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Biomedical subjects

D Arnold

Publications and source records attributed to D Arnold.

153 records · Page 9Linked to original sources
PubMedDate not supplied

A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway.

Major histocompatibility complex (MHC) class I molecules export peptides to the cell surface for surveillance by cytotoxic T lymphocytes. Intracellular peptide binding is critical for the proper assembly and transport of class I molecules. This mechanism is impaired as a result of a non-functional peptide supply factor gene (PSF) in several human mutant cell lines with genomic lesions in the MHC. We have now identified PSF in the MHC class II region by deletion mapping in mutants and chromosome-walking. PSF is homologous to mammalian and bacterial ATP-dependent transport proteins, suggesting that it operates in the intracellular transport of peptides.

Amino Acid Sequence↗
PubMedDate not supplied

[Assessment and therapeutic possibilities in posthemorrhagic hydrocephalus of the newborn infant].

Internal hydrocephalus follows intraventricular hemorrhage in about 10%. Progression is directly related to the degree of hemorrhage. Several studies confirmed that cerebral damage may occur without an increase of intracranial pressure or head circumference. Assessment and therapeutic consequences depend entirely on sonographic and clinical criteria. In our series, 40 of 135 neonates with intraventricular hemorrhage developed internal hydrocephalus. Therapy was necessary in 35 children, 11 died. Serial lumbar punctures were the most frequent therapeutic approach in 70% of the children. 40% required a shunt, usually a ventriculo-peritoneal system. In this group the proportion of Grade III and IV hemorrhage was high. In 25% external drainage for one week was necessary. 10% were treated with acetazolamide and furosemide. By this therapy shunt placement could be avoided in 9 children (69.2%), in the group with Grade III hemorrhage. In addition it was possible to postpone shunting to the third month on the average. 25 children were followed-up. 40% were normal or had a mild developmental delay. 60% were seriously handicapped. Poor neurodevelopmental outcome was related directly to hemorrhage Grade III and IV, therefore to brain damage in the early phase. To prevent additional lesions it should be emphasized that in infantile hydrocephalus best long-term results have been obtained if the process was controlled early rather than later.

Brain Damage, Chronic↗
PubMedDate not supplied

Ultrastructural aspects of autoschizis: a new cancer cell death induced by the synergistic action of ascorbate/menadione on human bladder carcinoma cells.

Scanning and transmission electron microscopy were employed to further characterize the cytotoxic effects of a ascorbic acid/menadione (or vitamin C/vitamin K3) combination on a human bladder carcinoma T24 cell line. Following 1-h treatment T24 cells display membrane and mitochondrial defects as well as excision of cytoplasmic fragments that contain no organelles. These continuous self-excisions reduce the cell size. Concomitant, nuclear changes, chromatin disassembly, nucleolar condensation and fragmentation, and decreased nuclear volume lead to cell death via a process similar to karyorrhexis and karyolysis. Because this cell death is achieved through a progressive loss of cytoplasm due to self-morsellation, the authors named this mode of cell death autoschizis (from the Greek autos, self, and schizein, to split, as defined in Scanning. 1998; 20: 564-575). This morphological characterization of autoschizic cell death confirms and extends the authors previous reports and demonstrates that this cell death is distinct from apoptosis.

Ascorbic Acid↗
PubMedDate not supplied

Troglitazone add-on therapy to a combination of sulfonylureas plus metformin achieved and sustained effective diabetes control.

OBJECTIVE: To elucidate the effect of triple combination oral agent therapy on type 2 diabetes. METHODS: We performed a prospective longitudinal study on 40 patients with type 2 diabetes who had failed to achieve a glycosylated hemoglobin (HbA1c) of < or = 8.0% despite optimal therapy with a combination of sulfonylureas plus metformin. Troglitazone was added and then titrated, with the intent to achieve at least a 1% reduction in HbA1c within 3 months. Responders were reassessed at 6 and 12 months. Nonresponders were reassessed at 6 months; in the absence of a significant HbA1c response, participation in the study was discontinued. RESULTS: Of the 40 study subjects, 25 were responders, 10 were nonresponders, and 5 were withdrawn from the study before completion of 3 months of therapy because of side effects. The 25 responders had a mean baseline HbA1c of 9.9%, which decreased significantly to 7.8% after 3 months of troglitazone therapy and to 7.4% at 6 months and at 12 months. In addition, the fasting blood glucose (FBG) in the responders decreased significantly from 168 mg/dL at baseline to 118 mg/dL at 6 months, which was sustained at 121 mg/dL at 12 months. In the responder group, a mean HbA1c < or = 8% was achieved in 68% at 6 months and sustained in 65% after 1 year. Furthermore, 40% of responders achieved a mean HbA1c < or = 7.0% at 6 months, and 39% sustained this degree of control at 12 months. The 10 nonresponders showed no significant change in HbA1c or FBG during the 6 months of troglitazone therapy. No difference existed in the mean baseline FBG, HbA1c, or C peptide level between the two groups. Responders, however, had a significantly lower mean body mass index (BMI) (31 kg/m2) than did nonresponders (37 kg/m2). Although responders were older than nonresponders (mean age, 65 years versus 55 years), no significant difference was noted in duration of diabetes (11.6 years versus 8.7 years). Multivariate analysis showed that male gender and BMI were the strongest predictors of a response to troglitazone add-on therapy to the prior combination of sulfonylureas plus metformin. CONCLUSION: This study showed that oral therapy with troglitazone added to sulfonylureas plus metformin achieved and sustained a significant improvement in control of diabetes in 71% of patients who had failed to achieve HbA1c < or = 8% with dual oral agent therapy. The positive response was evident within 3 months, reached maximum by 6 months, and was sustained to 12 months of therapy. Therefore, patients who fail to achieve HbA1c < or = 8% with sulfonylureas plus metformin should have at least 3 months of troglitazone add-on therapy before advancing to traditional insulin treatment.

