CALLA-positive myeloma: an aggressive subtype with poor survival

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.     

Alterations in the pituitary-thyroid axis and 5'-deiodinase activity in mice with muscular dystrophy

Mice with hereditary muscular dystrophy have reduced levels of serum T3. To determine possible causes of T3 deficits, we evaluated pituitary thyrotroph ultrastructure by electron microscopy, thyroid gland morphology by light microscopy, and T4 to T3 conversion by measuring iodothyronine 5'-deiodinase activity. Differences were not evident between dystrophic and normal littermates in either the structure of pituitary thyrotrophs or thyroid tissues. Dystrophic mice, however, had only 50% the normal hepatic 5'-deiodinase activity. Cerebral 5'-deiodinase, which does not appear to contribute significantly to serum T3, was similar in normal and dystrophic mice. Submandibular gland concentrations of nerve growth factor and epidermal growth factor are reduced in dystrophic mice but can be increased by T4 treatment. To distinguish whether growth factor deficits are due to reductions in serum T3 or to deficiencies in T4 5'-deiodinase activity and subsequent T3 utilization within the salivary gland, we measured submandibular deiodinase activity. Gland homogenates were active in the deiodinase assay, but no differences were detected between normal and dystrophic mice. In order to evaluate tissue responses to reductions in circulating T4, we treated mice with methimazole. Structural analyses revealed that thyrotrophs in dystrophic mice were less stimulated than thyrotrophs in similarly treated normal littermates. Likewise, thyroid follicular cells appeared less active, and thyroid weights increased only 40-50% as much as in normals. Liver 5'-deiodinase activity decreased in both normal and dystrophic mice. Cerebral 5'-deiodinase activity increased more than 4-fold in normal females but only 2-fold in dystrophic females; 2- to 3-fold increases occurred in both normal and dystrophic males. In summary, the structure of pituitary and thyroid glands in dystrophic mice is similar to that of tissues from normal littermates, but hepatic conversion of T4 to T3 is reduced. When challenged by methimazole-induced reductions in serum T4, pituitary and cerebral tissues in dystrophic mice respond abnormally.     

Plasma Concentrations of Immunoreactive Atrial Natriuretic Peptide in Hospitalized Cirrhotic and Noncirrhotic Patients: Evidence for a Role of Deficient Atrial Natriuretic Peptide in Pathogenesis of Cirrhotic Ascites

Atrial natriuretic peptide(s) (ANP), are thought to be released from the cardiac atria in response to distension. If decreased effective circulating blood volume is important in pathogenesis of ascites, plasma ANP levels would be expected to be decreased in ascitic subjects because of decreased atrial distension. To test this hypothesis, we measured plasma ANP by competitive radioimmunoassay in three groups of fasted, supine hospitalized subjects: nine noncirrhotic control subjects, 12 cirrhotics without ascites, and 17 cirrhotics with moderate to marked ascites. Immunoreactive plasma ANP concentrations were 195 +/- 41, 171 +/- 31, and 137 +/- 34 pg/ml (m +/- SD), respectively, in the three groups. The mean concentration in the group with cirrhosis and ascites was significantly (p less than or equal to 0.01) les than those of the other two groups, which did not differ from one another. These results support the concept that decreased effective circulating volume plays a role in pathogenesis of cirrhotic ascites, and that a relative deficiency of ANP plays a role in the sodium retention of decompensated cirrhosis.     

Pharmacogenomics of blood pressure response to antihypertensive treatment

PURPOSE IDENTIFICATION: Inter-individual variability in blood pressure response to treatment is well documented, but a clinically useful means to distinguish responders from non-responders has been elusive. With the advent of new technologies and genomic knowledge, more investigators are seeking to identify genetic determinants of blood pressure response to therapy. STUDY SELECTION: We identified studies of candidate polymorphisms from an initial PubMed search using the MESH terms 'Hypertension: Drug Therapy' and 'Genetics' or 'Pharmacogenetics', limiting results to English-language publications on studies in human adults. We further identified specific polymorphisms of interest noted in earlier reviews and performed additional PubMed searches based on these candidate genes. Pertinent studies were further extracted from the references of studies already identified. We focused on clinical trials that measured blood pressure response to a medication or class of medications over a minimum of 4 weeks. DATA EXTRACTION: We evaluated studies looking at blood pressure response to commonly used classes of antihypertensive medications by major genetic variants. RESULTS OF ANALYSIS: Although many studies show that blood pressure response to a given class of antihypertensive medications varies by genotype for different polymorphisms, none of the genotypes identified consistently predicted blood pressure response. CONCLUSIONS: Common variants may influence response to diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, but studies of polymorphisms have generally yielded conflicting results. The inclusion of pharmacogenomic studies in large clinical trials and other more innovative investigative methods may provide greater clarity of the potential role for genotyping in the treatment of patients with hypertension.     

Analysis of the ST-segment in terms of principal components: application on multichannel magnetocardiographic recordings

Parameterization of the ST-segment is used as a tool for risk stratification for patients to suffer from ventricular tachycardia. This parameterization is performed in terms of Principal Component Analysis (PCA) applied on multichannel magnetocardiographic (MCG) recordings. 55-channel MCG was recorded from 14 normal persons, 10 patients with CHD, 14 patients with MI, and six patients with VT. We found a significantly (p?<?0.05) lower PCA-score in patients with MI compared to normals. The lowest PCA-score was found in VT patients. Significant differences can be found between VT patients and normals and also between VT patients and CHD patients.