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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia, as well as diabetes mellitus. The neurological symptoms in affected patients include involuntary movements, ataxia, and dementia reflecting the sites of iron deposition detected by MRI, and the regions of neurodegeneration observed at autopsy. Excess iron functions as a potent catalyst of biologic oxidation. CSF from affected patients revealed a threefold increased iron concentration associated with increased superoxide dismutase activity and lipid peroxidation products. We found that the amount of iron accumulated in various regions of the brain and visceral organs is correlated with the levels of the oxysterols, including 7-hydroxycholesterol, and 7-ketocholesterol, which are directly produced from cholesterol by active oxygen species. Positron emission tomography done on brains of aceruloplasminemia patients showed cortical glucose hypometabolism. Enzyme activities in the mitochondrial respiratory chain of the cerebral cortices of the patients were reduced to approximate 62% and 71%, respectively, for complexes I and IV. These findings suggest that iron-mediated free radicals contribute to lipid peroxidation and the impairment of mitochondrial energy metabolism in aceruloplasminemia.
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PMID:[Neuronal cell damage in aceruloplasminemia]. 1121 1

In vivo NMR spectroscopy was performed on the brain of a patient with a leukoencephalopathy, revealing unknown resonances between 3.5 and 4.0 ppm. In addition, urine and CSF of the patient were measured using high-resolution NMR spectroscopy. Also in these in vitro spectra, unknown resonances were observed in the 3.5-4.0 ppm region. Homonuclear (1)H two-dimensional J-resolved spectroscopy (JRES) and (1)H-(1)H correlation spectroscopy (COSY) were performed on the patient's urine for more accurate assignment of resonances. The NMR spectroscopic studies showed that the unknown resonances could be assigned to arabinitol and ribitol. This was confirmed using gas chromatography. The arabinitol was identified as D-arabinitol. The patient is likely to suffer from an as yet unknown inborn error of metabolism affecting D-arabinitol and ribitol metabolism. The primary molecular defect has not been found yet. Urine spectra of patients suffering from diabetes mellitus or galactosemia were recorded for comparison. Resonances outside the 3.2-4.0 ppm region, which are the most easy to recognize in body fluid spectra, allow easy recognition of various sugars and polyols. The paper shows that NMR spectroscopy in body fluids may help identifying unknown resonances observed in in vivo NMR spectra.
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PMID:In vivo and in vitro NMR spectroscopy reveal a putative novel inborn error involving polyol metabolism. 1135 81

The author reported a case of a spontaneous rupture of a suprasellar cystic tumor. A 67-year-old man complained of bitemporal homonymous hemianopsia. His visual acuity was 0.02 on the right side and 0.04 on the left side. Skull XP revealed no abnormal findings, but brain CT scan showed a cystic mass without calcification in the suprasellar region. Brain MRI at the same lesion site depicted a low-intensity mass on T1-weighted image without gadolinium enhancement, and a high-intensity mass on T2-weighted image. The patient was treated conservatively because of complications such as diabetes mellitus, cerebral infarction and old myocardiac infarction. MRI taken 5 years after the initial MRI revealed disappearance of the suprasellar cystic mass. However, the patient's neurological findings, including visual signs, revealed no deterioration. His physical and radiological findings had remained uneventful. In this report, we reviewed the literatures about spontaneous rupture of suprasellar cystic tumors. It was considered that in this case, according to the neurological, radiological and CSF findings, the suprasellar cystic mass might be a Rathke's cleft cyst or arachnoid cyst.
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PMID:[A case of spontaneous rupture of a suprasellar cystic mass]. 1155 94

