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Biomedical subjects

A Ram

Publications and source records attributed to A Ram.

At least 19 recordsLinked to original sources

Evaluation of individual subjects in the analog classroom setting: I. Examples of graphical and statistical procedures for within-subject ranking of responses to different delivery patterns of methylphenidate.

In this article, we describe graphical and statistical methods developed to evaluate the response patterns of individual children with attention deficit hyperactivity disorder (ADHD) to different conditions of treatment with stimulant medication. We used data from an investigation of drug delivery patterns to demonstrate these methods. Thirty-one children with ADHD participated in a double-blind crossover study of four conditions (three patterns of delivery of methylphenidate and a placebo control). In each condition, the children were evaluated across an 11-hour (7:00 a.m. to 6:00 p.m.) laboratory school day, and ratings of classroom behavior were obtained at regular intervals across the day. Graphical procedures were developed to display, for each individual, time courses of multiple measures of behavior taken across each double-blind test day. Expert clinicians judged these graphs and used this information to rank-order the test days from best to worst. A within-subject variant of Kendall's W was used to evaluate, for each subject, whether the rankings of these multidimensional graphs were reliable (concordant) across judges. A generalized kappa statistic was used to evaluate, for each condition, the reliability of the judges' rankings across subjects. Friedman's analysis of variance of ranks was used to evaluate, for the study, whether the conditions differed in terms of the average (consensus) rank assigned by the judges.

Attention Deficit Disorder with Hyperactivity↗

CSF levels of prostaglandins, especially the level of prostaglandin D2, are correlated with increasing propensity towards sleep in rats.

The concentration of PGD2, PGE2, and of PGF2 alpha was measured in the cerebrospinal fluid (CSF) collected from the cisterna magna of conscious rats (n = 29), which, chronically implanted with a catheter for the CSF sampling, underwent deprivation of daytime sleep. Significant elevation of the CSF level of PGD2 was observed following 2.5-h sleep deprivation (SD), and the elevation became more marked following 5- and 10-h SD, apparently reaching the maximum at 5-h SD (703 +/- 140 pg/ml (mean +/- S.E.M.) for baseline vs. 1734 +/- 363 pg/ml for SD, n = 10). The levels of PGE2, and PGF2 alpha also significantly increased following 5- and 10-h SD, but not following 2.5-h SD. It is unlikely that these changes were simply caused by some responses of the animals to stress stimuli, because stress stimuli derived from restraint of the animal at the supine position to a board for 1 h did not produce any acute responses in the CSF levels of prostaglandins (n = 13). In a different group of animals (n = 11) implanted with electrodes for recording electroencephalogram (EEG) and electromyogram (EMG) in addition to the catheter, the levels of the prostaglandins in CSF were determined for slow-wave sleep (SWS) and wakefulness in the day and for SWS and wakefulness in the night. The highest PGD2 value was obtained at daytime SWS, whereas the lowest was at night wakefulness; furthermore, a significant difference was observed between SWS and wakefulness rather than between day and night. The CSF level of PGE2 also showed a similar tendency. In an additional group of animals (n = 6), not only PGD2 but also PGE2 and PGF2 alpha significantly increased the sleeping time of the animal when applied into the subarachnoid space underlying the ventral surface area of the rostral basal forebrain, the previously defined site of action for the sleep-promoting effect of PGD2. The promotion of sleep by PGE2 applied to the subarachnoid space was an effect completely opposite to the well-established awaking effect of the same prostaglandin demonstrated in the hypothalamic region in a series of previous studies. Based on these results, we conclude that increases in CSF levels of prostaglandins, especially that of PGD2, are correlated in rats with heightened propensity towards sleep and further with the depth of sleep under normal as well as SD conditions.

Animals↗

No abnormality in the gene for the G protein stimulatory alpha subunit in patients with bipolar disorder.

BACKGROUND: The available evidence for an involvement of the heterotrimeric guanine-nucleotide-binding proteins (G proteins) in bipolar disorder relies primarily on the effects of lithium salts on G protein function and on alterations in the concentration or function of G proteins (most notably Gs-alpha) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder. METHODS: The hypothesis that a mutation in Gs-alpha gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the Gs-alpha subunit gene coding sequences and promoter sequences by denaturing gradient gel electrophoresis in unrelated individuals with bipolar disorder and (2) association and linkage analyses with a common silent exonic polymorphism, using genetic allelic information from American families with at least 1 affected child. For association analysis, the transmission test for linkage disequilibrium was used; for linkage analysis, nonparametric methods were used. RESULTS: No structural or regulatory mutations in this gene were found in bipolar disorder; the results of association and genetic linkage were negative. CONCLUSION: Our results do not support the speculation that the Gs-alpha protein gene has a role in the genetic predisposition to bipolar disorder.

Base Sequence↗

Hypocholesterolaemic effects of Terminalia arjuna tree bark.

