Neuropsychologic and Functional Recovery From Severe Carbon Monoxide Poisoning Without Hyperbaric Oxygen Therapy

Study objective: To test the hypothesis that neuropsychologic test results and functional outcome will be abnormal if hyperbaric oxygen (HBO) is not used in patients with severe carbon monoxide (CO) poisoning. Methods: For a 1-year interval, we retrospectively identified all CO-poisoned patients who were comatose on presentation at a large, urban tertiary hospital and did not receive HBO therapy. Prospectively, 6 and 12 months after CO poisoning, we administered standardized questionnaires to assess functional outcome. At 6 months, we performed extensive neuropsychologic testing. Results: All four patients exhibited normal performance on a neuropsychologic test battery at 6 months. The Folstein Mini-Mental Status Examination was normal in all patients. All patients had normal functional outcomes. Conclusion: Normal neuropsychologic and functional outcomes are possible after severe CO poisoning without the use of HBO therapy. [Weaver LK, Hopkins RO, Larson-Lohr V: Neuropsychologic and functional recovery from severe carbon monoxide poisoning without hyperbaric oxygen therapy. Ann Emerg Med June 1996;27:736-740.]     

Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation

Factors affecting mobilization and engraftment were analysed in 54 patients undergoing transplant using autologous PBSCs mobilized with high-dose recombinant granulocyte stimulating factor (rhG-CSF). Patients received 5-7 d of rhG-CSF. 16 μg/kg/d, administered subcutaneously. PBSCs were harvested by leukapheresis using automated continuous-flow blood cell separators beginning on day 4 of rhG-CSF, processing 10 litres of whole blood, for 2-6 consecutive days. Transplants were performed for the following diseases: breast cancer (n = 22), non-Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7). Engraftment was rapid with patients reaching a neutrophil count of 1 × 10⁹/1a median of 12 d (range 9-22) after transplant. Platelets > 20 × 10⁹/1 independent of transfusion support were achieved a median of day 10 (range 7-60) after infusion. Multiple factors potentially influencing engraftment were examined using a Cox regression model. The number of CD34⁺ cells per kg was highly correlated with the time to achievement of granulocyte and platelet recovery (P < 0.012, 0.0001). The use of a post-infusion growth factor and a radiation preparative regimen was important for neutrophil recovery, and a diagnosis of breast cancer was important for platelet recovery. In an analysis by linear regression of the logarithm of CD34⁺ cells collected, lower age, marrow without disease, no prior radiation, and lower number of prior chemotherapy regimens, were important factors influencing larger numbers of CD34⁺ cells in collections.     

Chromosomal aberrations in PARP(-/-) mice: genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA

Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP(-/-) mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP(-/-)mice and immortalized PARP(-/-)fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP(-/-) cells stably transfected with PARP cDNA [PARP(-/-)(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP(-/-) cells, p53 expression was partially restored in PARP(-/-) (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP(-/-) mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency.     

A practical approach to reporting treatment abandonment in pediatric chronic conditions

Treatment abandonment, the failure to complete therapy that is required for definitive disease control, frequently causes treatment failure for pediatric patients in low‐ and middle‐income countries with chronic conditions, particularly cancer. Other forms of incomplete treatment affecting children in all settings, such as nonadherence and loss to follow‐up, are often confused with treatment abandonment. Unclear definitions of incomplete treatment dramatically affect reported outcomes. To facilitate disease‐specific and cross‐sector analyses, we outline a practical approach to categorize forms of incomplete treatment, present distinct semantic categories with case examples and provide an algorithm that could be tailored to disease‐ and context‐specific needs. Pediatr Blood Cancer 2015;62:565–570. © 2015 Wiley Periodicals, Inc.     

The influence of gender on the short and long-term effects of growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults: a 5-year study

OBJECTIVES: The objectives of this study were to investigate the effects of GH replacement therapy in hypopituitary adults with growth hormone deficiency (GHD) on activation of bone remodelling during dose titration and on BMD over a median of 58 months of continuous therapy. STUDY DESIGN: Open label study in adult patients with GHD. rhGH was commenced at dose of 0.8 IU subcutaneously daily (0.4 IU if hypertensive or glucose tolerance impaired) with subsequent dose titration based on 2 weekly measurement of serum IGF-I until levels reached the target range (between the median and upper end of the age related reference range). In patients previously commenced on GH using weight based regimens the dose of GH was adjusted during clinical follow-up in order to maintain serum IGF-I in the target range. PATIENTS: Initial effects of GH on bone remodelling during dose titration were studied in 17 patients (8F). Long-term effects of GH were determined in a separate group of 13 GHD adults (6F) over a median period of 58 months (range 44-72). MEASUREMENTS: Osteoblastic activity was estimated by measuring serum bone specific alkaline phosphatase (S-BAP). BMD was determined at both lumbar spine (L2-L4) and femoral neck by dual energy X-ray absorptiometry (DEXA). RESULTS: During dose titration a significant increment in S-BAP was observed by 10 weeks in females but occurred later in males (12-26 weeks). In the long term treatment group there was a significant increment in S-BAP compared to baseline (P = 0.013) after 6 months GH treatment. After long-term GH treatment (median 58 months) S-BAP levels decreased and were no longer statistically significantly different from baseline at the end of the study period. A similar response was observed in male and female patients. There were no significant differences in baseline BMD between male and female patients at either lumbar spine or femoral neck in the long term treatment group. No significant changes were observed in BMD after 6 months GH treatment in either lumbar spine or femoral neck but BMD increased over the remainder of the study at both sites (P = 0.023 and P = 0.03 respectively). When analysed by gender male patients showed a clear positive change in BMD after longer-term replacement in both lumbar spine and femoral neck (P = 0.01 and P = 0.02 respectively) but female patients showed no significant changes. Qualitatively similar results were observed when analysing changes in BMD expressed as Z scores. CONCLUSION: This study demonstrates an earlier onset of GH activation of bone remodelling as reflected by S-BAP in females compared to males and confirms that long-term GH treatment in hypopituitary adults with GH deficiency increases or preserves BMD both at lumbar spine and femoral neck. However male patients seem to derive the greater benefits in BMD from long-term GH replacement; in females BMD appears simply to be stabilized rather than increased. This constitutes a genuine gender difference in susceptibility given that serum IGF-I was in the upper part of the reference range in all subjects.     

