Use of a rate-limited ultrafiltration circuit with centrifugal ventricular assist

Renal insufficiency and pulmonary edema are frequently observed in patients who require centrifugal ventricular assist for postcardiotomy ventricular failure. We describe a technique of using a rate-limited ultrafiltration device in parallel with the assist device circuit to remove excess intravascular volume.     

An unusual presentation of hidradenitis suppurativa: case report and review of the literature

Hidradenitis suppurativa is a chronic suppurative and cicatricial process of apocrine gland-bearing skin. The clinical course can range from mild to severe. We present a case of a urethral fistula and phimosis occurring secondary to hidradenitis suppurativa, and review the literature.     

New platinum antitumor complexes

Over the past two decades, platinum-based drugs (cisplatin and, latterly, the less toxic analogue carboplatin) have conferred significant therapeutic benefit to a large number of cancer sufferers. However, there remains scope for substantial improvement in the clinical utility of metal coordination complexes through the discovery of additional platinum-based complexes (or possibly alternative metals). Future drug discovery strategies should focus on tumor resistance and its circumvention. To date, only one series of compounds, those containing a 1,2-diaminocyclohexane carrier ligand (e.g., oxaliplatin, tetraplatin), has entered clinical trial based on their circumvention of acquired cisplatin resistance in some (mainly murine) preclinical tumor models. At present these agents are in early clinical trial and thus their true clinical utility in cisplatin/carboplatin refractory disease is not yet determinable (and may not be due to dose-limiting neurotoxicity). Over the past few years, our understanding of mechanisms of resistance to cisplatin and its interaction with DNA has vastly increased. This new information will undoubtedly guide the development of new strategies aimed at the circumvention of intrinsic and acquired tumor resistance to cisplatin. Approaches to circumvent resistance will probably involve not only the rational development of a new generation of platinum-based drugs (e.g., compounds designed to overcome reduced cisplatin accumulation or enhanced removal of cisplatin-induced DNA adducts) but also non-platinum drugs which are capable of modulating resistance (e.g., modulators of signal transduction pathways, ras and myc oncogene expression and glutathione biosynthesis). One may look forward with a great deal of optimism that these promising new approaches will result in clinical benefit by the end of the century. Nevertheless, cisplatin and carboplatin remain the standard anticancer drugs to which novel platinum-based complexes must be compared.     

The single-stranded DNA aptamer-binding site of human thrombin

A new class of thrombin inhibitors based on sequence-specific single-stranded DNA oligonucleotides (thrombin aptamer) has recently been identified. The aptamer-binding site on thrombin was examined by a solid-phase plate binding assay and by chemical modification. Binding assay results demonstrated that the thrombin aptamer bound specifically to alpha-thrombin but not to gamma-thrombin and that hirudin competed with aptamer binding, suggesting that thrombin's anion-binding exosite was important for aptamer-thrombin interactions. To identify lysine residues of thrombin that participated in the binding of the thrombin aptamer, thrombin was modified with fluorescein 5'-isothiocyanate in the presence or absence of the thrombin aptamer, reduced, carboxymethylated, and digested with endoproteinase Arg-C. The digestion products were analyzed by reversed-phase high performance liquid chromatography and the peptide maps compared. Four peptides with significantly decreased modification in the presence of the aptamer were identified and subjected to N-terminal sequence analysis. Results indicated that B chain Lys-21 and Lys-65, both located within the anion-binding exosite, are situated within or in close proximity to the aptamer-binding site of human alpha-thrombin. The thrombin aptamer binds to the anion-binding exosite and inhibits thrombin's function by competing with exosite binding substrates fibrinogen and the platelet thrombin receptor.     

