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Biomedical subjects

N Levin

Publications and source records attributed to N Levin.

At least 19 recordsLinked to original sources
PubMed2003

Continuous flow peritoneal dialysis: a new double lumen catheter.

Continuous flow peritoneal dialysis (CFPD) is a therapy originally utilized in the sixties. It was then abandoned because of technical reasons, but, today, a new interest in this technique is emerging, because of new technical solutions and new hardware capabilities. CFPD is a peritoneal dialysis technique in which a certain amount of fluid is maintained in the peritoneal cavity, while a continuous inflow and outflow is provided via twin catheters or through a double lumen catheter. In this paper a new double lumen catheter is presented. The catheter is characterized by the presence of a diffuser in the inflow lumen, while a standard coiled shape characterizes the outflow lumen. The diffuser allows the use of high dialysate flows without peritoneal damage and with an excellent distribution of the fluid. The other feature of the catheter is the removable hub which allows for an easy subcutaneous tunneling of the catheter with a subsequent connection to the y segment. The special shape also guarantees a minimum recirculation during treatment. Data obtained in the first implanted catheter showed a progressive increase in small solute clearances in relation to an increase of the flow and the tidal volume in the peritoneal cavity. In particular, urea clearances up to 48 ml/min and creatinine clearances up to 39 ml/min were obtained. No major complications were observed after one year of use of the catheter.

Catheters, Indwelling↗
PubMed2001

Adsorption of cationized bovine serum albumin onto epithelial crypt fractions of the rat colon.

The purpose of the study was to characterize mucosal attachment of a cationized model protein, bovine serum albumin (BSA), onto the various fractions of colonic crypts epithelium in the rat. BSA was labeled with fluorescein isothiocyanate (FITC) and its surface net electric charge was modified from negative to positive. Attachment of the cationized protein (CF-BSA) onto rat colonic epithelium was performed by incubation of colonic everted sacs in medium containing cationized or non-cationized FITC-labeled BSA. Using a nonenzymatic isolation procedure, colonocytes were harvested from five horizontal fractions of the colonic crypts. BSA adhesion to the isolated colonocytes was quantified spectrofluorometrically. In addition, the effect of increasing concentrations of Mg(2+) on the adsorption of the cationized BSA onto the surface of colonic epithelium was evaluated by measuring its ability to displace the adhered BSA from its binding sites. BSA cationization facilitated protein adherence to the colon epithelium in a crypt depth-dependent manner. The largest extent of adherence was observed in the outer layer (first fraction) of the colon. Binding persisted to approximately half the depth of the crypts. The relation between CF-BSA concentration in the incubation medium and the amount of CF-BSA adsorbed onto the colonic epithelium was exponential in nature. The addition of electrolyte (Mg(2+)) caused a detachment of the CF-BSA. The adsorption process was characterized by Langmuir's adsorption isotherm. It is concluded that cationized BSA could be useful as a targetable drug platform in cases where the target site is the gastrointestinal epithelium.

Adsorption↗
PubMed2001

Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial.

Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

Aged↗
PubMed2001

Spinal cord involvement in uncomplicated herpes zoster.

We prospectively evaluated herpes zoster patients during the acute phase of the disease for central nervous system involvement. Of 24 patients with spinal zoster, 13 (54%) had spinal cord abnormality, which was asymptomatic in 12 of the 13. Age but not lack of acyclovir treatment was associated with such involvement. In all but 2, neurological involvement resolved within 6 months. Although the mechanism responsible for the neurological abnormalities is unknown, findings may support the hypothesis that zoster is associated with spread of viral infection into the spinal cord and therefore support the possibility that zoster is due to active viral replication in the ganglion.

Adult↗
PubMed2001

Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats.

In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg. kg(-1). day(-1) sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic beta-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.

3-O-Methylglucose↗
PubMed2001

A novel approach to the treatment of chronic fluid overload with a new plasma separation device.

