Feasibility Evaluation of an Interpersonal and Social Rhythm Therapy Group Delivery Model

The effectiveness of psychotherapies, such as interpersonal and social rhythm therapy (IPSRT), is supported by randomized controlled trials. These trials provide minimal direction regarding feasibility of psychotherapy delivery models. The study purpose was to identify factors facilitating implementation and sustainability of an IPRST group for patients with bipolar disorder. Qualitative data were assessed by the normalization process model (NPM). The results demonstrate feasibility of implementation with experienced clinicians, program coordination, and leadership support. Sustainability challenges include aftercare groups, space, and clinician time. The NPM provides a useful framework for evaluation of factors influencing the feasibility of psychotherapy delivery models.     

Initiation of a pharmacovigilance programme at a tertiary care hospital in South India

Objective India is a country with the availability of a large number of pharmaceutical preparations as branded generics. At the time of this study there was no established pharmacovigilance system at the national level except a co‐ordinating centre at the national capital. The study site was a tertiary care teaching hospital with a bed capacity of 500 and with an average of 200 outpatient visits and 50 inpatient admissions per day. The hospital did not have any system of monitoring and documenting adverse drug reactions. The objective of the study was to introduce an adverse drug reaction (ADR) monitoring programme at a tertiary care teaching hospital and assess ADR‐related issues in both inpatient and outpatient departments. Method All departments willing to report ADRs were included in the study, which was carried out for one year. Physicians and nurses filled in the notification forms when they encountered suspected ADR cases. These cases were then assessed by a panel of four judges. According to Naranjo's algorithm, the ADRs were assessed and classified based on World Health Organization (WHO) classification. Key findings A total of 288 suspected cases were reported and 264 ADRs were confirmed by the panel. According to Naranjo's probability scale, 83 cases were categorized as ‘probable’, 181 cases were classified as ‘possible’, and none were classified as ‘unlikely’ or ‘definite’. The most common classes of drugs involved were antibiotics (25%), psychotropics (20%), analgesic and cardiovascular agents (14% each). Generalised itch and rash, tremors, urticarial drug reaction, oral ulcer, gastritis and akathesia and extrapyramidal symptoms were found to be the most common ADRs observed; 2.1% of the patients in the studied departments had ADRs. Conclusion The ADR reporting system was initiated at the hospital and was well received by the physicians. Appreciable participation of physicians was noted during the study in reporting ADRs. The study also gave an insight into the awareness of physicians about ADR‐related issues. The number of ADRs reported was reasonably comparable with the findings of other authors from India.     

Adenoid cystic carcinoma of the cervix: a case report with implications for chemotherapeutic treatment

There have been 59 other cases of adenoid cystic carcinoma of the cervix reported in the literature. Therefore, little is known of the true biological behavior or therapeutic responsiveness of these tumors. We are reporting a case of adenoid cystic carcinoma of the cervix, FIGO Stage I-B, initially treated with radical hysterectomy and bilateral pelvic lymphadenectomy. Two years after surgery, the patient presented with recurrent disease in the pelvis and multiple lung metastasis. She subsequently was treated with chemotherapy consisting of cytoxan, Adriamycin, and cis-platinum with a sustained complete clinical response.     

Olfactory sensitivity, nasal resistance, and autonomic function in patients with multiple chemical sensitivities

A frequent, if not predominant, complaint of persons reporting symptoms of multiple chemical sensitivities (MCS) is that of heightened sensitivity to smells. In this study odor detection thresholds for phenyl ethyl alcohol (a major component of rose oil) and methyl ethyl ketone (a common solvent) were measured in 18 persons exhibiting symptoms of MCS and in 18 matched normal controls. In addition, nasal resistance, blood pressure, heart rate, and respiration rate were determined before and after the olfactory tests. Scores on the Beck Depression Inventory were obtained prior to testing. Although olfactory thresholds were equivalent in the two study groups, the MCS group evidenced significantly higher nasal resistances, respiration rates and Beck Depression Inventory scores. Decreases in systolic blood pressure and pulse were noted in both groups across the test sessions. These results do not support the hypothesis that MCS is associated with greater olfactory threshold sensitivity (at least to the two target chemicals), but do suggest that MCS is associated with depression, increased respiration rate, and decreased nasal airway patency.     

Neonatal isolation alters stress hormone and mesolimbic dopamine release in juvenile rats

Rat pups were individually isolated from the mother and nest for 1 h/day from postnatal days (PND) 2 to 9 and tested as juveniles (PND 26-30) compared to nonhandled (NH) controls. In response to 1 h of restraint stress, NH rats increased locomotor activity and dopamine (DA) levels, but neonatally isolated (ISO) rats did not. Both groups had increased plasma corticosterone levels in response to restraint, but corticosterone levels were higher in ISO than in NH. Brain allopregnanolone (3alpha,5alpha-THP) levels also increased in response to stress, but NH and ISO did not differ. Sex of the rats was not a factor for any of the measures except plasma corticosterone levels, where females had higher levels than males. These data indicate that the effects of neonatal isolation persist postweaning and that the effects are most evident in response to stress as opposed to under baseline conditions.     

Effect of nortriptyline and paroxetine on CYP2D6 activity in depressed elderly patients

This study was performed in elderly patients (1) to assess the degree to which CYP2D6 mediated metabolism of debrisoquine at baseline determines plasma concentration to dose quotients for nortriptyline or paroxetine after 4 weeks of treatment, and (2) to compare the effects of nortriptyline and paroxetine on debrisoquine metabolism after 6 weeks of treatment. CYP2D6 activity was estimated in 66 subjects (71.4 +/- 7.2 years) before initiating treatment and again after 6 weeks of treatment with either nortriptyline or paroxetine under randomized, double-blind conditions according to a standard protocol. CYP2D6 activity was estimated by the debrisoquine recovery ratio in a 6- to 8-hour urine sample collected after oral administration of 10 mg debrisoquine sulfate. Nortriptyline and paroxetine plasma concentrations were obtained weekly. Baseline debrisoquine recovery ratio values were significantly correlated with the plasma concentration to dose quotient at 4 weeks for both nortriptyline ( = -0.75, = 0.0001, N = 29) and paroxetine ( = -0.50, = 0.003, N = 33). Treatment with either nortriptyline or paroxetine was associated with a significant decrease in the median debrisoquine recovery ratio, reflecting inhibition of CYP2D6 metabolism. The percent decrease associated with nortriptyline was significantly smaller than that with paroxetine ( < 0.0001). None of the patients treated with nortriptyline but 19 of the 32 extensive metabolizers treated with paroxetine were converted to phenotypic poor metabolic status. Our observations of CYP2D6 inhibition are consistent with data and results obtained in younger healthy volunteers. The significant correlations between baseline debrisoquine recovery ratio and the plasma concentrations to dose quotients at 4 weeks for both nortriptyline and paroxetine are consistent with CYP2D6 playing a major role in the metabolism of both drugs. CYP2D6 inhibition by paroxetine, which effectively converted 59% of patients to phenotypic PMs, may be especially relevant for elderly patients given their generally higher concentration of paroxetine.     

Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors

The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.     

Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study

OBJECTIVE: Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex. METHOD: This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest. RESULTS: Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness. CONCLUSIONS: In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.