Renal humoral modulation of skeletal muscle tone in mice: implications for 'the pulmonary-renal cascade'

The pulmonary-renal cascade may regulate the respiration and skeletal muscle contractility. To evaluate this working hypothetical model, we conducted experiments to ascertain the skeletal muscle tone of the Swiss mice (20-35 g). The animals were evaluated for their skeletal muscle tone via several techniques i.e. inclined plane test, grip strength test and swim test. Groups of mice (n=6) were pre-treated with mefenamic acid (60 mg/kg, i.p), carbenoxolone (100 mg/kg i.p) or vehicle only 15 minutes before the treatment with heparin (500 U/kg, i.v), urokinase (5500 U/kg, i.v) and erythropoietin (150 U/kg, i.v). Heparin potentiated the loss of skeletal muscle tone induced by mefenamic acid and carbenoxolone while urokinase & erythropoietin significantly enhanced the skeletal muscle tone as evaluated by all or one of the tests. Other groups of mice (n=6) were pretreated with mefenamic acid (1 mg i.c.v), carbenoxolone (160 microg i.c.v) or minoxidil (30 microg i.c.v) and the effects of heparin & urokinase and erythropoietin on skeletal muscle tone were evaluated. To study the effects of heparin and urokinase on nerve regeneration, two groups of mice underwent a sham and sciatic nerve crush procedure. The mice treated with urokinase recovered much faster as compared to those treated with heparin or saline. These experimental results suggest that gap junction blockers and potassium channel openers interact with heparin, urokinase and erythropoietin to control the skeletal muscle tone.     

Preliminary trial of combination therapy with adriamycin and radiation in sarcomas and other malignant tumors

Based on reports of synergism between adriamycin and radiation therapy in experimental systems, a trial was initiated testing this combination in 53 adult patients with various advanced malignancies, especially sarcomas. Since studies have suggested a selective sensitization of hypoxic cells when this drug is given prior to radiation, an injection of low-dose adriamycin was given 90 min before radiation. This treatment was repeated every 7 days. The combination was most effective in the 30 patients with soft-tissue sarcomas, with 62% of these patients having partial or complete responses. Responses were less good in patients with gastric adenocarcinoma or with other tumors. The toxicity of the combined treatment was moderate. Further trials of this combination are warranted.     

Assessing glomerular filtration rate in healthy Indian adults: a comparison of various prediction equations

BACKGROUND: Accurate measurement of renal function is important for the diagnosis, stratification and management of kidney disease. As the use of recommended filtration markers is limited by cumbersome and costly techniques, renal function is typically estimated by using various specifically derived prediction equations. Most of these equations have been derived from Caucasian patients suffering from varying degrees of chronic kidney disease. This study considers the validity of these equations in an Indian population without known kidney disease. METHODS: One hundred and twenty-two consecutive renal donors who had undergone 99mTc-diethylenetriaminepentaaceticacid (DTPA) glomerular filtration rate (GFR) estimation were enrolled. The predictive capabilities of the Cockcroft and Gault equation for creatinine clearance corrected for body surface area (CG-CrCl), CG-CrCl corrected for GFR (CG-GFR), modification of diet in renal disease (MDRD) 1, MDRD 2 and 24-hr urinary creatinine clearance (urine-CrCl) were evaluated with DTPA GFR as measured GFR. RESULTS: The mean age of the study population was 44.7 yrs with 72.2% being female). The mean measured DTPA GFR was 83.42 ml/min with a range of 61-130 ml/min. The median % absolute difference between the calculated and measured GFR was 19.7, 15.4, 19.3, 20.8 and 25.5, respectively, for CG-CrCl, CG-GFR, MDRD 1, MDRD 2 and urine-CrCl. Pearson's correlation between the measured and estimated GFR varied from 0.09-0.27. The precision as reflected by R2 value was 0.05 for CG-CrCl and CG-GFR, 0.06 for MDRD 1 and MDRD 2 and 0.01 for urine-CrCl. The bias was -14.14, 1.46, 11.89, 17.70 and -2.80 for CG-CrCl, CG-GFR, MDRD 1, MDRD 2 and urine-CrCl, respectively. The accuracy within 30% was 71.3, 85, 86, 76 and 69% for CG-CrCl, CG-GFR, MDRD 1, MDRD 2 and urine-CrCl, respectively. CONCLUSIONS: Our results from a healthy Indian population suggest that of all the predictive equations, MDRD 1 and MDRD 2 were the most precise, MDRD 1 the most accurate and CG-GFR the least biased. However, the poor correlation and error level exhibited by these equations makes them sub-optimal for clinical use.     

Cell nanosurgery using ultrashort (femtosecond) laser pulses: applications to membrane surgery and cell isolation

Membrane surgery and nanosurgical cell isolation using high-intensity femtosecond laser pulses is reported. We demonstrate the applicability of using ultrashort (femtosecond) laser pulses for performing surgery on live mammalian cells. When sub-10 femtosecond pulses were focused onto the cell, precise sub-micron surgical cuts were made on the biological membrane. Traversing the cells relative to the focused laser spot, we report on localized nanosurgical ablation of focal adhesion adjoining epithelial cells. In each study, the surgery was conducted without morphologically compromising the cells.     

