Scintigraphic evaluation of primary congenital hypothyroidism: results of the Greek screening program

The Greek screening program for primary congenital hypothyroidism was initiated in 1979. By early 2000, thyrotropin measurements had been performed in 1,976,719 newborns, using dried blood spots obtained by heel prick. Among these children, 584 were diagnosed with congenital hypothyroidism (incidence: 1/3,384 births) and were given L-thyroxine (L-T4) replacement therapy. In order to further evaluate and classify the children as having either an aplastic (AT) or an ectopic thyroid gland (ET) or as showing thyroidal dyshormonogenesis (DN, with a nomotopic gland), scintigraphic studies were performed at the age of 2-3 years. In 413 children of this age group (including 24 subsequently diagnosed as having had transient hypothyroidism, in whom L-T4 therapy was not resumed), thyroid hormones were measured and scintigraphic studies were done after withdrawal of L-T4 replacement treatment for 3 weeks. Given the long duration of the study, we used various scintigraphic modalities. In 96 children (group A), scintigraphy was performed using technetium-99m pertechnetate (99mTcO4-; 18.5 MBq given i.v.) and a rectilinear scanner. Seventy-three children (group B) were studied with 99mTcO4- (18.5 MBq given i.v.) and a gamma camera equipped with a pinhole collimator. In these groups, atropine was administered 30 min prior to the study (0.02 mg/kg i.v. or i.m.) in order to reduce the secretion of saliva from the salivary glands. Finally, in the remaining 220 children (group C) iodine-123 sodium iodide (123I-Na) (0.74-1.85 MBq i.v.) and the same gamma camera were used. Between-group comparisons of scintigraphic findings were done with the chi square test. In 191 children from group C, thyroglobulin (Tg) was measured and in 49 children ultrasound (US) was performed (categorising the gland as AT or ET/DN). Comparison of these modalities was done with the kappa statistic. In group A, 61.5% of children had AT, 26.0% had ET and 12.5% had DN; in group B, 28.8% of children had AT, 52.0% had ET and 19.2% had DN; in group C, 23.2% of children had AT, 63.2% had ET and 13.6% had DN. Statistically significant differences in group A versus groups B and C were noted for AT and ET. The implementation of newer scintigraphic modalities, and especially the use of 123I-Na, indicates that the commonest finding in congenital hypothyroidism is ET. Scintigraphy was more concordant with Tg measurements (though at a moderate level) than with US. The latter was even less concordant with Tg values. These results show that the most appropriate approach for the evaluation and classification of congenital hypothyroidism is 123I-Na scanning.     

Prevalence of allergic symptoms among children with diabetes mellitus type 1 of different socioeconomic status

Abstract:  The aim of the study was to assess the possible associations between allergies and type 1 diabetes mellitus (DM1), stratified by social class. We studied 127 children with DM1 with a median age of 10.8 yr and 150 controls of comparable age and sex distribution. The parents completed questionnaires on their education and occupation and on their children's history of allergic symptoms, breast-feeding, viral infections, and measles–mumps–rubella (MMR) vaccination. Lower family's social class was more frequently encountered among the DM1 families than in the controls (OR = 0.56, 95% CI: 0.35–0.92). The occurrence of any allergic symptoms among children with DM1 (35.45%) was not significantly different from the controls (38.78%), neither in the total group (OR = 0.87, 95% CI: 0.52–1.45) nor in the stratified analysis by social class. Similar findings were observed regarding the different types of allergic symptoms. In the univariate analysis, breast-feeding, the experience of viral infections, and MMR vaccination were found to be protective of DM1 presentation in both upper and lower social classes. In the multiple logistic regression analysis, the experience of more than 2 infections/yr (OR = 0.12, 95% CI: 0.04–0.34), the origin from middle and upper social classes (OR = 0.42, 95% CI: 0.22–0.80) and breast-feeding (OR = 0.58, 95% CI: 0.31–1.07) were protective of DM1 occurrence. In children with DM1, the presence of allergic symptoms was not associated with the development of DM1. Among the environmental factors, the origin from middle or upper social classes, breast-feeding, the experience of viral infections, and MMR vaccination were found to have a protective effect on DM1 presentation.     