This study in undertaken to evaluate the pattern of sensory conduction abnormalities in Guillain-Barre (GB) Syndrome. Thirty six patients with GB Syndrome following clinical and CSF examination were subjected to motor conduction studies of median, ulnar and paroneal nerves including F wave latencies and sensory conduction studies of median, ulnar and sural nerves bilaterally. Motor conduction abnormalities were seen in 32 out of 36 patients (83%) and were seen more frequently in the lower limbs than upper. Median sensory conduction was abnormal more frequently than ulnar (21 Vs 17 patients). Median sensory conduction was abnormal in 21, ulnar in 17 and sural in 10 patients. In all the patients having abnormal ulnar sensory conduction, median sensory conductions were also abnormal. The patients with abnormal sural conductions had abnormal median sensory conductions in all except one patient. A pattern of normal sural with abnormal median sensory conductions was present in 12 patients. Both sural and median sensory conductions were abnormal in 9 patients and both normal in 14 patients. One patient had abnormal sural conduction with normal median sensory conduction but he had underlying diabetes. A similar pattern was found in relation to ulnar and sural sensory conductions although it was less frequent and less specific. The discordance of sural and median sensory conduction is important in GB Syndrome. Normal sural conductions with abnormal median sensory conductions is suggestive of GB Syndrome in the presence of an appropriate clinical setting, but a reverse pattern should alert an underlying polyneuropathy.
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PMID:Pattern of sensory conduction in Guillain-Barre Syndrome. 1172 Dec 99

Granulocyte macrophage-colony stimulating factor (GM-CSF) is one of the most widely used growth factors for enhancing immune responses and is known to recruit and activate antigen-presenting cells (APCs). This study hypothesized that overexpression of this cytokine within the pancreatic beta-cells would recruit, expand, and activate APCs. The question was whether this would lead to tolerance or autoimmunity to pancreatic antigens. This possibility was tested by preparing transgenic mice (ins-GM-CSF) whose islets expressed murine GM-CSF. By 6-8 weeks of age, these mice developed a profound mononuclear cell infiltration that often overwhelmed the exocrine pancreas, although no changes in enzyme or hormone function were apparent. The majority of the mononuclear infiltrate within the pancreas was identified as F4/80+ macrophages. Transgenic ins-GM-CSF mice had splenomegaly due to a massive increase in the macrophage population. Additionally, mononuclear cells were found within the livers of transgenic mice, with F4/80+ cells also identified within the infiltrate, indicating that GM-CSF-activated mononuclear cells circulated to organs other than the pancreas. To assess the disease potential, this study tested whether macrophage recruitment to the pancreas might accelerate or protect the islets from diabetes. It was found that the induction of diabetes by low-dose streptozotocin (STZ) was delayed and reduced within ins-GM-CSF transgenic mice, in comparison with negative littermates. Together, these data highlight the role of GM-CSF in recruiting APCs such as macrophages. Advanced cellular infiltration does not overtly harm, and may even protect, pancreatic function, as seen with the delay in chemically induced diabetes.
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PMID:Granulocyte macrophage-colony stimulating factor (GM-CSF) recruits immune cells to the pancreas and delays STZ-induced diabetes. 1174 49

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 +/- 0.2 ng/ml) as compared with controls (1.5 +/- 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 +/- 0.2 ng/ml vs. polysulfone 3.8 +/- 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca x P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.
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PMID:Serum levels of macrophage colony-stimulating factor and aortic calcification in hemodialysis patients. 1179 63

Hypertension is proposed as a risk factor among others (high age, diabetes mellitus, and pre- and intraoperative bleeding) for adverse outcomes, such as severe infections, leading to sepsis and to multiple organ failure as the most deleterious complication. Hypertension was modeled with spontaneous hypertensive rats (SHR) and Dahl salt-sensitive (DS) rats and the infective complication by polymicrobial, peritoneal contamination, and infection (PCI). The concept of clinic modeling randomized trials was used to simulate clinical complexity, including a relevant antibiotic prophylaxis in combination with granulocyte-colony stimulating factor (G-CSF) and clinical trial conditions. Outcome parameters were: survival, systemic cytokines (protein), and organ-specific cytokine levels (mRNA). With low complexity (no prophylaxis), 28% of the animals in the Wistar and 50% in the SHR group survived (P=0.17). Tumor necrosis factor-alpha levels were lower in the liver of SHR vs. Wistar rats with PCI (P<0.01). The anti-inflammatory cytokine interleukin (IL)-10 was expressed on a higher level in SHR with PCI compared with Wistar rats (P<0.01). With increased complexity (antibiotic and G-CSF prophylaxis) the survival rate was increased from 50% in Wistar rats to 89% in SHR (P<0.01) and the mRNA expression of IL-6 was decreased in the kidney of SHR (P<0.05). Survival rate was 44% in the DS rats vs. 67% of the Wistar rats (P=0.18). The mRNA expression of tumor necrosis factor-alpha and IL-10 was reduced (P<0.01) by pretreatment in the liver of DS rats with PCI. The hypertensive, genetically distinct SHR and DS rats express different patterns of pro- and anti-inflammatory cytokine levels after PCI. G-CSF and antibiotic prophylaxis increases only in SHR survival and decreases IL-6 mRNA expression in the kidney significantly.
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PMID:The genetic background of hypertensive, septic rats determines outcome improvement with antibiotic and G-CSF prophylaxis. 1450 46

