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Biomedical subjects

U Rao

Publications and source records attributed to U Rao.

At least 37 records · Page 2Linked to original sources
PubMed1999

Depression of the xylanase-encoding cgxA gene of Chaetomium gracile in Aspergillus nidulans.

Regulation of the Chaetomium gracile xylanase A gene (cgxA) was investigated using Aspergillus nidulans as an intermediate host. Deletion of a 185 bp DNA fragment from its promoter region led to higher levels of the cgxA gene expression, indicating that the 185 bp DNA fragment contains an element involved in repression of the gene. A nuclear extract was assayed for proteins which bind to the 185 bp DNA fragment. A protein designated AnRP bound sequence specifically to the DNA fragment. The minimum sequence required for AnRP binding, 5'TTGACAAAT-3', was determined by means of gel mobility shift assays with various double-stranded oligonucleotides. Furthermore, this sequence repressed the expression of the cgxA gene when inserted at the 5' end of the cgxA gene on pXAH, which was deleted for the repressive element from the promoter region.

Amino Acid Sequence↗
PubMed1999

The context of depression in clinic-referred youth: neglected areas in treatment.

OBJECTIVE: To review the empirical, methodological, and conceptual limitations of psychotherapy and pharmacotherapy for childhood and adolescent depression and to present descriptive data on key characteristics of a depressed sample to illustrate gaps in treatment. METHOD: Interview-based assessment of psychiatric features and psychosocial functioning, family psychopathology and marital adjustment, and child and parent stressful life events was performed in a sample of 43 depressed youngsters seeking outpatient treatment. RESULTS: The empirical and conceptual review indicated that treatments based on downward extensions of adult procedures are limited in number and success. Also, the treatments generally neglect the following characteristics revealed in the descriptive data: depressed youngsters have high rates of recurrent depression and comorbid conditions, impaired academic and social functioning, exposure to high rates of parental psychopathology, parental assortative mating, severe marital dysfunction, and high rates of severe stressors. CONCLUSIONS: Treatments need to be informed by and address the actual characteristics of depressed youngsters and their environments, which are highly dysfunctional.

Adolescent↗
PubMed1999

Continuity of depression during the transition to adulthood: a 5-year longitudinal study of young women.

OBJECTIVE: To characterize the clinical course and psychosocial correlates of unipolar depression in late adolescent women and to examine the continuity in affective disturbance from adolescence to early adulthood during the post-high school transition. METHOD: One hundred fifty-five women aged 17 or 18 years were recruited from 3 local public high schools and were followed at yearly intervals for 5 years for clinical and psychosocial outcomes. RESULTS: The 5-year incidence of first major depressive episode was 36.9%, and overall, 47% of the women had one or more episodes of major depression. Risk for recurrence was substantial, and those with onsets prior to the study were more likely to have depressive episodes during the post-high school period. The presence of nonaffective disorder also increased the risk for depression. Young women with major depression during the post-high school transition had more negative functional outcomes in school and intimate romantic relationships. CONCLUSIONS: These results suggest that there is substantial continuity in affective disturbance from adolescence to adulthood. The risk for both new onset of depression and recurrence is remarkably high during late adolescence, and the risk continues throughout early adult years, accompanied by notable interpersonal dysfunction.

Adolescent↗
PubMed1999

Factors associated with the development of substance use disorder in depressed adolescents.

OBJECTIVE: To document rates of substance use disorders (SUD) in adolescents with unipolar major depressive disorder and to examine demographic, clinical, and biological factors associated with the development of SUD. METHOD: Twenty-eight adolescents with unipolar major depression and no SUD history and 35 group-matched normal controls who participated in a cross-sectional sleep polysomnography and neuroendocrine study were reassessed clinically 7 years later. RESULTS: The risk for SUD was high in both groups (34.6% in the depressed group and 24.2% in the controls). Depressed adolescents had earlier onset of SUD than controls. Depressed adolescents who developed SUD had more significant psychosocial impairment than depressed adolescents who did not develop SUD. More anxiety traits and elevated cortisol secretion near sleep onset were associated with SUD in depressed teenagers, whereas less emotional responsiveness to exciting stimuli and higher density of eye movements during REM sleep were related to depression without SUD. CONCLUSIONS: Depressed adolescents who have anxiety traits and whose hypothalamic-pituitary-adrenal axis is active when the system is normally quiescent may be at risk for developing SUD. Co-occurrence of depression and SUD is associated with serious psychosocial morbidity. Identification of risk factors for SUD in depressed teenagers may be helpful in developing more effective treatment and prevention programs.

Adolescent↗
PubMed1999

The pharmacotherapy of depressive illness in adolescents: an open-label comparison of fluoxetine with imipramine-treated historical controls.