Fibrillary Glomerulonephritis Presenting as Rapidly Progressive Renal Failure in a Young Female: A Case Report

Fibrillary Glomerulonephritis (FGN) is a rare clinical entity presenting in majority of patients with nephrotic range proteinuria, microscopic hematuria, impaired renal function and hypertension. The mean age of presentation is reported to be beyond 50 years with 50 patients developing end stage renal disease within a few years. A 28-year-old female presented to us with non-nephrotic range proteinuria, rapidly progressive renal failure (RPRF), microscopic hematuria and mild hypertension. The patient had undergone a renal biopsy at a peripheral center, which was reported as membranoproliferative glomerulonephritis (MPGN) and was being treated with steroids without any benefit. The patient on re-biopsy at our center was diagnosed as FGN on electron microscopy (EM). The patient responded to intravenous pulse methylprednislone and oral cyclophosphamide and is off dialysis for 10 months now. This case highlights the varied clinical and histological presentations of FGN which makes the disease difficult to diagnose more so, in a country like ours where EM is available in only a few centers. An accurate diagnosis aided by high index of clinical suspicion and EM can help in the initiation of appropriate therapy, thereby improving the outcome in this disease which otherwise has a poor prognosis.     

Phagocytic polymorphonuclear function in patients with progressive uremia and the effect of acute hemodialysis

BACKGROUND: Susceptibility to infections is a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Polymorphonuclear leukocytes (PMNs) play a major role in the host defense against various infections. Although the phagocytic function of PMNs in uremic patients has been subjected to repeated evaluation, results have been inconsistent. Also, the effects of progressive uremia and acute hemodialysis (HD) on polymorphonuclear function have been scarcely evaluated. METHODS: In this study, we assessed the phagocytic index (PI) of PMNs following their uptake of IgG-coated sheep erythrocytes in patients with varying severity of CKD and in healthy controls. In patients with advanced renal failure, the effects of acute HD on PI pre- and post-HD were also studied. RESULTS: A total of 30 patients with CKD and 15 healthy controls were studied. Patients with CKD were categorized into two groups: mild to moderate renal failure (S. Creatinine 2-6 mg/dL) and advanced renal failure (S. Creatinine >6 mg/dL) (n=15 for each). All three groups were age and sex matched. Patients with advanced renal failure had significantly impaired PI (4.03 +/- 1.15) as compared to patients with mild to moderate renal failure (7.17 +/- 2.62) and normal controls (8.13 +/- 3.31) (p < 0.001 for both). There was a statistically insignificant decline in the PI in patients with mild to moderate RF when compared to controls (7.17 +/- 2.62 versus 8.13 +/- 3.31). In patients with advanced renal failure, acute HD led to a significant improvement in PI (5.52 +/- 1.55 versus 4.03 +/- 1.15, p < 0.01). CONCLUSION: In patients with CKD, there is a progressive decline in the phagocytic index of the PMNs with increasing severity of uremia. Significant improvement in the phagocytic index following acute hemodialysis suggests the role of a circulating uremic toxin in this PMN dysfunction.     

Giant epidermoid cyst as an unusual presentation of hypoglobus and ptosis

A 24-year-old man presented with a large right frontal epidural epidermoid cyst that resulted in right hypoglobus and right upper eyelid ptosis. CT and MRI revealed a bone-destroying mass involving the right frontal bone and eroding through the right orbital roof. Complete surgical removal was performed through a frontal craniotomy. After surgery, there was near-complete resolution of the hypoglobus and ptosis.     

Evaluation of fluid absorption during holmium laser enucleation of prostate by breath ethanol technique

PURPOSE: In a prospective manner we studied various factors affecting fluid absorption during HoLEP. We also simultaneously evaluated changes in serum electrolytes and hemoglobin decrease during HoLEP. MATERIALS AND METHODS: This prospective study comprised of 53 patients who underwent HoLEP at our institute. Irrigation fluid was normal saline tagged with ethanol (1% w/v). Intraoperatively a standard breath analyzer was used to monitor expired breath ethanol levels during the procedure at 10-minute intervals. Patients who absorbed irrigating fluid as indicated by positive intraoperative breath tests were considered absorbers. Serum electrolyte and hemoglobin estimations were done before and after surgery. Total irrigation time, amount of irrigation fluid used, weight of resected tissue and presence of capsular perforation were recorded. Statistical analysis was performed to observe the effects of various factors on the amount of intraoperative fluid absorption. RESULTS: Of 53 patients studied 14 (26.41%) demonstrated fluid absorption in the range of 213 to 930 ml (mean 459). Preoperative prostate weight, total irrigation time, amount of irrigation fluid used and resected tissue weight were all significantly greater in absorbers. Similarly, absorbers had a statistically significant decrease in hemoglobin level postoperatively. There was no statistically significant change in serum electrolytes between absorbers and nonabsorbers. CONCLUSIONS: Preoperative weight of prostate, total irrigation time, amount of irrigation fluid used and weight of resected tissue all directly influence the amount of fluid absorption during HoLEP. There is no significant change in serum electrolytes and no risk of the transurethral resection syndrome.