Demonstration of immunoglobulin G, A, and E autoantibodies to the human thyrotropin receptor using flow cytometry

Human TSH receptor (TSHR) autoantibodies with biological activity result in thyroid dysfunction, but antibodies that simply bind do not. We have applied flow cytometry to the measurements of IgG, IgA, and IgE immunoreactivity to the TSHR in patients with Graves' disease (GD) and thyroid eye disease (TED) and in normal controls. CHO cells stably expressing the extracellular domain of the TSHR with a glycophosphatidylinositol anchor were produced and found to express approximately 4 times as many receptors, but of similar affinity, as JP09 in TSH binding studies. Substantial increases in median fluorescence and peak channel fluorescence were obtained by flow cytometry using TSHR monoclonal antibodies on the glycophosphatidylinositol cells. IgG autoantibodies were demonstrated in 55 of 65 untreated GD patients, 3 of 25 normal subjects, and 4 of 8 atypical TED sera (negative for TSHR autoantibodies with biological activity) by flow cytometry and correlated poorly with thyroid-stimulating antibodies. IgA antibodies were present in 1 of 12 normal, 1 of 7 treated GD with TED, and 3 of 8 atypical TED sera. IgE binding was observed in 1 of 12 normal, 2 of 8 treated GD without TED, 1 of 6 treated GD with TED, and 0 of 8 atypical TED sera. In conclusion, we have demonstrated autoantibodies that bind directly to the TSHR in the majority of GD patients and in 50% of patients with atypical TED and a small number of normal controls lacking TSHR antibodies that affect function. Although predominantly IgG lambda, TSHR autoantibodies of the IgA and IgE isotypes are also detectable.     

Subclinical peripheral neuropathy associated with chronic obstructive pulmonary disease

Peripheral nervous system disorders in COPD (chronic obstructive pulmonary disease) have been found more frequently than usual neurologic practice. We planned this prospective clinical and electrophysiological study to determine the incidence and characteristics of neuropathy in patients with COPD. We studied 49 patients with COPD in whom other causes of polyneuropathy had been excluded. COPD patients were divided into two groups: 21 hypoxemic and 28 normoxemic. Age and sex matched, nonsmoker, 21 healthy subjects were included as the control group. We investigated the results of clinical (neurological symptom score-NSS, neurological disability score-NDS and vibration perception thresholds- VPT) and neurophysiological evaluations in COPD patients and the control group. A value over the mean +/- 2.5 SD of control group were accepted pathologic. NSS results were pathologic in 34% of COPD patients, NDS in 42% and VPT in 94%. Carpal tunnel syndrome was found in 24% of the patients, neuropathy in 55%, and polyneuropathy in 44.8%. In conclusion, the incidence of neuropathy was more than expected, the rate of axonal neuropathy was significantly higher in the hypoxemic group than normoxemic group and the severity of neuropathy was correlated with the degree of hypoxemia.     

Effect of Abdominal Obesity on Insulin Resistance and the Components of the Metabolic Syndrome: Evidence Supporting Obesity as the Central Feature

Background: Metabolic syndrome includes abdominal obesity, diabetes type 2, hypertension, dyslipidemia, derangements of fibrinolysis, and atherosclerosis. Since abdominal obesity is one of the major components of the insulin resistance syndrome (IRS), an attempt was made to evaluate the interrelationships between the magnitude of obesity and the components of the syndrome. Methods: A cross-sectional study of 123 subjects with type 2 diabetes, of whom 31 were normal body weight and 92 had varying degrees of obesity was conducted. The participants were investigated in terms of clinical and laboratory findings of IRS. Fasting and 30-min (early) plasma glucose and serum insulin excursions in response to oral glucose challenge (75 g) were determined. The peripheral and hepatic insulin resistance (insensitivity) was calculated by homeostasis model assessment (HOMA). Results: Clinical and biochemical findings were compared with the components of the IRS, and demonstrated that a rise in fasting as well as 30-min insulin secretion increases as abdominal body fat (obesity) increases. There was also a significant and proportional correlation between the magnitude of abdominal obesity and the components of metabolic syndrome. Conclusion: Abdominal adiposity appears to have a pivotal role in the development of IRS.     

Andermann syndrome in a Turkish patient

Agenesis of the corpus callosum with peripheral neuropathy or Andermann syndrome is an autosomal recessive disorder rarely found outside certain regions of the province of Quebec, Canada. We report a 5-year-old Turkish patient with Andermann syndrome born to consanguineous parents. She presented with diffuse hypotonic weakness, predominantly in the distal extremities, and mild mental retardation. Electromyography showed axonal-demyelinating sensorimotor neuropathy. Sural nerve biopsy was compatible with demyelinating neuropathy. Cranial magnetic resonance imaging revealed total agenesis of the corpus callosum, dilatation of the interhemispheric fissure, and enlargement of the cisterna magna. The molecular genetic analysis using microsatellite DNA markers covering the agenesis of the corpus callosum with peripheral neuropathy locus on chromosome 15q13-q15 showed that the patient is homozygous for the whole region. Our findings confirm that Andermann syndrome is a genetically homogeneous disorder.     