BACKGROUND: This open-label, 6-week clinical trial investigated the response to fluoxetine in medication-naive adolescents hospitalized for treatment of major depression. METHOD: A total of 52 consecutively admitted patients (mean age = 15.7 years) fulfilling Research Diagnostic Criteria for unipolar, nonpsychotic major depression received fluoxetine monotherapy (mean dose = 33.2 mg/day) in conjunction with psychosocial therapies. Outcome was assessed weekly using the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Scale (CGI). Response in this cohort was compared with that observed in 28 historical controls treated with imipramine (mean dose = 217 mg/day) who were consecutively admitted patients to this same facility and assessed in an identical, standardized, open-label protocol. RESULTS: HAM-D scores decreased by a mean of 13.2 in the fluoxetine group compared with 10.2 in the group receiving imipramine (p<.002). The mean percentage decreases in HAM-D scores in the 2 groups were 54.3% and 41.4%, respectively (p<.003). The percentages of patients classified as responders based on a final CGI score of 2 or less were 48.1% and 17.9%, respectively (p = .009). Medications were generally well tolerated with only 5 patients failing to complete the full 6 weeks of their original treatment. CONCLUSION: In spite of the uncontrolled nature of these data, the findings add to recent evidence suggesting more favorable response to selective serotonin reuptake inhibitors than tricyclics in adolescents with depressive illness.

Adolescent↗
PubMed1998

Effects of electroconvulsive therapy in adolescents with severe endogenous depression resistant to pharmacotherapy.

BACKGROUND: This open, prospective study examined the effects of electroconvulsive therapy (ECT) in 10 adolescents with primary, endogenous, psychotic depression who were resistant to antidepressant pharmacotherapy. METHODS: Change in symptom severity from baseline was assessed weekly with Hamilton Depression Rating Scale (HDRS) ratings, and outcome was measured additionally at 1 month, and again at 1 year, post-ECT. RESULTS: All but 1 patient demonstrated dramatic improvement, with statistically significant decreases in mean HDRS score detected after the first week of treatment. All responders maintained the benefits of their treatment. CONCLUSIONS: The results provide evidence of the clinical effectiveness of ECT in adolescents with phenomenological characteristics shown to be predictive of ECT response in adults.

Adolescent↗
PubMed1998

Inflammatory cell infiltrate in a responding metastatic nodule after vaccine-based immunotherapy.

A patient with von Hippel Lindau disease, bilateral symmetric renal cell carcinoma and pulmonary metastases treated with immunotherapy is the subject of this study. A left kidney and tumour mass were removed and the tumour cells used to make an autologous tumour/bacille Calmette-Guérin (BCG) vaccine as part of the treatment protocol. The patient's pulmonary nodules responded, but the remaining renal nodule subsequently grew. Samples of both tumours were obtained allowing for an internally controlled evaluation of the histological and immunohistologic differences between a responding and non-responding tumour nodule after therapy. The immunotherapy protocol is designed to promote a T cell response to autologous tumour. Cellular infiltrates were demonstrated in both responding and non-responding nodules compared with the pretreatment tumour specimen, but the responding nodule contained proportionately more T cells as well as markedly increased numbers of plasma cells and granulocytes. This suggested that several arms of the immune system may have been operative in the responding nodule.

Adult↗
PubMed1998

Limb xenotransplantation using FK506 and RS61443 immunosuppression.

A new model of limb xenotransplantation has been developed to determine whether the newer immunosuppressive agents, FK-506 and RS-61443, either alone or in combination, can delay the rejection of a composite limb xenograft from donor Golden Syrian hamsters to recipient Lewis rats. Using a short-term course of immunosuppression for 14 days post-transplant, both FK-506 2 mg/kg/day and RS-61443 30 mg/kg/day were able to delay rejection. FK-506-treated animals had a mean rejection time of 10.2 days and RS-61443-treated animals had a mean rejection time of 10 days, compared with a mean rejection time of 6.4 days in non-immunosuppressed controls. Combination and sequential immunosuppression with both FK-506 and RS-61443 did not produce any improvement, compared with single-agent immunosuppression, and were quite toxic. Histologically, FK-506 seemed to prevent signs of rejection in the skin and muscle components of the limb xenograft better than RS-61443.

Animals↗
PubMed1998

Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression.

OBJECTIVE: To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD). METHOD: Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo. RESULTS: There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL. CONCLUSIONS: No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD.

Adolescent↗
PubMed1997

Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.

BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

5-Hydroxytryptophan↗
PubMed1997

Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data.

OBJECTIVE: To describe the psychometric properties of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) interview, which surveys additional disorders not assessed in prior K-SADS, contains improved probes and anchor points, includes diagnosis-specific impairment ratings, generates DSM-III-R and DSM-IV diagnoses, and divides symptoms surveyed into a screening interview and five diagnostic supplements. METHOD: Subjects were 55 psychiatric outpatients and 11 normal controls (aged 7 through 17 years). Both parents and children were used as informants. Concurrent validity of the screen criteria and the K-SADS-PL diagnoses was assessed against standard self-report scales. Interrater (n = 15) and test-retest (n = 20) reliability data were also collected (mean retest interval: 18 days; range: 2 to 36 days). RESULTS: Rating scale data support the concurrent validity of screens and K-SADS-PL diagnoses. Interrater agreement in scoring screens and diagnoses was high (range: 93% to 100%). Test-retest reliability kappa coefficients were in the excellent range for present and/or lifetime diagnoses of major depression, any bipolar, generalized anxiety, conduct, and oppositional defiant disorder (.77 to 1.00) and in the good range for present diagnoses of posttraumatic stress disorder and attention-deficit hyperactivity disorder (.63 to .67). CONCLUSION: Results suggest the K-SADS-PL generates reliable and valid child psychiatric diagnoses.

