The microstructure of ultra-high molecular weight polyethylene used in total joint replacements

The microstructure of ultra-high molecular weight polyethylene (UHMWPE) has been studied using a range of techniques. Both the unprocessed base powder and ram-extruded polymer have been examined using optical microscopy, scanning and transmission electron microscopy and small-angle light scattering. By examining the microstructure of samples compression moulded at a range of temperatures, techniques have been developed to assess the degree of consolidation of the processed polymer. The raw polymer is a powder with a particle size in the range 50-250 microm. These particles are themselves agglomerates of much finer particles typically 0.5-1 microm in size. It has been suggested that these sub-micron particles may be the origin of the sub-micron wear debris found in tissues around total joint replacements. However, examination of the ram-extruded polymer, from which implants are machined, shows a different structure from the powder, with no evidence of retention of the 0.5-1 microm structure seen in the powder in the processed material. It thus appears that the similarity in size between the sub-micron wear debris particles and the fine structure seen in the unprocessed UHMWPE resin is coincidental. Processed UHMWPE does show a 'memory' of the grain boundaries between powder particles and the degree of consolidation can be assessed by observing the distinctiveness of these boundaries.     

Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy

OBJECTIVES: We sought to characterize the clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. BACKGROUND: Patients with ischemic cardiomyopathy may have a worse prognosis than patients with nonischemic cardiomyopathy. Few studies have assessed the effect of ischemic versus nonischemic etiology on outcomes. METHODS: We analyzed prospectively collected data on 3,787 patients with a left ventricular ejection fraction < or = 40% who underwent coronary angiography. Patients were considered to have ischemic cardiomyopathy (n = 3,112) if they had a history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery or at least one major epicardial coronary artery with > or = 75% stenosis; all others were considered to have nonischemic cardiomyopathy (n = 675). RESULTS: The median age, ejection fraction and proportion of patients with New York Heart Association functional class III or IV symptoms for the nonischemic and ischemic groups were 55 years versus 63 years, 27% versus 32% and 57% versus 25%, respectively. After adjustment for baseline clinical risk factors and presenting characteristics, ischemic etiology remained an important independent predictor of 5-year mortality (p < 0.0001). The extent of coronary artery disease was a better predictor of survival than ischemic or nonischemic etiology (log likelihood chi-square 700 vs. 675, respectively). CONCLUSIONS: Ischemic etiology is a significant independent predictor of mortality in patients with cardiomyopathy. However, the extent of coronary artery disease contributes more prognostic information than the clinical diagnosis of ischemic or nonischemic cardiomyopathy. Further research is needed to refine the clinical definition of ischemic cardiomyopathy so that physicians can appropriately prescribe treatment and accurately predict outcome.     

Double coupling Edman chemistry for high-sensitivity automated protein sequencing

Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) is a promising new method for the analysis of protein sequencing products. It gives 10 zmol (1 zmol = 10(-21) mol) limits of detection (3 sigma) for fluorescein thiohydantoin (FTH) amino acids. We have developed a separation for the (FTH)-amino acid products generated from 18 of the 20 coded amino acids. The extremely low volume requirement associated with CE-LIF makes it incompatible with commercial sequencers. For this reason, we have also been developing a miniaturized sequencer that can be more easily coupled to our detection system. Both the CE-LIF system and the miniaturized sequencer are described.     

Structural characterization of the molecular dimer of the peptide antibiotic vancomycin by distance geometry in four spatial dimensions

