Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.     

HIV-1 Tat increases the adhesion of monocytes and T-cells to the endothelium in vitro and in vivo: implications for AIDS-associated vasculopathy

HIV-1-infected patients exhibit severe damages of the aortic endothelium, develop angioproliferative lesions such as Kaposi's sarcoma (KS), and have an increased risk of cardiovascular diseases and atherosclerosis. An increased adhesion of leukocytes to the endothelium is a common pathogenic parameter of AIDS-associated vascular diseases. Here we show that the HIV-1 Tat protein, a regulatory protein of HIV-1 released by infected cells, and TNF-alpha, a cytokine increased in sera and tissues of HIV-1-infected patients, activate synergistically the adhesion of leukocytes to endothelial cells both in vitro and in vivo. This effect is selectively mediated by HIV-1 Tat, since HIV-1 Nef, another HIV-1 regulatory protein, and the HIV-1 envelope protein gp41, had no effect. In vitro adhesion assays with PBMC and quantitative cell type analysis of adherent cells by FACS demonstrated that HIV-1 Tat selectively activates the adhesion of T-cells and monocytes but not of B-cells. Intravital microscopic studies in mice confirmed the synergistic activity of HIV-1 Tat and TNF-alpha on leukocyte adhesion to the endothelium in vivo. These data indicate that HIV-1 Tat in cooperation with TNF-alpha may contribute to the vascular damage and cardiovascular diseases observed in AIDS patients but also to the prominent extravasation of T-cells and monocytes which is a key process in the formation and progression of KS lesions.     

Oocyte morphology predicts outcome of intracytoplasmic sperm injection

To examine the influence of cytoplasmic morphology on the success rate of intracytoplasmic sperm injection (ICSI), the morphology of 837 metaphase II oocytes was assessed after cumulus stripping. The main abnormalities detected were excessive granularity, cytoplasmic inclusions such as vacuoles, smooth endoplasmic reticulum clustering and refractile bodies. Microinjection was performed in 538 oocytes with normal cytoplasm, 142 out of 161 with excessive granularity and 112 out of 138 with cytoplasmic inclusions. Very poor oocytes were not injected. No difference was found in fertilization rate. The embryos achieved cleaved normally and a similar number of good quality embryos among the three groups was noted. The outcome of transfer of embryos derived solely from normal oocytes (group A: 72 patients, 183 embryos) was compared with those from oocytes with cytoplasmic abnormalities (group B: 34 patients, 85 embryos). In group A, 17 clinical pregnancies (24% per patient, implantation rate 10%) were established. In group B, only one clinical pregnancy (3% per patient, implantation rate 1%) was established, from the transfer of embryos derived from oocytes with homogeneous granularity of the cytoplasm. No pregnancy resulted following the transfer of embryos from eggs with cytoplasmic inclusions. The difference was statistically significant. The outcome of ICSI is dependent on the quality of the oocytes retrieved. Normal fertilization and early embryo development were achieved in oocytes with abnormal cytoplasm morphology, but the resulting embryos failed to demonstrate the same implantation potential as those derived from oocytes with normal cytoplasm.      

Comparison of the structure of human intervertebral discs in the cervical,thoracic and lumbar regions of the spine

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.     

The distribution of erythrocyte phospholipids in hereditary spherocytosis demonstrates a minimal role for erythrocyte spectrin on phospholipid diffusion and asymmetry

In the human erythrocyte membrane phosphatidylcholine and sphingomyelin reside mainly in the outer leaflet, whereas the aminophospholipids, phosphatidylethanolamine and phosphatidylserine, are mainly found in the inner leaflet. Maintenance of phospholipid asymmetry has been assumed to involve interactions between the aminophospholipids and the membrane skeleton, in particular spectrin. To investigate whether spectrin contributes to maintaining the phospholipid transbilayer distribution and kinetics of redistribution, we studied erythrocytes from hereditary spherocytosis patients whose spectrin levels ranged from 34% to 82% of normal. The phospholipid composition and the accessibility of membrane phospholipids to hydrolysis by phospholipases were in the normal range. Spin-labeled phosphatidylserine and phosphatidylethanolamine analogues that had been introduced into the outer leaflet were rapidly transported at 37 degrees C to the inner leaflet, whereas the redistribution of spin-labeled phosphatidylcholine was slower. The kinetics of transbilayer movement of these spin-labeled phospholipid in all samples was in the normal range and was not affected by the level of spectrin. Although these erythrocyte membranes contained as little as 34% of the normal level of spectrin and were characterized by several physical abnormalities, the composition, distribution, and transbilayer kinetics of the phospholipids were found to be normal. We therefore conclude that spectrin plays, at best, only a minor role in maintaining the distribution of erythrocyte membrane phospholipid.     

