after only 2 h. OBJECTIVE: The purpose of this study was to use this method to investigate the effects of newer antidepressants on 5-HT(1A) receptor-mediated function. METHODS: Twelve healthy male volunteers took part in a random order, double blind study, in which 18.75 mg venlafaxine, 5 mg paroxetine or placebo was administered 3 h before infusion of l-TRP. RESULTS: Pretreatment with venlafaxine significantly enhanced the growth hormone (GH) response to the infusion compared with pretreatment with placebo. There was no significant difference between the GH response following paroxetine compared with placebo or with venlafaxine. CONCLUSIONS: The data suggest enhancement of transmission through postsynaptic 5-HT(1A) receptors by venlafaxine but not paroxetine, after only 3 h.

Adolescent↗
PubMed1999

Role of FcgammaRI (CD64) in erythrocyte elimination and its up-regulation in thalassaemia.

To examine any role of the high affinity Fcgamma class I receptor (FcgammaRI) (CD64) in erythrocyte elimination by mononuclear phagocytes (MP) in thalassaemia (thal), we investigated the in vitro interaction of beta-thalassaemic erythrocytes with monocytes (Mo) whose FcgammaR expression had been modulated by cytokines. Treatment of Mo with interferon (IFN)-gamma or interleukin (IL)-10 which up-regulate FcgammaRI, caused a dose-dependent increase in binding of beta-thalassaemic erythrocytes, whereas stimulation with IL-4 which down-regulates the receptor, reduced this interaction, in a dose-dependent manner, to that of normal erythrocytes. Binding of thalassaemic erythrocytes by IFN-gamma or IL-10-treated Mo was inhibited by FcgammaRI-specific reagents. In addition, Mo expression of FcgammaRI and HLA class II DR was determined by flow cytometry in Thai patients with HbH disease (alpha1/alpha2 or alpha1/Hb Constant Spring) (n = 15) or beta degrees -thal/HbE (n = 16). In both groups of patients FcgammaRI expression was increased as compared to normal controls (n = 14): mean fluorescence intensity (+/-SD) 124.79 +/- 38. 77 in HbH disease and 121.86 +/- 18.23 in beta degrees -thal/HbE versus 91.94 +/- 17.36 in normal controls (P < 0.01 and P < 0.001, respectively). In contrast, HLA class II DR expression was similar in patients and controls. The results suggest that, in thalassaemia, up-regulated FcgammaRI on mononuclear phagocytes plays a role in their interaction with erythrocytes and that this process can be modified by cytokines.

Dose-Response Relationship, Drug↗
PubMed1998

5-Hydroxytryptamine receptor function in humans is reduced by acute administration of hydrocortisone.

5-Hydroxytryptamine1A (5-HT1A) receptors have been shown to be suppressed by corticosteroid hormones in a variety of animal experimental paradigms. It has been suggested that this effect may be central to the pathophysiology of severe clinical depressive illness, a condition in which 5-HT1A receptor function is reduced and corticosteroid hormones are elevated. We report the effects of acute administration of hydrocortisone in normal volunteers on a neuroendocrine model of 5-HT1A receptor function. Fifteen healthy male volunteers took part in a random order, double blind, placebo controlled study, in which 100 mg hydrocortisone or placebo was administered 11 h before infusion of L-tryptophan (L-TRP). Pre-treatment with hydrocortisone significantly reduced the growth hormone (GH), but not the prolactin (PRL) response to the infusion. These data are consistent with the view that acute administration of corticosteroid hormones significantly impairs 5-HT1A receptor mediated function in healthy human volunteers and are in line with animal studies of the effects of corticosteroid hormones on 5-HT1A receptors. We propose that this finding is relevant to the pathophysiological processes which cause severe depressive illness.

Adolescent↗
PubMed1998

Inclusive dielectron cross sections in p + p and p + d interactions at beam energies from 1.04 to 4.88 GeV.

Measurements of dielectron production in p + p and p + d collisions with beamkinetic energies from 1.04 to 4.88 GeV are presented. The differential cross section is presented as a function of invariant pair mass, transverse momentum, and rapidity. The shapes of the mass spectra and their evolution with beam energy provide information about the relative importance of the various dielectron production mechanisms in this energy regime. The p + d to p + p ratio of the dielectron yield is also presented as a function of invariant pair mass, transverse momentum, and rapidity. The shapes of the transverse momentum and rapidity spectra from the p + d and p + p systems are found to be similar to one another for each of the beam energies studied. The beam energy dependence of the integrated cross sections is also presented.

Electrons↗
PubMed1998

Economic factors in the development of new antiepileptic drugs.

The development of new antiepileptic drugs is closely linked to a series of economic factors and perceptions. Industrial interest in such drugs continues to be relatively low, and few companies presently have active discovery programs. The market, however, is large and growing and should encourage more industrial interest in the future.

Anticonvulsants↗