Management of Posttraumatic Ankle Arthritis: Literature Review

Purpose of Review

Trauma is the principle cause of osteoarthritis in the ankle, which is associated with significant morbidity. This review highlights the current literature for the purpose of bringing the reader up-to-date on the management of posttraumatic ankle arthritis, describing treatment efficacy, indications, contraindications, and complications.

Recent Findings

Recent studies on osteoarthritis have demonstrated variability among anatomic locations regarding the mechanisms and rates of development for posttraumatic osteoarthritis, which are attributed to newly discovered biological differences intrinsic to each joint. Regarding surgical management of posttraumatic ankle arthritis, osteochondral allograft transplantation of the talus, and supramalleolar osteotomies have demonstrated promising results. Additionally, the outpatient setting was found to be appropriate for managing pain following total ankle arthroplasty, associated with low complication rates and no readmission.

Summary

Management for posttraumatic ankle arthritis is generally progressive. Initial treatment entails nonpharmacologic options with surgery reserved for posttraumatic ankle arthritis refractory to conservative treatment. Patient demographics and lifestyles should be carefully considered when formulating a management strategy, as outcomes are dependent upon the satisfaction of each set of respective criteria. Ultimately, the management of posttraumatic ankle arthritis should be individualized to satisfy the needs and desires, which are specific to each patient.

     

Type 2 Diabetes and Anxiety Symptoms Among Women in New Delhi,India

Objectives. We explored the relationship between mental health and type 2 diabetes among women in New Delhi, India, in 2011.Methods. We recruited a convenience sample of 184 diabetic women from 10 public and private clinics. They completed a finger-stick blood test and a questionnaire assessing demographic characteristics, depression and anxiety symptoms, and diabetes-related disabilities restricting their performance of daily tasks. A subsample of 30 women participated in follow-up qualitative interviews at their homes.Results. More than one quarter of our sample of diabetic women reported high levels of anxiety symptoms, whereas 18% reported high levels of depression symptoms. Anxiety symptoms were patterned according to recency of diabetes diagnosis, with 40% of women diagnosed less than 2 years before their interview reporting high anxiety symptom levels, as opposed to 23% of women diagnosed more than 2 years in the past. Depression and anxiety scores differed with respect to their relationship to recency of diagnosis, number of children, blood glucose level, and functional disabilities restricting performance of daily tasks.Conclusions. Screening for anxiety among people with diabetes has been overlooked in the past. Anxiety appears more prevalent than depression, especially during the first 2 years of the disease.Chronic and noncommunicable diseases (CNCDs) are emerging as major research foci in tandem with their increasing global prevalence. In both developed and developing regions of the world, including South Asia, CNCDs are now leading causes of morbidity and mortality.1 With their complicated etiologies, long durations, frequent comorbidities, and lack of “cures,” CNCDs pose unique challenges for global health. In particular, CNCDs can have far-reaching personal and interpersonal effects that are difficult to capture in epidemiological and biomedical studies, yet are crucial to the trajectory of these illnesses. It is therefore necessary to adopt an analytic perspective that embraces the complex natural histories of chronic diseases as well as their potential comorbidities.A particularly well-studied instance of comorbidity is the overlap between type 2 diabetes and depression. This comorbidity has been estimated to affect anywhere from 11% to 71% of individuals with diabetes, depending on the population studied and the diagnostic method used,2–4 and it is strongly associated with physical and mental morbidity and even mortality.2–6 Clinical and epidemiological studies have demonstrated the cyclical nature of diabetes–depression comorbidity,7 and medical social scientists have identified some of the social determinants linking the 2 conditions, including socioeconomic status (SES),8 the social significance of foods and activity patterns,9,10 and gendered social roles.11–13The similarity between depression and anxiety symptoms, etiologies, and methods of diagnosis, as well as their common comorbidity,14 suggests that anxiety should be as great a concern in CNCD comorbidity as depression. Indeed, according to findings from the World Mental Health Survey, diabetes is roughly equally associated with depression and anxiety around the world.15 Yet, with one very recent exception,16 the potential impact of anxiety disorders on diabetes has received much less attention than diabetes–depression comorbidity.Here we detail the findings of an exploratory mixed-method study of type 2 diabetes (hereafter diabetes) and mental health symptoms among women in New Delhi, India, with a special focus on symptoms of anxiety. India is home to the second-largest population of individuals with type 2 diabetes in the world.17 The limited existing evidence suggests that depression and anxiety are also common,18–20 although prevalence studies are few. Little is known about how diabetes and poor mental health co-occur in this setting or about what social determinants might shape their comorbidity.On the basis of the observation that high levels of anxiety symptoms were significantly more prevalent than depression symptoms in our study, we believe that it is important to consider the causes and correlates of anxiety comorbid with diabetes. We propose a socially grounded interpretation of the patterns emerging from our preliminary data and offer suggestions for future research designed to assess the broader applicability of this interpretation for CNCD–anxiety comorbidity in other contexts.