Elevated Bile Acid 3ß,5α,6ß-Trihydroxycholanoyl Glycine in a Subset of Adult Ataxias Including Niemann-Pick Type C.

Ataxia is a common neurological feature of Niemann-Pick disease type C (NPC). In this disease, unesterified cholesterol accumulates in lysosomes of the central nervous system and hepatic cells. Oxidation by reactive oxygen species produces oxysterols that can be metabolised to specific bile acids. These bile acids have been suggested as useful biomarkers to detect NPC. Concentrations of 3ß,5α,6ß-trihydroxycholanyl glycine (3ß,5α,6ß-triOH-Gly) and 3ß,7ß-dihydroxy-5-cholenyl glycine (3ß,7ß-diOH-Δ5-Gly) were measured in plasma of 184 adults with idiopathic ataxia. All patients were tested with whole genome sequencing containing hereditary ataxia panels, which include NPC1 and NPC2 mutations and other genetic causes of ataxia. Plasma 3ß,5α,6ß-triOH-Gly above normal (>90 nM) was found in 8 out of 184 patients. One patient was homozygous for the p.(Val1165Met) mutation in the NPC1 gene. The remaining seven included one patient with Friedreich's ataxia and three patients with autoimmune diseases. Oxidative stress is known to be increased in Friedreich's ataxia and in autoimmune diseases. Therefore, this subset of patients possibly shares a common mechanism that determines the increase of this bile acid. In a large cohort of adults with ataxia, plasma 3ß,5α,6ß-triOH-Gly was able to detect the one patient in the cohort with NPC1 disease, but also detected oxidation of cholesterol by ROS in other disorders. Plasma 3ß,7ß-diOH-Δ5-Gly is not a potential biomarker for NPC1.

Exclusion of Patients with Autoimmune Disease in Lung Cancer Clinical Trials.

BACKGROUND: The exclusion of patients with autoimmune disease has been a topic of cancer immunotherapy trial. This study aims to find recent trends in exclusion of autoimmune disease. METHODS: Using the website clinicaltrials.gov, we searched for clinical trials that were initiated in 2012 or later and enrolled patients with lung cancer who were treated with PD-1/PD-L1 therapy. Only trials including US locations were analyzed. RESULTS: A total of 198 trials met screening criteria in this study. There were 68 trials which had complete exclusion of any autoimmune disease in patients. In addition, 13 trials excluded active autoimmune disease and 87 trials excluded active autoimmune disease requiring treatment. The remaining 37 trials had undefined exclusion.  Studies that had larger enrollment of patients with autoimmune diseases were largely in industry. The complete exclusion of patients with autoimmune diseases has decreased recently. CONCLUSION: Exclusion of patients with active autoimmune disease requiring treatment was one of the common exclusion criteria found.  Strict exclusion of patients with autoimmune diseases has been decreasing over the years.

Stakeholders' perspective on mental health laws in Pakistan: A mixed method study.

The present study explored awareness and opinions pertaining to mental health legislation in Pakistan in the context of the United Nation Convention on Rights of People with Disabilities (UNCRPD) through a mixed method research design. In the quantitative arm of the study, a structured questionnaire examined awareness and opinions of key stakeholders pertaining to national mental health legislation. In the qualitative arm, face-to-face interviews further elaborated stakeholders perspectives pertaining to these topics with thematic analysis conducted. Stakeholders demonstrated a good awareness of legislation pertaining to guardianship (83.0 %) appointment of property managers (89.7%) and salary or pension entitlements (89.2%). Compared to other stakeholders, patients had less understanding of processes pertaining to involuntary admission (χ2 = 20.54, p = 0.02) and appointing a guardian (χ2 = 34.67, p < 0.01). High consensus across stakeholders was noted for processes of involuntary detention (83.5%) and appointment of guardians or property managers (80.0%) albeit patients demonstrated less agreement on these topics (p <0.01). Minimal support was noted for an involuntary patient to be discharged solely on a psychiatrist's recommendation (25.4%). Thematic analysis indicated fifteen emergent themes: 1) Alienation/ Seclusion; 2) Capacity building; 3) Communication Gap; 4) Conflict of interests; 5) Discomfort at hospital; 6) Economic burden; 7) Government's liability; 8) Family involvement; 9) Imbalance; 10) Acceptance of Legal Incapacity; 11) Legal reforms; 12) Patient centred environment; 13) Quality assurance; 14) Under developed infrastructure and 15) Potential unethical practices. This study advocates for increased patient involvement in collaborative decision making with mental health professionals and the creation of more appropriate inpatient treatment environments.

