Parathyroid hormone in serum during lithium therapy

In ten patients parathyroid hormone, urinary calcium excretion, and fractional tubular reabsorption of calcium were determined at intervals during three months of lithium treatment. Parathyroid hormone increased more than 40% within the first week and remained elevated throughout the treatment period. Calcium excretion fell by more than 30% within the first week and remained low throughout the treatment period. The reduction in urinary calcium excretion could be accounted for by an increase in fractional tubular reabsorption of calcium. There were no significant changes in serum calcium and inorganic phosphate or in urinary inorganic phosphate. The results indicate that lithium treatment affects the hormonal regulation of calcium metabolism.     

Structural analysis and fatty acid-binding properties of two Croatian variants of human serum albumin

BACKGROUND: The aim of the present work was to characterize the molecular defects of a slow-migrating (albumin Zagreb) and a fast-migrating (albumin Krapina) genetic variant of human serum albumin detected in heterozygous persons living in Croatia and to elucidate the fatty acid-binding properties of the two alloalbumins. METHODS: Purification and structural identification of the variants were performed by conventional protein chemistry methods, whereas types and amounts of albumin-bound, endogenous fatty acids were determined by gas chromatography. RESULTS: Protein sequencing established that albumin Zagreb is a proalbumin variant (-1Arg-->Gln), and that albumin Krapina is due to a mutation within the mature polypeptide chain (573Lys-->Glu). The gas chromatographic results showed that the fatty acid-binding properties of the proalbumin variant are normal, while the amino acid substitution in position 573 resulted in a general decrease of fatty acid binding. CONCLUSIONS: The structural defects of the first alloalbumins, detected by routine clinical electrophoresis among the Croatian population, were characterized. Albumin Zagreb is caused by a hot-spot mutation occurring in a CpG sequence in the albumin gene. It is commonly assumed that bisalbuminaemia has no direct clinical relevance. However, the present study suggests that naturally occurring mutations can affect the ligand-binding properties of human serum albumin.     

Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy

Oestrogen therapy is the gold standard treatment for hot flushes/night sweats, but it and oestrogen/progestin are not suitable for all women. MPA (medroxyprogesterone acetate) reduces hot flushes, but its effectiveness compared with oestrogen is unknown. In the present study, oral oestrogen [CEE (conjugated equine oestrogen)] and MPA were compared for their effects on hot flushes in a planned analysis of a secondary outcome for a 1-year randomized double-blind parallel group controlled trial in an urban academic medical centre. Participants were healthy menstruating women prior to hysterectomy/ovariectomy for benign disease. A total of 41 women {age, 45 (5) years [value is mean (S.D.)]} were enrolled; 38 women were included in this analysis of daily identical capsules containing CEE (0.6 mg/day) or MPA (10 mg/day). Demographic variables did not differ at baseline. Daily data provided the number of night and day flushes compared by group. The vasomotor symptom day-to-day intensity change was assessed by therapy assignment. Hot flushes/night sweats were well controlled in both groups, one occurred on average every third day and every fourth night. Mean/day daytime occurrences were 0.363 and 0.187 with CEE and MPA respectively, but were not significantly different (P=0.156). Night sweats also did not differ significantly (P=0.766). Therapies were statistically equivalent (within one event/24 h) in the control of vasomotor symptoms. Day-to-day hot flush intensity decreased with MPA and tended to remain stable with CEE (P<0.001). In conclusion, this analysis demonstrates that MPA and CEE are equivalent and effective in the control of the number of hot flushes/night sweats immediately following premenopausal ovariectomy.     

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.     

Amino acid substitutions in the melanoma antigen recognized by T cell 1 peptide modulate cytokine responses in melanoma-specific T cells

Single amino acid substitutions in melanoma-associated peptides dramatically enhance T-cell cytotoxicity against target cells presenting the modified peptides (often referred to as heteroclitic peptides). The authors tried to determine whether peptide modifications influence other aspects of T-cell immunity toward malignant melanoma. A heteroclitic peptide, E26F, with an E to F substitution in melanoma antigen recognized by T cell 1 (MART-1)26-35, triggers an enhanced tyrosine phosphorylation response when compared with the native- and other-modified MART-1 peptides. Similarly, the E26F peptide enhances the production of mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-gamma and significantly enhances release of IL-13 and IL-10 from anti-MART-1 cytotoxic T cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-1(27-35), also enhances the tyrosine phosphorylation response in anti-MART-1 cytotoxic CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2-like cytokines (IL-10 and IL-13). Together these data show that minor amino acid modifications of immunodominant melanoma peptides profoundly influence the cytokine response in melanoma-specific T cells.     

Detection of Undiagnosed Coeliac Disease with Atypical Features Using Antireticulin and Antigliadin Antibodies

Eighteen patients with a variety of non-gastrointestinal symptomswere incidentally found to have circulating antireticulin antibodyand on subsequent testing were also positive for antigliadinantibody. They prospectively underwent jejunal biopsy to determinewhether or not they had coeliac disease. Their age range was21–79 years (mean 42 years). Enteropathy was present in13 (72 per cent) and was always associated with circulatingIgA antigliadin antibody. Enteropathy was not present in thefive cases who had only IgG antibody. Clinical improvement occurredin eight of 11 patients who complied with a gluten-free dietand was paralleled by an improvement in the mucosal histologyin seven of eight who were re-biopsied. The most remarkablecases were two patients who presented with severe debility andno apparent haematological or biochemical abnormalities, andwho subsequently made a dramatic recovery on a gluten-free diet.It is concluded that antireticulin antibody detected by routineautoantibody screening and confirmed to have IgA antigliadinantibody specificity is a useful indicator of an otherwise undiagnosedenteropathy. This serves to emphasize that the condition cansometimes be associated with atypical features and significantmorbidity.