Pretransplant bilateral hand-assisted laparoscopic nephrectomy in adult patients with polycystic kidney disease.

Laparoscopic procedures continue to gain popularity over traditional open procedures for a number of abdominal and pelvic surgeries. With increasing experience, the application of this technique is rising because it provides an alternative, less invasive, approach to various surgical procedures. Herein, we report our experience with adult patients with polycystic kidney disease, requiring bilateral laparoscopic nephrectomy before renal transplantation.     

The Cellular Lesion of Humoral Rejection: Predominant Recruitment of Monocytes to Peritubular and Glomerular Capillaries

Accumulation of inflammatory cells within capillaries is a common morphologic feature of humoral renal allograft rejection and is most easily appreciated if it occurs in glomeruli. The aim of our study was to determine the amount and composition of immune cells within glomeruli and peritubular capillaries (PTC) in cellular and humoral allograft rejection. Immunofluorescent double-labeling for CD31 and CD3 or CD68 was used for phenotyping and enumerating immune cells within glomeruli and PTC. The major findings are: (1) accumulation of immune cells in PTC is far more common than it would be anticipated based on the assessment by conventional histology; (2) it is not the absolute number of immune cells accumulating within capillaries, but rather the composition of the intracapillary cell population that distinguishes humoral rejection from cellular rejection and (3) in C4d positive biopsies a predominantly monocytic cell population accumulates not only within glomeruli but also within PTC. The median value of monocyte/T-cell ratio within PTC was 2.3 in C4d positive biopsies but only 1 (p = 0.0008) in C4d negative biopsies. Given their prominent presence within capillaries and their extensive biological versatility monocytes might contribute to the capillary damage observed in acute and chronic allograft rejection.     

Effects of endurance exercise on the morphology of mouse neuromuscular junctions during ageing

Summary It has been suggested that age changes in the morphology of the neuromuscular junction (NMJ) may reflect altered physical activity levels rather than the unique effects of ageing. Additionally, previous studies have indicated that the structure of the NMJ may be modulated with exercise. To investigate these questions, quantitative morphometry was determined on soleus and extensor digitorum longus (EDL) nerve terminals stained with zinc iodide-osmium from C57BL/6NNia mice under control and endurance exercised conditions at 12, 18 and 24 months of age.As previously observed, the area, perimeter, extent length and branch number of nerve terminals increased with age in both soleus and EDL. The changes were similar between the muscle types, although the changes were more pronounced in the phasic EDL. In 12-month-old animals, 2 months of endurance exercise resulted in significantly larger nerve terminals in both soleus and EDL, suggesting a functional adaptation. Exercised 18- and 24-month-old nerve terminals were smaller than corresponding controls, which indicated that exercise minimized or prevented further age-related nerve terminal elaboration. At all ages the exercised nerve terminals comprised a more homogeneous population than corresponding controls, which indicates that uniform physical activity can modulate NMJ morphometry. The magnitude of the changes suggests that subtle alterations in normal cage activity with advancing age do not have a significant effect on the morphology of nerve terminals. However, the morphology of the NMJ does change significantly in response to physical exercise training.     

Cystic echinococcosis in Central Saudi Arabia: A 5-year experience.

Background/aims: In this series of patients we aim to describe aspects of presentation, diagnosis and management of patients suffering from Echinococcosis in an endemic region. Methods: This is an observational study done at Riyadh Medical Complex, Saudi Arabia from 1999 to 2004. All adult patients admitted with the primary or incidental diagnosis of echinococcosis were included. These patients were followed up for 6 months. Data relating to patients' demographic characteristics, mode and duration of presentation, investigations, complications and treatment offered was collected. This data was then analyzed using SPSS 11.0. Result: 117 patients with a mean age of 40.9+/-20.7 years were admitted, male to female ratio being 1.7:1. 114 (97.4%) originated from Middle East which is an endemic area. Pain right upper quadrant (RUQ), followed by cough were the commonest symptoms. Nine patients presented with jaundice +/- choleangitis: 3 patients had intrabiliary rupture of the hydatid cyst, while 6 had extrinsic compression. Six patients had infected cyst. Fourteen patients had intrabronchial rupture diagnosed on bronchoscopy. Twenty five (21.4%) patients presented with recurrent disease. The Haemagglutination Inhibition test gave a sensitivity of 78.6. All cysts were visualized using USG, CXR and CT scan. Endocystectomy was the most frequent procedure. Post op 8 patients had biliary leakage and 3 had bronchopleural fistula a majority of whom settled conservatively while two required ERCP and one patient with bronchopleural fistula required surgery. Fifteen patients had infection related complications. During our follow up period no recurrences were recorded. All patients undergoing surgery also received medical treatment. Twenty five patients (21.4%) were unable to undergo operative treatment due to multiple reasons. They were medically treated. Conclusion: Cystic Echinococcosis is a disease of the middle aged. Ultrasonogram combined with a serological assay is the best diagnostic tool available for abdominal echinococcosis allowing diagnosis and staging, while chest X ray is the best screen for the pulmonary disease. The recommended treatment is endocystectomy with antihelmenthic therapy. But the problem of early detection of echinococcosis in endemic areas needs attention by workers as this approach can potentially prevent the devastating complications due to this disease.     

