Functional recovery after surgical resection of low grade gliomas in eloquent brain: hypothesis of brain compensation

OBJECTIVES: To describe functional recovery after surgical resection of low grade gliomas (LGG) in eloquent brain areas, and discuss the mechanisms of compensation. METHODS: Seventy-seven right-handed patients without deficit were operated on for a LGG invading primary and/or secondary sensorimotor and/or language areas, as shown anatomically by pre-operative MRI and intraoperatively by electrical brain stimulation and cortico-subcortical mapping. RESULTS: Tumours involved 31 supplementary motor areas, 28 insulas, 8 primary somatosensory areas, 4 primary motor areas, 4 Broca's areas, and 2 left temporal language areas. All patients had immediate post-operative deficits. Recovery occurred within 3 months in all except four cases (definitive morbidity: 5%). Ninety-two percent of the lesions were either totally or extensively resected on post-operative MRI. CONCLUSIONS: These findings suggest that spatio-temporal functional re-organisation is possible in peritumoural brain, and that the process is dynamic. The recruitment of compensatory areas with long term perilesional functional reshaping would explain why: before surgery, there is no clinical deficit despite the tumour growth in eloquent regions; immediately after surgery, the occurrence of a deficit, which could be due to the resection of invaded areas participating (but not essential) to the function; and why three months after surgery, almost complete recovery had occurred. This brain plasticity, which decreases the long term risk of surgical morbidity, may be used to extend the limits of surgery in eloquent areas.     

Intestinal parasites in children, in highly deprived areas in the border region of Chiapas, Mexico

OBJECTIVE: To assess the prevalence of intestinal parasitic infections among children in highly deprived areas, and its possible association with demographic and socioeconomic indicators. MATERIAL AND METHODS: From March to September 1998 in a convenience sample of 32 communities of the border region of Chiapas, Mexico, selected at random based on the level of poverty and distance from the community to the nearest health care unit (< 1 hour; 1 hour or more), one of every four households with children under 15 years of age was randomly selected to provide three stool samples from their children (n 1478). Bivariate and multivariate (generalized linear models for correlated binary data), analysis were performed. RESULTS: The global prevalence of intestinal parasitosis was 67% (95% confidence interval [CI] 64-70%). Sixty percent had multiple parasites. The prevalence of Entamoeba histolytica/E dispar was 51.2%, that of Giardia lamblia 18.3%, and that of Ascaris lumbricoides 14.5%. Multivariate analysis showed that age and speaking an indigenous language were significantly associated with the presence of E histolytical E dispar and Giardia lamblia. Source of water and lacking a refrigerator and electricity were associated with the presence of Ascaris lumbricoides. CONCLUSIONS: Measures should be taken to improve water quality, sewage disposal, and domestic hygiene. Furthermore, health programs should be established to promote breast-feeding, and education policies aimed at reinforcing the use of indigenous languages by physicians in the health services.     

Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen in stable kidney transplant recipients: a randomized,controlled study

BACKGROUND: Long-term maintenance immunosuppression with cyclosporine (CsA) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile. Several nonrandomized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil (MMF; CellCept). METHODS: A randomized, controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF (2 g/day), CsA (Neoral), and corticosteroids. The primary endpoint was creatinine clearance at 6 months after complete withdrawal. RESULTS: In the intent-to-treat population, CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol (-0.3 mmol/L, P=0.02; -0.4 mmol/L, P=0.015). There was a trend toward improved creatinine clearance (4.5 mL/min, P=0.16) and serum creatinine (-1 vs. +4 micromol/L, P=0.34). In the per-protocol population, which excluded patients with acute rejections, the improvements in creatinine clearance and serum creatinine were statistically significant (7.5 mL/min, P=0.02; -11 vs. +4 micromol/L, P=0.0003). Reversible acute rejections, the majority of which were mild, occurred in nine CsA withdrawal versus two CsA continuation patients (10.6% vs. 2.4% of each group, P=0.03), with no graft loss. CONCLUSION: Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections, without graft loss.     

