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Biomedical subjects

Daniel Stein

Publications and source records attributed to Daniel Stein.

36 records · Page 2Linked to original sources

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.

Adolescent↗

Electroconvulsive therapy in adolescent and adult psychiatric inpatients--a retrospective chart design.

BACKGROUND: The knowledge available on electroconvulsive therapy (ECT) in adolescents is largely anecdotal, or based on findings from adults. The aim of the present study is to compare the use of ECT in adolescent and adult inpatients. METHODS: We retrospectively analyzed the files of all 36 adolescent (between the ages of 13 and 19) and 57 randomly selected adult inpatients (above the age of 20) treated with ECT in a university-affiliated mental heath center in Israel between 1991 and 1997. RESULTS: Sixty one percent of the adolescents improved by the end of treatment, and 53% were not hospitalized in the subsequent year. The respective percentages among adults were 83% and 49%. Whereas most adults were treated with ECT because of schizophrenic disorders, almost half of the adolescents received ECT for affective disorders. Significantly more adolescents were treated with ECT because of acute life-endangering conditions (catatonia or severe suicidal risk). No significant adverse effects were found in both groups. LIMITATIONS: Our study is based on a retrospective chart review. The adolescent and adult groups are different in psychiatric morbidity, diagnosis and outcome, have not been assessed in a blind manner, and we have not used standardized psychometric batteries for the evaluation of ECT-related memory disturbances. CONCLUSIONS: ECT may be an effective, well-tolerated and safe procedure in both adult and adolescent inpatients.

Adolescent↗

Combined blockade of the chemokine receptors CCR1 and CCR5 attenuates chronic rejection.

BACKGROUND: Chemokine-chemokine receptor interaction and the subsequent recruitment of T-lymphocytes to the graft are early events in the development of chronic rejection of transplanted hearts or cardiac allograft vasculopathy (CAV). In this study, we sought to determine whether blockade of chemokine receptors CCR1 and CCR5 with Met-RANTES affects the development of CAV in a murine model. METHODS AND RESULTS: B6.CH-2(bm12) strain donor hearts were transplanted heterotopically into wild-type C57BL/6 mice (myosin heavy chain II mismatch). Recipients were treated daily with either Met-RANTES or vehicle starting on postoperative day 4 and were euthanized on postoperative days 24 and 56. We found that Met-RANTES significantly reduced intimal thickening in this model of chronic rejection and that Met-RANTES markedly decreased the infiltration of CD4 and CD8 T lymphocytes and MOMA-2+ monocytes/macrophages into transplanted hearts. Met-RANTES also suppressed the ex vivo and in vitro proliferative responses of recipient splenocytes to donor antigens. Finally, Met-RANTES treatment was associated with a marked reduction in RANTES/CCL5 and monocyte chemoattractant protein-1 gene transcript levels in the donor hearts. CONCLUSIONS: Antagonism of the chemokine receptors CCR1 and CCR5 with Met-RANTES attenuates CAV development in vivo by reducing mononuclear cell recruitment to the transplanted heart, proliferative responses to donor antigens, and intragraft RANTES/CCL5 and monocyte chemoattractant protein-1 gene transcript levels. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and may serve as potential therapeutic targets.

Animals↗

Pain perception in recovered bulimia nervosa patients.

OBJECTIVE: Decreased pain sensitivity is found in individuals who are ill with bulimia nervosa (BN). The purpose of this study is to determine whether altered pain perception persists after recovery from bulimia nervosa (RBN). METHODS: Eleven women who were recovered from BN for more than 1 year were compared with 15 healthy volunteer women. The participants received two pain evaluations--thermal pain stimulation (TPS), which evaluates threshold and tolerance to heat, and the submaximal effort tourniquet test (SETT), which assesses threshold and tolerance to ischemic pain induced by inflation of a blood pressure cuff. RESULTS: Compared with the controls, the RBN women showed elevated pain threshold as measured with the SETT and a tendency to elevated pain threshold on the TPS. DISCUSSION: Decreased pain sensitivity persists after recovery from BN and may reflect altered modulatory function in this illness.

Adult↗

Stunting of growth as a major feature of anorexia nervosa in male adolescents.

