Hyperinsulinaemia and Na+, K+ -ATPase activity in thyrotoxic periodic paralysis

OBJECTIVE Thyrotoxic periodic paralysis (TPP) usually follows a heavy carbohydrate meal and this may be explained by hyperinsulinaemia stimulating Na⁺, K⁺ -ATPase activity. To clarify this the effect of glucose load on serum insulin concentration and platelet Na⁺, K⁺ -ATPase activity In thyrotoxic periodic paralysis (TPP) was examined. DESIGN In all subjects a standard 75-g glucose tolerance test was done and blood samples were taken at 0, 1 and 2 hours. SUBJECTS Twenty-five healthy controls (8 M and 17 F), 17 uncomplicated thyrotoxic patients (7M and 10 F), 15 TPP patients who presented with paralysis and 4 TPP patients after treatment with antithyrold drugs. MEASUREMENTS Plasma glucose was measured by the glucose oxidase method, serum insulin by radioimmunoassay and platelet Na⁺, K⁺ -ATPase by the release of phosphate from ATP. RESULTS TPP patients showed glucose intolerance (area under the curve (AUC) 16·5 ± 4·4 (mean ± SD) In TPP compared to 12·9 ± 4·5 In controls (P < 0·01) and hyperinsulinaemia (AUC 189·6 ±100·6 vs 98·5 ±53·4, P < 0·001). In uncomplicated thyrotoxicosis the results were similar to that in healthy controls. Platelet Na⁺, K⁺ -ATPase were significantly higher in thyrotoxic patients compared to controls and In TPP patients were even higher. Ingestion of glucose increased platelet Na⁺, K⁺ -ATPase in all groups. AUC for platelet Na⁺, K⁺ -ATPase in TPP patients were significantly higher than in uncomplicated thyrotoxicosis (601 ±99·3 vs 482 ± 109·4, P < 0·01) or healthy controls (320 ± 107·3). In the 4 TPP patients studied after antithyroid treatment the results were similar to healthy controls. CONCLUSION Patients with thyrotoxic periodic paralysis have hyperinsulinaemia and this is accompanied by higher Na⁺, K⁺-ATPase activity.     

Tubular Cell and HIV-1 gp120 Interaction Products Promote Migration of Monocytes

Renal interstitial accumulation of monocytes is an important feature of HIV-associated nephropathy. We studied the effects of proximal tubular cell products (TCP) and proximal tubular cell-gp120 interaction products (TC-120IP) on the migration of monocytes across a modified Boyden chamber. TC-120IP promoted (P<0.001) the migration of monocytes when compared with TCP (TCP, 45.0 ± 5.9 vs. TC-120IP, 192.3 ± 39.5 migrated monocytes/field). This effect of TC-120IP on monocyte migration was dose dependent. Anti-MCP-1 (TCP, 24.7 ± 2.6; TC-120IP, 82.3 ± 5.5; TC120-IP + anti-MCP-1 antibody, 46.5 ± 3.5 migrated monocytes/field) as well as anti-TGF- antibodies (TCP, 25.8 ± 3.4; TC120-IP, 80.3 ± 6.9; TC-120IP + anti-TGF- antibody, 43.8 ± 5.6 migrated monocytes/field) partly attenuated TC-120IP-induced migration of monocytes across a filter. Moreover, anti-MCP-1 and anti-TGF antibodies showed an additive inhibitory effect on TC-1201P-induced migration of monocytes across a filter. These results suggest that TC-120IP-induced migration of monocytes may be mediated through the generation of MCP-1 and TGF- by tubular cells. The present study provides the basis for a hypothesis that HIV-1 gp120 protein may be contributing to the infiltration of monocytes in the renal interstitium of patients with HIV-associated nephropathy.     

