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Biomedical subjects

S Lal

Publications and source records attributed to S Lal.

At least 181 records · Page 10Linked to original sources
PubMed1987

The pharmacokinetics of nedocromil sodium, a new drug for the treatment of reversible obstructive airways disease, in human volunteers and patients with reversible obstructive airways disease.

1. The plasma concentrations and urinary excretion of nedocromil sodium have been determined following single dose administration in six healthy volunteers dosed orally (1 mg kg-1) and intravenously (0.2 microgram kg-1 for 30 min). Similar parameters were measured in six volunteers and twelve asthmatic patients dosed by inhalation (4 mg). Multiple dose kinetic measurements were also made. 2. The intravenous data demonstrated that nedocromil sodium is a high clearance drug (10.2 +/- 1.3 ml min-1 kg-1). The data were fitted by a two compartment model with very rapid elimination from the central compartment (k10 = 0.088 +/- 0.021 min-1; beta = 0.013 +/- 0.002 min-1). 81% of the dose was excreted in the urine. 3. Oral absorption was low (2-3% of the dose) and contributed negligibly to the plasma profile after inhalation. 4. After inhalation of single doses of 4 mg in volunteers and patients plasma concentration rose rapidly, plateaued and then fell monoexponentially with a half-life of approximately 2 h. The data fitted a 'flip-flop' model with two absorption components. The extent of absorption was up to 6% of the dose with less in patients. 5. After multiple dosing with 4 mg four times daily for 7 days in volunteers negligible accumulation was observed. The pattern was similar in patients treated with 4 mg four times daily after 1, 6 and 12 months.

Administration, Inhalation↗
PubMed1987

Effect of estrogen on the growth hormone response to the alpha-adrenergic agonist clonidine in women with menopausal flushing.

The serum GH response to the alpha 2-adrenergic receptor agonist clonidine (0.15 mg, iv) was measured in 8 postmenopausal women with hot flushes before and during treatment with the conjugated estrogen premarin (1.25 mg, orally daily for 4 weeks), 9 normal premenopausal women, and 12 normal men. The men had a significantly greater GH response than did the age-matched premenopausal women (P less than 0.05). The mean individual peak GH response was significantly higher in the premenopausal compared with the postmenopausal women (P less than 0.05). Premarin decreased the number of hot flushes (P less than 0.01), but had no effect on the GH response to clonidine. These results suggest that estrogens do not enhance alpha 2-adrenergic mechanisms that regulate GH secretion and that improvement in menopausal flushing after estrogen therapy is not mediated by an effect on central alpha 2-adrenergic function.

Adrenergic alpha-Agonists↗
PubMed1987

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Cerebrovascular Disorders↗
PubMed1987

Failure to demonstrate anti-lymphocytic antibody in serum of patients with AIDS.

Several studies have produced evidence for anti-lymphocytic antibodies (ALA) in AIDS. We attempted to demonstrate ALA by immunofluorescent flow cytometry. Normal human peripheral blood lymphocytes (PBL) and the T-cell line, CEM, were incubated with sera from patients with AIDS, patients with chronic HIV infection and HIV-seronegative blood donors. ALA were not detected in the AIDS sera with fluorescein isothiocyanate (FITC)-labelled rabbit anti-mu, anti-alpha or the F(ab)2 fragment of anti-human gamma. A small number of CEM cells (2%) fluoresced with either AIDS or normal serum. A larger proportion of PBL were immunofluorescent after serum treatment but there was no difference between normal and AIDS serum. We were able to detect ALA in the serum of patients with systemic lupus erythematosus with both CEM and PBL. In contrast, incubation of either CEM or PBL with some AIDS sera, and to a lesser degree normal sera, enhanced the binding of intact FITC-rabbit anti-gamma. Anti-gamma was not bound by CEM cells unexposed to human serum. The binding was blocked by rabbit immunoglobulin, demonstrable with CEM fixed in 1% formalin, and unrelated to the density of CD4 on CEM cells.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effect of guanfacine, an alpha-adrenergic agonist, on menopausal flushing.

The effect of guanfacine (0.5 mg/day), an alpha-adrenergic agonist, on menopausal flushing, was studied in a double-blind, placebo-controlled crossover study in 11 patients. Both guanfacine and placebo significantly decreased the total number of flushes from baseline values. There was, however, no significant difference between placebo and guanfacine. Larger doses of guanfacine may be required to exert a therapeutic effect similar to that reported in the literature with the alpha-adrenergic agents, clonidine and alpha-methyldopa.

Climacteric↗
PubMed1986

Tourette-like syndrome following low dose short-term neuroleptic treatment.

