Evaluation of Early Renal Involvement in Essential Hypertension by Measuring Urinary Biomarkers.

Hypertensive kidney damage results in glomerular as well as tubular dysfunction. Albuminuria is a well-known marker of glomerular damage. On the other hand, urinary uromodulin is increasingly considered as a potential biomarker of early tubular dysfunction. The aim of the study was to assess glomerular and tubular function of the kidney by measuring urinary albumin and uromodulin excretion in hypertensive subjects. This cross-sectional study was conducted from July 2018 to June 2019 in Hypertension Clinic of Dhaka Medical College Hospital, Dhaka and Kidney Care and Research Centre, Sonargaon, Narayanganj, Bangladesh. In this study 122 hypertensive subjects with age >30 years, duration of hypertension <5 years, without accelerated or malignant BP, absence of dipstick proteinuria and eGFR >60ml/min were included. There were also 33 normotensive individuals included as healthy controls. Albumin-creatinine ratio (uACR mg/g), urine uromodulin-creatinine ratio (uUMODµg/g), urinary sodium-creatinine ratio (mEq/g) and potassium-creatinine ratio (mEq/g) were measured from single morning spot urine sample. Urinary uromodulin levels were measured by ELISA method. The hypertensive and normotensive subjects were age matched 49.0±12.0 vs. 48.0±11.0, years (p=NS). The mean uACR was 29.0±65.0 versus 5.6±2.7mg/g, (p<0.001) respectively. The median uUMOD in hypertensive subjects was 3.38 (1.73-9.06) and in normotensives 3.85(2.28-5.69) µg/g (p=non significant). Multivariate analysis showed significant inverse association between diastolic blood pressure and urinary uromodulin excretion. A uUMOD cut-off of 2.9 (25th percentile) showed eGFR, urinary sodium and potassium excretions were significantly lower at low uromodulin group. The glomerular involvement was found in 21.0% of hypertensive subjects as evidenced by albuminuria. No difference was observed in urinary uromodulin level between hypertensive and normotensive subjects. Low urinary uromodulin level was associated with lower eGFR, Na+ and K+ excretion which indicate simultaneous tubular and glomerular involvement.

Extra Skeletal Ewing's Sarcoma Involving Perineum of a Young Male Patient.

Ewing's Sarcoma is the second most common primary malignant bone tumor in children and young adults after osteosarcoma but exceptionally it can arise from extra skeletal sites also. Extra skeletal Ewing's sarcoma is of neuroectodermal origin and usually involves extremities, retroperitoneum and paravertebral regions. No case of extra skeletal Ewing's sarcoma involving perineum is yet reported. A 16 years old male patient admitted to colorectal surgery department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh in July 2015 having swellings in perineum as well as both inguinal regions. The swelling was near to anal verge. FNAC from perineal swelling and inguinal lymph node demonstrate small blue round cell tumor. After operation the tumor size was 5cm×4cm, cell type was malignant round cell arranged in sheet and perivascular forming rosette. Extra skeletal Ewing's sarcoma can be a differential diagnosis of soft tissue tumor arising in perineum.

A case report of right ventricular mass.

Primary Cardiac tumors are uncommon during infancy and childhood. Myxomas originating in the right ventricles are even less common in paediatric patient. Our patient baby Rani, 3 months of age presented with shortness of breath and chest indrawing. Antenatal history and delivery was uneventful. The baby was under weight and also malnourished but there was no cyanosis and clubbing. Her respiratory rate was 25/minute. On precordium examination, first heart sound (S1) was normal but pulmonary component of second heart sound (P2) was soft. There was an ejection systolic murmur (Grade-3/6) in the left upper para-sternal area. Chest X-ray revealed cardiomegaly. Echocardiogram revealed a large mass (11x10mm) in the right ventricle, dynamically obstructing the right ventricular out-flow tract and compressing the left ventricle. There was a Tricuspid regurgitation (Grade-2) and moderate pulmonary hypertension (PASP-50 mmHg).

Autologous olfactory [corrected] mucosal transplant in chronic spinal cord injury: an Indian Pilot Study.

STUDY DESIGN: Prospective Pilot Study. OBJECTIVES: To determine the safety and feasibility of autologous olfactory mucosal transplantation into the spinal cord in chronic spinal cord injured using the technique developed by Carlos Lima et al. SETTING: Spinal Injury Center, New Delhi. METHODS: Five chronic, motor complete, traumatic spinal cord injury (SCI) patients with neurological level C5-T12 underwent the procedure. Participants were assessed at baseline and at 6 monthly intervals. Safety and tolerability were evaluated through monitoring for any adverse events and tests including magnetic resonance imaging (MRI) evaluation. Efficacy assessment was done through neurological, functional and psychological evaluation, electrophysiological studies and urodynamics. RESULTS: Surgery was tolerated well by all American Spinal Injury Association (ASIA) Impairment Scale (AIS) A participants. The only AIS B participant lost sensory scores significantly after surgery but is gradually regaining it. MRI evaluation revealed a syrinx in one participant and increase in length of myelomalacia in four participants. There were no other adverse findings on MRI evaluation. There was no significant improvement in any of the neurological, electrophysiological or urodynamic efficacy variables. Statistically significant improvement was seen in functional scores as evaluated by Spinal Cord Independence Measure, Beck Depression Inventory scores and life impact scores on International Spinal Cord Injury Scale. CONCLUSIONS: The procedure is relatively safe and feasible in AIS A participants with thoracic level injuries at 18 month follow-up. No efficacy could be demonstrated which could be attributed to the procedure.

