Search PubMed⌕ Search

Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 37 records · Page 2Linked to original sources

Variations of dose and electrode spacing for rat breast cancer electrochemical treatment.

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P </= 0.001). Electrodes spacing was not an important factor within a given range. At 5, 10, and 15 mm spacing, the fraction showing the necrosis were 54.1, 60.4, and 59.2%, respectively (P = 0.552). The overlap rate of necroses was similar in the 5 and 10 mm groups (82.5 and 85%) and lower in the 15 mm group (65%). We conclude that the tumor responses to EChT, local control, survival rates, and necrosis percentages were significantly increased with increasing dose. The changes in electrode spacing (3, 5, and 10 mm) did not significantly affect the tumor responses to EChT within the same dose. For a diameter of 2.0-2.5 cm rat breast cancer, EChT should be applied with 5-10 mm spacing and a minimum dosage of 80 C.

Animals↗

[A structured pain interview for geriatric patients].

BACKGROUND: In old age, assessment of pain often is hampered by sensory and cognitive deficits that do not allow the patients to fill in standardized questionnaires without help from significant others. Therefore, as an alternative, we developed a structured pain interview, and examined its properties and acceptance in a sample of geriatric patients with pain. METHODS: The interview covers site of pain, intensity of pain, its duration and persistency, pain related disability and, finally, emotional and cognitive variables. In addition, the interviewer addresses significant others to get information about medication, previous treatment, and residence, and administers the Mini-Mental-State-Examination (MMSE). The analysis includes 128 patients of pain centers older than 74 years, of whom 80% are female. RESULTS: Forty percent of the subjects score below the critical MMSE value < or =23 indicative of cognitive impairment. These patients are responsible for 36 out of a total of 39 missing values. A significant increase of missing values is observed in patients with a MMSE score below 10. Cognitive impairment goes along with greater functional and social disability. On the other hand, cognitive impairment is unrelated to localization, intensity, and duration of pain. The memory item of the MMSE can be used as a screening tool for cognitive impairment. Patients, who are unable to recall any of the three objects, comprise 80% of the total of missing values and demonstrate a low MMSE score. CONCLUSION: As long as geriatric patients are able to communicate verbally, they are most likely to profit from the structured pain interview in spite of existing cognitive impairment. A MMSE score <10 indicates that the interpretation of the data obtained may be difficult, especially due to a high frequency of missing values.

Aged↗

[Primary pulmonary hypertension in human immunodeficiency virus infection. Study of 9 cases amd review of the literature].

PURPOSE: In medical literature, primary pulmonary hypertension occurs in 0.5% of human immunodeficiency virus (HIV)-infected patients, irrespective of the stage of the HIV disease, and is more frequent in drug users. Plexogenic arteriopathy is the most frequent histological lesion. METHODS: We retrospectively report on nine cases of primary pulmonary hypertension during HIV infection. RESULTS: The subjects were four women and five men, mean age 38 years old. Four of them had been sexually contaminated and five had contracted the disease through intravenous drug use. At the time primary pulmonary hypertension was diagnosed, mean CD4 cell count was 234 +/- 217/mm3 and the viral load was low or undetectable. Primary pulmonary hypertension has been diagnosed an average of 7 months after the first cardiovascular clinical signs had started. Despite anti-coagulant (7/9 cases), vasodilatator (4/9 cases) and/or diuretic (7/9 cases) therapy, the progression of the disease quickly turned out to be negative (seven deaths). CONCLUSION: Diagnosis of primary pulmonary hypertension should be considered when unexplained dyspnea occurs in an HIV-positive patient. At initial evaluation, alterations of hemodynamic parameters are usually less severe than during idiopathic primary pulmonary hypertension, but their progression is quicker and more severe, independent of the patient's immune status. Current data do not allow the determination of whether antiretroviral therapy is active in primary pulmonary hypertension evolution. Therapeutic evaluation with prostacyclin is currently being carried out. While the life expectancy of HIV-infected patients extends, primary pulmonary hypertension occurrence could increase and call for early diagnosis, thus allowing for specific care.

Adult↗

[Chronic cough in children: signs of serious disease and investigations].

