Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.     

High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors

Introduction The aim of the study was to determine the prevalence of vitamin D deficiency, secondary hyperparathyroidism (sHPT), generalized bone pain and predictors of vitamin D deficiency in a cohort of 994 healthy adult urban residents (589 males, 405 females; age range: 16–69 years) consisting of 101 Germans, 327 Turkish residents of Turkey and 566 Turkish immigrants living in Germany.Methods The mean (± standard deviation) for 25-hydroxyvitamin D [25(OH)D] and biointact parathyroid hormone (BioPTH) for the German men and women was 68.4 nmol/l and 26.7 pg/ml, respectively. Turkish residents of Turkey had a mean 25(OH)D and BioPTH of 40.6 nmol/l and 27.5 pg/ml, respectively, whereas Turkish residents of Germany had a 25(OH)D of 38.1 nmol/l and a BioPTH of 35.6 pg/ml.Results Vitamin D insufficiency was common among Turkish nationals independent of whether they lived in Turkey or Germany; 75% had 25(OH)D levels of <50 nmol/l. Turkish females had a higher prevalence of 25(OH)D deficiency (<25 nmol/l) than Turkish males: 30 and 19% of Turkish females living in Germany and Turkey were severely vitamin D deficient compared to 8% and 6% of Turkish males living in Germany and Turkey, respectively. With respect to BioPTH levels, 31% of Turkish females and 21% of Turkish males had elevated BioPTH levels in contrast to only 15% of females and 4% of males living in Turkey. Unconditional logistic regression analysis identified the most important predictors for low 25(OH)D levels as sex, body mass index, lack of sun exposure and living at a higher latitude. Additionally, wearing a scarf and number of children were found to be an independent risk factor for vitamin D deficiency in Turkish women living in Turkey and Germany. A strong correlation between low 25(OH)D levels and higher rates and longer duration of generalized bone and/or muscle aches and pains (often diagnosed as fibromyalgia) was observed.Conclusion Secondary hyperparathyroidism and vitamin D deficiency was found to be common among Turkish immigrants living in Germany, especially in veiled women. Therefore, the monitoring of vitamin D status – i.e. 25(OH)D and PTH – in Turkish immigrants is warranted and once a deficiency is identified, it should be appropriately treated.     

Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men

We determined the quantitative relationships between graded oral dosing with vitamin D₃, 25(OH)D₃, and 1,25(OH)₂D₃ for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 + 4 years, with usual milk consumption of 40.47 l/day and mean serum 25(OH)D of 67 + 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D₃ (25, 250 or 1250 mg/day for 8 weeks), 25(OH)D₃ (10, 20 or 50 mg/day for 4 weeks) and 1,25(OH)₂D₃ (0.5, 1.0 or 1.0 mg/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum calcium, parathyroid hormone, vitamin D₃, 25(OH)D and 1,25(OH)₂D immediately before and after treatment. In the three groups treated with vitamin D₃, mean values for circulating vitamin D₃ increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D₃ increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)₂D levels. However, treatment with 1,25(OH)₂D₃ increased circulating 1,25(OH)₂D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D₃ at 10 mg/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D₃ at 20 mg/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)₂D₃ at 0.5 mg/day would raise serum 1,25(OH)₂D by 17 pmol/l. Received: 4 August 1997 / Accepted: 14 October 1997     

Caudal-posteroanterior view in coronary arteriography

Posteroanterior (PA) and caudally angulated PA views were obtained in 20 patients undergoing routine coronary arteriography. Although the left main coronary artery (LMCA) was seen well on both views in all patients, the PA-caudal view improved depiction of the LMCA bifurcation in 15 (75%). In addition, the PA-caudal view markedly improved depiction of the circumflex artery, affording optimal depiction of this artery and its branches in 78%-89% of patients. Neither the PA nor the PA-caudal view allowed adequate depiction of the left anterior descending artery. Thus, the PA-caudal view should supplant the PA view in routine coronary arteriography.     

Standard multivitamin supplementation does not improve vitamin D insufficiency after burns

Children suffering severe burns develop progressive vitamin D deficiency because of inability of burned skin to produce normal quantities of vitamin D₃ and lack of vitamin D supplementation on discharge. Our study was designed to determine whether a daily supplement of a standard multivitamin tablet containing vitamin D₂ 400 IU (10 μg) for 6 months would raise serum levels of 25-hydroxyvitamin D [25(OH)D] to normal. We recruited eight burned children, ages 5–18, whose families were deemed reliable by the research staff. These children were given a daily multivitamin tablet in the hospital for 3 months in the presence of a member of the research staff and then given the remainder at home. At 6 months, the subjects returned for measurements of serum levels of 25(OH)D,1,25-dihydroxyvitamin D [1,25(OH)₂D], intact parathyroid hormone (iPTH), Ca, P, albumin, and total protein as well as bone mass by dual energy X-ray absorptiometry. Serum 25(OH)D levels were compared to a group of seven age-matched burned children studied at an earlier date without the vitamin supplement but with the same method of determination of 25(OH)D at 6 months post-burn. In addition, the chewable vitamins were analyzed for vitamin D₂ content by high performance liquid chromatography. Serum concentration of 25(OH)D was 21 ± 11(SD) ng/ml (sufficient range 30–100) with only one of the eight children having a value in the sufficient range. In comparison, the unsupplemented burn patients had mean serum 25(OH)D level of 16 ± 7, P = 0.33 versus supplemented. Serum levels of 1,25(OH)₂D, iPTH, Ca, P, albumin, and total protein were all normal in the supplemented group. Vitamin D₂ content of the chewable tablets after being saponified and extracted was 460 ± 20 IU. Bone mineral content of the total body and lumbar spine, as well as lumbar spine bone density, failed to increase as expected in the supplemented group. No correlations were found between serum 25(OH)D levels and age, length of stay, percent body surface area burn or third-degree burn. Supplementation of burned children with a standard multivitamin tablet stated to contain 400 IU of vitamin D₂ failed to correct the vitamin D insufficiency.     

The pentose phosphate pathway and pyruvate carboxylation after neonatal hypoxic-ischemic brain injury

The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-¹³C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using ¹H- and ¹³C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.     

Further specificity characterization of von Willebrand factor inhibitors developed in two patients with severe von Willebrand disease

Circulating inhibitors against von Willebrand factor (vWF) that show the properties of heterologous IgG antibodies have been described in a few patients with severe von Willebrand disease (vWD). The present study provides further characterization of inhibitors from two patients with severe vWD. Inhibitors in both, like polyclonal rabbit antibody, detected all sizes of multimers and the complex structure of each multimer from platelets and plasma of normal individuals as well as from plasma of patients with IIA, IIB, and IIC vWD. Both inhibitors and the rabbit antibody reacted mainly with the intact 225-Kd vWF subunit and the 189-H and 140-Kd fragments in contrast to monoclonal antibodies specific for vWF fragments that detected a higher relative proportion of 176-Kd fragment. Furthermore, all these antibodies recognized fragment III, although one inhibitor and rabbit polyclonal antibody reacted poorly and the other inhibitor did not react at all with reduced fragment II of vWF digested with Staphylococcus aureus V-8 protease. These data suggest that although human inhibitors from severe vWD patients may behave, to some extent, as polyclonal heterologous antibodies against native vWF, the former show striking differences in their target specificity as well as a much broader specificity than that described for human factor VIII inhibitors.