Peptide-induced conformational changes in class I molecules. Direct detection by flow cytometry

Activation of a T cell in response to peptide bound to class I MHC occurs by the sum of interactions across the area of contact between the TCR, the peptide, and class I MHC. It has been observed recently that substitution of the peptide residue at a position that is not accessible from the exterior of the class I molecule modulates T cell responses, raising the possibility that there may be indirect structural effects in the peptide-class I complex as a consequence of peptide binding. This report describes the use of mAbs to probe the conformation of the alpha 1 and alpha 2 domains of the mouse class I molecule Kb when bound to ovalbumin peptide and a panel of 19 peptide analogues that differ at position 2 (P2). By crystallographic data, side chains of this position are buried in the Ag binding cleft and have no direct access to the TCR. Substitution of position 2 results in a measurable change in conformation of the class I molecule, a change that correlates with the ability to stimulate T cells. This leads to a model that T cell activation by the peptide-class I complex may occur in three ways: 1) direct interaction of the TCR with the class I heavy chain, 2) direct interaction of the TCR with solvent-accessible peptide side chains, and 3) indirect interaction of peptide with TCR mediated via conformational perturbations in the class I complex.     

Prison inmates with a history of inpatient psychiatric treatment

Radiation enteric disorders are rare and difficult to treat. A case of radiation duodenitis treated by hyperbaric oxygen is reported. A sixty-year-old man underwent right nephroureterectomy, chemotherapy (platin and 5 fluorouracil) and radiation therapy (54 Gy) for excretory urinary carcinoma. Six months later, even though he was under omeprazole therapy for reflux oesophagitis, he experienced antroduodenitis, duodenal ulceration, and duodenal telangiectasia. Symptoms and duodenal ulcer disappeared 2 months later with hyperbaric oxygen (10 one hour sessions at 2 ATA). Most likely, hyperbaric oxygen can reduce the consequences of obliterative endarteritis due to irradiation, responsible for ischaemia and fibrosis later on.     

Effect of parathyroid hormone-related peptide supplementation of soy protein formulas in the neonatal pig model

PTH-related peptide (PTHrP) is found in all milks, including human and pig. To define a role for PTHrP in milk, 2-day-old piglets were randomized to receive soy formula devoid of PTHrP or supplemented with 1 nM synthetic PTHrP(1-86) (n = 8 per group). The number of serum samples with detectable PTHrP by immunoassay (Incstar) and radiometric assay (Nichols) was 9 of 33 and 3 of 13 in PTHrP- and 8 of 27 and 3 of 15 in PTHrP+ formula-fed piglets and 8 of 14 and 7 of 12 in naturally suckling piglets, respectively. Serum and urine concentrations of calcium and magnesium and total and bone alkaline phosphatase were similar in both groups at 3, 6, 10, and 17 days of age. No differences were seen in bone mineral content of the tibia measured by single-photon absorptiometry (BMC 0.22 +/- 0.06 and 0.22 +/- 0.10) or dual x-ray absorption (BMC 1.43 +/- 0.36 and 1.31 +/- 0.78) either in vivo or on excised bone or by measurement of Ca, Mg, or P content or total bone ash (1.26 +/- 0.26 and 1.38 +/- 0.28 mg). Intestinal histology, serum intestinal alkaline phosphatase, and net absorption and retention of Ca, Mg, and P in balances from age 11-17 days were all similar. As in humans, however, a developmental pattern was seen for phosphorus regulation in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

A clinico-pathological study of cutaneous leishmaniasis in British troops from Belize

Thirty-four cases of cutaneous leishmaniasis contracted by British soldiers in Belize were studied. Pre- and post-treatment biopsies were taken from all patients. The range of histological appearances is described and the value of histological examination (including Giemsa staining and immunohistochemistry), cytological preparations and microbiological culture in diagnosis and clinical management assessed. Histology and culture were found to be complementary techniques in reaching a positive diagnosis, whilst cytological preparations were of no additional value. Histological examination of post-treatment biopsies merely confirmed the clinical impression of healing or non-healing whilst culture identified viable organisms in apparently healed lesions, which were subsequently re-treated.