Subcellular distribution of cardiac 5'-nucleotidase: alteration of microsomal pool in hypertrophied pig heart

The subcellular distribution of the 5'-nucleotidase activity was investigated in normal and hypertrophied pig hearts; normal rat hearts were used for comparison. The left ventricular hypertrophy was induced in pigs by banding the supravalvular aorta for 4, 8 and 12 weeks. By employing different procedures for the isolation of cardiac membranes, a major catalytic site for 5'-nucleotidase was found to be located at sarcolemma in rat heart and microsomes (sarcoplasmic reticulum) in pig heart. A progressive decrease in the homogenate and microsomal 5'-nucleotidase activity occurred upon the development of myocardial hypertrophy in pigs. This reduction in microsomal 5'-nucleotidase activity was characterized by a depression in both apparent Vmax and Km values. These results indicate that a primary 5'-nucleotidase pool is present in the intracellular compartment of the pig heart and is altered during the development of hypertrophy.     

Multichannel Intraluminal Impedance–pH Testing Is Clinically Useful in the Management of Patients with Gastroesophageal Reflux Symptoms

Background

Multichannel intraluminal impedance–pH testing (MII–pH) allows for the detection of acid and non-acid reflux, thus, increasing yield over pH testing. Limited data exist on how physicians use test results in practice.

Aim

The aim of our study was to evaluate the influence of MII–pH testing on patient care.

Methods

We reviewed records of patients with symptoms of gastroesophageal reflux disease who underwent MII–pH testing. Management decisions evaluated included changes in prescribed medications and surgical consultation for anti-reflux surgery. Statistical analysis was performed using Pearson Chi square test, and multivariable logistic regression.

Results

MII–pH testing resulted in a medication change in 41 % of patients, surgical consultation in 19.7 %, and anti-reflux surgery in 11.1 %. In patients who were not on proton pump inhibitor (PPI) therapy, MII–pH results were most useful in the decision to start a PPI. On PPI therapy, results were more often used to decide whether to increase (32.3 %) or switch the PPI (23.5 %) in patients with continued acid reflux. Results were most useful to stop the PPI in normal studies (11.1 %). More patients with non-acid reflux (14.3 %) and normal results (19.7 %) were started on a neuromodulator compared to other diagnoses. The MII–pH result was most useful in the decision to start baclofen or bethanecol when the patient was found to have non-acid reflux (25 %). Patients with an abnormal MII–pH or abnormal MII alone were more likely to be referred to surgery (OR 19.5, p < 0.001; OR 19.77, p < 0.001).

Conclusions

MII–pH testing impacted medical or surgical management in over half the patients tested.     

Antibody Deficiency Secondary to Chronic Lymphocytic Leukemia: Should Patients be Treated with Prophylactic Replacement Immunoglobulin?

Hypogammaglobulinemia is a common finding in chronic lymphocytic leukemia (CLL). Its incidence increases with disease duration and stage such that it is present in up to 85 % of patients at some point in their disease course. It is therefore important to monitor patients for the development of an antibody deficiency. However, not all patients with antibody deficiency secondary to CLL are symptomatic with bacterial infections. In addition patients are susceptible to viral, fungal and opportunistic infections as a result of iatrogenic immunosuppression and through a variety of disease-related mechanisms, which affect cellular immunity and phagocytes. Published guidelines suggest that patients with a history of recurrent bacterial infections and a documented failure of antibody production should be treated with antibiotic prophylaxis in the first instance, with replacement immunoglobulin reserved for those who continue to suffer with significant bacterial infections. Here we present a review of the existing literature in order to provide a practical approach, based on best available evidence, to the investigation, monitoring and treatment of patients with antibody failure secondary to CLL; and we highlight areas in which further studies are needed.     

Adenosine A₁ receptors do not play a major role in the regulation of lipogenic gene expression in hepatocytes

Activation of adenosine A? receptors was reported to promote fatty acid synthesis in AML-12 cells, by increasing the expression of SREBP-(1c) (sterol regulatory binding protein 1c) and FAS (fatty acid synthase). Since these findings have important therapeutic implications for the discovery of adenosine A? receptor agonists, further studies were undertaken to determine the expression and functional relevance of adenosine A? receptor in the liver. To that end, we used two classes of distinct adenosine A? receptor agonists: CPA (N?-cyclopentyl-adenosine), a full agonist and GS-9667 (2-{6-[((1R,2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol), a partial agonist. Treatment of AML-12 cells, HepG2 cells and primary human hepatocytes with either CPA or GS-9667 did not increase the gene expression of SREBP-(1c) or FAS. Furthermore, in AML-12 and HepG2 cells, CPA did not antagonize forskolin-stimulated cAMP production, a characteristic of adenosine A? receptor activation, indicating that these cells lack adenosine A? receptor function. Consistent with this finding, adenosine A? receptor gene expression was found to be very low and adenosine A? receptor protein levels were hardly detectable by radioligand binding assays in hepatic cell lines such as AML-12 and HepG2 as well as in both mouse and human liver tissues. Finally, acute treatment with adenosine A? receptor agonist GS-9667 had no significant effect on gene expression of both SREBP-(1c) and FAS in livers of Sprague Dawley rats. Taken together, our data suggest that the expression of adenosine A? receptor is too low to play a major role in the regulation of lipogenic gene expression in hepatocytes.     