Endogenous Aspergillus endophthalmitis (AE) is a rare complication of invasive aspergillosis (IA) in transplant patients. In this report, we describe two patients with polycystic kidney disease, who developed AE with cerebral involvement after renal transplantation. Both patients received intense immunosuppression with methyl prednisolone and mycophenolate mofitil (MMF) because of persistent rejection, which rendered them diabetic and vulnerable to opportunistic infections. Endophthalmitis developed within six months of transplantation and was confirmed by microscopy and culture of the vitreous fluid. Patients were treated with combinations of different anti-fungal agents including liposomal amphotericin B, 5-flucytosine, itraconazole, voriconazole and terbinafine. In an electronic MEDLINE review, we found eight further cases of AE in renal transplant patients between 1959 and September 2002. Based on this review, we identified possible risk factors including CMV infection, diabetes mellitus and treatment for rejection with agents such as methyl prednisolone and MMF. In 70% of cases the histology, microscopy or culture of vitreous fluid confirmed the diagnosis. The outcome of AE in renal transplant patients was poor with 70-100% mortality. The review of reported cases and current practice guidelines suggests that vitrectomy and intravitreal amphoterecin B is the treatment of choice. In addition, new antifungal agents with good CSF and ocular penetration such as voriconalzole should be considered for the treatment of invasive cerebral/ocular aspergillosis.
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PMID:Aspergillus endophthalmitis: an unusual complication of disseminated infection in renal transplant patients. 1455 60

The advances in endoscopic instruments have eased the approach to the sellar region through the nasal cavity. We carry out an analysis of the surgical results on 20 patients that underwent surgery for sellar tumours through a transeptal-transphenoidal approach in the last 2 years in our hospital. The average was 45.6 years old, and 75% were females. 30% of cases were pituitary adenomas and another 30% acromegaly, 25% Cushing's disease and 10% prolactinomas. No complications were encountered during surgery being the most common postoperative complications, diabetes insipida in two cases (10%) and CSF leak in one case. At present 2 patients are having hormonal treatment for panhypopituitarism. No patients developed a septal perforation, nasal deformity, epistaxis, meningitis, lip numbness or oronasal fistula. The rest did have good results noith no recurrence and hormonal values back to normal.
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PMID:[Trans-septal endoscopic approach of pituitary tumors]. 1475 17

Aberrant prostaglandin synthase 2 (PGS2/COX2) expression constitutes an antigen presenting cell (APC) dysfunction seen in monocytes of humans at risk for or with Type 1 diabetes. During endotoxin activation of PGS2 expression in healthy monocytes, granulocyte-monocyte colony stimulating factor (GM-CSF) is activated and, in turn, promotes PGS2 gene activation. GM-CSF is considered a major target the action for IL10 in its suppression of PGS2. We found that the PGS2 expression in monocytes from 47% of at-risk and diabetic humans tested were highly resistant to suppression by IL10 (maintaining > or =50% of their untreated expression), and had significantly increased GM-CSF production in vitro (1043+/-SD2798 pg/10(6)cells, subject n=35, vs 29.7+/-SD91 pg/10(6)cells, control n=20; P=0.0165). The PGS2 insensitivity to IL10 of these cells was not due to a lack of IL10 functionality or its suppression of GM-CSF. In contrast to its effects on PGS2, IL10 regulation of GM-CSF and other monocyte factors (i.e., DR, IL1beta, TNFalpha, IL12, CD54, and CD64) remained intact. These findings suggest that the inability of IL10 to properly downregulate PGS2 gene expression may contribute to its dysregulation in Type 1 diabetes.
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PMID:IL10 resistant PGS2 expression in at-risk/Type 1 diabetic human monocytes. 1504 Oct 43


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