Diet-induced hyperlipidaemic rabbits were given 50% ethanolic extract of Terminalia arjuna tree bark in doses of 100 mg/kg (Group B, n = 6) and 500 mg/kg (Group C, n = 6) and compared with controls (Group A). At 60 days of intervention in Groups A, B and C mean +/- S.E.M. total cholesterol was 574 +/- 61, 320 +/- 29 and 217 +/- 44 mg/dl, respectively (P < 0.01); LDL cholesterol was 493 +/- 57, 271 +/- 30 and 162 +/- 44 mg/dl (P < 0.01); HDL cholesterol was 59 +/- 7, 36 +/- 3 and 35 +/- 4 mg/dl (P = n.s.); triglyceride was 108 +/- 13, 67 +/- 6 and 101 +/- 26 mg/dl (P = n.s.); cholesterol/HDL ratio was 10.1 +/- 1.3, 9.2 +/- 1.1 and 6.1 +/- 1.0 (P = n.s.); and LDL/HDL ratio was 8.7 +/- 1.3, 7.8 +/- 1.1 and 4.5 +/- 1.0 (P < 0.01). The extract did not adversely affect biochemical tests of liver and renal function and haematological parameters.

Animals↗

Hypolipidaemic effect of Myristica fragrans fruit extract in rabbits.

The ethanolic extract of nutmeg (Myristica fragrans) was studied in albino rabbits for its effects on experimentally induced hyperlipidaemia. After inducing hyperlipidaemia in 12 rabbits a dose of 500 mg/kg of the extract was administered orally daily for a period of 60 days in 6 rabbits (experimental group); the rest of the rabbits were observed as controls. When compared with the control of rabbits the levels of lipoprotein lipids were significantly lower in the experimental group after 60 days; total cholesterol 573 +/- 61 vs. 209 +/- 27 mg/dl, low density lipoprotein (LDL) cholesterol 493 +/- 57 vs. 131 +/- 25 mg/dl, and triglycerides 108 +/- 14 vs. 67 +/- 9 mg/dl P < 0.001). High density lipoprotein (HDL) cholesterol levels were not significantly different (59 +/- 7 vs. 65 +/- 4 mg/dl, P = n.s.). Total cholesterol:HDL ratio and LDL:HDL ratio were significantly lower in the experimental group. The Myristica fragrans extract showed platelet anti-aggregatory ability. There were significantly lower levels of total cholesterol in heart (3.7 +/- 0.5 vs. 2.2 +/- 0.5 mg/100 g) and liver (11.9 +/- 1 vs. 1.5 +/- 0.4 mg/100 g). The toxicity studies showed absence of any adverse effects on various haematological and biochemical parameters.

Animals↗

Circadian variations of prostaglandins D2, E2, and F2 alpha in the cerebrospinal fluid of anesthetized rats.

Circadian variations in the levels of prostaglandins (PGs) D2, E2, and F2 alpha were studied in the cerebrospinal fluid (CSF) of rats. We collected CSF samples from the cisterna magna of anesthetized rats at different clock-hours (1000, 1400, 1800, 2200, 0200, and 0600 hr), and measured the concentrations of the three PGs. PGD2, which appeared to be the most abundant among the three, showed a circadian variation; and the mean of the day-time levels (145 pg/ml) was significantly higher than that of the nighttime ones (111 pg/ml). Day/night variations were also noticed with the levels of PGE2 and PGF2 alpha; however, these levels remained 3-4 times lower than those of PGD2. The general day/night variation seen in the CSF concentration of PGD2 conforms well with the postulated role of PGD2 as an endogenous sleep-promoting factor acting on a certain brain surface area defined as its site of action.

Anesthesia↗

Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome.

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D2 receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequences differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG-->TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS.

Adult↗

Concentration of prostaglandin D2 in cerebrospinal fluid exhibits a circadian alteration in conscious rats.

Cerebrospinal fluid (CSF) was withdrawn from the cisterna magna of unanesthetized conscious rats (n = 14) through a chronically implanted catheter, and prostaglandins (PGs) D2, E2, and F2 alpha were measured. From each rat, CSF samples were taken at different clock-hours of the day (1000, 1400, and 1800 hr) and night (2200, 0200, and 0600 hr) in succession at 76-hour intervals. The concentration of PGD2 alone exhibited a significant circadian fluctuation, with its peak value at 1400 hr (mean +/- SEM: 1197 +/- 361 pg/ml) and its lowest level at 0600 hr (438 +/- 106 pg/ml). Thus, the mean level of PGD2 during the daytime (903 +/- 162 pg/ml) was significantly higher than that during the night (503 +/- 78 pg/ml). The results obtained are consistent with the postulated role of PGD2, acting in the surface layer of the rostral basal forebrain, as an endogenous factor to promote sleep.

Analysis of Variance↗

No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis.

