Mild Renal Artery Stenosis Can Induce Renovascular Hypertension and is Associated with Elevated Renal Vein Renin Secretion

Renovascular hypertension is a syndrome which encompasses the physiological response of the kidney to changes in renal blood flow and renal perfusion pressure. Such physiological changes can occur with renal artery occlusion irrespective of the severity of the lesion. We have analyzed hypertensive patients with mild renal artery stenosis and compared them to patients with no stenosis. Renal vein renin sampling from catheterization of the renal vein was performed in all these patients. Patients with mild stenosis had higher renal vein renin ratio (3.01 ± 1.5) than the patients with no stenosis (1.10 ± 0.29; p = 0.002). Patients with mild stenosis were also found to have higher diastolic blood pressure and renal artery resistive indices when compared to patients with no stenosis. We therefore conclude that mild stenosis can precipitate renin‐mediated hypertension in renovascular stenosis and also emphasis that parameters pertinent to renal physiology need to be evaluated before considering treatment options in patients with renal artery stenosis and medical management with RAAS blockade is the preferred modality of therapy for patients with renin‐mediated hypertension.     

Demonstration of a ubiquitin binding site on murine haemopoietic progenitor cells: implication of ubiquitin in homing and adhesion

Summary. Investigations into the nature of the molecular interactions mediating the recognition of the haemopoietic progenitor cells by the haemopoietic stroma, indicate that ubiquitin mediates the binding between murine haemopoietic progenitors and the haemopoietic stroma. The adhesion of haemopoietic progenitors to anti-ubiquitin antibody treated bone marrow stromal cultures, shows inhibition of binding by approximately 78%. Affinity purification of the 1% Triton X-100 soluble stromal membrane fraction, on anti-ubiquitin-sepharose revealed a ubiquitinated 55 kD subunit. Progenitor cells treated with ubiquitin show approximately 58% inhibition in their ability to home into spleen, indicating the direct involvement of ubiquitin in homing. Histochemical staining of bone marrow cells using ubiquitin as a probe further delineates a population of cells possessing specific binding sites for ubiquitin. We demonstrate here the presence of a ubiquitin binding site on the haemopoietic progenitor cells, which may play a major role in the targeting of such progenitors to their 'niche' within the haemopoietic tissue. Such ubiquitin-mediated recognition may thus constitute a common molecular mechanism for homing and adhesion to both bone marrow and spleen, and may be implicated in the homing of more primitive, less differentiated haemopoietic progenitors. The results also indicate that the homing of haemopoietic progenitors within the haemopoietic micro-environment may be mediated by both a ubiquitin dependent and another ubiquitin independent mechanism.     

Pharmacokinetics of First-Line Antituberculosis Drugs in HIV-Infected Children with Tuberculosis Treated with Intermittent Regimens in India

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (C_max) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median C_max and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC_0–8]) of INH (C_max, 2.5 versus 5.1 μg/ml, respectively [P = 0.016]; AUC_0–8, 11.1 versus 22.0 μg/ml · h, respectively [P = 0.047[) and PZA (C_max, 34.1 versus 42.3 μg/ml, respectively [P = 0.055]; AUC_0–8, 177.9 versus 221.7 μg/ml · h, respectively [P = 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median C_max of RMP (1.0 versus 2.8 μg/ml, respectively; P = 0.002) and PZA (31.9 versus 44.4 μg/ml, respectively; P = 0.045) were significantly lower. Among all factors studied, the PZA C_max influenced TB treatment outcome (P = 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP C_max. The PZA C_max significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.     

Reentrant para‐Hisian ventricular tachycardia eliminated from the noncoronary cusp: Importance of regional anatomy for vantage‐point ablation

We present a rare case of reentrant ventricular tachycardia proven by entrainment maneuvers that was successfully ablated from the noncoronary cusp. The case highlights regional anatomy, pacing maneuvers with multi‐modality images from fluoroscopy, intracardiac echo, and electroanatomical mapping.     

Hepaticoduodenostomy versus hepaticojejunostomy after resection of choledochal cyst: A systematic review and meta-analysis

Background

Excision has been established as a standard management practice for choledochal cysts in the last few decades. The two most commonly performed methods of reconstruction after excision are hepaticoduodenostomy (HD) and Roux-en-Y hepaticojejunostomy (HJ), of which the HJ is favored by most surgeons. Evidence concerning the optimal method of reconstruction is, however, sparse.

Materials and Methods

Studies comparing outcomes from HD and HJ after choledochal cyst excision were identified by searching Medline, Ovid, Search Medica, Elsevier Clinicalkey, Google Scholar and Cochrane library. Suitable studies were chosen and data extracted for meta-analysis. Outcomes evaluated included operative time, hospital stay and incidence of postoperative bile leak, cholangitis, reflux/gastritis, anastomotic stricture, bleeding, intestinal obstruction and re-operative rate. Pooled odds ratios (OR) were calculated for dichotomous variables; pooled mean differences (MD) were measured for continuous variables.

Results

Six retrospective studies were included in this meta-analysis, comprising a total of 679 patients, 412 of whom (60.7%) underwent HD, and the remainder, 267(39.3%) underwent HJ. Although, HD group had slightly shorter hospital stay (MD: 0.30; 95% CI: −0.22–0.39; P < 0.00001) it showed a higher incidence of postoperative reflux/gastritis (OR: 0.08; 95% CI: − 0.02–0.39; P = 0.002). However, the other outcomes such as bile leak, cholangitis, anastomotic stricture, bleeding, operative time, reoperation rate and adhesive intestinal obstruction did not differ between HD and HJ groups.

Conclusions

HD shows higher postoperative reflux/gastritis than HJ but a shorter hospital stay. There are few good-quality studies that compare the outcomes from HD and HJ, meaning that caution should be exercised in the generalization of the results of this meta-analysis, which suggests HD to be comparable with HJ in terms of other complications, operative benefits and outcomes.