Many patients with congestive heart failure suffer at some point in their therapy from severe fluid overload, and a significant proportion of patients become unresponsive to diuretic drug therapy. In this paper, we propose a new experimental approach to plasma purification and the treatment of severe fluid overload in acute care patients. Plasma can be extracted directly from the patient through an intracorporeal catheter temporarily placed within the inferior vena cava. Plasma separation is accomplished through a proprietary membrane placed on the tip of the catheter. A simple circuit performs plasma removal. The extracted plasma is then available for any type of treatment before being returned to the patient via a second lumen in the same catheter. Plasma flow rates between 3 and 8 ml/min have been achieved and animal tests led to the removal of more than 2,000 ml of plasma water in 24 h. The current varieties of blood purification or ultrafiltration techniques employ extracorporeal extraction of blood from the patient in order to perform treatment. Removal of the cellular component in the extracorporeal fluid circuit may reduce the current problems associated with extracorporeal circuits, such as cellular lysis and viscosity-related problems. Plasma treatment is already successfully performed in a variety of therapies, including renal replacement therapies and plasmapheresis. The therapy proposed here may extend the utility of plasma treatment to the acute cardiology patient. The system could become an important complementary therapy for patients with congestive heart failure for whom classic methods of treatment have failed or simply are not available.

Animals↗
PubMed2001

Machine washing or brushing of clothing and its influence on shooting distance estimation.

Experiments were conducted to assess the effect of machine washing or brushing of clothing items on Gunshot Residue (GSR) patterns (gunpowder residues, lead, and copper, deposits) around bullet entrance holes. Results show that those treatments decrease considerably the amount and density of GSR. However, for close shooting distances not all of the GSR deposits are removed. Remaining patterns may be visualized by specific color reactions and used for shooting distance estimation.

Journal Article↗
PubMed2000

Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different beta-adrenoceptor subtypes.

The three known subtypes of beta-adrenoreceptors (beta(1)-AR, beta(2)-AR, and beta(3)-AR) are differentially expressed in brown and white adipose tissue and mediate peripheral responses to central modulation of sympathetic outflow by leptin. To assess the relative roles of the beta-AR subtypes in mediating leptin's effects on adipocyte gene expression, mice with a targeted disruption of the beta(3)-adrenoreceptor gene (beta(3)-AR KO) were treated with vehicle or the beta(1)/beta(2)-AR selective antagonist, propranolol (20 microgram/g body weight/day) prior to intracerebroventricular (ICV) injections of leptin (0.1 microgram/g body weight/day). Leptin produced a 3-fold increase in UCP1 mRNA in brown adipose tissue of wild type (FVB/NJ) and beta(3)-AR KO mice. The response was unaltered by propranolol in wild type mice, but was completely blocked by this antagonist in beta(3)-AR KO mice. In contrast, ICV leptin had no effect on leptin mRNA in either epididymal or retroperitoneal white adipose tissue (WAT) from beta(3)-AR KOs. Moreover, propranolol did not block the ability of exogenous leptin to reduce leptin mRNA in either WAT depot site of wild type mice. These results demonstrate that the beta(3)-AR is required for leptin-mediated regulation of ob mRNA expression in WAT, but is interchangeable with the beta(1)/beta(2)-ARs in mediating leptin's effect on UCP1 mRNA expression in brown adipose tissue.

Adipose Tissue↗
PubMed2000

Sustained release of recombinant human insulin-like growth factor-I for treatment of diabetes.