OBJECTIVE: To assess growth retardation in male adolescent patients who have a diagnosis of anorexia nervosa (AN) and the effect of weight restoration on catch-up growth. METHODS: Medical charts of all male adolescent AN patients (n = 12) who were admitted to the Pediatric Psychosomatic Department at the Sheba Medical Center from January 1, 1994, to December 31, 1998, were reviewed. Height and weight measurements were obtained before the onset of AN, at admission, and thereafter routinely during hospitalization and follow-up. RESULTS: Eleven patients exhibited growth retardation during the course of their illness, as evident in a decrease in their height standard deviation score (SDS). The mean height SDS at the time of admission (-0.81 +/- 0.93) was significantly lower than the premorbid SDS (-0.21 +/- 0.91). Weight restoration resulted in accelerated linear growth (up to 2 cm/mo) in all patients. Positive weight gain (weight gain rate >1 kg/y) was associated with a mean height gain of 6.97 +/- 6.48 cm/y, whereas weight loss or failure to gain weight (weight gain rate <or=1 kg/y) was associated with a mean of 2.7 +/- 3.9 cm/y. This between-group difference was highly significant. Complete catch-up growth was not achieved in 9 of 12 patients. There was a trend for the mean adult final height SDS (-0.52 +/- 0.84) to be higher than the admission height SDS but lower than both the premorbid height SDS and the midparental target height SDS (-0.21 +/- 0.79). CONCLUSIONS: Linear growth retardation was a prominent feature of AN in our sample of male adolescent patients, preceding, in some cases, the reported detection of the eating disorder. Weight restoration, particularly when target weight is based on the premorbid height percentile, may be associated with significant catch-up growth, but complete catch-up growth may not be achieved.

Adolescent↗

Perimenstrual psychosis among female adolescents: two case reports and an update of the literature.

OBJECTIVES AND METHODS: Perimenstrual psychosis is an uncommon disorder, not included under the accepted classifications of functional psychoses. Our aim was to describe two Israeli female adolescents who fit this diagnosis. RESULTS: Both youngsters developed an acute psychosis a few days before menstruation, which subsided several days after bleeding, only to reappear in the same form in subsequent cycles. An extensive medical work-up did not show any significant disturbances, with the exception of anovulatory cycles in one youngster. Psychotropic treatment had no effect on the course of the psychosis. Treatment with a combined progesterone/estrogen contraceptive agent in one patient resulted in full recovery within several cycles. The second patient showed a spontaneous remission within four cycles. Follow-up for two to three years indicated a complete remission, with no need to reintroduce any psychotropic agent. CONCLUSIONS: Perimenstrual psychosis may represent a cycloid disorder or an atypical affective disorder, associated with anovulation. The use of psychotropic treatment is considered inconclusive, whereas hormonal agents may prove effective.

Acute Disease↗

Defense mechanisms in a community-based sample of female adolescents with partial eating disorders.

OBJECTIVES: The purpose of this study is to assess whether female adolescents diagnosed with partial eating disorders (EDs) will show less adaptive defense mechanisms compared to female controls with no-ED. METHODS: The following questionnaires were administered to 423 female high-school students: The Eating Attitudes Test (EAT-26), the Defense Style Questionnaire (DSQ), and Life Style Index (LSI) (both tapping defense mechanisms), and a structured questionnaire assessing eating-related issues. Weight and height were also recorded. Partial anorexia nervosa (AN) and bulimia nervosa (BN) were defined with the combination of a maladaptive EAT score and fulfillment of adapted DSM-IV criteria. RESULTS: Compared to non-ED controls, participants with partial AN and partial BN used more immature defenses, including the DSQ-immature defense style (only those with partial BN) and LSI-regression, as well as more neurotic defenses, namely the DSQ-neurotic defense style, and LSI-compensation and displacement. CONCLUSIONS: The combined use of immature and neurotic defenses may be associated with a greater risk to develop a partial ED in adolescent females.

Adolescent↗

Munchausen Syndrome by Proxy: two case reports and an update of the literature.

OBJECTIVES AND METHODS: Munchausen Syndrome by Proxy (MSP) may significantly hamper the normal development of children. Our aim was to describe the first two Israeli children who fit this diagnosis. RESULTS: Case #1 was diagnosed at the age of seven months with failure to thrive, severe recurrent vomiting, and recurrent unexplained fever. Medical tests performed were normal. No improvement was noted following prolonged treatment, which included several surgical interventions. Case #2 was hospitalized at the age of four years because of recurrent convulsive episodes. Medical examinations performed were normal, and there was no improvement in the reported seizure disorder despite continuous treatment. In both cases, MSP was suspected because of a persistent illness that could not be explained by adequate medical basis, and because the symptoms and signs occurred only in the mother's presence. A confrontation was made, leading to rapid deterioration of the hitherto devoted relationship of the mother of case #1 with her child, and of the previous cooperative relationship of both mothers with the medical staff. Removal of both children from their families ensued, with considerable improvement within a brief period, which continued in a one- to two-year follow-up period. CONCLUSIONS: The study reviews the required diagnostic criteria for MSP and possible treatment options.

Adult↗

Contribution of elevated free fatty acid levels to the lack of glucose effectiveness in type 2 diabetes.

