Aggressive surgical palliation for advanced girdle tumours

Background:

The surgical management of advanced, incurable, malignant disease presents particular ethical and technical challenges. The clear goal is palliation and the surgical futility must be avoided. This case series presents some particular challenges in end-of-life surgery.

Materials and Methods:

Fifteen patients referred with advanced malignant disease involving a limb girdle were reviewed.

Results:

In one case, a patient pleaded for surgery after initially requesting a delay to seek treatment from a Chinese Traditional Herbalist. The increase in tumour bulk led to problems with surgery and the patient died in a hospital a few weeks later. This case illustrates ‘futility’ not recognized and encountered. The remaining 14 patients exhibited positive palliation with improved quality of dying and appreciation expressed by patients, relatives and staff.

Conclusion:

In selected cases, with a skilled and experienced surgical team, patients with advanced malignant disease can still benefit from aggressive surgical palliation. The margin of error is small between palliation being attempted and futility being achieved. This considerably adds to the challenge of end-of-life surgery.KEY WORDS: Futility, palliation, quality of life, surgery     

Critical illness hyperglycemia in pediatric cardiac surgery

Critical illness hyperglycemia (CIH) is common in pediatric and adult intensive care units (ICUs). Children undergoing surgical repair or palliation of congenital cardiac defects are particularly at risk for CIH and its occurrence has been associated with increased morbidity and mortality in this population. Strict glycemic control through the use of intensive insulin therapy (IIT) has been shown to improve outcomes in some adult and pediatric studies, yet these findings have sparked controversy. The practice of strict glycemic control has been slow in extending to pediatric ICUs because of the documented increase in the incidence of hypoglycemia in patients treated with IIT. Protocol driven approaches with more liberal glycemic targets have been successfully validated in general and cardiac critical care pediatric patients with low rates of hypoglycemia. It is unknown whether a therapeutic benefit is obtained by keeping patients in this more liberal glycemic control target. Definitive randomized controlled trials of IIT utilizing these targets in critically ill children are ongoing.     

Service availability and utilization and treatment gap for schizophrenic disorders: a survey in 50 low- and middle-income countries

Objective

To outline mental health service accessibility, estimate the treatment gap and describe service utilization for people with schizophrenic disorders in 50 low- and middle-income countries.

Methods

The World Health Organization Assessment Instrument for Mental Health Systems was used to assess the accessibility of mental health services for schizophrenic disorders and their utilization. The treatment gap measurement was based on the number of cases treated per 100 000 persons with schizophrenic disorders, and it was compared with subregional estimates based on the Global burden of disease 2004 update report. Multivariate analysis using backward step-wise regression was performed to assess predictors of accessibility, treatment gap and service utilization.

Findings

The median annual rate of treatment for schizophrenic disorders in mental health services was 128 cases per 100 000 population. The median treatment gap was 69% and was higher in participating low-income countries (89%) than in lower-middle-income and upper-middle-income countries (69% and 63%, respectively). Of the people with schizophrenic disorders, 80% were treated in outpatient facilities. The availability of psychiatrists and nurses in mental health facilities was found to be a significant predictor of service accessibility and treatment gap.

Conclusion

The treatment gap for schizophrenic disorders in the 50 low- and middle-income countries in this study is disconcertingly large and outpatient facilities bear the major burden of care. The significant predictors found suggest an avenue for improving care in these countries.     

Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1

The calcium activated K⁺ channel KCa3.1 plays an important role in T lymphocyte Ca²⁺ signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca²⁺ influx. We previously showed that nucleoside diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, is required for KCa3.1 channel activation in human CD4 T lymphocytes. We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1. Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity. Decreased expression of PHPT-1 by siRNA in human CD4 T cells resulted in an increase in KCa3.1 channel activity and increased Ca²⁺ influx and proliferation after T cell receptor (TCR) activation, indicating that endogenous PHPT-1 functions to negatively regulate CD4 T cells. Our findings provide a previously unrecognized example of a mammalian histidine phosphatase negatively regulating TCR signaling and are one of the few examples of histidine phosphorylation/dephosphorylation influencing a biological process in mammals.     

Abolition of endocrine dimorphism in hyperthyroid males? An argument for the positive feedback effect of hyperoestrogenaemia on LH secretion

Our aim was (i) to investigate the hypothalamo-hypophyseal-gonadal axis in hyperthyroid Indian males, (ii) to rule out the modulatory role of adrenal steroids on it and (iii) to determine if the simultaneous rise in oestradiol and luteinising hormone (LH) in hyperthyroid males is due to a positive feedback action of oestradiol on pituitary LH release. Age- and BMI-matched men were divided into two groups, I, euthyroid subjects (n = 17) and II, hyperthyroid patients (n = 12) on the basis of their thyroid hormone levels. Serum levels of thyroid-stimulating hormone, triiodothyronine, thyroxine, LH, follicle-stimulating hormone (FSH), prolactin, E(2), T, P(4), sex hormone binding globulin and dehydroepiandrosterone sulphate (DHEAS) were assayed. Mean levels of T and E(2) were approximately two times higher in group II in comparison with group I. DHEAS levels were similar in both groups ruling out any adrenal involvement. Mean serum LH level was 2.6 folds higher in group II in comparison with group I. Mean serum levels of FSH were higher in group II, it was marginally nonsignificant. On the basis of these and previous observations, we hypothesise that endocrinological dimorphism in human male and female is not rigid; a sustained rise in serum oestradiol probably induces a positive feedback action on pituitary leading to elevated gonadotrophin levels.