The impact of comorbid anxiety and depression on alcohol treatment outcomes

AIMS: This study examines the impact of comorbid Diagnostic and Statistical Manual version IV (DSM-IV) anxiety and/or depression on out-patient treatment for alcohol problems. DESIGN: A prospective correlational design. PARTICIPANTS AND SETTINGS: Seventy-one clients seeking alcohol out-patient treatment at two treatment sites were interviewed at commencement of a treatment episode for alcohol problems and reinterviewed using the same measures 3 months later. Comorbid DSM-IV anxiety and/or depression were measured by the Composite International Diagnostic Interview (CIDI), a comprehensive interview developed by the World Health Organization to assess current and life-time prevalence of mental disorders. Outcome measures included standardized measures of disability [the short form (SF)-12 Mental Health Summary Score and the number of days taken out of role] and the average amount of alcohol consumed. Clients were also asked to rate their satisfaction with the services received. FINDINGS: Participants with comorbid DSM-IV anxiety and/or depressive disorders were more disabled and drank more heavily than those without these comorbid disorders at entry to treatment. At 3-month follow-up both groups of participants (i.e. those with and without DSM-IV comorbid anxiety and/or depression) were significantly less disabled and also drank significantly less alcohol on an average drinking occasion than at baseline. Despite this, the comorbid group remained more disabled and drank more heavily than the non-comorbid group at follow-up. CONCLUSIONS: Further research is needed to determine the most appropriate model of care for alcohol treatment seekers with comorbid DSM-IV anxiety and/or depression.     

Parathyroid hormone expression in a patient with metastatic nasopharyngeal rhabdomyosarcoma and hypercalcemia

Ectopic PTH secretion by tumor cells has been described as the cause of hypercalcemia associated with malignancy in the absence of osteolytic bone lesions. Although there have been case reports of elevated PTH and hypercalcemia in patients with rhabdomyosarcoma, to date ectopic PTH secretion by malignant cells has not been definitively shown. The possibility of PTH production by pleural-based metastatic nasopharyngeal rhabdomyosarcoma cells in a 62-yr-old Japanese male with hypercalcemia was investigated. The patient's serum PTH level was found to be elevated at 62.22 pmol/L, and pleural fluid PTH level was 47.28 pmol/L and PTHrP level was 3.7 pmol/L. RT-PCR of mRNA extracted from rhabdomyosarcoma cells in the pleural fluid was performed with the addition of PTH and PTHrP exonic primer sets yielded only a cDNA fragment of approx 150 bp consistent with the expected PTH fragment. Sequence analysis of a nested primer PCR fragment confirmed PTH mRNA sequence. We believe this patient to have had hypercalcemia secondary to ectopic PTH secretion, as we have identified the presence of PTH mRNA in tumor cells. We speculate that the overexpression of PTH in rhabdomyosarcoma cells results from molecular rearrangement of the PTH gene. The finding of a normal PTH DNA sequence of the PCR fragment suggests the likelihood of alterations in regulatory sequences.     

Experience with inhaled nitric oxide therapy in hypoxic respiratory failure of the newborn

BACKGROUND: Respiratory diseases are the commonest cause of morbidity and mortality in newborns. Inhaled nitric oxide (iNO) has been shown to be effective in the management of persistent pulmonory hypertension of newborn (PPHN). OBJECTIVES: To retrospectively analyse data to determine the effectiveness of inhaled nitric oxide (iNO) in the management of newborns with PPHN in terms of survival and changes in oxygenation status. METHODS: Neo-natal data since inception of iNO therapy at the unit (past six years) was reviewed. Pertinent demographic and clinical information was collected from medical records of newborns that received inhaled nitric oxide therapy during their stay. Details of underlying illnesses, other therapeutic modalities, arterial blood gas, ventilatory and nitric oxide parameters were assessed and analysed to ascertain efficacy of iNO. RESULTS: A total of 36 babies (gestational age ranging from 24-41 weeks) received iNO during this period; two were excluded from final analysis. Overall survival rate was 80 percent. There was a statistically significant increase in systemic oxygenation (PaO2) from 41.1 +/- 2.1 mmHg to 128.5 +/- 13.2 mmHg and a decline in oxygenation index (OI) from 49.4 +/- 5.9 to 17.3 +/- 2.5, when assessed after four hours (P < 0.001). Mean duration of iNO therapy was 63 +/- 7.3 hours and the maximum methaemoglobin levels were noted to be 2.1 percent. CONCLUSIONS: Inhaled nitric oxide appears to be an effective rescue therapy for the management of PPHN associated with hypoxic respiratory failure. It is safe and well tolerated with no evidence of clinical or biochemical side effects.     

Formulation and feedback: an illustration of two methods for improving access to effective therapies

It is now recognised that therapists require career-long training in order to maintain and improve their expertise. However, training will fail to improve services to clients unless the work environment supports staff in its use. Although this "training transfer" problem is widely acknowledged, to the authors' knowledge the way that the work environment influences clients' access to effective therapies has not been subjected to a detailed and systematic formulation. Therefore, this small study illustrates a suitable formulation, based on the training received by a group of National Health Service (NHS) staff in "psychosocial interventions", and proposes its use as a "feedback fascia" to managers and others. To do this, structured interviews were held with a self-selected sample of n = 20 therapists (mostly nurses) and all of their managers (n = 11) in one NHS Trust. The results indicated an impressive degree of training transfer. It is concluded that staff training can improve clients' access to effective treatments, but that significant organisational support for innovation is required. A feedback fascia can guide such support.     

Synthesis and biological evaluation of a new class of geldanamycin derivatives as potent inhibitors of Hsp90

The heat shock protein Hsp90 has increasingly become an important therapeutic target especially for treatment of cancers. Inhibition of the ATPase activity of Hsp90 by natural products (e.g., 17-allylaminogeldanamycin or radicicol) leads to the ubiquitination of oncogenic client proteins such as Her-2, Raf-1, and p-Akt followed by their proteasomal degradation. Hsp90 inhibitors simultaneously target multiple oncogenic proteins and provide an advantage for cancer therapy due to the potential for increased efficacy and overcoming drug resistance. In an effort to convert geldanamycin into a druglike compound with better pharmacokinetic properties and efficacy in human tumor xenograft models, geldanamycin was derivatized on the 17-position to prepare new analogues such as 17-geldanamycin amides, carbamates, and ureas and 17-arylgeldanamycins. All the compounds were first evaluated ex vivo using a cell-based Her-2 degradation assay and in vitro using biochemical assays that measure recombinant Hsp90 (rHsp90) competitive binding and changes in rHsp90 conformation. In addition, we confirmed the selectivity of geldanamycin analogues for Hsp90 derived from tumor cells using a novel cell lysate binding assay.