Acute and chronic effects of domperidone on gastric emptying in diabetic autonomic neuropathy

Gastric emptying was studied with a double radioisotopic method in 12 patients with insulin-dependent diabetes mellitus complicated by autonomic neuropathy and in 22 control subjects. In the diabetics, the acute and chronic effects of oral domperidone on gastric emptying, symptoms of gastroparesis, and glycemic control were assessed. Gastric emptying of solid and liquid was slower in diabetics than controls (P<0.001). Acute administration of domperidone increased the rate of both solid and liquid emptying (P<0.005). Domperidone was most effective in those patients with the greatest delay in gastric emptying. After chronic administration (35–51 days), domperidone had no significant effect on solid emptying (P>0.05), but was still effective in increasing liquid emptying (P<0.025). Symptoms of gastroparesis were less after domperidone (P<0.001).Dr. M. Horowitz was supported by a grant from the National Health and Medical Research Council of Australia.     

Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring

Reduced size at birth in humans has been associated with altered function of the hypothalamic-pituitary-adrenal (HPA) axis in childhood and adult life. Experimentally, maternal undernutrition has also been associated with altered fetal HPA function. However, the relationship between birth size, fetal nutrition, and adult pathophysiology is not clear. We recently have reported that glucose tolerance, blood pressure, and IGF-I levels in adult sheep were more closely associated with birth weight than with nutritional insult in late gestation or with current weight. Here, we report adult HPA function in the same group of animals. Pregnant ewes were severely undernourished for 10 d (UN10) or 20 d (UN20) from 105 d gestation (term, 146 d), or were ad libitum-fed controls. At 30 months, female offspring were subjected to an insulin tolerance test and a CRH plus arginine vasopressin (AVP) challenge. UN20 lambs were lighter at birth, but there were no significant differences in weight at 30 months. Adult UN10 ewes had an increased ACTH response to both CRH+AVP challenge and insulin tolerance test, but no differences in cortisol response. UN10 ewes also demonstrated elevated 11-deoxycortisol concentrations, but lower progesterone concentrations, in response to CRH+AVP challenge. In contrast, the responses of UN20 ewes to these challenges were not different from ad libitum controls. Protein levels of P450(c17) and P450(11beta1) were not significantly different among groups. We conclude that brief maternal undernutrition for 10 d, but not 20 d, in late gestation alters HPA function in adult offspring. In contrast to our previous findings, these HPA effects are independent of birth weight and current weight, suggesting that different mechanisms may be involved in programming different physiological axes.     

Living with AIDS in Uganda: a qualitative study of patients’ and families’ experiences following referral to hospice

Background

Globally, the majority of people with HIV/AIDS live in sub-Saharan Africa. While the increasing availability of antiretroviral therapy is improving the outlook for many, its effects are yet to reach all of those in need and patients still present with advanced disease. This paper reports findings from qualitative interviews with patients living with AIDS and their caregivers who were receiving palliative care from Hospice Africa Uganda (HAU). We aimed to understand what motivated patients and their families to seek formal healthcare, whether there were any barriers to help- seeking and how the help and support provided to them by HAU was perceived.

Methods

We invited patients with AIDS and their relatives who were newly referred to HAU to participate in qualitative interviews. Patients and carers were interviewed in their homes approximately four weeks after the patient’s enrolment at HAU. Interviews were translated, transcribed and analysed using narrative and thematic approaches.

Results

Interviews were completed with 22 patients (10 women and 12 men) and 20 family caregivers, nominated by patients. Interviews revealed the extent of suffering patients endured and the strain that family caregivers experienced before help was sought or accessed. Patients reported a wide range of severe physical symptoms. Patients and their relatives reported worries about the disclosure of the AIDS diagnosis and fear of stigma. Profound poverty framed all accounts. Poverty and stigma were, depending on the patient and family situation, both motivators and barriers to help seeking behaviour. Hospice services were perceived to provide essential relief of pain and symptoms, as well as providing rehabilitative support and a sense of caring. The hospice was perceived relieve utter destitution, although it was unable to meet all the expectations that patients had.

Conclusion

Hospice care was highly valued and perceived to effectively manage problems such as pain and other symptoms and to provide rehabilitation. Participants noted a strong sense of being “cared for”. However, poverty and a sense of stigma were widespread. Further research is needed to understand how poverty and stigma can be effectively managed in hospice care for patients for advanced AIDS and their families.

     

TLR2 engagement on CD4+ T cells enhances effector functions and protective responses to Mycobacterium tuberculosis

We have previously demonstrated that mycobacterial lipoproteins engage TLR2 on human CD4⁺ T cells and upregulate TCR‐triggered IFN‐γ secretion and cell proliferation in vitro. Here we examined the role of CD4⁺ T‐cell‐expressed TLR2 in Mycobacterium tuberculosis (MTB) Ag‐specific T‐cell priming and in protection against MTB infection in vivo. Like their human counterparts, mouse CD4⁺ T cells express TLR2 and respond to TLR2 costimulation in vitro. This Th1‐like response was observed in the context of both polyclonal and Ag‐specific TCR stimulation. To evaluate the role of T‐cell TLR2 in priming of CD4⁺ T cells in vivo, naive MTB Ag85B‐specific TCR transgenic CD4⁺ T cells (P25 TCR‐Tg) were adoptively transferred into Tlr2^?/? recipient C57BL/6 mice that were then immunized with Ag85B and with or without TLR2 ligand Pam₃Cys‐SKKKK. TLR2 engagement during priming resulted in increased numbers of IFN‐γ‐secreting P25 TCR‐Tg T cells 1 week after immunization. P25 TCR‐Tg T cells stimulated in vitro via TCR and TLR2 conferred more protection than T cells stimulated via TCR alone when adoptively transferred before MTB infection. Our findings indicate that TLR2 engagement on CD4⁺ T cells increases MTB Ag‐specific responses and may contribute to protection against MTB infection.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.