Adolescent↗
PubMed1996

The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression.

This study examined the relationship between longitudinal clinical course and sleep and cortisol findings in adolescent unipolar major depressive disorder (MDD). Subjects were 28 adolescents (15.4 +/- 1.3 years) systematically diagnosed with unipolar MDD and 35 group-matched normal controls who participated in EEG sleep and neuroendocrine studies. Follow-up clinical assessments were conducted 7.0 +/- 0.5 years later in 94% of the original cohort. Although initial group comparisons failed to show significant differences in biologic measures, analyses incorporating clinical follow-up reveal that changes in sleep and cortisol measures are associated with differential longitudinal course. Normal controls who would develop depression after the biologic studies had shown significantly higher density of rapid eye movements (REM) and a trend for reduced REM latency compared to controls with no psychiatric disorder at follow-up. Depressed subjects with a recurrent unipolar course showed a trend towards elevated plasma cortisol near sleep onset compared to MDD subjects with no further episodes during the follow-up interval.

Adolescent↗
PubMed1996

Corticotropin-releasing hormone challenge in prepubertal major depression.

This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.

Adolescent↗
PubMed1996

Local recurrence and survival in soft-tissue sarcomas.

BACKGROUND: There is a continuous interest in the literature concerning the management and survival after treatment of local recurrence in sarcomas because it is one of the most common types of recurrence. DESIGN: We retrospectively reviewed 93 patients treated for local recurrence from soft-tissue sarcoma. METHODS: We evaluated prognostic parameters (grade, tumor size, location) and the effect of treatment on survival. RESULTS: Resection of all the gross tumor at first visit to our Institute for local recurrence was accomplished in 88 patients (95%). Of the 59 patients with extremity tumors, six (10%) required an amputation. At a mean follow-up of 66 months, further local recurrence was noted in 27%. The estimated 5-year survival rate was 100% for patients with grade I tumors (n = 16), 77% for grade II (n = 31), and 45% for grade III tumors (n = 46) (p = 0.0002). This value was 78% for tumors < or = 5 cm and 57% for those > 5 cm (p = 0.03). CONCLUSIONS: Local recurrence is resectable and limb preservation is possible in the majority of patients. The overall 5-year survival rate was 65%. Survival after treatment of local recurrence is determined mainly by the grade and secondarily by the size of the tumor as for primary sarcomas.

Adolescent↗
PubMed1996

Bundle pattern of the flexor digitorum profundus tendon in zone II of the hand: a quantitative assessment of the size of a laceration.

Assessing the cross-sectional area of a partial laceration of a flexor digitorum profundus tendon based on its width, using magnification and calipers, is often inaccurate. As the threshold for repairing a partial laceration for most surgeons is the involvement of 50% of the tendon area, an accurate method of naked-eye evaluation to detect a 50% (or larger, or smaller) laceration was developed. This assessment is based on the size of the radial and ulnar bundles in the tendon. The relative area of the two bundles at four levels in zone II in the index, middle, ring, and small fingers was measured. In the index and small fingers, the ulnar bundle had a mean area consistently greater than and the radial bundle consistently less than 50% of the total tendon area. In the middle finger, the mean areas of both bundles were close to 50% of the total tendon area, but the radial bundle was reduced at the level of the proximal interphalangeal joint and distally. In the ring finger, both bundles remained close to 50% of the total tendon area at all levels. The bundles involved in a laceration can be easily identified with the naked eye; the data provided by this study may improve the accuracy of partial laceration size assessment.

Aged↗
PubMed1996

Rejection of the component tissues of limb allografts in rats immunosuppressed with FK-506 and cyclosporine.

One-hundred and fourteen limb transplantations have been performed across a major histoincompatibility barrier between donor ACI (RT1a) and recipient Lewis (RT1l) rats immunosuppressed with various dosages of FK-506 and cyclosporine. Three-hundred and thirty biopsy specimens from 64 animals have been evaluated histologically for signs of rejection. A new histologic grading system is introduced to classify the process of rejection in the component tissues (skin, muscle, bone, and articular cartilage) of a limb allograft. The results indicate that FK-506 is a more potent immunosuppressive agent than cyclosporine in preventing the rejection of the skin component of a limb transplant. With twice-weekly intermittent immunosuppression with FK-506, the rejection of muscle, bone, and cartilage can be prevented for an indefinite time, although all long-term surviving animals died at around 300 days, probably of graft-versus-host disease. Based on the histologic stages of rejection in the different tissues at the same point in time, it is evident that each component tissue of a limb transplant rejects over a different time period. This probably reflects a hierarchy of antigenicity, with skin being most antigenic, muscle being intermediate in antigenicity, and bone and cartilage being least antigenic. Although this grading system is not the ultimate solution, it may allow a more objective comparison of experimental limb transplantation in the future.

Analysis of Variance↗