Barriers of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness studies

Barriers to participation in an HIV vaccine trial have been examined in many HIV vaccine preparedness studies (VPS). These barriers can be understood in terms of the locus of the barrier (personal vs. social) and the nature of the barrier (risk vs. cost). Another type of barrier is perceived misconceptions. In this systematic review, we categorize barriers, and compare these barriers between the Organization for Economic Co-operation and Development (OECD) countries and the non-OECD countries. In the OECD countries, we retrieved 25 studies reporting personal risks (PR), 9 studies reporting social risks (SR), 10 studies reporting personal costs (PC), and 16 studies reporting misconceptions. In the non-OECD countries, we retrieved 27 studies reporting PR, 19 studies reporting SR, 18 studies reporting PC, 1 study reporting social costs (SC), and 13 studies reporting misconceptions. Important PR were “adverse effects” and “vaccine-induced seropositivity”, “distrust of institutions”, and “temptation to have unsafe sex” in men who have sex with men (MSM). “Discrimination” was a common SR. “Time commitment” was an important PC, and “family commitments” were a SC in one non-OECD country. “HIV infection from the vaccine” was a common misconception. Both the OECD and the non-OECD countries have similar barriers, and people's decisions to participate in a clinical trial involve multiple barriers. However, these barriers apply to hypothetical HIV vaccine trials, and barriers for actual vaccine trials need further assessment.     

Efficient sweep buffering in swept source optical coherence tomography using a fast optical switch

We describe a novel buffering technique for increasing the A-scan rate of swept source optical coherence tomography (SSOCT) systems employing low duty cycle swept source lasers. This technique differs from previously reported buffering techniques in that it employs a fast optical switch, capable of switching in 60 ns, instead of a fused fiber coupler at the end of the buffering stage, and is therefore appreciably more power efficient. The use of the switch also eliminates patient exposure to light that is not used for imaging that occurs at the end of the laser sweep, thereby increasing the system sensitivity. We also describe how careful management of polarization can remove undesirable artifacts due to polarization mode dispersion. In addition, we demonstrate how numerical compensation techniques can be used to modify the signal from a Mach-Zehnder interferometer (MZI) clock obtained from the original sweep to recalibrate the buffered sweep, thereby reducing the complexity of systems employing lasers with integrated MZI clocks. Combining these methods, we constructed an SSOCT system employing an Axsun technologies laser with a sweep rate of 100kHz and 6dB imaging range of 5.5mm. The sweep rate was doubled with sweep buffering to 200 kHz, and the imaging depth was extended to 9 mm using coherence revival. We demonstrated the feasibility of this system by acquiring images of the anterior segments and retinas of healthy human volunteers.OCIS codes: (170.4500) Optical coherence tomography     

Outcomes and reasons for dacryocystorhinostomy (DCR) at KCMC, a Tanzanian referral hospital, 2001-2006

Background

External dacryocystorhinostomy (DCR) is a surgical intervention aimed to treat blocked nasolacrimal ducts of almost all causes. To date there is only limited data available from the Sub Saharan African setting.

Objectives

This study aimed to provide further information of the outcomes of DCR in Africa.

Methods

Records of all patients undergoing external DCR operations from January 2001 to April 2006 were systematically searched. 55 patients were identified and notes were available for 45 patients.

Results

Discharge and epiphora were resolved in 90.9% (30/33) and 84.4% (27/32) of patients respectively. Over half the cases (51.1%) were children. The commonest reason for operation was chronic dacryocystitis (51.1%). Outcomes for DCR were not significantly different for either children or adults and a clear improvement of symptoms was found in the vast majority of cases.

Conclusion

This study provides information on the outcomes of DCR in the African population. An 84.4% cure rate of epiphora and 90.9% cure rate of discharge is comparable with findings in other developing countries. This study supports the continued use of this intervention in skilled hands for treatment of blocked nasolacrimal duct.