Only in some particular cases chronic cough requires special investigations. Respiratory diseases linked to environment are frequent in children. Cough is the most common symptom in child asthma and usually occurs during sleep or exercise. Environmental tobacco smoke exposure may concern up to 30% of families. Questioning should systematically check for parental smoking in children with chronic cough since avoidance is the only effective treatment. The incidence of whooping cough appears to be increasing and the diagnosis may be difficult among already immunized children in whom symptoms are often nonspecific. Nowadays Bordetella pertussis can easily be detected on nasal smears (ELISA, PCR, cultures). Swallowing dysfunction may cause productive cough in toddlers, most often related to functional dyspraxia, yet possibly due to aerodigestive tract malformation. Unrecognized bronchial foreign body is a well-known pitfall particularly between 9 and 36 months of age. Bronchiectasis and cystic fibrosis are responsible for chronic productive cough in toddlers and older children. In teenagers, psychogenic coughing is difficult to manage and usually requires psycho- and speech therapy.

Asthma↗

The immunomodulator Linomide: role in treatment and prevention of autoimmune diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is considered to be an autoimmune disorder characterized by destruction of the pancreatic beta-cells by auto-reacting lymphocytes. An attractive therapeutic approach to this disease would be to abrogate the autoimmune process at an early stage, thus preserving a critical mass of pancreatic beta-cells necessary for maintenance of normal glucose tolerance. Linomide (quinoline-3-carboxamide, Roquinimex, LS 2616), is a novel, orally absorbed, immunomodulatory drug that has been shown to be effective in various models of autoimmunity without causing non-specific immunosuppression. In this review, we describe the efficacy of Linomide for ameliorating the autoimmune process and diabetes in the non-obese diabetic (NOD) model of IDDM when administered at early stages of the disease. We also show that advanced disease in the NOD mouse can be treated effectively by combining Linomide with therapeutic modalities designed to increase pancreatic beta-cell mass. Subsequent clinical studies have shown that Linomide preserves beta-cell function in individuals with new-onset IDDM. Based on these data, Linomide or derivatives thereof might be useful for treatment of human IDDM.

Adjuvants, Immunologic↗

Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE).

The aim of the present study was to investigate the prevalence of C4 and C2 deficiencies and to characterize genomic alterations in C4 genes in a large cohort of 125 unselected patients with SLE. We determined the protein concentration and functional activity of C2 and C4, as well as the C4 phenotype. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFLP) analysis and polymerase chain reaction using sequence-specific primers (SSP-PCR). Type I C2 deficiency was diagnosed by PCR. Overall, 79.2% of the patients exhibited abnormalities of the C4 genes including deletion, non-expression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52.8% prevalence), 41.0% of the patients exhibited a C4A deficiency and 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion. There was a strong association between C4A and C4B gene deletion and the presence of the DRB1*03 allele. Among the silent C4A genes, only two cases were related to a 2-bp insertion in exon 29 of the C4A gene. A gene conversion was demonstrated in eight patients (6.4%). One patient had a homozygous C4A deficiency. Three (2.4%) patients presented with a heterozygous type I C2 deficiency and none with homozygous deficiency. Our results argue against a specific role for C4A gene deficiency in determining disease susceptibility among patients with SLE that are C4-deficient.

Adolescent↗

Long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products.