Case report. Chronic necrotizing pulmonary aspergillosis in a non-neutropenic patient treated with liposomal amphotericin B

Chronic necrotizing pulmonary aspergillosis is a rare infection encountered mainly in immunocompromised patients. We present the case of a young woman where the diagnosis of chronic necrotizing pulmonary aspergillosis was established after an open biopsy of the right lung. Liposomal amphotericin B was administered postoperatively for 10 days with moderate success. In a concise review we summarize the basic notions of chronic necrotizing pulmonary aspergillosis.     

New adjuvant therapy for colon cancer: justified hope or commercial hype

This article discusses the role of adjuvant chemotherapy for colon cancer. Six months of adjuvant 5-FU/leucovorin represent the standard of care for resected stage III colon cancer patients. The role of adjuvant chemotherapy for stage II patients remains controversial. Future directions in the adjuvant treatment of colon cancer include incorporation of newer agents such as irinotecan, oxaliplatin, oral fluorinated pyrimidines, and immunotherapeutic approaches.     

Exclusive characteristics of graft survival and risk factors in recipients with immunoglobulin A nephropathy: a retrospective analysis of registry data

BACKGROUND: Some studies have claimed that patients with immunoglobulin A (IgA) nephropathy have better graft survival than other renal graft recipients, whereas others have rejected this statement. We have addressed this paradox in the present study. METHODS: In all, 1,207 patients with IgA nephropathy who received a primary cadaveric renal graft from 1990 to 2002 were identified in the Eurotransplant database. For comparison, we analyzed 7,935 patients with nonglomerular diseases. Death-censored graft survival was calculated using Kaplan Meier estimates and a multivariable Cox regression analysis was used for risk calculations. RESULTS: Death-censored graft survival was superior in patients with IgA nephropathy in the first period after transplantation. After 3 years posttransplant, however, there was an accelerated decline in graft survival in recipients with IgA nephropathy. The fully adjusted risk of graft loss in the first year was increased by 40% in the control group compared to IgA nephropathy (hazard ratio [HR] 1.40, 95% CI 1.12-1.75), whereas the risk was significantly lower in the control group after the first year posttransplant (HR 0.75, 95% CI 0.63-0.88). Cold ischemia time, immunization and HLA-DR mismatch were risk factors for graft loss in the control group but not for IgA nephropathy, whereas HLA-AB mismatch was an independent risk factor, exclusively for the IgA nephropathy group. CONCLUSIONS: Recipients with IgA nephropathy have better 1-year graft survival, presumably due to favorable immunological behavior. This benefit was however abolished in the long-term by increased graft loss with time. Studies are needed to explain the difference in graft survival and the reason why different risk factors are involved in graft failure.     

Intramuscular administration of ACTH1-24 vs. 24-hour blood sampling in the assessment of adrenocortical function

The standard intravenous short Synacthen test (SSST) has long been accepted as one of the most reliable diagnostic tests of adrenocortical insufficiency. Intramuscular (i.m.) administration of ACTH obviates the need of venous cannulation and can be used as an alternative to the intravenous test. Nevertheless, reports of correlation between cortisol response to i.m. ACTH1-24 and 24-hr average cortisol concentration are scarce. We studied this relation in 64 nonobese healthy men. Blood samples for serial cortisol measurements were collected hourly over 24 hrs. The following day, blood samples were collected at baseline and at 30 and 60 min after intramuscular (i.m.) administration of 250 microg of ACTH1-24. All healthy men reached 24-hr serum cortisol peak values (Cmax) between 0600 h and 1000 h. Following i.m. ACTH1-24, cortisol levels significantly increased at both 30 (C30ACTH) and 60 (C60ACTH) minutes, when compared to baseline values. C30ACTH and C60ACTH significantly correlated with Cmax and with the 24-hr time-integrated cortisol concentration (AUC0-24). Morning mean cortisol was calculated as the average of serum concentrations measured between 0600 h and 1000 h (C(av)6-10) and correlated very well with AUC0-24. In conclusion, we confirmed that i.m. administration of ACTH1-24, followed by a single blood sampling at 60 min for cortisol measurement represents a valid, convenient and cost- effective screening test of adrenal function.     

