L-thyroxine requirement in patients with autoimmune hypothyroidism and parietal cell antibodies

BACKGROUND: Hypothyroid patients on l-T(4) therapy may require replacement doses exceeding the theoretical needs to normalize serum TSH due to low patient compliance, drugs interference, and malabsorption. OBJECTIVE: We examined whether autoimmune gastritis might cause increased l-T(4) requirement in patients with autoimmune thyroiditis receiving l-T(4) replacement. PATIENTS: We studied 391 patients with clinical or subclinical hypothyroidism from autoimmune thyroiditis who had achieved normal serum TSH concentration (0.3-3.0 microU/ml) under l-T(4) for at least 6 months. Patients were screened for serum parietal cell antibodies (PCA) as a marker of autoimmune gastritis, and the PCA status was correlated with the l-T(4) dose. We also studied a group of 60 patients receiving l-T(4) replacement after total thyroidectomy. RESULTS: PCA-positive (155 of 391) and PCA-negative (236 of 391) patients did not differ for pretherapy serum TSH levels and thyroid volume. The l-T(4) requirement was significantly (P = 0.002) higher in PCA-positive (1.24 +/- 0.40 microg/kg x d) than in PCA-negative patients (1.06 +/- 0.36 microg/kg x d), and a significant positive correlation was found between l-T(4) requirement and serum PCA levels. Among PCA-positive patients, l-T(4) requirement was even higher in those with proven gastritis (1.52 +/- 0.40 microg/kg x d) compared with those without gastric damage (1.15 +/- 0.33 microg/kg x d) (P < 0.0001). The increased l-T(4) requirement was confirmed also in PCA-positive thyroidectomized patients (1.81 +/- 0.27 microg/kg x d) compared with PCA-negative thyroidectomized patients (1.52 +/- 0.24 microg/kg x d). Independent variables affecting l-T(4) requirement were PCA and serum TSH at diagnosis. CONCLUSIONS: Autoimmune gastritis is an additional factor affecting l-T(4) requirement in patients with autoimmune thyroiditis. Serum PCA measurement should be considered in patients with an unexplained high requirement of l-T(4).     

Insulin sensitivity in women: a comparison among values derived from intravenous glucose tolerance tests with different sampling frequency, oral glucose tolerance test or fasting

OBJECTIVE: To determine the correlation between insulin sensitivity (S(I)) obtained by the minimal model method applied to a frequently sampled (n=33) intravenous glucose tolerance test (FSIGT(33)), and values obtained by reduced FSIGTs, oral glucose tolerance test (OGTT), or fasting. DESIGN: Retrospective analysis on tests performed in prospective studies. METHODS: A total of 78 FSIGT(33), and 59 OGTT were performed in non-diabetic women of which 10 were young cyclic females in the early follicular menstrual phase, 10 were young non-obese subjects with polycystic ovary syndrome (PCOS) and 30 were in post-menopause. Some of these individuals were investigated both prior to and during specified treatments. FSIGT(33) was transformed into FSIGT(22) and FSIGT(12) by removing samples from the analysis. Values of SI derived from reduced FSIGTs or calculations performed on glucose and insulin values observed in fasting conditions and/or during OGTT were related to those of FSIGT(33). RESULTS: S(I) values derived from FSIGT(33) were highly correlated with those derived from FSIGT(22) (r=0.965) or FSIGT(12) (r=0.955), but were only weakly correlated with those derived from fasting or OGTT calculations (r below 0.5). Between-group (PCOS vs normal) or within-group (prior to and during treatment) comparisons showed that reduced FSIGTs were only slightly less powerful than FSIGT(33) in detecting differences in S(I). CONCLUSIONS: In non-diabetic women, reduced FSIGTs but not calculations based on fasting or OGTT values may be used in place of FSIGT(33) to document S(I) and its variation.     

Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy

OBJECTIVE: Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated. DESIGN: Randomised, double-blind placebo controlled study. PATIENTS: Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). MEASUREMENTS: Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin. RESULTS: In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024). CONCLUSIONS: The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.     

Enzyme Replacement Therapy Improves Respiratory Outcomes in Patients with Late-Onset Type II Glycogenosis and High Ventilator Dependency

Purpose

Type II glycogenosis (GSDII) is a rare and often fatal neuromuscular disorder caused by acid alpha-glucosidase deficiency. Although alglucosidase alfa enzyme replacement therapy (ERT) significantly improves outcomes in subjects with the infantile form, its efficacy in patients with the late-onset one is not entirely clear. The long-term efficacy of ERT in late-onset GSGII complicated by severe pulmonary impairment causing high mechanical ventilation dependency was investigated in this study.

Methods

The long-term clinical efficacy of ERT was assessed in eight late-onset GSDII patients using home mechanical ventilation (HMV) by comparing their outcomes with those of six historical control patients (GSDII patients) who had received HMV alone. The number of hospitalizations due to pulmonary exacerbations and of hours of daily use of HMV were considered the study’s primary efficacy endpoints.

Results

The treatment group showed an increased tendency toward shorter follow-up compared to the control group (35.8 ± 29.2 vs. 52.6 ± 8.55 months; p = 0.04). At the end of the study period, the daily use of HMV (12.5 ± 7.6 vs. 19 ± 14.3 h; p = 0.004) and the hospitalization rate [incidence rate ratio = 0.43 (95 % confidence interval 0.18–0.93); p = 0.03] were significantly lower in the patients receiving ERT. The differences in the forced vital capacity absolute value and percentage change from baseline were not significantly different in the two groups.

Conclusions

ERT reduces ventilator dependency in late-onset GSDII patients and the need for hospitalization due to respiratory exacerbations.     

An Italian research project to study the play of children with motor disabilities: the first year of activity

Purpose : The paper presents the main outline of a new research project carried out by the SIVA research team concerning the development of methodologies to select and use assistive technology to allow children with motor disabilities to play with toys. Conclusion : Giving them the same opportunities to play as their peers without disabilities can best enhance their cognitive and social development. A review of the literature in the field is also included.     

Glycogen branching enzyme deficiency in adult polyglucosan body disease

Branching enzyme activity was assayed in muscle, peripheral nerve, and leukocytes from 2 Ashkenazi-Jewish patients with adult polyglucosan body disease and 1 African-American and 3 Caucasian patients with the same clinical and pathological features. Branching enzyme activity was normal in the muscle specimens from both Jewish and non-Jewish patients. However, the activity was markedly decreased not only in the leukocytes from the 2 Jewish patients (confirming previous findings), but also in peripheral nerve specimens, whereas it was normal in nerve tissue and leukocytes from all non-Jewish patients. These data confirm a branching enzyme deficiency in a subgroup of patients with adult polyglucosan body disease, and show that the defect is tissue-specific, suggesting that adult polyglucosan body disease has more than one biochemical basis.     

Identification of picobirnavirus from faeces of Italian children suffering from acute diarrhea

Polyacrylamide gel electrophoresis of nucleic acid extracted from stool samples of diarrhoeic children revealed in 3 out of 690 (0.43 %) specimens two electrophoretic bands with a migration pattern characteristic of picobirnavirus ds-RNA. In none of the 92 control children were similar bands detected. No other potential enteric pathogens were found in the patients with picobirnavirus infection.