BACKGROUND: Glucose degradation products (GDPs) are cytotoxic in vitro and potentially toxic in vivo during peritoneal dialysis (PD). We are presenting the results of a two-year randomized clinical trial of a new PD fluid, produced in a two-compartment bag and designed to minimize heat-induced glucose degradation while producing a near neutral pH. The effects of the new fluid over two years of treatment on membrane transport characteristics, ultrafiltration (UF) capacity, and effluent markers of peritoneal membrane integrity were investigated and compared with those obtained during treatment with a standard solution. DESIGN: A two-group parallel design with 80 continuous ambulatory peritoneal dialysis patients was used. The patients were randomly assigned to either the new fluid (N = 40) or to a conventional one (N = 40), and were stratified with respect to age, diabetes, and time on PD. Peritoneal transport characteristics were assessed by the Personal Dialysis Capacity (PDCtrade mark) test at 1, 6, 12, 18, and 24 months after inclusion and by weighing the overnight bag daily. Infusion pain and handling were evaluated using a questionnaire. Peritoneal mesothelial and interstitial integrity were evaluated by analyzing overnight effluent dialysate concentrations of CA 125, hyaluronan (HA), procollagen-1-C-terminal peptide (PICP), and procollagen-3-N-terminal peptide (PIIINP) at 1, 6, 12, 18, and 24 months. RESULTS: The handling of the new two-compartment bag was considered easy, and there were no indications of increased discomfort with the new system. Furthermore, no changes in peritoneal fluid or solute transport characteristics were observed during the study period for either fluid, and neither were there any differences with regard to peritonitis incidence. However, significantly higher dialysate CA 125 (73 +/- 41 vs. 25 +/- 18 U/mL), PICP (387 +/- 163 vs. 244 +/- 81 ng/mL), and PIIINP (50 +/- 24 vs. 29 +/- 13 ng/mL) and significantly lower concentrations of HA (395 +/- 185 vs. 530 +/- 298 ng/mL) were observed in the overnight effluent during treatment with the new fluid. CONCLUSIONS: We conclude that the new fluid with a higher pH and less GDPs is safe and easy to use and has no negative effects on either the frequency of peritonitis or peritoneal transport characteristics as compared with conventional ones. Our results indicate that the new solution causes less mesothelial and interstitial damage than conventional ones; that is, it may be considered more biocompatible than a number of conventional PD solutions currently in use.

Adult↗

Flexible dosing schemes for recombinant human erythropoietin--lessons from our daily practice.

The availability of recombinant human erythropoietin (rh-Epo) has revolutionized the treatment of renal anaemia. Subcutaneous (s.c.) administration of rh-Epo offers significant advantages over the intravenous (i.v.) route, and numerous studies have demonstrated its efficacy and tolerability when administered two or three times weekly. Most of these studies showed a significant reduction in rh-Epo dosage requirements with s.c. administration compared with the i.v. route, offering clear benefits in terms of reduced costs. In addition, s.c. administration is more convenient and flexible than i.v. administration, and is recommended by European and US guidelines. Dosing frequency of rh-Epo is also an important issue in clinical practice, particularly when customizing therapy to meet individual patient needs. A few small-scale studies have shown comparable efficacy and tolerability of different s.c. dosing frequencies. Recently, a comprehensive randomized controlled trial has shown that once weekly s.c. epoetin beta effectively manages anaemia in haemodialysis patients, even in patients requiring a high dose. Once weekly dosing of s.c. epoetin beta adds greater flexibility and an improved capacity to tailor dosing frequency to patient needs. This reduces clinic time for patients who do not self-administer and, together with improved convenience of new formulations and delivery systems, has the potential to improve compliance and encourages self-administration.

Dose-Response Relationship, Drug↗

West Nile fever in Israel 1999-2000: from geese to humans.

West Nile virus (WNV) caused disease outbreaks in Israel in the 1950s and the late 1970s. In 1998 an outbreak of WNV in goose farms and evidence of infection in dead migratory birds were reported. Consequently, human diagnostic services for WNV were resumed, including virus isolation, serology, and RT-PCR. Risk factors for infection were assessed by a serological survey in 1999, which revealed a seroprevalence of (a) 86% in people who had close contact with sick geese, (b) 28% in people in areas along bird migration routes, and (c) 27% in the general population. Following two fatal cases in Tel Aviv in September 1999 and one encephalitis case in the southern Eilot region, a regional serological survey was initiated there. The survey revealed two more WNV-associated acute encephalitis cases, an IgG seroprevalence of 51%, and an IgM seroprevalence of 22%. In the summer of 2000, acute cases of WN disease were identified in the central and northern parts of Israel, involving 439 people. The outbreak started in mid-August, peaked in September, and declined in October, with 29 fatal cases, primarily in the elderly. During the outbreak, diagnosis was based on IgM detection. Four virus isolates were subsequently obtained from preseroconverted frozen sera. Sequence and phylogenetic analysis of 1662 bases covering the PreM, M, and part of the E genes revealed two lineages. One lineage was closely related to a 1999 Israeli bird (gull) isolate and to a 1999 New York bird (flamingo) isolate, and the other lineage was closely related to a 1997 Romanian mosquito isolate and to a 1999 Russian human brain isolate.