Partitioning of limiting protein and energy in the growing pig: description of the problem, possible rules and their qualitative evaluation

A core part of any animal growth model is how it predicts the partitioning of dietary protein and energy to protein and lipid retention for different genotypes at different degrees of maturity. Rules of partitioning need to be combined with protein and energy systems to make predictions. The animal needs describing in relation to its genotype, live weight and, possibly, body composition. Some existing partitioning rules will apply over rather narrow ranges of food composition, animal and environment. Ideally, a rule would apply over the whole of the possible experimental space (scope). The live weight range over which it will apply should at least extend beyond the 'slaughter weight range', and ideally would include the period from the start of feeding through to maturity. Solutions proposed in the literature to the partitioning problem are described in detail and criticised in relation to their scope, generality and economy of parameters. They all raise the issue, at least implicitly, of the factors that affect the net marginal efficiency of using absorbed dietary protein for protein retention. This is identified as the crucial problem to solve. A problem identified as important is whether the effects of animal and food composition variables are independent of each other or not. Of the rules in the literature, several could be rejected on qualitative grounds. Those rules that survived were taken forward for further critical and quantitative analysis in the companion paper.     

Differential immunogenicity of HLA mismatches in clinical transplantation

Although HLA matching is beneficial in clinical transplantation, it is not feasible to select a completely HLA matched donor for every potential recipient because of the enormous polymorphism of the HLA system. As a consequence, the majority of the recipients will be transplanted with a mismatched donor organ or hematopoietic stem cell transplant. For this large group of patients it is important to take advantage of the differential immunogenicity of HLA mismatches and to select for them a donor with HLA mismatches of low immunogenicity, the so-called acceptable mismatches. The differential immunogenicity of HLA mismatches can be determined by either retrospective analysis of graft survival data or by in vitro assays measuring T-cell and B-cell alloreactivity. A recently developed computer algorithm (HLAMatchmaker) can be instrumental in selecting donors with HLA mismatches, which do not lead to alloantibody formation. The theoretical background and practical implications of this acceptable mismatch approach are discussed.     

Evaluation and treatment of Cushing's syndrome

Cushing’s syndrome results from sustained pathologic hypercortisolism caused by excessive corticotropin (ACTH) secretion by tumors in the pituitary gland (Cushing’s disease, 70%) or elsewhere (15%), or by ACTH-independent cortisol secretion from adrenal tumors (15%). The clinical features are variable, and no single pattern is seen in all patients. Those features most specific for Cushing’s syndrome include abnormal fat distribution, particularly in the supraclavicular and temporal fossae, proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in a child. Patients with characteristics of glucocorticoid excess should be screened with measurements of saliva or urine cortisol or dexamethasone suppression testing. The diagnosis of Cushing’s syndrome should be followed by the measurement of plasma ACTH concentration to determine whether the hypercortisolism is ACTH-independent. In ACTH-dependent patients, bilateral inferior petrosal sinus sampling with measurement of ACTH before and after administration of ACTH-releasing hormone most accurately distinguishes pituitary from ectopic ACTH secretion. Surgical resection of tumor is the optimal treatment for all forms of Cushing’s syndrome; bilateral adrenalectomy, medical treatment, or radiotherapy are sought in inoperable or recurrent cases. The medical treatment of choice is ketoconazole. The prognosis is better for Cushing’s disease and benign adrenal causes of Cushing’s syndrome than adrenocortical cancer and malignant ACTH-producing tumors.