Axillary and tympanic membrane temperature measurements are unreliable early after cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Inaccurate measurements of body temperature following cardiopulmonary bypass may be associated with serious complications. The purpose of this study was to determine whether axillary and tympanic temperature measurements correlate with the urinary bladder temperature in the early postcardiac surgery period. METHODS: Forty-nine adult patients who underwent cardiac surgery under cardiopulmonary bypass at our institution were prospectively studied. Urinary bladder, right axillary, right tympanic and left tympanic temperature measurements were simultaneously recorded at 0, 6, 12 and 18 h following cardiopulmonary bypass. Patients had one to four sets of recordings and a total of 629 temperature measurements were recorded. The mean difference (bias) between the bladder and each of the other methods and limits of agreement were calculated using Bland and Altman method. RESULTS: The mean core body temperature recorded from the bladder on admission to the intensive care unit was 36.4 degrees C. After 6, 12 and 18 h the mean core body temperature was 37.4 degrees C (range: 35.2-39.0), 37.5 degrees C and 37.45 degrees C, respectively. The mean differences (bias) between the bladder temperature and the other three methods were: left tympanic, 0.65 degrees C (95% CI: -0.24 to 1.58); right tympanic, 0.57 degrees C (95% CI: -0.48 to 1.63) and right axillary, 0.55 degrees C (95% CI: -0.27 to 1.36). CONCLUSIONS: The axilla and tympanic membrane are unreliable sites for core body temperature measurement early after cardiopulmonary bypass in adult patients and clinical decisions should be based on more reliable methods.

Gene therapy progress and prospects: therapeutic angiogenesis for limb and myocardial ischemia.

After extensive investigation in preclinical studies and recent clinical trials, gene therapy has been established as a potential method to induce therapeutic angiogenesis in ischemic myocardial and limb disease. Advancements in viral and nonviral vector technology including cell-based gene transfer will continue to improve transgene transmission and expression efficiency. An alternative strategy to the use of transgenes encoding angiogenic growth factors is therapy based on transcription factors such as hypoxia-inducible factor-1alpha (HIF-1alpha) that regulate the expression of multiple angiogenic genes. Further understanding of the underlying biology of neovascularization is needed to determine the ability of growth factors to induce functionally significant angiogenesis in patients with atherosclerotic disease and associated comorbid conditions including endothelial dysfunction, which may inhibit blood vessel growth. The safety and tolerability of therapeutic angiogenesis by gene transfer has been demonstrated in phase I clinical trials. However, limited evidence of efficacy resulted from early phase II studies of angiogenic gene therapy for ischemic myocardial and limb disease. The utility of therapeutic angiogenesis by gene transfer as a treatment option for ischemic cardiovascular disease will be determined by adequately powered, randomized, placebo-controlled phase II and III clinical trials.

TNF-alpha and IL-6 expression in perfused rat liver after intraportal candidemia vs. E. coli or S. aureus bacteremia.

We tested the hypothesis that regulation of tumor necrosis factor-alpha (TNF-alpha) and IL-6 by the liver differs after intraportal challenge with Candida albicans spp. vs. gram-negative or gram-positive bacteria, independent of microbial clearance kinetics or hepatic O2 consumption (VO2). Buffer-perfused rat livers were infected with equivalent inocula (10(9) colony-forming units) of viable Escherichia coli serotype 055:B5 (EC), exotoxin C-producing Staphylococcus aureus (SA), or two strains of yeast phase C. albicans (CA-1 and CA-2). Microbial clearance and circulating cytokine levels were assessed over 180 min while monitoring VO2 and functional parameters, after which organ-based microbial killing, cell-associated TNF-alpha, and cytokine mRNA levels were determined. Compared with saline controls (normal saline solution; NSS), circulating and cell-associated TNF-alpha and TNF-alpha transcripts minimally increased after CA. In contrast, large increases in perfusate TNF-alpha occurred after EC, peaking at 180 min [135 +/- 32 U/ml (mean + SE)], concomitant with rises in cell-associated cytokine and TNF-alpha transcripts (P < 0.01 vs. NSS). Circulating TNF-alpha also rose after SA but neither cell-associated nor mRNA levels exceeded NSS values. There were no pathogen-specific differences in microbial clearance or VO2. IL-6 gene expression paralleled that for TNF-alpha, but IL-6 bioactivity in perfusates was inhibited by TNF-alpha-dependent and -independent mechanisms. We conclude that hepatic TNF-alpha and IL-6 expression are differentially regulated after taxonomically diverse microbial challenges, with E. coli eliciting the strongest and Candida spp. the weakest stimulatory responses.