Increased circulating free fatty acids (FFAs) inhibit both hepatic and peripheral insulin action. Because the loss of effectiveness of glucose to suppress endogenous glucose production and stimulate glucose uptake contributes importantly to fasting hyperglycemia in type 2 diabetes, we examined whether the approximate twofold elevations in FFA characteristic of poorly controlled type 2 diabetes contribute to this defect. Glucose levels were raised from 5 to 10 mmol/l while maintaining fixed hormonal conditions by infusing somatostatin with basal insulin, glucagon, and growth hormone. Each individual was studied at two FFA levels: with (NA+) and without (NA-) infusion of nicotinic acid in nine individuals with poorly controlled type 2 diabetes (HbA(1c) = 10.1 +/- 0.7%) and with (LIP+) and without (LIP-) infusion of lipid emulsion in nine nondiabetic individuals. Elevating FFA to approximately 500 micro mol/l blunted the ability of glucose to suppress endogenous glucose production (LIP- = -48% vs. LIP+ = -28%; P < 0.01) and increased glucose uptake (LIP- = 97% vs. LIP+ = 51%; P < 0.01) in nondiabetic individuals. Raising FFA also blunted the endogenous glucose production response in 10 individuals with type 2 diabetes in good control (HbA(1c) = 6.3 +/- 0.3%). Conversely, normalizing FFA nearly restored the endogenous glucose production (NA- = -7% vs. NA+ = -41%; P < 0.001) and glucose uptake (NA- = 26% vs. NA+ = 64%; P < 0.001) responses to hyperglycemia in individuals with poorly controlled type 2 diabetes. Thus, increased FFA levels contribute substantially to the loss of glucose effectiveness in poorly controlled type 2 diabetes.

Biomarkers↗

Dream content of schizophrenic, nonschizophrenic mentally ill, and community control adolescents.

This study compared the manifest dream content of 20 schizophrenic adolescent inpatients whose medications were stable for at least four weeks, 21 adolescent inpatients with other mental disorders (nonschizophrenic group) matched for age and gender, and 31 matched community controls. All participants were administered the standardized Formal Dream Content Rating Scale (FDCRS), which evaluates dream-related anxiety, cognitive disturbance, implausibility, involvement, primitivity, and recall, as well as two additional scales measuring emotional expression and duration of dream report. The Positive and Negative Symptoms Scale (PANSS) was administered to the two inpatient groups. The community controls demonstrated more involvement and emotional expression than the schizophrenic patients; furthermore, they demonstrated more implausibility and had a greater duration of dream report compared with the nonschizophrenic group. In the schizophrenic patients only, elevated scores on the negative subscale of the PANSS were significantly correlated with lower scores on involvement, emotional expression, and dream recall. No relationship was found between the positive subscale of the PANSS and any of the FDCRS subscales. These results suggest that psychopathology per se, rather than the specific psychiatric disturbance, may be associated with impoverishment of dream content, and that negative, rather than positive, schizophrenic symptomatology may be influential in the dream content of schizophrenic youngsters.

Adolescent↗

Serum creatine kinase levels in untreated hospitalized adolescents during acute psychosis.

OBJECTIVE: Psychosis-associated creatine kinase (CK)-emia (PACK) is a common and pronounced laboratory abnormality that accompanies adult psychotic conditions. Adult PACK is a relatively consistent individual trait. The authors investigated whether psychotic adolescents also present with such PACK characteristics. METHOD: Participants were 127 newly admitted, drug-free, psychotic Israeli adolescents. Measures were baseline psychotic severity, serum creatine kinase (CK0), lactate dehydrogenase (LDH0), glutamate oxaloacetate transaminase (SGOT0), white blood cell count (WBC0), urine myoglobulin, and the repeated CK (RepCK) measurements taken during recurrent psychotic episodes. RESULTS: Schizophrenia was the prevalent diagnosis (53%). CK0 levels did not correlate with the severity of the psychotic symptoms. Twenty-one percent of patients had a CK0 level >1,000 IU/L. CK0 and RepCK levels were higher in males than in females (p < or = .001) and in Jewish Sephardi patients than in Ashkenazi patients (p < .007). There was no difference by diagnosis. Logarithmic (Ln) CK0 correlated with RepCK, SGOT0, LDH0, and WBC0 (r = +0.32-0.74, p < .001) but correlated inversely with serum cholesterol0 (r = -0.36, p = .002) in males. Even prominent PACK was not associated with myoglobinuria. These findings remained significant among the younger patients (aged <18 years). In males from this subgroup, LnCK0 also correlated with age (p < .007) but not with weight. CONCLUSIONS: In psychotic adolescents, PACK is common, is more prevalent among males, is independent of diagnosis, is influenced by ethnicity, and tends to recur.

Adolescent↗

Central administration of oleic acid inhibits glucose production and food intake.