Negative socio-emotional resonance in schizophrenia: a functional magnetic resonance imaging hypothesis

The aim of the present study is to use neuroscience theories about brain function (mirror-neurons MN) to draw inferences about the mechanisms supporting emotional resonance in two different groups of schizophrenia patients (with flat affect FA+ n = 13 and without flat affect FA- n = 11). We hypothesize that FA+ will not activate key brain areas involved in emotional processing. Conversely, FA- will have a functional mirror system for emotional resonance confirmed by activation of the prefrontal cortex and behavioral results. To test this hypothesis, we compared the two groups using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) displaying a passive visual task (44 negative IAPS pictures and 44 neutral pictures). A random-effects analysis, for schizophrenia patients FA-, revealed significant loci of activation in the left mesial prefrontal (MPFC), right orbitofrontal (OFC) and left anterior cingulate cortices (ACC). Correlational analyses carried out between self-report ratings of negative feelings and BOLD signal changes revealed the existence of positive correlation in the LACC, LMPFC and ROFC. Conversely, FA+ did not show significant activation in the prefrontal cortex. We propose that negative emotional resonance induced by passively viewing negative pictures may be a form of "mirroring" that grounds negative feelings via an experiential mechanism. Hence, it could be argued that FA- were able to 'feel' emotions through this resonance behavior. Conversely, we suggest that the dysfunction seen in the FA+ group is a failure or distortion in the development of the MN system. This could be due to genetic or other endogenous causes, which affected prefrontal cortex MN involved in emotional resonance.     

Effect of exercise on physiological age-related change at mouse neuromuscular junctions

To determine the effect of endurance exercise on physiological age-related change at the mouse neuromuscular junction (NMJ), synaptic function was studied for extensor digitorum longus (EDL) and soleus muscles of three C57BL/6J mouse groups, 1) young adult control (YC: 10 months), 2) old control (OC: 20 months), and 3) old mice which exercised (OE: 20 months) since young-adulthood. Electrophysiological properties were studied with intracellular recording techniques. Safety margin was studied by measuring indirect isometric twitch tension in different calcium concentrations. With sedentary aging, EDL and soleus quantal contents increased. Following aging combined with 10 months of exercise, the EDL quantal contents in OE and YC animals were similar. In contrast, soleus quantal content was greater in OE than in YC animals. Determined safety margins were OC greater than YC = OE for EDL, and OC = YC = OE for soleus. This is the first study to indicate that physiological age-related changes at NMJs of EDL and soleus muscles are affected differently by endurance exercise. Exercise prevented all physiological age-related changes in EDL NMJs but not in soleus NMJs, this suggests that EDL changes are associated with inactivity during aging, while soleus changes are "fundamental" age changes.     

Hemodynamic responses to hypoxia and hypercapnia during acute normovolemic hemodilution in anesthetized cats

The present study was undertaken to evaluate the effects of hypoxia and hypercapnia on circulatory parameters during acute normovolemic hemodilution. Cats anesthetized with a mixture of alpha-chloralose and urethane were maintained by positive pressure ventilation. Muscles were paralysed by intramuscular vecuronium (0.1 mg/kg) to eliminate reflex respiratory movements. Cats were exposed to hypoxia (12% O(2) and 7% O(2)) and hypercapnia (4% CO(2) and 7% CO(2)) at normal hematocrit (Ht 40.1 +/- 2.8%) and then at graded levels of normovolemic hemodilution (Ht 24.0 +/- 2.0% and Ht 13.0 +/- 1.5%, respectively). Left ventricular pressure (LVP), LV dP/dt(max), arterial blood pressure (ABP), heart rate (HR), and right atrial pressure (RAP) were recorded on a polygraph. Cardiac output (CO) was measured using a cardiac output computer. Hemodilution per se did not produce any significant change in ABP, RAP or LV dP/dt(max), however, it produced a significant rise in HR and a significant fall in total peripheral resistance (TPR). Exposure to hypoxic gas mixtures caused significant increases in HR and CO at control Ht; but after hemodilution it caused the reverse effects. Hypercapnia did not produce any significant effect on ABP, LV dP/dt(max) or RAP either at control Ht or after hemodilution. Hypercapnia produced a fall in HR, CO and stroke volume (SV) at normal Ht and percent fall in HR response was enhanced following hemodilution. The reversal of chronotropic response to hypoxia and enhanced bradycardia response to hypercapnia, under conditions of acute normovolemic hemodilution would be deleterious as the tissues would become more hypoxic. Such a response may be attributed to altered control mechanisms under such conditions of severe stress.     