Differential diagnosis of jaundice: a pocket diagnostic chart

Based on extensive clinical and clinical chemical information (107 different items) from 1002 jaundiced patients, we developed a diagnostic algorithm which was evaluated on a test sample of another 110 jaundiced patients. A primary classification into categories of obstructive jaundice (probability of obstruction greater than or equal to 0.80), non-obstructive jaundice (probability of obstruction less than or equal to 0.20), and of doubtful causes of jaundice (probability of obstruction: 0.20-0.80) was attempted. Among 234 patients in the data base who were classified as obstructive, 220 (94%) proved to be so, as did 36 (97%) of 37 in the test sample. The corresponding figures for non-obstructive jaundice were 463 (96%) of 483 patients correctly classified in the data base and 47 (92%) of 51 patients in the test sample. Altogether 69% of the patients in the data base and 75% of those in the test sample were correctly classified, in 27% and 20% the cause of jaundice was doubtful, and only 4% and 5%, respectively, were misclassified. A slight majority of the patients in whom the algorithmic diagnoses were doubtful proved obstructive. A close correlation was found between the preliminary diagnoses made by the algorithm and by the clinicians. A secondary classification of the patients by the algorithm into benign versus malignant causes of obstructive jaundice performed equally well in the data base and the test sample.     

A decision tree for early differentiation between obstructive and non-obstructive jaundice

We present a method for early differentiation between obstructive and non-obstructive jaundice. On the basis of 14 variables (clinical data and clinical chemical tests, all available within 48 h) a simple decision tree or flow chart has been constructed. The diagnostic yield was as follows: 857 of 982 consecutive jaundiced patients (87%) in a data base and 98 of 108 patients in an independent test sample (91%) were correctly classified. Decision trees for the differentiation between benign or malignant causes within the obstructive group and between acute or chronic causes within the non-obstructive group are also presented. The resulting four-way classification was correct for 77% of the patients in the data base and for 72% of the patients in the test sample. The decision trees are compared with previous methods founded on Bayes' rule and logistic discrimination. The decision trees enable a quick and reliable classification of jaundiced patients, thus providing a valid basis for rational planning of the further diagnostic study.     

Alterations of serum concentrations of thyroid hormones and sex hormone-binding globulin, nuclear binding of tri-iodothyronine and thyroid hormone-stimulated cellular uptake of oxygen and glucose in mononuclear blood cells from patients with non-thyroidal illness

Nuclear tri-iodothyronine (T3) binding and thyroid hormone-stimulated oxygen consumption and glucose uptake were examined in mononuclear blood cells from patients with non-thyroidal illness (NTI) in which serum T3 was significantly (P less than 0.05) depressed (0.62 +/- 0.12 (S.D.) nmol/l) compared with healthy control subjects (1.45 +/- 0.30 nmol/l). Neither serum TSH nor sex hormone-binding globulin differed from that of the control group. Nuclear T3 binding capacity was increased (P less than 0.05) in patients with NTI (10.1 +/- 3.0 fmol/100 micrograms DNA) compared with controls (2.5 +/- 0.9 fmol/100 micrograms DNA). Unstimulated glucose uptake was increased in cells from patients with NTI (2.03 +/- 0.49 mmol/l per mg DNA per h, P less than 0.01) compared with controls (1.13 +/- 0.20 mmol/l per mg DNA per h). Thyroxine-stimulated glucose uptake (stimulated glucose uptake--unstimulated glucose uptake) was increased in cells from patients with NTI (2.06 +/- 1.67 mmol/l per mg DNA per h, P less than 0.01) compared with controls (0.26 +/- 0.12 mmol/l per mg DNA per h), and T3-stimulated glucose uptake was also increased in cells from patients with NTI (1.34 +/- 0.81 mmol/l per mg DNA per h, P less than 0.05) compared with controls (0.24 +/- 0.10 mmol/l per mg DNA per h). In contrast, neither unstimulated nor thyroid hormone-stimulated oxygen consumption differed. We conclude that both increased nuclear T3 binding and increased thyroid hormone-induced glucose uptake may represent counter-regulatory mechanisms which tend to maintain intracellular homeostasis.