Adult↗

Cryptogenetic multifocal ulcerous stenosing enteritis: an atypical type of vasculitis or a disease mimicking vasculitis.

BACKGROUND/AIMS: Cryptogenetic multifocal ulcerous stenosing enteritis (CMUSE) is a rare disease whose origin is unknown. The aim of this study was to describe the clinical spectrum of CMUSE, to determine the origin and pathophysiology of the disease, and to propose a treatment strategy. METHODS: A total of 220 French gastroenterology departments were contacted to review patients with unexplained small bowel strictures. Of 17 responses, 12 corresponded to a diagnosis of CMUSE. These patients were hospitalised between 1965 and 1993 and their medical records were reviewed. RESULTS: All patients (mean age 42.1 (4.4) years) had intestinal and five had extraintestinal symptoms (peripheral neuropathy, buccal aphthae, sicca syndrome, polyarthralgia, Raynaud's phenomenon, arterial hypertension). One patient had heterozygous type I C2 deficiency (28 base pair gene deletion). Two to 25 (mean 8.3 (1.9)) small intestine strictures were found. Stenoses of the large jejunoileal arteries were observed on two and aneurysms on three of five mesenteric angiograms. Despite surgery, symptoms recurred in seven of 10 patients and strictures in four. Steroid therapy was effective but caused dependence. One untreated patient died. Small bowel pathology showed superficial ulceration of the mucosae and submucosae, and an inflammatory infiltrate made of neutrophils and eosinophils. CONCLUSIONS: CMUSE is an independent entity characterised by steroid sensitive inflammation of the small bowel which often recurs after surgery. CMUSE may be related to a particular form of polyarteritis nodosa with mainly intestinal expression or with an as yet unclassified vasculitis.

Adolescent↗

Plasma levels of immunoinflammatory markers in De Novo coronary atherosclerosis and coronary restenosis postangioplasty.

OBJECTIVE: To compare circulating plasma levels of immunoinflammatory markers in patients with known de novo coronary artery disease and patients with postangioplasty restenosis. METHODS: Using enzymatic immunoabsorbent assay, we measured plasma levels of soluble interleukin-2 receptosr, tumor necrosis factor alpha, and soluble tumor necrosis alpha receptors I and II in 11 patients with restenosis postcoronary angioplasty (restenosis group), in 10 patients with primary atherosclerosis (de novo group) who were referred for coronary angiography because of stable or unstable angina, and in 9 healthy volunteers (control group). Levels of soluble interleukin-2 receptors were significantly higher in the de novo group compared with that in the restenosis and control groups. Levels were also higher in the restenosis group compared with that in the control group. Plasma levels of tumor necrosis alpha and receptor levels were significantly higher in the de novo group compared to with that in the restenosis and control groups, but levels in the restenosis group were not different from that in the controls. CONCLUSION: Coronary artery disease, either primary or secondary to restenosis, is associated with significant immunoinflammatory activity, which can be assessed by examining the extent of circulating plasma levels of inflammatory markers. Moreover, patients with de novo lesions appear to have increased inflammatory activity compared with patients with restenosis.

Analysis of Variance↗

Sulfated glycans induce rapid hematopoietic progenitor cell mobilization: evidence for selectin-dependent and independent mechanisms.