Morphine Stimulates Mesangial Cell TNF-α and Nitrite Production

Background: Intravenous opiate abusers are susceptible to develop heroin and HIV-associated nephropathies; however, the role of opiates in the development of these kidney lesions is not clear. Patients with opiate addiction are prone to recurrent infections. Methods: The effect of morphine was studied on the generation of TNF- with or without LPS (lipopolysaccharide) by cultured mouse mesangial cells. In addition, the effect of morphine was evaluated on mesangial cell nitrite production. To evaluate the role of opiate receptors, we studied the effect of naloxone and naltrexone on mesangial cell TNF- and nitrite production. To determine the role of TNF- on mesangial cell nitrite production, we examined the effect of anti-TNF- antibody on morphine-induced nitrite production. Assay of TNF- and nitrite production was carried by ELISA and Griess method respectively. Results: Morphine alone did not enhance the generation of TNF- by mesangial cells, however, an enhanced (P < 0.001) TNF- production was observed when mesangial cells were first treated with morphine for 18 h and then activated further with LPS. Maximum release of TNF- was seen at a concentration of 10^–12 M of morphine. Opiate receptor antagonists (naloxone and naltrexone) inhibited the effect of morphine. Morphine also amplified (P < 0.0002) the effect of LPS on mesangial cell nitrite production. Anti-TNF- antibody attenuated morphine induced nitrite generation. Conclusion: We conclude that morphine stimulates the generation of TNF- by LPS-activated mesangial cells. This effect of morphine seems to be opiate receptor mediated and has a downstream effect in the form of mesangial cell nitrite generation. The present in vitro study provides the basis for a hypothesis that morphine may be playing a role in the development of heroin and HIV-associated nephropathies.     

Morphine stimulates superoxide formation by glomerular mesangial cells

Focal glomerulosclerosis is the predominant glomerular lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the formation of superoxide by glomerular mesangial cells. Mesangial cells preincubated with morphine (10^–8 M) showed a higher (P<0.001) production of superoxide when compared to control cells (control) 401±21 vs. morphine 610±41 nM/mg protein/h). This effect of morphine on mesangial cells was dose dependent. Naloxone, an opiate antagonist, attenuated morphine-induced formation of Superoxide by mesangial cells [control, 317±4; morphine (10^–8 M), 573±9; and naloxone (10^–8 M) + morphine (10^–8 M), 333±6 nM/mg protein/h]. We conclude that morphine enhances formation of superoxide by mesangial cells and this effect of morphine seems to be mediated through opiate receptors. Since superoxide has been demonstrated to cause mesangiolysis, we propose that morphine may be playing a role in the induction of mesangial injury in patients with opiate abuse.This work was supported by National Institute of Health Grant R01-DA-06753.     

Anhidrotic ectodermal dysplasia presenting as nasal myiasis

An interesting case of anhidrotic Ectoderml Dysplasia (A.E.D.) which came with epistaxix, headache and maggots in nose is presented. Histopathology of forearm shin, scalp and Exercise test helped to confirm the diagnosis, AED is an X-linked recessive condition and has no cure but symptomatic treatment along with heat protection and protection of eyes especially in summer season has a role to play in the management of these cases.     

Morphine modulates cathepsin B and L activity in isolated glomeruli and mesangial cells

Altered matrix degradation may be playing a role in the development of initial mesangial expansion and subsequent glomerulosclerosis in persons with heroin abuse. We studied whether morphine, a metabolite of heroin, had any effect on lysosomal content of cathepsin B and L in mesangial cells. Morphine (10^–6 M) increased (P<0.01) mesangial cathepsin B and L activity (control, 22.1+2.2 vs. morphine, 31.4+1.4 mol NMec/g protein,N=5). Morphine (10^–6 M) also increased (P<0.01) glomerular cathepsin B and L activity (control, 0.1+0.01 vs. morphine, 2.2±0.2 pmol NMec/g protein,N=3). This effect of morphine occurred in a dose-dependent manner. These results suggest that morphine enhances cathepsin B and L activity in mesangial cells and isolated glomeruli. This effect of morphine may enhance capacity of mesangial cells to degrade increased amount of mesangial macromolecules.     