Outcome of modified open surgery in tennis elbow.

BACKGROUND: Tennis elbow is a common disorder of upper extremity. It can be treated conservatively in majority of the patients but some resistant cases eventually need surgery. MATERIAL & METHODS: This descriptive study was conducted at Department of Orthopaedics, Ayub Teaching Hospital, Abbottabad, from January 2002 to June 2006. Sixteen patients had surgical release of the extensor tendon origin along with excision of the lateral epicondyle ridge. These patients did not respond to conservative treatment i.e. rest, non- steroidal anti inflammatory drugs (NSAIDS), local steroid injections and physiotherapy. Patients were followed upto six months. Outcome was graded as excellent, good and poor according to pain relief and function of the hand. RESULTS: Sixteen patients (17 elbows) were studied. Thirteen were female (81.25%) and three were male (18.75%). Fifteen patients (93.75%) had unilateral Tennis Elbow, while one had bilateral involvement (6.25%). In unilateral disease, right side was affected in eleven patients (68.75%) and left side in four (25%). Excellent outcome was noticed in eleven patients (68.75%) and good result in five patient (31.25%). CONCLUSION: Open surgical technique of releasing extensor tendon origin along with excision of lateral condylar ridge of the humerus is new and simple procedure and yields excellent and good result in patients with resistant Tennis Elbow.

Malaria in children: study of 160 cases at a private clinic in Mansehra.

BACKGROUND: This study was conducted in a private clinic to report frequency, presentation and management of malaria in children presenting with fever. METHODS: 160 Children of age varying from 42 days to 15 years were included in this study, during a period of 1999-2004. RESULTS AND CONCLUSIONS: Malaria was confirmed in 154 cases, including 114 male and 46 female children. In 6 cases malarial parasite was not seen on microscopic examination of their blood films. 142 cases were found to be suffering from vivax and 12 were suffering from falciparum malaria. Most of the cases were treated with amodiaquine and some of them were treated with other antimalarial drugs.

Comparison of metoclopramide, prochlorperazine and placebo in prevention of postoperative nausea and vomiting (PONV) following tonsillectomy in young adults.

BACKGROUND: Postoperative nausea and vomiting following anaesthesia and surgery are common and can create considerable problems regarding management of patients and outcome of the surgical procedure. METHODS: This study evaluates and compares the efficacy and safety of the metochlopramide to that of prochlorperazine in the prevention of postoperative nausea and vomiting after tonsillectomy in young adult patients. 150 patients, of either sex, undergoing tonsillectomy under the same anaesthetic technique were studied in a randomized, double blind, placebo controlled manner. Either metoclopramide 0.1-0.2 mg kg(-1), prochlorperazine 0.1-0.2 mg kg(-1) or 5% Dextose and normal saline (5% D/N.S) (2ml) as placebo was injected intravenously 10 minutes before induction of general anaesthesia. Episodes of nausea, retching/vomiting, adverse events, vital signs, the need for rescue antiemetic drug (metoclopramide 0.1-0.2 mg kg(-1) IV) were recorded until four hours from the end of the surgical procedure. RESULTS: The overall frequency of PONV was 18%, 16%, and 24% in group A (metoclopramide), B (prochlorperazine) and C (placebo) respectively. The need for rescue antiemetic was 2%, 8% and 12% in Prochloperazine group, metoclopramide group and control group respectively. These differences did not reach statistical significance (P>0.05). During the study period 82%, 84% and 76% of patients in group A, B and C respectively were found free from postoperative nausea and vomiting, and no adverse events related to either of the test medication were noted in any patient. CONCLUSION: It is concluded that the differences in the results of occurrence of PONV in the experimental group and control group are not statistically significant. However either Prochloperazine 0.1 - 0.2 mg kg(-1) or metoclopramide 0.1 - 0.2 mg kg(-1) can be safely administered as Prophylactic antiemetic till the availability of more efficacious and safe antiemetic drugs.