A Tourette-like syndrome (TLS) may occur after long-term neuroleptic treatment. A review of 11 cases reported in the literature is given. We describe the onset of a TLS in a 13-year old boy with childhood schizophrenia after short term, low-dose treatment with thioridazine. The syndrome resolved 5 months after neuroleptic withdrawal. Subsequent exposure to neuroleptics (mainly perphenazine) induced a recurrence of motor tics and involuntary vocalizations which resolved on drug discontinuation. Awareness that neuroleptics may induce a TLS may lead to prompt recognition and avoidance of labelling the manifestations as symptoms of the underlying psychosis or attention-seeking behaviour.

Adolescent↗
PubMed1986

CCK-8 antagonizes apomorphine-induced growth hormone secretion in normal subjects.

Cholecystokinin octapeptide (CCK-8) (5 ug iv over 10 minutes) administered to normal men had no effect on basal growth hormone (GH) or prolactin secretion but significantly antagonized the GH response to the dopamine (DA) receptor agonist, apomorphine HCI (Apo) (0.5 mg sc), 30 (P less than 0.05) and 45 minutes (P less than 0.01) after Apo injection (n = 8). These results are compatible with an inhibitory effect of CCK-8 on certain DA mechanisms in the hypothalamic-pituitary axis. Whether CCK-8 affects DA function in other brain regions in man is unknown.

Adolescent↗
PubMed1986

Increase in the content of quinolinic acid in cerebrospinal fluid and frontal cortex of patients with hepatic failure.

Quinolinic acid (QUIN), an excitotoxic tryptophan metabolite, has been identified and measured in human cerebrospinal fluid (CSF) using a mass-fragmentographic method. Furthermore, its content has been evaluated in frontal cortex obtained at autopsy from the cadavers of patients who died after hepatic coma. During the coma, the concentration of QUIN in the CSF was 152 +/- 38 pmol ml-1. In contrast, the concentration in control patients affected by different pathologies was 22 +/- 7 pmol ml-1. In the frontal cortex of patients who died after episodes of hepatic encephalopathy, the content of QUIN was three times higher than in controls (2.6 +/- 0.6 versus 0.80 +/- 0.08 nmol/g wet weight). As a result of these investigations we are now able to extend our previous observations on the increase of QUIN in the brains of rats used as experimental models of hepatic encephalopathy to man. QUIN should therefore be added to the list of compounds possibly involved in the pathogenesis and symptomatology of brain disorders associated with liver failure.

Aged↗
PubMed1986

Respiratory irregularity and tardive dyskinesia. A prevalence study.

In a survey of 351 chronically hospitalized adult psychiatric patients, clinical evidence of irregular respiration compatible with respiratory tardive dyskinesia was present in eight subjects (2.3%). In four, audible involuntary respiratory noises were present. All patients with respiratory irregularities had a facio-bucco-lingual dyskinesia and in four the dyskinesia also involved extremities and/or other regions of the body. The prevalence of respiratory irregularities amongst patients with tardive dyskinesia was eight out of 108 (7.4%); none of the patients without tardive dyskinesia had respiratory irregularities. The prevalence of respiratory irregularities was significantly greater in patients with an organic mental disorder (11.1%) compared with those without (1.3%) (P less than 0.005). None of the patients complained of their respiratory symptoms and none had been diagnosed as having a respiratory dyskinesia prior to the survey. In two patients the symptoms were severe, leading in one case to prominent gasping, dysphagia, severe choking when eating, and episodes of aspiration pneumonia. In a second patient the noisy respiration was interpreted as attention-seeking and intimidating behaviour which led to rejection by the staff. In the remaining six patients respiratory symptoms were relatively minor.

Adult↗
PubMed1986

Prevalence of the rabbit syndrome.

Among 266 chronic inpatients receiving neuroleptics, six of the 137 (4.4%) receiving neuroleptics alone and none of the 129 receiving concomitant anticholinergics manifested the rabbit syndrome. Procyclidine resolved the signs of all affected patients. The syndrome's potential prevalence remains unknown.

Adult↗
PubMed1986

An open assessment study of the acceptability, tolerability and safety of nedocromil sodium in long-term clinical use in patients with perennial asthma.

