Gamma delta lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes.

Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes which use the gamma delta heterodimer as T cell receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine autoimmunity we have determined the proportion of gamma delta T cells in the peripheral blood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves' disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow cytometry on peripheral blood mononuclear cells using MoAbs UCHT1 (CD3), TCR delta 1 (gamma delta TCR), WT31 and beta F1 (alpha beta TCR) and both the percentage of T cells expressing gamma delta and the ratio gamma delta/alpha beta were calculated. In the diabetic patients gamma delta cells were not significantly different from the control group (7.7 +/- 54% versus 8.0 +/- 5.5% of T cells, P NS). There was no relation between the proportion of gamma delta lymphocytes and the presence of islet cell antibodies (ICA) in the sera. The Graves' patients showed a tendency towards a higher proportion of gamma delta T lymphocytes than the controls (gamma delta/alpha beta ratios: 0.095 +/- 0.047 versus 0.063 +/- 0.022, P = 0.03). In 14 Graves' patients the number of gamma delta were measured in paired samples of peripheral and intrathyroidal lymphocytes, demonstrating an expansion of gamma delta within the thyroid glands (0.21 +/- 0.3 versus 0.095 +/- 0.047, P = 0.032). Immunohistochemical studies showed that gamma delta cells were scattered among the predominant alpha beta lymphocytes infiltrating the thyroid gland and that they account for 10% of intraepithelial lymphocytes. No relation was found between the increase of gamma delta lymphocytes and any clinical features.     

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging

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Adolescents who are frequent attenders to primary care: contribution of psychosocial factors

Background  

Frequent attendance to primary care services has shown an association with psychosocial factors in adult and child populations. Little is known about the psychosocial correlates of attendance in adolescents.     

Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA)

OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.     

Validation of a new standardized cystatin C turbidimetric assay: Evaluation of the three novel CKD-EPI equations in hypertensive patients

Objectives

Analytical and clinical performances of the new standardized cystatin C particle-enhanced turbidimetric immunoassay (PETIA) using DiaSys reagents on Olympus AU2700® analyzer were evaluated.

Design and methods

We have studied imprecision, linearity, limit of detection and limit of quantification of this new immunoassay. Method comparison was assessed in relation to results generated by the standardized Siemens-particle-enhanced nephelometric immunoassay (PENIA). In order to evaluate the clinical relevance of this assay, estimated glomerular filtration rate (GFR) was calculated using MDRD, CKD-EPI creatinine, CKD-EPI cystatin C 2012 and CKD-EPI creatinine–cystatin C 2012 equations and compared to GFR measured using urinary clearance of ^99mTc-DTPA in 100 hypertensive patients.

Results

Cystatin C measurements using DiaSys reagents have reliable analytical performances and are comparable to the standardized Siemens-PENIA method (bias of 0.01 mg/L). The mean measured GFR was 90.0 ± 29.7 mL/min/1.73 m². Bias and accuracy of the three CKD-EPI equations were better than the MDRD. Both CKD-EPI creatinine-based and cystatin C-based formulae had similar bias, precision and accuracy. The combined creatinine–cystatin C equation was significantly more accurate and precise than the CKD-EPI creatinine equation in patients with GFR above 60 mL/min/1.73 m².

Conclusions

The use of cystatin C in a combined equation with creatinine could improve the accuracy of eGFR in the reference interval.     

Endoscopic Treatment of Persistent Alveolar-Pleural Air Leaks With a Unidirectional Endobronchial Valve

The persistent air leaks due to alveolopleural fistula is not an uncommon complication of pneumothorax, particularly secondary ones. Unidirectional flow endobronchial valves initially designed for lung volume reduction are the latest tool in the therapeutic armamentarium.We present a patient with chronic obstructive pulmonary disease (COPD) with a persistent pneumothorax in spite of three pleurodesis, which was able to be resolved with the placement of two IBV? valves.     

Fatal hydrogen sulfide poisoning

Two cases of fatal hydrogen sulfide poisoning are described which occurred during cleaning of a tank that had transported polysulfides. The most characteristic findings of the autopsy were: a blackish-green pigmentation at macroscopic examination; pulmonary edema, steatosis, intrahepatic cholestasis and renal tubular necrosis at microscopic examination. The blood concentration of sulfide ions exceeded 3.5 mg/l. These cases are compared to others described in the literature. The preventive measures that should be adopted to avoid this type of poisoning are stressed.     

Adaptive behaviour in Angelman syndrome: its profile and relationship to age

Background Angelman syndrome (AS) is a neurodevelopmental disorder usually caused by an anomaly in the maternally inherited chromosome 15. The main features are severe intellectual disability, speech impairment, ataxia, epilepsy, sleep disorder and a behavioural phenotype that reportedly includes happy disposition, attraction to/fascination with water and hypermotoric behaviour. Method We studied the level of adaptive behaviour and the adaptive behavioural profile in the areas of ‘motor skills’, ‘language and communication’, ‘personal life skills’ and ‘community life skills’ in a group of 25 individuals with genetically confirmed AS, to determine whether there is a specific adaptive behaviour profile. Results and conclusions None of the individuals, whatever their chronological age, had reached a developmental age of 3 years. A specific adaptive behaviour profile was found, with ‘personal life skills’ emerging as relative strengths and ‘social and communication skills’ as weaknesses.     

Diagnostic Interview for Genetic Studies (DIGS): inter-rater and test-retest reliability and validity in a Spanish population.

OBJECTIVE: To test the reliability and validity of the DIGS in Spanish population. METHODS: Inter-rater and test-retest reliability of the Spanish version of DIGS was tested in 95 inpatients and outpatients. The resultant diagnoses were compared with diagnoses obtained by the LEAD (Longitudinal Expert All Data) procedure as "gold standard". The kappa statistic was used to measure concordance between blind inter-raters and between the diagnoses obtained by LEAD procedure and through the DIGS. RESULTS: Overall kappa coefficient for inter-rater reliability was 0.956. The kappa value for individual diagnosis varied from major depression=0.877 to schizophrenia=1. Test-retest reliability was 0.926. Kappa for all individual target diagnoses ranged from 0.776 (major depression) to 1. Kappa between LEAD procedure and DIGS ranged from 0.704 (major depression) to 0.825 (bipolar I disorder). CONCLUSION: Most of the DSM-IV major psychiatric disorders can be assessed with acceptable to excellent reliability with the Spanish version of the DIGS interview. The Spanish version of DIGS showed an acceptable to excellent concurrent validity. Giving the good reliability and validity of Spanish version of DIGS it should be considered to identify psychiatric phenotypes for genetics studies.