A case presentation of bilateral simultaneous Bell's palsy

Bilateral simultaneous facial paralysis is an extremely rare clinical entity. Unlike the unilateral form, bilateral facial paralysis seldom falls into Bell's category. It is most often a special finding in a symptom complex of a systemic disease; many of them are potentially life-threatening, and therefore the condition warrants urgent medical intervention. Lyme disease, Guillian-Barre syndrome, Bell's palsy, leukemia, sarcoidosis, bacterial meningitis, syphilis, leprosy, Moebius syndrome, infectious mononucleosis, and skull fracture are the most common cause of bilateral facial paralysis. Here we present a 16-year-old patient with bilateral simultaneous Bell's palsy.     

Risk factors for permanent laryngeal nerve paralysis in patients with thyroid carcinoma.

OBJECTIVES: This study investigated the incidence of and risk factors for permanent recurrent laryngeal nerve paralysis for patients with thyroid malignancy. DESIGN: Retrospective chart review. SETTING: Tertiary oncology referral centre. PARTICIPANTS: Records of 290 consecutive patients treated between 1997 and 2001 were reviewed. All patients who have had one or more operations. Patients with preoperative recurrent laryngeal nerve paralysis and patients who underwent thyroidectomy in conjunction with laryngectomy were excluded. The incidence of postoperative permanent cord palsy was calculated in relation to the number of patients. MAIN OUTCOME MEASURES: Age, gender, thyroid functions, tumour localisations and size, multicentricity, thyroid capsule invasion, extrathyroidal soft tissue invasion, differentiation, histological type, co-existence of lymphocytic thyroiditis, total number of dissected and metastatic nodes, type of surgery, the place of surgery and number of operations were the risk factors investigated for permanent recurrent laryngeal nerve paralysis. Univariate and multivariate analyses were performed. RESULTS: Permanent recurrent laryngeal nerve paralysis developed in 27 (9%) of 290 patients with thyroid carcinoma. Transient and permanent paralysis rates in total or subtotal thyroidectomy, completion thyroidectomy and neck dissection groups were 5/3%, 7/3% and 24/17% respectively. Cox regression analysis identified the type of surgery [adjusted relative risk (RR) = 2.1, 95% confidence interval (CI) = 1.1-4.0, P = 0.01], extrathyroidal soft tissue invasion (RR = 5.7, 95% CI = 2.0-15.7, P = 0.001) and number of metastatic nodes (RR = 1.6, 95% CI = 1.1-2.5 P = 0.01). CONCLUSIONS: The factors related with recurrent laryngeal nerve paralysis post-thyroid carcinoma surgery are linked to special features of the tumour and to the type of surgery.     

Synthesis and biological evaluation of new N-substituted-N'-(3,5-di/1,3,5-trimethylpyrazole-4-yl)thiourea/urea derivatives.

Several thiourea and urea derivatives were prepared by the reaction of 4-aminopyrazoles with substituted isothiocyanates or isocyanates. The novel compounds were tested anticonvulsant activity using by pentylenetetrazole-induced seizure (PTZ) and maximal electroshock seizure (MES) tests. Among the tested compounds, thiourea derivatives of 4b were afforded 90 and 100% protection in PTZ and MES tests at 50mg/kg, respectively. Urea derivatives of 5a and 5b were afforded 82 and 100% protection both at 25 and 50mg/kg. Also synthesized compounds were screened for antituberculosis activity against Mycobacterium tuberculosis H37Rv at 6.25 microg/mL concentration but they were not found active at these concentration. In addition, some selected compounds were evaluated for in vitro anti-HIV activity and they were all negative.     

Glutathione S-transferase gene polymorphisms in presbycusis.

HYPOTHESIS: Glutathione and glutathione-related antioxidant enzymes are involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species. Reactive oxygen species generation occurs in prolonged relative hypoperfusion conditions such as in aging. The etiology of presbycusis is much less certain; however, a complex genetic cause is most likely. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of (glutathione S-transferase (GST) M1, T1 and P1 genotypes may be associated with the risk of age-related hearing loss. PATIENTS AND METHODS: We examined 68 adults with presbycusis and 69 healthy controls. DNA was extracted from whole blood, and the GSTM1, GSTT1 and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. RESULTS: Gene polymorphisms at GSTM1, GSTT1, and GSTP1 in subjects with presbycusis were not significantly different than in the controls (p > 0.05). Also, the combinations of different GSTM1, GSTT1, and GSTP1 genotypes were not an increased risk of presbycusis (p > 0.05). CONCLUSION: We could not demonstrate any significant association between the GSTM1, GSTT1, and GSTP1 polymorphism and age-related hearing loss in this population. This may be because of our sample size, and further studies need to investigate the exact role of GST gene polymorphisms in the etiopathogenesis of the presbycusis.