OBJECTIVE: The objectives of this study were to know the prevalence of hepatitis C virus (HCV) in a population of pregnant women, to evaluate the vertical transmission rates of HCV in a prospective study and to determine the repercussions and consequences in children born to infected mothers. PATIENTS AND METHODS: A total of 6556 pregnant women were tested for HCV antibodies from January 1993 to August 1995. We followed 50 babies born to infected mothers for at least 12 months (mean 15 months). Serological assays employed included a screening ELISA II confirmed with immunoblot. Viral detection was performed by qualitative and quantitative PCR for HCV-RNA. RESULTS: Fifty-nine pregnant women were AcHCV(+). This represents a seroprevalence of 0.9%. Of the 50 babies followed, 6 were PCR(+) and 44 were PCR(-). The risk of transmission is correlated with the titer of HCV-RNA in the mother. All mothers of infected babies were HIV (-). CONCLUSIONS: The rate of prevalence in our pregnant women population is 0.9%. We found a vertical transmission rate of 12%. The high serum HCV-RNA titers in the mothers are a risk factor of transmission of HCV. The viremia in the children does not predict the apparition of the clinical disease, although they can exhibit intermittent increases of transaminases.     

Heart rate changes during the Valsalva maneuver in patients with isolated aortic insufficiency

To determine the possible relationship between left ventricular dilatation and heart rate changes provoked by the Valsalva maneuver (Valsalva ratio), we studied 9 patients with isolated chronic aortic insufficiency. Left ventricular systolic function was assessed by two-dimensional echocardiography and cardiac catheterization. All patients were asymptomatic (functional class I of the New York Heart Association). The left ventricular internal diameters and volumes were significantly increased in all patients. The asymptomatic patients had either normal or slightly depressed ejection fraction (EF > 0.40). The Valsalva ratio of these asymptomatic patients showed no significant correlation with the left ventricular volumes or with the left ventricular ejection fraction. In other words, parasympathetic heart rate control, as expressed by the Valsalva ratio, was normal in the asymptomatic patients with left ventricular dilatation and preserved left ventricular ejection fraction. Therefore, left ventricular dilatation may not be the major mechanism responsible for the abnormal parasympathetic heart rate control of patients with acquired heart disease.     

Misplacement of endoscopic biliary endoprostheses

We report the case of a 72 year-old man with advanced, stage IV, prostate cancer who underwent osteosynthesis of the cervical spine for nerve root decompression due to metastasis which was causing severe pain in his right upper limb. After three months in the hospital, he developed occlusive thrombosis of the right axillosubclavian vein as a complication of prolonged catheterization of the right subclavian vein for treatment of septicemia secondary to a hospital acquired pneumonia. The patient received thrombolytic therapy with IV streptokinase in the contralateral arm in the following dosage: 250,000 units in 15 minutes followed by 100,000 units per hour during five days. This led to total recanalization of the thrombus, with significant reduction of the arm edema. Twenty-four hours after the end of the thrombolytic therapy, the patient started to complain of dysfagia to solids and liquids and a contrasted esophagogram revealed extensive extrinsic compression of the esophagus due to a probable retroesophageal hematoma. The patient required enteral nutrition via nasoenteral tube during three months after which swallowing returned to normal and a repeat upper GI series confirmed that the hematoma had been reabsorbed, with normal passage of contrast through the esophagus. On late follow-up, the patient did not show evidence of any sequelae of deep venous thrombosis nor any residual dysfagia and is currently in use of elastic stockings and low molecular weight heparin.     

Molecular modelling of mammalian CYP2B isoforms and their interaction with substrates, inhibitors and redox partners

1. The construction of three-dimensional models of CYP2B isozymes from rat (CYP2B1), rabbit (CYP2B4) and man (CYP2B6), based on a multiple sequence alignment with CYP102, a unique eukaryotic-like bacterial P450 (in terms of possessing an NADPH-dependent FAD- and FMN-containing oxidoreductase redox partner) of known crystal structure, is reported. 2. The enzyme models described are shown to be consistent with experimental evidence from site-directed mutagenesis studies, antibody recognition sites and amino acid residues identified as being associated with redox partner interactions, together with the location of a key serine residue (Ser-128) likely to be involved in protein kinaseA-mediated phosphorylation. 3. A substantial number of known substrates and inhibitors of CYP2B isozymes are shown to fit the putative active sites of the enzyme models in agreement with their reported position of metabolism or mode of inhibition respectively. In particular, there is complementarity between the characteristic non-planar geometries of CYP2B substrates and key groups in the enzymes' active sites. 4. Molecular modelling of CYP2B isozymes appears to rationalize a number of the reported findings from quantitative structure-activity relationship investigations on series of CYP2B substrates and inhibitors.     