Recombinant human insulin-like growth factor-I (rhIGF-I) was found to improve glycemic control and enhance insulin sensitivity in patients with a syndrome of severe insulin resistance. Therefore, the protein may be considered as an alternative therapy in the treatment of diabetes when the patients become insensitive to insulin treatment. Because the protein was administered twice per day in the clinical trials, a sustained release polylactic-co-glycolic acid (PLGA) formulation for rhIGF-I with low initial burst (<20%), maximum possible protein loading (15-20%) and a continuous release of 1-2 weeks may provide greater patient convenience and compliance. The protein was encapsulated in PLGA for sustained release using a spray freeze-drying technique. Formulation parameters such as protein loading, polymer end group, and the presence of zinc carbonate were studied for their effects on in vitro release of rhIGF-I from PLGA microspheres. As the protein loading was increased, the initial burst increased. Due to the hydrophilic properties of the polymers, rhIGF-I encapsulated in unblocked PLGA (free acid end groups) gave a lower initial burst and a more steady-state release profile than the blocked PLGA (hydrocarbon end groups) with the same protein loading and PLGA molecular weight. At 15% w/w protein loading, the addition of 6% w/w zinc carbonate as a protein release modifier to the unblocked PLGA (12 kDa) decreased the initial burst of rhIGF-I. Therefore, a formulation consisting of 15% rhIGF-I and 6% zinc carbonate in 12 kDa, unblocked 50:50 PLGA can provide the required release characteristics in vitro. Rat studies revealed that rhIGF-I in this formulation was released in vivo at a rate which was comparable to that observed in vitro. These studies demonstrate the potential for a sustained release, 14-day formulation for rhIGF-I.

Animals↗
PubMed2000

Quantitative expression analysis of genes regulated by both obesity and leptin reveals a regulatory loop between leptin and pituitary-derived ACTH.

Absence of the hormone leptin leads to dramatic increases in appetite, food intake, and adiposity. The primary site of action, at least with respect to appetite, is the hypothalamus. Leptin also has significant effects on the function(s) of peripheral organs involved in maintaining body composition. Some of these effects are mediated through direct interaction of leptin with its receptor on the target tissue, and some effects are indirectly mediated through secondary hormonal and neural pathways. Few of the genes that are responsible for regulating body composition and the peripheral effects of leptin are known. We have used a new gene profiling technology to characterize gene expression changes that occur in the pituitary, hypothalamus, fat, muscle, and liver in response to both obesity and treatment with exogenous leptin. These differences were then overlaid to allow the identification of genes that are regulated by obesity and at least partially normalized by leptin treatment. By using this process we have identified five genes (POMC, PC2, prolactin, HSGP25L2G, and one novel) that are both abnormally expressed in the pituitaries of obese mice and are sensitive to the effects of leptin. We also show that adrenocorticotropic hormone appears to be involved in a regulatory loop involving leptin.

Adipose Tissue↗
PubMed2000

Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing.

Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC(50) of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.

Adrenal Glands↗
PubMed2000

Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial.

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

Anemia, Iron-Deficiency↗
PubMed2000

Determining the time and day of photography.

Photographs taken by crime victims and perpetrators are at times important evidence. Their time of photography may also affect their value as such. Three methods of determining when a picture was taken by using the content of the picture are presented. The methods utilize solar direction-measured from shadows in the photograph, identifying flowering wild plants and correlating cloudiness with meteorological observations. Solar direction is the most accurate and involved method and therefore is the main part of this paper. A case using all three methods is described.

Crime↗
PubMed2000

Improved method for shooting distance estimation. Part 1. Bullet holes in clothing items

An improved method for firing distance estimation on clothing is described. The novel part of the method includes transfer of total nitrite (nitrite ions and smokeless powder residues) from the target to an adhesive lifter. After the transfer, lead and copper deposits around the bullet entrance hole are visualized by rhodizonate and rubeanic acid, respectively. The Modified Greiss Test is carried out after alkaline hydrolysis of the smokeless powder residues on the adhesive lifter.

Journal Article↗
PubMed2000

Improved method for shooting distance estimation. Part III. Bullet holes in cadavers.

An improved method to estimate firing distance on human body surfaces is described. The novel part of the method includes a chemical test in addition to the traditional visual and microscopic examinations of the gunshot wounds. This chemical test consists of a transfer of the gunpowder residues from the area of a gunshot wound to an adhesive lifter; the residues are then visualized as total nitrite after alkaline hydrolysis by the Modified Griess Test (MGT). When cadavers are in an advanced stage of decomposition or when gunshot wounds are in hairy areas, the information obtained by this chemical test can be crucial for shooting distance evaluation. In other cases it may improve the accuracy of the examination. In some cases, the results obtained by this test may assist in the discrimination between entrance and exit gunshot wounds.

Adhesives↗