Allied studies on the effect of Rosmarinus officinalis L. on experimental hepatotoxicity and mutagenesis

The hepatoprotective and antimutagenic effects of the rosemary essential oil and the ethanolic extract were investigated using carbon tetrachloride and cyclophosphamide as hepatotoxic and mutagenic compounds, respectively. Our results revealed that i.g. administration of the rosemary ethanolic extract (0.15 g/100 g BW) to rats for 3 weeks produced the most pronounced hepatoprotective effect compared to silymarin (reference compound) due to the amelioration of most of the studied serum and liver parameters and confirmed by histopathological examination of the liver tissue. Pretreatment of mice for 7 days with the rosemary essential oil (1.1 mg/g BW) followed by i.p. injection with cyclophosphamide reduced significantly the induced mitodepression in the bone marrow cells of the animals. The potential hepatoprotective and antimutagenic activities of the rosemary ethanolic extract and essential oil, respectively, are attributed to the presence of a relatively high percentage of phenolic compounds with high antioxidant activity (according to our chemical studies).     

Molecular Docking Studies of Phytocompounds from the Phyllanthus Species as Potential Chronic Pain Modulators

The study of inflammatory pain has been one of the most rapidly advancing and expanding areas of pain research in recent years. Studies from our lab have demonstrated the chronic pain-modulating potential of the Phyllanthus species and their probable interaction with various inflammatory mediators involving enzymes like COX-2 and PGE synthase, cytokines like TNF-alpha and IL-1 beta, and with the NMDA receptor. Inflammatory mediators which play a crucial role in chronic inflammatory hyperalgesia and its subsequent modulation were selected for their interactions with 86 structurally diverse phytoconstituents identified from the Phyllanthus species.The docking analysis of the target proteins with the phytochemical ligands was performed using VLifeMDS software. The docking scores and analysis of the interactions of the phytocompounds with target proteins suggest that important molecules like lupeol, phyllanthin, hypopyllanthin, corilagin, epicatechin, and most of the other compounds have the ability to bind to multiple targets involved in inflammatory hyperalgesia.Our study strongly suggests that the findings of the present study could be exploited in the future for designing ligands in order to obtain novel molecules for the treatment and management of chronic pain.     

Pioglitazone administration decreases cardiovascular disease risk factors in insulin-resistant smokers

Insulin sensitivity varies in cigarette smokers, and there is evidence that cardiovascular disease (CVD) risk is greatest in those smokers who are also insulin resistant. To extend these observations, we sought to (1) compare CVD risk factors in smokers who do not plan to stop smoking, divided into insulin-resistant (IR) and insulin-sensitive (IS) subgroups, and (2) evaluate the ability of drug-induced changes in insulin sensitivity to decrease CVD risk. Thirty-six cigarette smokers were divided into IR (n = 19) and IS (n = 17) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test (the higher the SSPG, the more insulin resistant the individual). In addition, baseline measurements were made of fasting lipid and lipoprotein concentrations; inflammatory markers; and daylong glucose, insulin, and free fatty acid responses to test meals. All subjects were treated with pioglitazone for 12 weeks, after which all baseline measurements were repeated. Baseline triglyceride and high-density lipoprotein cholesterol concentrations were significantly different in IR as compared with IS smokers (P < .05) both before and after adjustment for differences in sex and body mass index. After pioglitazone treatment, SSPG concentration significantly fell in the IR smokers (P < .001), associated with a significant improvement in the atherogenic lipoprotein profile seen at baseline (P ≤ .03) and a decrease in soluble intercellular adhesion molecule 1 and C-reactive protein concentrations (P = .01 and .02, respectively), whereas the IS smokers only had a significant increase in high-density lipoprotein cholesterol (P = .004) and a decrease in soluble intercellular adhesion molecule 1 (P = .02) and CRP (P = .07) levels. In conclusion, cigarette smokers have profound differences in CVD risk factors related to their degree of insulin sensitivity. It is suggested that, in addition to smoking cessation efforts, attention should be given to identifying the subgroup of smokers most at risk for CVD, but unwilling or unable to stop smoking, and to initiating appropriate therapeutic interventions to decrease CVD in this high-risk group.