Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes

CD4+ CD25+ T-cells appear to play a crucial role in regulating the immune response. Therefore, we evaluated the peripheral blood frequency and function of CD4+ CD25+ T-cells in 70 type 1 diabetic patients and 37 healthy individuals. Interestingly, a positive correlation was observed between increasing age and CD4+ CD25+ T-cell frequency in both subject groups. In contrast to previous studies of nonobese diabetic mice and type 1 diabetic patients, similar frequencies of CD4+ CD25+ and CD4+ CD25(+Bright) T-cells were observed in healthy control subjects and type 1 diabetic patients of similar age. There was no difference between type 1 diabetic subjects of recent-onset versus those with established disease in terms of their CD4+ CD25+ or CD4+ CD25(+Bright) T-cell frequency. However, type 1 diabetic patients were markedly defective in their ability to suppress the proliferation of autologous effector T-cells in vitro. This type 1 diabetes-associated defect in suppression was associated with reduced production of interleukin (IL)-2, gamma-interferon, and transforming growth factor-beta, whereas other cytokines including those of adaptive and innate immunity (IL-10, IL-1beta, IL-6, IL-8, IL-12p70, and tumor necrosis factor-alpha) were similar in control subjects and type 1 diabetic patients. These data suggest that age strongly influences the frequency of CD4+ CD25+ T-cells and that function, rather than frequency, may represent the means by which these cells associate with type 1 diabetes in humans.     

Crystal methamphetamine-associated cardiomyopathy: tip of the iceberg?

BACKGROUND: Crystal methamphetamine has become a drug of widespread use. Previous reports describe myocardial infarction, pulmonary edema, and aortic dissection related to methamphetamine use. Cardiomyopathy due to methamphetamine exposure has been rarely described. METHODS: We identified 1640 patients admitted in a 4-yr period with a primary or secondary diagnosis of cardiomyopathy. We excluded patients with known cause of cardiomyopathy other than substance abuse. We found 120 patients had a diagnosis of substance abuse, including 21 patients with methamphetamine use. We retrospectively reviewed the medical records of these 21 crystal methamphetamine users. RESULTS: Nineteen (84%) underwent echocardiography with consistent findings of dilated cardiomyopathy and global ventricular dysfunction. Of five who had a nuclear myocardial perfusion study, none had evidence of ischemia or infarct. Of six who underwent cardiac catheterization, only one had evidence of coronary stenosis. CONCLUSION: Methamphetamine use appears to produce cardiomyopathy in some users. The pathogenesis is probably similar to that of cocaine and catecholamine-induced cardiomyopathy. Cellular, animal, and clinical data support the link between methamphetamine exposure and myocardial pathology.     

Update on oncocytoma

Oncocytoma is the most common benign solid renal tumor, comprising roughly 5% of resected renal masses. Typically discovered incidentally, oncocytoma is generally asymptomatic and very rarely metastasizes; however, multifocal disease and coexistence with renal cell carcinoma can occur. No currently used imaging techniques can reliably distinguish between oncocytoma and malignant lesions; therefore, patients must undergo resection, or in certain circumstances, biopsy, to definitively establish diagnosis. Careful attention to pathologic features and the adjunctive use of immunostains can aid in discriminating oncocytoma from other renal tumors characterized by granular, eosinophilic cytoplasm, especially chromophobe renal cell carcinoma. Nephron-sparing and laparoscopic surgical approaches can be used to treat appropriately selected patients.     

Blood lymphocyte chimerism associated with IVF and monochorionic dizygous twinning: case report

We report on dizygotic (DZ) twins, conceived by IVF and ICSI with assisted hatching, who each had a mixture of 46,XX and 46,XY cells in blood lymphocytes. The female twin had mild genitalia abnormalities but further study revealed anatomically normal reproductive anatomy. Chromosome and fluorescence in situ hybridization studies of buccal, skin and ovarian tissue were normal, as were buccal tissue DNA studies. Fetal ultrasound and fetal membrane pathology were consistent with a monochorionic, diamniotic placenta (MCDAP). These twins thus have blood chimerism but are not chimeric in the other tissues studied. The mechanism for the chimerism could be due to either placental vascular anastamoses (after the development of the haematoblast stem cells) or due to an admixture of trophoblast cells during early blastocyst development. Such trophoblast cell admixtures would be restricted to the extraembryonic tissues so that general physical development in the fetus is normal and without somatic cell chimerism. This case in combination with others previously reported suggests that in IVF conceptions, the prevalence of blood chimerism associated with twinning, and the occurrence of DZ twinning associated with MCDAP, may be higher than previously thought.     

Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc

Chromosomal translocations involving immunoglobulin heavy chain (Igh) switch regions and an oncogene such as Myc represent initiating events in the development of many B cell malignancies. These translocations are widely thought to result from aberrant class-switch recombination. To test this model, we measured translocations in mice deficient in activation-induced cytidine deaminase (AID) that lack class-switch recombination. We found that AID made no measurable contribution to the generation of initial translocations, indicating that the intrinsic fragility of the switch regions or a pathway unrelated to AID is responsible for these translocations. In contrast, the outgrowth of translocation-positive cells was dependent on AID, raising the possibility that AID is important in tumor progression, perhaps by virtue of its mutagenic properties.     

Transvenous n-butyl-cyanoacrylate infusion for complex dural carotid cavernous fistulas: technical considerations and clinical outcome

BACKGROUND AND PURPOSE: Endovascular transvenous embolization has been advocated as the treatment technique for dural carotid cavernous fistulas (dCCFs). Most centers use platinum coils primarily. The purpose of this study was to evaluate the technical aspects, efficacy, and safety of transvenous n-butyl cyanoacrylate (n-BCA) infusion in dCCFs as a primary alternative or adjunct to coil embolization. METHODS: We retrospectively evaluated 14 patients with dCCFs who were treated at this institution from 1999 to 2004 by using n-BCA infusion alone or in combination with coils. The efficacy of treatment and safety aspects were studied in dCCFs of Barrow type B (4/14), C (2/14), and D (8/14). Six patients were treated with transvenous n-BCA infusion alone in the cavernous sinus, 7 with a combination of transvenous n-BCA and coil embolization, and one with transvenous n-BCA combined with transarterial polyvinyl alcohol (PVA)-particle embolization of the feeding arteries. RESULTS: An angiographic obliteration and clinical cure was achieved in all patients. Technical complications were nonsymptomatic and included spillage of an n-BCA droplet into a middle cerebral artery branch retrograde through the arteriovenous fistulas in one patient and perforation of the inferior petrosal sinus during microcatheter placement in another. A third patient developed temporary palsy of the sixth cranial nerve a few days after the treatment. CONCLUSION: In this small series, the use of n-BCA either alone or in conjunction with detachable coils was a safe and effective technique for the treatment of symptomatic patients presenting with complex dCCFs.     

Autoimmunity to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease

The pathogenic mechanisms underlying Batten disease are unclear. Patients uniformly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct from subjects with autoimmune type 1 diabetes or stiff-person syndrome. Batten patients did not possess autoantibodies against other type 1 diabetes-associated autoantigens and human leukocyte antigen genotypes revealed no specific associations with this disease.     

Videotape preparation of patients before hip replacement surgery reduces stress

OBJECTIVE: Elective surgery represents a considerable source of stress for the patient. Many attempts have been made to prepare patients before surgery with the aim of reducing stress and improving outcome. This study used a novel approach to fulfill this aim by showing a videotape of a patient undergoing total hip replacement surgery, covering the time period from hospital admission to discharge, that strictly keeps to the patient's perspective. METHODS: Before elective total hip replacement surgery, 100 patients were randomly assigned to a control group or a preparation group; the latter group was shown the videotape on the evening before surgery. Anxiety and pain were evaluated daily for 5 days, beginning with the preoperative day, by means of the State-Trait Anxiety Inventory and a visual analog scale. Intraoperative heart rate and blood pressure, as well as postoperative intake of analgesics and sedatives, were recorded. Urinary levels of cortisol, epinephrine, and norepinephrine were determined in 12-hour samples collected at night for 5 nights, beginning with the preoperative night. RESULTS: Compared with the control group, the preparation group showed significantly less anxiety on the morning before surgery and the mornings of the first 2 postoperative days, and significantly fewer of them had an intraoperative systolic blood pressure increase of more than 15%. The pain ratings did not differ significantly between the two groups, but the prepared patients needed less analgesic medication after surgery. Prepared patients had significantly lower cortisol excretion during the preoperative night and the first 2 postoperative nights. Excretion of catecholamines did not differ significantly between groups. CONCLUSIONS: We conclude that use of the videotape decreased anxiety and stress, measured in terms of urinary cortisol excretion and intraoperative systolic blood pressure increase, in patients undergoing hip replacement surgery and prepared them to cope better with postoperative pain.