Spontaneous tumour rupture and prognosis in patients with hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease in Taiwan. Ruptured HCC is an uncommon and potentially fatal complication of the condition. Information on the impact of ruptured HCC on hepatic resection is, however, limited. METHODS: The clinical features of 60 patients with ruptured HCC who underwent hepatic resection from 1986 to 1998 were reviewed. Clinical features and factors influencing the outcome of 475 patients with non-ruptured HCC were used for comparison. RESULTS: Of 535 surgically resected HCCs, 60 (11.2 per cent) were ruptured. Univariate analysis showed that sudden onset of abdominal pain, physical signs of haemodynamic unstability, reduced haemoglobin level and a raised aspartate aminotransferase level were more frequently found in patients with ruptured HCC than in those with non-ruptured tumours. Multivariate stepwise logistic regression analysis revealed sudden-onset abdominal pain to be the only independently significant factor in patients in the ruptured HCC group. The 1-, 3- and 5-year survival rates of patients with non-ruptured HCC were 72.1, 47.3 and 33.9 per cent, and those of patients with ruptured HCC were 54.2, 35.0 and 21.2 per cent respectively. Similar overall survival rates were found in patients with ruptured and non-ruptured HCC, although patients in the non-ruptured HCC group had a significantly better disease-free survival rate (P = 0.023). CONCLUSION: The presence of sudden-onset abdominal pain is the only independent indicator of ruptured HCC. Hepatic resection, when feasible, is the treatment of choice and can result in an overall survival rate comparable to that of patients with non-ruptured HCC.     

Lead intoxication in gestational and lactation periods alters the development of male reproductive organs

The effect of lead (Pb) intoxication during pregnancy and lactation on the male reproductive system was studied to evaluate the alterations caused by Pb in the development of pups. The investigations covered the effect of lead on the course of spermatogenesis and the development of the epididymis and reproductive glands. For this purpose, dams were intoxicated with 300 mg/L Pb during the gestational period and through lactation. Pups were sacrificed on Postnatal (PN) Days 12 and 21. Blood lead (PbB) and plasma iron concentrations were measured, and blood cells counted. Biochemical studies as well as histochemical analyses were performed on testes and accessory glands of the reproductive system. Lead intoxication resulted in a decrease in testis and seminal vesicle weights and an increase in DNA and RNA levels on PN Day 21. Total protein was significantly decreased by the toxicant, and alkaline and acid phosphatase levels of the gonads were reduced. Effects were also reflected in the reduction of the thickness of epithelium and of seminiferous tubule diameter (STD) as a consequence of the action of lead in the reduction in numbers of prospermatogonia and spermatocytes. Results indicate that the reproductive system targets of lead intoxication are not only the testes; lead intoxication results in the inhibition of testicular, epididymal, and seminal vesicle function, altering the biochemical composition of these organs, and consequently, affecting the normal development of germinal cells.     

Differential subcellular localization of the 5-HT3-As receptor subunit in the rat central nervous system

Following the cloning and sequencing of the A subunit of the 5-HT3 receptor, two alternatively spliced isoforms, 5-HT3-AS and 5-HT3-AL, have been identified. In order to analyse the distribution of the receptor, a polyclonal antibody has been produced against the short form which is the most abundant in the central nervous system [Doucet et al. (2000) Neuroscience 95, 881-892]. As expected from the recognition of functional 5-HT3 receptors, immunostaining by this anti-5-HT3-R-AS antibody matched the distribution of the high-affinity 5-HT3 binding sites in the rat brain and spinal cord. 5-HT3-AS-like immunoreactivity was detected at low levels in the limbic system, particularly in the amygdala and the hippocampus, and in the frontal, piriform and entorhinal cortices. High levels of immunoreactivity were found in the brainstem, mainly in the nucleus tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve, and in the dorsal horn of the spinal cord. At the ultrastructural level, immunostaining was generally found associated with axons and nerve terminals (70-80%) except in the hippocampus, where labelled dendrites were more abundant (56%). This preferential localization on nerve endings is consistent with the well-documented physiological role of 5-HT3 receptors in the control of neurotransmitter release. However, the different distribution in the hippocampus raises the question of whether differential addressing mechanisms exist for preferentially targeting 5-HT3 receptors to postsynaptic dendritic sites as compared to presynaptic nerve endings, depending on the nature of the neurons bearing these receptors.     