OBJECTIVE: To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene. DESIGN: Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants. SETTING: Patients and controls from clinical and epidemiologic collections in the United States and Europe. PATIENTS: A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taql site 3' to the DRD2 gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white. MAIN OUTCOME MEASURES: Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups. RESULTS: We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia. CONCLUSION: No structural coding abnormalities in the DRD2 gene are present in alcoholism or schizophrenia.

Alcoholism↗

Allelic variation in the D4 dopamine receptor (DRD4) gene does not predict response to clozapine.

OBJECTIVE: To test the hypothesis that interindividual differences in response to clozapine therapy might be attributable to the D4 dopamine receptor (DRD4) alleles they carry. Different alleles of the D4 dopamine receptor, coded by the DRD4 gene, differ in the affinity with which they bind the atypical antipsychotic drug clozapine in vitro. This may have physiologic implications. Clinical response to clozapine therapy varies among patients. The observation that, in vitro, clozapine binds the protein products of different DRD4 alleles with differing affinity characteristics suggested this hypothesis. METHOD: The region of the DRD4 gene that encodes the putative third cytoplasmic loop of the D4 receptor contains a 48-base pair sequence repeated a variable number of times. With use of polymerase chain reaction amplification, we assessed this variable number of tandem repeats polymorphism in a series of schizophrenic and schizoaffective subjects who had been treated with clozapine, and related genotype with treatment response, to test the hypothesis that DRD4 alleles lead to varying response to clozapine. RESULTS: Allelic variation at the DRD4 locus does not predict clinical response to clozapine relative to either fluphenazine hydrochloride or placebo in subjects with treatment-refractory schizophrenia or schizoaffective disorder. CONCLUSIONS: DRD4 alleles do not predict therapeutic response to clozapine in schizophrenic and schizoaffective patients. There are implications from these data for the pathophysiology of schizophrenia and the mechanism of clozapine's therapeutic effect are discussed.

Alleles↗

Outcome of Israeli adolescents with anorexia nervosa whose ambulatory treatment was abruptly interrupted during the Gulf War.

We recently presented the theory that parents should be intensively involved in the treatment of adolescents with anorexia nervosa during the acute re-feeding period and during follow-up. Thirteen anorectic patients with a mean age of 14.6 years (range: 12.6-16.5 years) were being treated in our pediatric day-care unit in Israel according to this treatment model when the Gulf War broke out. Because of the war, treatment was abruptly interrupted for approximately 6 weeks. Immediately after the war the patients were re-evaluated. We found that all of them maintained their weight, and two had even continued to gain weight. These results encouraged us to assume that our treatment model, based on intensive parental involvement especially during the acute re-feeding period, was effective.

Adolescent↗

A study of aluminum phosphide (AlP) poisoning with special reference to electrocardiographic changes.

Ninety patients with aluminum phosphide poisoning have been studied over a period of 3 years. Epigastric pain and vomiting were the common initial clinical features, followed 12 to 24 hours later by cardiogenic shock, oliguria, altered mental state and respiratory distress. Death occurred within 24 to 72 hours presumably due to poison-induced toxic chemical myocarditis as reflected by electrocardiographic changes. The overall mortality was 63.3%. Intravenous magnesium sulphate, probably due to its membrane stabilizing action, appears to be related to the reduction in mortality from 90% to 52% in the latter 62 cases.

Adolescent↗

Serotonin 5-HT2 receptor binding on blood platelets--a peripheral marker for depression?

Several methods of platelet membrane preparation and binding conditions were screened in order to optimize the labeling of serotonergic 5-HT2 receptors on previously frozen human platelet membranes with tritiated ketanserin. Under optimal conditions, 5-HT2 receptors in normal subjects (5 males, 7 females, age range 21 to 71) have a Kd of 1.5 +/- 0.2 nM and a Bmax of 33.9 +/- 5.3 fmole/mg protein. In a group of patients with major depressive disorder exactly matched for age and sex with the normal control group, we find a significant increase in receptor density, to 66.8 +/- 11.4 fmole/mg, with no significant change in the affinity (2.3 +/- 0.5 nM). Four weeks of treatment with antidepressant drugs result in a significant decrease of Bmax, down to control levels (29.4 +/- 3.9). Thus, ketanserin can be used to monitor changes in platelet serotonin 5-HT2 receptors which may be a relevant marker for the state of depression.

Adult↗

Bilateral floating knees in a multiple injured patient. A case report.

Bilateral floating knees are rarely seen in orthopedic practice. Ipsilateral fractures of the femur and tibia are becoming more common due to an increase of high-velocity accidents. The following case presents a 23-year-old male motorcyclist who sustained multiple musculoskeletal injuries including a burst fracture of the elbow and fractures of both femurs and both tibiae. Early operative stabilization of all the fractures was performed. A comminuted fracture of the ulna was fixed with a Dynamic Compression Plate (DCP) and the fractures of both femurs and both tibiae were fixed with Enders nailing. Operative treatment produced excellent results without significant complications. As a result of this study it is concluded that Enders nailing of long bone fractures is a useful procedure in selected patients and can produce desirable results.

Adult↗