Fifty-one patients (22 male, 29 female) aged 22-60 years (mean age 41.2 years), predominantly extrinsic asthmatics, took part in this study, a follow-up to a 28-day, double-blind trial (Lal et al., Thorax 1984: 39: 809). Forty-four patients completed 12 months of treatment after a 4-week baseline; seven withdrew. A number of symptoms (e.g. coughing, wheezing, sore throat) were reported but none appeared particularly frequently; most were attributable to the technique of inhalation. After 4 weeks of treatment with nedocromil sodium (Tilade 4 mg q.i.d.), patients were encouraged to reduce use of inhaled corticosteroids (48 patients) and sodium cromoglycate (16). Inhaled bronchodilators were to be used as required and other medication was to continue as before. At the end of the study, 28 patients had stopped using inhaled steroids and 10 had significantly reduced the dosage (p less than 0.001, week 5 to end). Ten patients had stopped using sodium cromoglycate. Inhaled bronchodilator use was significantly reduced (p less than 0.001, weeks 1-8; p less than 0.05, weeks 9-12) early in the study but returned to baseline as inhaled steroid usage was reduced. Diary card assessments of wheezing and shortness of breath showed significant improvement, particularly in the early part of the study. Diary card PEFRs showed no marked changes but significant decreases, though small, were found in FEV1, FVC and PEFR on clinic visits. Clinical assessment showed improvement in the first half of the study; the differences were less marked as inhaled steroid usage declined. Final opinions of treatment effectiveness significantly favoured nedocromil sodium. This study demonstrates the acceptability, tolerability and safety of nedocromil sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1986

Pulmonary defence mechanism in mice. A comparative role of alveolar macrophages and polymorphonuclear cells against infection with Candida albicans.

The protective roles of alveolar macrophages and polymorphonuclear cells were analyzed against intratracheal challenge with Candida albicans in mice. When mice were treated with carrageenan, a known cytotoxic agent for macrophages, there was no change in susceptibilities to the challenge in terms of the survival and the progressive elimination of fungi from the lung and kidney, in spite of a decreased in vitro phagocytosis of Candida albicans by their alveolar macrophages. On the other hand, irradiated mice (whole body irradiation with 800 rads) showed an enhanced mortality and a progressive growth of Candida albicans in their lungs and kidneys, although no change was observed in the in vitro phagocytic activity of alveolar macrophages until day 6 after irradiation. In normal and carrageenan treated mice, there was a progressive increase in the recruitment of polymorphonuclear cells into the lung after the challenge as shown by bronchoalveolar lavage and histological examination. In irradiated mice, on the other hand, there was a decreased recruitment of polymorphonuclear cells at 24 hr after the challenge, and a complete impairment at a late stage. When phagocytes were obtained from normal mice and examined for in vitro phagocytic activity to Candida albicans, polymorphonuclear cells showed higher activity than that of alveolar macrophages. These results suggest that polymorphonuclear cells play a very important role in the protection against intratracheal infection with Candida albicans.

Animals↗
PubMed1986

Enhanced clearance of Candida albicans from lung after intratracheal immunization.

The comparative effect of immunization by intratracheal and intraperitoneal routes was assessed against intratracheal challenge with Candida albicans. When mice were immunized intratracheally with 5 X 10(6) cfu of viable or heat-killed C. albicans 2 weeks before challenge, they showed an enhanced resistance against intratracheal challenge with C. albicans, in spite of a decrease in phagocytosis of C. albicans in vitro by alveolar macrophages from intratracheally immunized mice. In these mice, 100% survival and an accelerated elimination of C. albicans from their lungs were observed after intratracheal challenge with C. albicans. In contrast, intratracheal immunization with same high dose of viable or heat-killed C. albicans 1 week before challenge, and intraperitoneal immunization with same high or low doses of viable or heat-killed C. albicans 1 or 2 weeks before intratracheal challenge with C. albicans, could not induce such high resistance against intratracheal challenge with same high dose of viable C. albicans. Comparing to normal and intraperitoneally immunized mice, number of C. albicans recovered from the lung 48 hr after challenge was approximately 100 fold smaller in mice immunized by intratracheal route 2 weeks before challenge. When cellular response was determined by bronchoalveolar lavage after intratracheal inoculation of C. albicans, a prominent recruitment of polymorphonuclear cells was observed 12 and 36 hr after challenge in control mice, intraperitoneally and intratracheally immunized mice. Among these groups, sustained polymorphonuclear cell recruitment by 72 hr after challenge was seen only in the group immunized by intratracheal route with high dose of heat-killed C. albicans 2 weeks before challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effect of naloxone on menopausal flushes, skin temperature, and luteinizing hormone secretion.

The effect of naloxone (1.4 mg/hr for 3 hours) on subjectively experienced menopausal flushes, skin temperature, and luteinizing hormone secretion was investigated in seven women in a double-blind, saline-controlled, crossover study. Naloxone had no effect on the number of subjective flushes, episodic skin temperature elevation, luteinizing hormone pulses, variability of luteinizing hormone secretion, or total luteinizing hormone secretion. This study suggests that a naloxone-sensitive opioid mechanism is not active in modulating luteinizing hormone secretion in the postmenopausal woman and that opioid receptor blockade is not effective in altering the frequency of menopausal flushes.

Climacteric↗