Late lower extremity fractures in patients with paraplegia

We report the result of the treatment of 26 lower limb fractures in patients with established paraplegia. We treated one fracture of the femoral neck, one intertrochanteric, two subtrochanteric, two of the femoral shaft, seven of the supracondylar region, six of the proximal tibia, one of the tibial shaft, and six pilon fractures. Nine fractures were treated non-operatively, and the remaining fractures were treated operatively. Union was achieved in all the patients, but we think that open reduction and internal fixation may improve the level of independence and mobility of these patients during fracture healing.     

Age,gender and seasonal patterns of asthma in emergency departments of southern Puerto Rico

We report findings derived from 55,547 emergency department records of asthmatic patients in the city of Ponce, Puerto Rico over a period of six years. The analysis of the data revealed that mean age of the asthmatic cases were 18.7 +/- 17.8 years, with 45% percent of the patients in the 1-9 years age range, and proportionally decreasing with age. In children 1-9 years the percent of males was 1.5 times that of females, and in 10-19 year-old group, admissions to the emergency room for males and females was identical, and between 20-69 years of age, the female ratio ranged from 1.5-2.12. The data also demonstrated that there is a seasonal variation in the asthma attacks reaching its peak in December, and the lowest in June. In conclusion, in the city of Ponce, Puerto Rico, emergency department usage due to asthma attacks show a seasonal variation, and males are more affected by asthma at younger ages while females are more affected at older ages. These findings strongly suggest that emergency department usage due to asthma attacks is highly common and represents an important place where specialized health care delivery is needed. With the implementation of dedicated asthma centers, specialized health care delivery can be easily accomplished. In addition, our data supports the that asthma should be declared a public health problem and a reportable disease.     

Mutant K-ras oncogene regulates steroidogenesis of normal human adrenocortical cells by the RAF-MEK-MAPK pathway

The result of our previous study has shown that the K-ras mutant (pK568MRSV) transfected human adrenocortical cells can significantly increase cortisol production and independently cause cell transformation. The aim of this study is to investigate the effect of the active K-ras oncogene on the cortisol production in normal human adrenocortical cells. First we used isopropyl thiogalactoside to induce the inducible mutant K-ras expression plasmid, pK568MRSV, in the stable transfected human adrenocortical cells. The result showed that the increase of RasGTP levels in transfected cells was time-dependent after isopropyl thiogalactoside induction. Additionally, results from Western blot analysis revealed significant elevation in phosphorylation of c-Raf-1 and Mitogen-activated protein kinase. We also detected the levels of mRNA encoding Cholesterol side-chain cleavage enzyme (P450(SCC)), 17alpha-Hydroxylase/17,20-lyase (P450(c17)) and 3beta-Hydroxysteroid dehydrogenase (3betaHSD) were increased in human adrenocortical cells transfected with mutant K-ras after IPTG treatment. The increase of mRNA amount in P450(scc) P450(c17) and 3betaHSD and the elevation of cortisol level were inhibited with a pretreatment of PD098059, a specific extracellular signal-regulated kinase inhibitor. In our previous report, we proved that lovastatin, a pharmacological inhibitor of p21(ras) function, also reversed the increase of cortisol level in mutant K-ras stably transfected human adrenocortical cells. Taken together, these findings proved that the active mutant Ras enhanced not only cell proliferation but also steroidogenesis in steroidogenic phenotype cells by activating Raf-MEK-MAPK related signal transduction pathway. Therefore, we believe that K-ras mutants influence regulation of steroidogenesis in adrenocortical cells through RAF-MEK-MAPK pathway.