Administration, Oral↗
PubMedDate not supplied

Seven rules of international distribution.

A multinational entering a new market in a developing country knows that on its own, it cannot master local business practices, meet regulatory requirements, hire and manage local personnel, and gain access to potential customers. So it partners with a local distributor. At first, sales take off, revenues grow, and the entry seems like a smart move. But when sales plateau, the corporation begins blaming the distributor for not investing sufficiently in business growth or expanding markets, and the distributor claims that it hasn't received enough support and that the corporation's expectations are too high. The key to solving such problems lies in recognizing that the phases are predictable and can be planned for. As a new business grows in an emerging market, its marketing strategy needs to evolve, and each sequential phase requires different skills, financial investments, and management resources. The author offers seven strategies to manage the multinational-distributor partnership. He discusses what to consider when choosing a distributor, how to structure the relationship between the two partners, what resources the multinational should commit, and what can be expected in return. He states that a successful distributor must risk investing in training, information services, and advertising and promotion in order to implement the company's marketing strategy and grow the business. Paying attention at the start of a partnership can result in a better working relationship between a multinational and a distributor, along with more consistent sales and growth for the corporation.

Contract Services↗
PubMedDate not supplied

Accuracy of intravenous infusion pumps in continuous renal replacement therapies.

Most extracorporeal continuous renal replacement therapies (CRRT) require inflow pumping of either dialysate, filtrate replacement solution, or both. Outflow of spent dialysate and ultrafiltrate can be accomplished by gravity drainage or pump. Intravenous infusion pumps have been commonly used for these purposes, although little is known about the accuracy of these pumps. To evaluate accuracy of two different types of intravenous infusion pumps used in CRRT, we studied flow rates at nine different pressure variations in three piston type and three linear peristaltic pumps. The results showed that error of either pump was not different for flow rates of 4 and 16 ml/min. Both types of pumps were affected by fluid circuit pressures, although pressure conditions under which error was low were different for each pump type. The linear peristaltic pumps were most accurate under conditions of low pump inlet pressure, whereas piston pumps were most accurate under conditions of low pump pressure gradient (outlet minus inlet) of 0 or -100 mmHg. The magnitude of error outside these conditions was substantial, reaching 12.5% for the linear peristaltic pump when inlet pressure was -100 mmHg and outlet pressure was 100 mmHg. Error may be minimized in the clinical setting by choosing the pump type best suited for the pressure conditions expected for the renal replacement modality in use.

Equipment Design↗
PubMedDate not supplied

[Persistent pulmonary hypertension of the newborn infant (PPHN)].

Persistent pulmonary hypertension of newborn (PPHN) is due to a defect in the adaptation of pulmonary resistance. The primary form occurs idiopathically, with meconium aspiration syndrome and with hypoplasia of the lung and is characterised by excessive muscular hyperplasia of pulmonary arteries. Secondary PPHN following hypoxia, septicaemia and shock is due to pulmonary vasoconstriction whereby thromboxane, leukotrienes and prostaglandins play a decisive role. Diseases of the pulmonary parenchyma and congenital cardiac malformations have to be excluded. The increased pulmonary resistance can be demonstrated by two-dimensional cardiography. The therapy consists of hyperventilation and tolazoline, which can be complicated by severe side-effects. High frequency oscillation and jet-ventilation are employed experimentally, Extracorporeal Membranoxygenation is a promising new method.

Echocardiography↗
PubMedDate not supplied

Trace analysis of chloramphenicol residues in eggs, milk, and meat: comparison of gas chromatography and radioimmunoassay.

A radioimmunological assay (RIA) to detect chloramphenicol (CAP) residues in eggs, milk, and meat is described. For tissues and other edible products of chloramphenicol-treated animals (chickens, cows, and pigs), the limit of detection is about 200 ng/kg. Residue levels above 1 microgram/kg can easily be quantitated. When highly specific antisera produced in sheep were used, cross-reactivity was insignificant except for metabolites deviating from the parent compound in the acyl side chain only. Thiamphenicol fails to bind to the antisera; hence, it does not interfere with the assay. In the procedure described, the role of cleanup is merely to remove lipids. Thus, skim milk can be analyzed following appropriate dilution without cleanup. The results obtained by RIA were confirmed by gas chromatography with electron capture detection. The new RIA allows rapid, sensitive, and specific screening of large numbers of samples.

Animals↗