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Biomedical subjects

E Zachariah

Publications and source records attributed to E Zachariah.

9 recordsLinked to original sources

Cognitive functioning in siblings discordant for schizophrenia.

OBJECTIVE: The objective of this study was to investigate neuropsychological impairment as a genetically mediated risk indicator for schizophrenia while accounting for prevalence of schizotypy signs/symptoms in siblings. METHOD: Cognitive functioning in 25 individuals with schizophrenia, 25 unaffected siblings and 25 unrelated healthy controls, was assessed using neuropsychological tests of sustained attention, memory and learning, executive function, visual-spatial ability and psychomotor performance. RESULTS: Unaffected siblings demonstrated better performance than patients on some measures of memory and learning and executive function. Patients and siblings demonstrated impaired Full Scale IQ and verbal fluency, otherwise siblings performed similarly to healthy controls. Controlling for differences in IQ, the shared deficit in verbal fluency disappeared. CONCLUSION: Patients with schizophrenia and unaffected siblings (without schizotypy personality disorder) shared a neuropsychological deficit in verbal fluency. This deficit appeared to be mediated by IQ. Deficits, which differentiated patients from controls, may not be inherited and perhaps are related to the manifestation or treatment of schizophrenia.

Adult↗

Effects of 10 mg and 15 mg oral procyclidine on critical flicker fusion threshold and cardiac functioning in healthy human subjects.

The critical flicker fusion threshold (CFFT) is thought to index alertness and cortical arousal. Sedative drugs reduce CFFT while psychostimulants increase it. Procyclidine is an anticholinergic that is used to control the extrapyramidal side-effects of antipsychotics in schizophrenia. This study examined the effects of clinically relevant doses of oral procyclidine administration on CFFT and heart rate in two separate experiments (Experiment 1, drug dose: 10 mg, n = 16; Experiment 2, drug dose: 15 mg, n = 12) involving healthy subjects using a double-blind, placebo-controlled, cross-over design. 10 mg procyclidine had no significant effect on CFFT, heart rate or self-ratings of mood, but the 15 mg dose significantly lowered CFFT at 1 h and 2 h after procyclidine administration, increased drowsiness ratings and produced a drop in heart rate. The effects observed in this study may have implications for treatment compliance of schizophrenic patients, choice of antipsychotics, prescribing to patients with heart disease and monitoring of cardiac function under treatment. Further investigations are required to quantify the effects of procyclidine on CFFT and cardiac function in patients with schizophrenia.

Adult↗

Effects of procyclidine on prepulse inhibition of the acoustic startle response in healthy human volunteers.

RATIONALE: Prepulse inhibition (PPI) of the startle response refers to an attenuation in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). Patients with schizophrenia have repeatedly been found to show reduced PPI when compared to healthy people. Anticholinergic drugs are often used to control extrapyramidal symptoms induced by antipsychotic medication in schizophrenic patients. Antipsychotic medication, in particular with atypical drugs, has been shown to improve a range of cognitive functions and normalize PPI deficits in schizophrenia, whereas anticholinergic drugs disrupt cognitive functions in both normal and schizophrenic populations and also impair PPI in experimental animals. No previous study has investigated the effects of anticholinergic drugs on human PPI. OBJECTIVES: This study determined the effects of procyclidine, an anticholinergic drug, on PPI in healthy male volunteers, employing a double-blind placebo-controlled cross-over design. METHODS: Subjects underwent testing for PPI on two occasions: once after the oral administration of a placebo and once after the oral administration of procyclidine in two separate experiments. Experiment 1 examined the effects of 10 mg procyclidine, whereas experiment 2 examined the effects of 15 mg procyclidine. RESULTS: Procyclidine at a 10 mg dose, as compared to placebo, had no effect on PPI, but caused impairments at a 15 mg dose. In both experiments, procyclidine reduced response amplitude over the pulse-alone trials and heart rate 1-2 h post-administration. CONCLUSIONS: PPI of the human acoustic startle response is modulated by procyclidine. The use of anticholinergics needs to be considered in PPI studies in schizophrenia.

Acoustic Stimulation↗

Risk factors for acute myocardial infarction in Indians: a case-control study.

BACKGROUND: South Asians who have settled overseas and those in urban India have an increased risk of ischaemic heart disease (IHD). Reasons for this increased risk are unclear. Most studies have been based on migrants to western nations, so their findings may not apply to most south Asians, who live in their own countries. Therefore, we assessed the relative importance of risk factors for IHD among South Asians in Bangalore, India. METHODS: We conducted a prospective hospital-based case-control study of 200 Indian patients with a first acute myocardial infarction (AMI) and 200 age and sex matched controls. We recorded prevalence of the following risk factors for IHD: diet, smoking, alcohol use, socioeconomic status, waist to hip ratio (WHR), blood glucose, serum insulin, oral glucose tolerance test, and lipid profile. FINDINGS: The most important predictor of AMI was current smoking (odds ratio [OR] 3.6, p < 0.001) of cigarettes or beedis (a local form of tobacco), with individuals who currently smoked 10 or more per day having an OR of 6.7 (p < 0.001). History of hypertension and of overt diabetes mellitus were also independent risk factors (OR 2.69 [p = 0.001] and 2.64 [p = 0.004], respectively). Among all individuals, fasting blood glucose was a strong predictor of risk over the entire range, including at values usually regarded as normal (OR adjusted for smoking, hypertension, and WHR 1.62 for 1 SD increase, p < 0.001). Abdominal obesity (as measured by WHR) was also a strong independent predictor across the entire range of measures (OR adjusted for smoking, hypertension, and blood glucose 2.24 for 1 SD increase; p < 0.001). Compared with individuals with no risk factors, individuals with multiple risk factors had greatly increased risk of AMI (eg, OR of 10.6 for the group with smoking and elevated glucose). Lipid profile was not associated with AMI. In univariate analyses, higher socioeconomic (income) status (OR 0.32, p = 0.005 highest vs lowest; OR 0.75 middle vs lowest) and vegetarianism (OR = 0.55, p = 0.006), seemed to be protective. The impact of vegetarianism was closely correlated with blood glucose and WHR. INTERPRETATION: Smoking cessation, treatment of hypertension, and reduction in blood glucose and central obesity (perhaps through dietary modification) may be important in preventing IHD in Asian Indians.