Testicular "tumor" of the adrenogenital syndrome: a case report of an unusual association with myelolipoma and seminoma in cryptorchidism

BACKGROUND: Males with congenital adrenal hyperplasia may develop bilateral testicular masses in early adult life. These are not malignant and generally regress with corticosteroid therapy. The authors report a case occurring in a 44-year-old man with associated seminoma and myelolipoma in an undescended testis. METHODS: The testicular tumors were analyzed by histologic, flow cytometric, and ultrastructural techniques. RESULTS: The tumors in both testes were comprised of polygonal cells with abundant granular eosinophilic cytoplasm, occasionally with brown (lipochrome) pigment and round nuclei of various sizes with prominent nucleoli. These cells were grouped into nodules by dense and sometimes thick fibrous trabeculae in the right testis. The areas corresponding to the fibrous trabeculae in the left (intraabdominal) testis were replaced by mixture of hematopoietic (myeloid) and fatty tissue in various proportions characteristic of myelolipoma. The left testis also had a well demarcated tumor that was diagnostic of seminoma. Electron microscopy demonstrated abundant smooth endoplasmic reticulum, a moderate number of mitochondria with tubulovesicular cristae, lipid droplets, and lipofuscin granules in the polygonal cells. No Reinke's crystals were observed. The patient received corticosteroids for his adrenocorticoid deficiency and also underwent external beam irradiation to the retroperitoneum for seminoma. CONCLUSIONS: This case illustrates an unusual presentation of a testicular tumor in a patient with the adrenogenital syndrome as well as with myelolipoma and seminoma in a cryptorchid testis. The possibility of an associated neoplasm that could be potentially fatal should be considered whenever a testicular tumor of the adrenogenital syndrome continues to grow despite adequate hormonal treatment.     

A role for oestrogens in the male reproductive system

Oestrogen is considered to be the 'female' hormone, whereas testosterone is considered the 'male' hormone. However, both hormones are present in both sexes. Thus sexual distinctions are not qualitative differences, but rather result from quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males, oestrogen is present in low concentrations in blood, but can be extraordinarily high in semen, and as high as 250 pg ml(-1) in rete testis fluids, which is higher than serum oestradiol in the female. It is well known that male reproductive tissues express oestrogen receptors, but the role of oestrogen in male reproduction has remained unclear. Here we provide evidence of a physiological role for oestrogen in male reproductive organs. We show that oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis. Disruption of this essential function causes sperm to enter the epididymis diluted, rather than concentrated, resulting in infertility. This finding raises further concern over the potential direct effects of environmental oestrogens on male reproduction and reported declines in human sperm counts.     

Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes

Congenital alveolar proteinosis is a recently described cause of lung dysfunction and respiratory distress in term neonates. In several cases a deficiency or insufficiency of surfactant apoprotein B (SP-B) has been caused by a frameshift mutation in the gene encoding SP-B. Five full-term children in three unrelated families from The Netherlands are reported. Immunohistochemistry demonstrated large amounts of surfactant proteins A and C (SP-A and SP-C) and precursors in alveolar cells and in intra-alveolar material. Results were positive for antibovine SP-B antibody but negative for antipig SP-B1 antibody, most probably reflecting differences in the antibody specificity. The findings suggest abnormal SP-B function. In two sibs, no pre-SP-C was demonstrated in the alveoli, although it was found in considerable amounts in alveolar cells. One such case has previously been reported. In two families, the parents were heterozygous for the 121 ins 2 mutation in the SP-B gene. Our findings suggest that congenital alveolar proteinosis may result from abnormalities in one or more of the surfactant proteins.