Effect of human insulin administration on urinary acidification in patients with insulin-dependent diabetes

A previous study has shown that oral glucose administration results in a transient fall in urinary acid excretion in humans. The present study was undertaken to determine the effect of physiologic doses of insulin on urinary acidification while maintaining serum glucose concentration constant. This was accomplished by using a euglycemic insulin clamp method. Eight patients with insulin-dependent diabetes and no clinical or laboratory evidence of detectable renal disease were studied. Data obtained during two 2-hour periods of steady state insulin infusion rates of 0.2 and 0.5 mU/kg/min were compared. This resulted in steady state serum free insulin levels of 15 +/- 0.1 and 39 +/- 0.6 uU/ml respectively. Urinary pH and bicarbonate excretion rate rose while the excretion rates of titratable acid, ammonium and net acid fell significantly with increased insulin administration. These changes occurred in the absence of any significant changes in serum glucose, potassium, Ca2+ or phosphorus concentrations or urinary excretion rates of Na+, K+, phosphorus or Ca2+. These data suggest that increased insulin levels within the physiological range can result in a transient fall in the rate of urinary acid excretion. These findings confirm previous observations in animals and suggest that insulin may be the cause of post prandial urinary "alkaline tide".     

The value of two-step operative laparoscopy with interval pituitary suppression in the treatment of infertility caused by severe endometriosis

PURPOSE OF REVIEW: To appraise a new approach to laparoscopic surgery for infertility caused by advanced endometriosis. RECENT FINDINGS: Endometriosis is a common systemic and local disease with altered peritoneal function, which requires both systemic and local treatment. Medication alone cannot improve infertility, and laparoscopic treatment, particularly in severe endometriosis, has a high recurrence rate and is often limited by technical difficulties. Novel treatment strategies have therefore to be sought, especially in women who do not want in-vitro fertilization as a first option, either because they suffer from pain in addition to infertility or want to enhance their fertility over many cycles. SUMMARY: Two-step operative laparoscopy with interval pituitary suppression by means of gonadotrophin-releasing hormone analogues reduces the extent of endometriosis, as classified by the American Fertility Association, and appears to be a promising method of achieving optimal cytoreduction and facilitating complicated surgery in severe endometriosis, while protecting the ovary from unnecessary trauma. A large-scale well-designed study is needed to confirm that this treatment leads to improved pregnancy rates.     

Rural-urban differences in the presentation, management and survival of breast cancer in Western Australia

From all women diagnosed with invasive breast cancer in 1999 in Western Australia, rural and urban women were compared with regard to mode of detection, tumour characteristics at presentation, diagnostic investigations, treatment and survival. Women from rural areas with breast cancer (n=206, 23%) were less likely to have open biopsy with frozen section (P<0.001), breast-conserving surgery (P<0.001), adjuvant radiotherapy (P=0.004) and hormonal therapy (P=0.03), and were less likely to be treated by a high caseload breast cancer surgeon (P<0.001). Adjusting for age and tumour characteristics, rural women had an increased likelihood of death within 5 years of breast cancer diagnosis (HR 1.62, 95% CI 1.10-2.38). This difference was not significant after adjustment for treatment factors (HR 1.36, 95% CI 0.90-2.04).     

Embolisation of spinal dural arteriovenous fistulae with Onyx

Surgery is currently the standard treatment for spinal dural arteriovenous fistulae (DAVF). Endovascular embolisation of these lesions using N-butyl cyanoacrylate (NBCA) has a high success rate. Onyx is a new liquid embolic agent whose viscosity makes it suitable for treatment of spinal DAVF where penetration into the proximal radicular vein is required. It is delivered with greater control than NBCA without the necessity for rapid withdrawal of the catheter and may therefore overcome some of the drawbacks of NBCA. We report two patients who underwent Onyx embolisation of spinal DAVF; to our knowledge this is the first such report.     

The functional characterization of interleukin-10 receptor expression on human natural killer cells

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.     

Validity and reliability of the Geriatric Anxiety Inventory in Parkinson's disease*†

Aim: To examine the psychometric properties of a novel anxiety rating scale, the Geriatric Anxiety Inventory (GAI) in Parkinson's disease (PD). Method: The predictive validity of the GAI was tested against the presence of any DSM‐IV anxiety disorders in 58 PD patients using receiver operating curve analysis. The concurrent validity of this scale was also studied against the state half of the Spielberger State Trait Anxiety Inventory (STAI). The internal consistency and test–retest reliability of the GAI were also examined. Results: The GAI displayed good concurrent validity against the STAI and the DSM‐IV. It also showed good internal consistency and test–retest reliability. Conclusions: This study suggested that the GAI is an appropriate scale to use in non‐demented PD patients.