The hypothalamus and other regions within the central nervous system (CNS) link the sensing of nutrients to the control of metabolism and feeding behavior. Here, we report that intracerebroventricular (ICV) administration of the long-chain fatty acid oleic acid markedly inhibits glucose production and food intake. The anorectic effect of oleic acid was independent of leptin and was accompanied by a decrease in the hypothalamic expression of neuropeptide Y. The short-chain fatty acid octanoic acid failed to reproduce the metabolic effects of oleic acid, and ICV coadministration of inhibitors of ATP-sensitive K(+) channels blunted the effect of oleic acid on glucose production. This is the first demonstration that fatty acids can signal nutrient availability to the CNS, which in turn limits further delivery of nutrients to the circulation.

Adenosine Triphosphate↗

Attempted suicide and self-injury in patients diagnosed with eating disorders.

Eating disorders (ED) patients are at high risk for developing suicidal behavior. The aim of the present study was to investigate factors associated with suicidal behavior in ED patients. One hundred fifty patients at an outpatient ED clinic were included in the study. Data were gathered by retrospective chart analysis. We found that 48 patients (32%) had a history of parasuicide (i.e., suicide attempts, self-injury, or both). A significantly greater percentage of parasuicidal patients than nonparasuicidal patients had EDs with bingeing/pursing symptomatology, used more than one type of purging method, and had a lifetime history of a drug use disorder, impulse control problems, and bipolar disorder, as well as a more extensive outpatient and inpatient treatment history. The findings of this study support an increased tendency toward impulsivity among parasuicidal ED outpatients.

Adult↗

Obstetric complications in individuals diagnosed with autism and in healthy controls.

The aim of the present study was to investigate birth complications in Israeli autistic probands. We interviewed 206 mothers of autistic probands and 152 healthy control mothers with a structured tool encompassing prenatal, perinatal, and neonatal complications. Analysis of obstetric suboptimality, derived by summing all positive items of each of the 3 categories and dividing them by the number of patients analyzed, revealed no prenatal between-group difference. The controls had a somewhat elevated perinatal suboptimality score, whereas the autistic probands had a significantly greater neonatal suboptimality score. These differences in obstetric suboptimality were retained after controlling for the demographic parameters found different between the 2 groups (sex of participants and mothers' years of schooling). Our findings suggest that the presence of nonspecific neonatal factors, rather than the specific influence of individual severe insults, may account for the elevated neonatal suboptimality found in probands diagnosed with autism compared with healthy controls.

Adult↗

Suicidal tendencies and body image and experience in anorexia nervosa and suicidal female adolescent inpatients.

BACKGROUND: The aim of this study was to assess the relationship between body image and suicidal tendencies in anorexia nervosa (AN). METHODS: Three groups of hospitalized female adolescents--nonsuicidal AN, suicidal psychiatric and nonsuicidal psychiatric patients, as well as a community control group with no psychiatric disturbances were compared with regard to suicidal tendencies (in the form of attitudes to life and death), body image and experience, depression and anxiety. RESULTS: The AN and suicidal patients showed less attraction to but more repulsion by life, and more attraction to and less repulsion by death compared with the other two groups. The AN and suicidal patients were also different from either one or both control groups in showing more negative attitudes and feelings towards their bodies, lower sensitivity to body clues, less body control, and elevated depression and anxiety. These between-group differences in suicidal tendencies were retained after controlling for age, body mass index, the different body image dimensions, anxiety and depression. CONCLUSIONS: Our findings suggest that female AN inpatients with no evidence of overt suicidal behavior demonstrate elevated suicidal tendencies that are similar to those of suicidal psychiatric inpatients. These self-destructive tendencies are highly associated with a pervasive sense of disturbance of body image and experience.

Adolescent↗

Sleep disturbances in adolescents with symptoms of attention-deficit/hyperactivity disorder.

We evaluated 32 nonmedicated male adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) in childhood, 35 male adolescents similarly diagnosed who were receiving methylphenidate (MPH), and 77 control boys. Both ADHD groups completed self-report questionnaires assessing sleep disturbances; weekday and holiday sleep duration; and symptoms of ADHD, anxiety, and depression. Parents and teachers rated the severity of the participants' ADHD. The control group completed self-report questionnaires assessing sleep disturbances. We found that nonmedicated participants and controls did not differ in the severity of sleep disturbance. In contrast, the medicated participants demonstrated a significantly greater severity of sleep disturbance compared with the nonmedicated participants and reported elevated levels of symptoms of ADHD, anxiety, and depression. Specific analyses showed that depressive symptoms contributed significantly to the degree of sleep disturbance when controlling for ADHD diagnosis and MPH treatment. These findings suggest that among adolescents with ADHD symptoms, the severity of symptoms of depression may contribute to the degree of sleep disturbance in addition to the effect of their primary disorder and MPH treatment.

Adolescent↗