Adult↗

Gadopentetate dimeglumine-enhanced chemical-shift MR imaging of the breast.

Standard T1-weighted MR images enhanced with gadopentetate dimeglumine show relatively minimal enhancement of breast lesions due to the high background signal from fat in the breast. Strongly enhancing lesions may become isointense relative to the fat signal and become invisible or indistinct after contrast administration. Fat-suppressed chemical-shift imaging (CSI) combined with administration of gadopentetate dimeglumine improves lesion detection and characterization in other areas of the body where a strong lipid signal is present. We evaluated this technique in the breast. Twenty patients with mammographic lesions were studied with standard unenhanced T1- and T2-weighted images and enhanced T1-weighted images, as well as with CSI before and after administration of gadopentetate dimeglumine. The series were ranked independently for border and matrix characteristics. The border was assessed for a smooth, irregular, or spiculated margin. The matrix or internal substance was evaluated for visibility and type of enhancement, homogeneous or inhomogeneous. The enhanced CSI images were superior to all other images in the depiction of border and matrix characteristics. Of 20 patients, a corresponding mass was detected on MR in 14. In two of the 14 patients, the lesion was seen only in the enhanced CSI images. Chemical-shift artifacts on enhanced T1-weighted images obscured border detail in several cases. Enhanced CSI improves visualization of breast lesions as compared with conventional MR imaging with or without enhancement. The enhanced CSI technique produces differential enhancement between glandular tissue and lesions while suppressing the signal from fat. This improves the visualization of border and matrix characteristics and depicts lesions that otherwise might be obscured.

Breast Neoplasms↗

Plasma estradiol and lipid profile in perimenopausal women.

This study was conducted to examine the estradiol level and plasma lipid profile in perimenopausal women. The estradiol and HDL levels were higher and LDL levels lower in premenopausal women than in postmenopausal women of the same age group. Higher HDL and lower LDL levels in premenopausal women are likely to protect them against atherosclerosis, and the difference may be casually related to estradiol levels.

Adult↗

Analysis of androgen action on pituitary gonadotropin and prolactin secretion in ewes.

To study the role of androgens in the control of gonadotropin and prolactin secretion in ther ewe, we have characterized androgen receptors in pituitary cytosol, and investigated the effect of androgens on pituitary hormone release in vivo and in vitro. High affinity, low capacity receptors, with an affinity for methyltrienolone (R1881) greater than 5 alpha-dihydrotestosterone (5 alpha-DHT) greater than testosterone (T) much greater than androstenedione (A4), estradiol-17 beta (E2) and progesterone (P), were identified in pituitary cytosol. Addition of 1 nM 5 alpha-DHT, but not A4, inhibited luteinizing hormone (LH) release from pituitary cells in vitro, induced by 10(10) to 10(-7) M luteinizing hormone releasing hormone (LHRH). The release of follicle-stimulating hormone (FSH) with 10(-9) M LHRH was inhibited when cells were incubated with 1 nM 5 alpha-DHT. 5 alpha-DHT had no effect when higher or lower doses of LHRH were used. In ovariectomized ewes, neither an i.v. injection of 1 mg, nor intracarotid injections of up to 1 mg, 5 alpha-DHT affected plasma LH, FSH or prolactin levels, despite dose-related increases in plasma 5 alpha-DHT levels. Daily or twice daily i.m. injections of 5 mg 5 alpha-DHT in oil did not affect LH or FSH levels, but daily injections of 20 mg significantly reduced plasma LH levels within 4 days and plasma FSH levels within 6 days. Thus, despite the presence of androgen receptors in the ewe pituitary, we conclude that androgens per se are of minimal importance in the regulation of pituitary LH, FSH and prolactin secretion in the ewe. The low binding affinity of A4 and the lack of its effect on hormone secretion in vitro suggests that A4 may act as an estrogen precursor rather than an androgenic hormone. The function of the pituitary androgen receptor remains to be established.

Androgens↗

Enzymic changes in the cervix of the rat and hamster during the oestrous cycle and the effect of steroids.

Changes in four hydrolytic enzymes, namely acid phosphatase, alkaline phosphatase, arylsulphatase A and B, of the cervix of the rat and hamster have been studied during the 4-day oestrous cycle. All four enzymes showed maximal activity on the day of oestrus and least activity on day 2 of dioestrus. All the enzymes showed significant reduction of activity after ovariectomy, arylsulphatase A and B showing the earliest changes in specific activity. A single subcutaneous injection of 0-02 microng oestradiol-17beta/rat increased the especific activity of arylsulphatase A and B from the low ovariectomized level to that observed in control oestrous animals within 18 and 6 h respectively. A higher concentration of oestradiol 17beta (2-0 microng) had an inhibitory effect. Progesterone was without effect on arylsulphatase B activity, but when given (2-0 mg) with 0-02 microng oestradiol-17beta, it inhibited the response to oestrogen. Cycloheximide prevented the rise in arylsulphatase B activity occurring after oestrogen injection, suggesting a regulation of cervical arylsulphatase B at the level of protein biosynthesis. These results suggest that arylsulphatase B activity may be induced by oestrogen in the cervix of the rat.

Acid Phosphatase↗