A receptor for interleukin 10 is related to interferon receptors.

We isolated cDNAs encoding a mouse interleukin 10 receptor (mIL-10R) from mouse mast cell and macrophage cell lines. The two cDNAs are substantially identical and express an approximately 110-kDa polypeptide in COS7 cells, which binds mIL-10 specifically. A mouse pro-B-cell line (Ba/F3) expressing transfected recombinant mIL-10R binds IL-10 with high affinity (approximately 70 pM) and proliferates in response to mIL-10. mIL-10R is structurally related to interferon receptors (IFNRs). Since IL-10 inhibits macrophage activation by IFN-gamma, a possible implication of this relationship interaction of IL-10R and IFN-gamma R or their signaling pathways.

Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI.

Complementary DNA clones encoding mouse cytokine synthesis inhibitory factor (CSIF; interleukin-10), which inhibits cytokine synthesis by TH1 helper T cells, were isolated and expressed. The predicted protein sequence shows extensive homology with an uncharacterized open reading frame, BCRFI, in the Epstein-Barr virus genome, suggesting the possibility that this herpes virus exploits the biological activity of a captured cytokine gene to enhance its survival in the host.

Effect of proximal selective vagotomy on the canine lower esophageal sphincter.

The effect of proximal selective vagotomy on the lower esophageal sphincter was studied in 13 dogs by manometry and cinefluorography. The studies, done under resting conditions and during abdominal compression, were repeated 8 weeks after proximal selective vagotomy in seven animals and after truncal vagotomy in six animals. Proximal selective vagotomy had no significant effect on the pressures in the lower esophageal sphincter; the resting pressures were 32.1 +/- 4.1 cm H2O before and 28.9 +/- 3.7 after operation, and the pressures on abdominal compression were 50.6 +/- 6.5 and 41.6 +/- 3.8 cm H2O, respectively (p < 0.05). Truncal vagotomy decreased the lower esophageal sphincter pressures at rest from 28.2 +/- 4.0 to 18.0 +/- 2.2 cm H2O (p = 0.1) and those during abdominal compression from 44.7 +/- 5.6 to 15.5 +/- 2.6 cm H2O (p < 0.01). Gastroesophageal reflux was not seen after proximal selective vagotomy but was seen in one animal in the truncal vagotomy group. Since proximal selective vagotomy does not decrease lower esophageal sphincter function, it offers an advantage over truncal vagotomy in the treatment of duodenal ulcer. The data also indicate that vagal afferents from the proximal stomach are not important in reflex control of lower esophageal sphincter activity.

An experimental study of the correction of gastroesophageal reflux by gastroplasty.

The rationale and efficacy of gastroplasty in controlling gastroesophageal reflux were studied by manometry and cinefluorography in the dog. The pressure in a 7 by 3 centimeter gastric tube, constructed from the lesser curvature of the stomach and interposed between the esophagus and the stomach, was 3.6 +/- 1.0 centimeters higher than in the stomach. When abdominal compression was applied, the pressures were similar in the tube and the adjacent stomach, 19.0 +/- 4.0 and 19.4 +/- 4.0 centimeters, and free reflux was demonstrated between the two. When the gastric fundus was wrapped around the gastroplasty tube, its resting pressure was 13.1 +/- 0.5 centimeters higher than gastric pressure. During abdominal compression, the pressure in the gastric tube increased to 23.0 +/- 0.6 centimeters suggesting a flutter-valve arrangement that produced an effective antireflux barrier. These data suggest that gastroplasty can be an effective antireflux method only when combined with fundic wrap.

Evaluation of posterior gastropexy for gastroesophageal reflux.

The efficacy of posterior gastropexy as an antireflux procedure and its mechanism of action were studied by manometry and cinefluorography in a canine model. Gastroesophageal incompetence was produced in 13 dogs by dividing the vagi below the diaphragm and displacing the gastroesophageal junction into the chest. Reflux was associated with a decrease in the lower esophageal sphincter (LES) pressure measurements and in its response to abdominal compression. Posterior gastropexy done in seven dogs, improved both the resting and compression pressures in the LES, increased the length of the LES, and corrected reflux in five dogs. Replacement of the LES in the abdomen and crural (Allison) repair resulted in a similar increase in LES pressures and restored competence in four of the six animals. Neither procedure was able to restore the LES response to abdominal compression. Posterior gastropexy, like Allison repair, improves LES function by replacing it below the diaphragm, but does not produce a new valve.

Spontaneous resolution of a pancreatic pseudocyst by perforation into the colon.

Spontaneous perforation of a pancreatic pseudocyst into the colon, diagnosed radiologically, resulted in spontaneous cure. Disappearance of a previously palpable abdominal mass suggested perforation of the cyst into the stomach or colon. Surgical treatment was not required. Such an occurrence has not been reported previously; it opens to doubt dicta regarding treatment of this rare complication of pancreatic pseudocyst by immediate colostomy.