Three-Dimensional Echocardiographic Reconstruction of the Left Ventricle by a Transesophageal Tomographic Technique: In Vitro and In Vivo Validation of its Volume Measurement

Accurate determination of left ventricular (LV) volume has important therapeutic and prognostic implications in patients with cardiac disease. Volume estimations by two-dimensional techniques are not very accurate due to geometric assumptions. OBJECTIVES: To validate LV volume determinations by a new transesophageal three-dimensional echocardiographic technique. We performed three-dimensional reconstruction of the LV using an echo-computed tomographic (CT) technique based on serial pullback parallel slice imaging technique in both in vitro and in vivo settings. Fourteen latex balloons with various sizes (30-235 mL) and shapes (conical, pear shaped, round, elliptical, and aneurysms in various locations) filled with known volumes of water were imaged in a water bath. From the static three-dimensional image, the LV long axis was defined and the LV was sectioned perpendicular to this axis into 2-mm slices. The volume of each slice was calculated with the observer blinded to the actual volume as the product of the slice thickness and the manually traced perimeter of the slice and the LV volume as the sum of the volumes of the slices (Simpson's method). The calculated LV volume closely correlated with the actual volume (r = 0.99, P < 0.0001, calculated volume = 1.06x - 11.3, Deltavolume = -5.7 +/- 10.0 cc). Using the same system, transesophageal echocardiographic (TEE) images of the LV were obtained in 15 patients gated to respiration and ECG. Satisfactory dynamic three-dimensional reconstruction of the LV was possible in ten patients. The three-dimensional LV volumes (systolic and diastolic) using Simpson's method correlated well with those obtained from biplane or multiplane TEE images using the area length method (r = 0.89, p < 0.0001, y = 12.7 + 0.84x, Deltavolume = 1.3 +/- 18.1 cc). The LV major-axis diameters by the two methods showed very close correlations as well (r = 0.86, P < 0.0001, y = 19 + 0.74x, Deltadiameter = 1.0 +/- 7.2 mm). We conclude that three-dimensional LV volume calculation by the echo-CT technique is intrinsically sound, is independent of LV geometry, and with some limitations, is applicable in vivo. (ECHOCARDIOGRAPHY, Volume 13, November 1996)     

Soft tissue sarcomas: ultrasonographic evaluation of local recurrences

OBJECTIVE: The diagnosis of early local recurrence of soft tissue sarcomas, especially in those treated with surgery and radiotherapy, is a difficult clinical problem. Financial constraints led us to use ultrasonography instead of CT or MR imaging. The aim of this study was to evaluate the role of ultrasonography (US) in detecting local recurrence. METHODS AND RESULTS: Fifty patients with previous treatment for soft tissue sarcomas were evaluated prospectively for recurrence by US and histopathology. Seven of the 50 patients were clinically suspected to have recurrent tumour. Ultrasonography showed recurrence in 26, no recurrence in 18, benign disease in four and was indeterminate in two cases. Ultrasonography was instrumental in guiding fine needle aspiration biopsies of small local recurrences and indeterminate lesions in 17 patients. In the sonographically tumour positive patients, histopathology confirmed recurrence in 24; one case had benign disease and one patient refused surgery. Thirteen of the 18 sonographically tumour negative patients were operated upon; all were negative for tumour on histopathology. Both the indeterminate cases showed recurrence on histopathology. The benign cases were confirmed by histopathology correlation. Ultrasound guided fine needle aspiration cytology (FNAC) was positive in 14 out of 17 patients (88%). The sensitivity and specificity of US was 92.30% and 94.4% respectively. CONCLUSION: Our study concludes that US is an extremely useful and cost effective method in the detection of early local recurrences of soft tissue sarcomas and should therefore be used for initial routine follow-up and guided biopsies.