The adhesive mechanisms leading to the mobilization of hematopoietic progenitor cells (HPCs) from the bone marrow into the blood are poorly understood. We report on a role for selectins and fucoidan in progenitor mobilization. Baseline levels of circulating HPCs are increased in endothelial selectin-deficient (P/E-/-) mice. Similar levels are observed when E-selectin null (E-/-) mice are treated with anti-P-selectin antibody or with fucoidan (which inhibits P- and L-selectin function). In particular, administration of 2 doses of fucoidan (25 mg/kg) over 6 hours produces profound mobilization of progenitors in wild-type mice and the response is greatly enhanced in E-/- and P/E-/- mice. Competitive reconstitution experiments reveal that fucoidan also elicits long-term (more than 6 months) repopulating stem cells. Mobilization assays using chimeric mice harboring L-selectin-deficient progenitors and wild-type progenitors expressing the green fluorescence protein suggest that L-selectin expression is not required but confers an advantage for fucoidan-induced mobilization. Sulfation is critical as desulfated fucoidan is ineffective. In addition, sulphogalactosylceramide (sulfatide) but not heparin can induce HPC mobilization. Our results indicate that administration of sulfated glycans, especially with concurrent inhibition of E-selectin function, represents a powerful novel method for rapid mobilization of long-term-repopulating stem cells. These findings may help elucidate the mechanisms of HPC trafficking during development and adult life.

Animals↗

Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy.

BACKGROUND: The prognostic value of discordant immunologic (CD4 cell increase) and virologic (plasma HIV RNA level decrease) responses to antiretroviral treatment is not known. OBJECTIVE: To study the relation between clinical outcome of HIV-infected patients receiving highly active antiretroviral therapy (HAART) and early immunologic and virologic responses to such therapy. DESIGN: Prospective cohort study. SETTING: 68 hospitals in France. PATIENTS: 2236 protease inhibitor-naive patients. INTERVENTION: Initiation of HAART with one protease inhibitor and two nucleoside analogues between July 1996 and March 1997. MEASUREMENTS: Immunologic and virologic response at 6 months. Multivariate Cox models were used to assess the relation between these responses and progression to a new AIDS-defining event or death. RESULTS: On the basis of 6-month immunologic and virologic responses, patients were classified into four groups: complete response (47.5%), complete nonresponse (16.2%), immunologic response only (19.0%), and virologic response only (17.3%). After month 6 and within a median of 18 months, 69 patients died and 123 experienced a new AIDS-defining event. After adjustment, complete nonresponders and those with only a virologic response had significantly higher risks for clinical progression at 6 months (relative risk, 3.38 [95% CI, 2.28 to 5.02] and 1.98 [CI, 1.26 to 3.10], respectively) than complete responders. The difference between complete responders and those with only an immunologic response at 6 months was weaker and nonsignificant (relative risk, 1.55 [CI, 0.96 to 2.50]). CONCLUSIONS: Immunologic response after 6 months of HAART indicates a favorable clinical outcome in HIV-infected patients regardless of virologic response. This suggests that both immunologic and virologic markers should be used in clinical practice to evaluate treatment response.

Adult↗

High levels of drug-resistant human immunodeficiency virus variants in patients exhibiting increasing CD4+ T cell counts despite virologic failure of protease inhibitor-containing antiretroviral combination therapy.

The genotypic mutations associated with indinavir resistance were analyzed in 27 patients who exhibited sustained CD4+ T cell responses to highly active antiretroviral therapy (HAART), despite virologic failure of treatment. After 12 months of HAART, 1 or 2 primary resistance mutations had occurred in 18 (66%) of the patients, and secondary mutations had accumulated in 22 (88%) of the patients. The number and patterns of mutations in the patients who exhibited discrepant responses to HAART did not differ from those observed in patients who exhibited immunologic and virologic failure to therapy. Results indicate that many patients have prolonged immunologic benefits, despite the development of virologic failure and protease inhibitor mutations. The clinical course of this group of patients calls into question the relevance of genotypic resistance and plasma human immunodeficiency virus RNA level as surrogate markers in patients receiving HAART.

Amino Acid Sequence↗

Efficacy and safety of combination therapy with interferon-alpha2b and ribavirin for chronic hepatitis C in HIV-infected patients.

OBJECTIVES: To evaluate the efficacy and safety of a combination therapy of interferon-alpha2b (IFN) and ribavirin for the treatment of chronic hepatitis C in HIV-seropositive patients. DESIGN: Open prospective trial. METHODS: Twenty patients co-infected with hepatitis C virus (HCV) and HIV, with a mean CD4 cell count of 350 +/- 153 x 10(6)/l were treated with IFN (3 MU three times per week) in combination with ribavirin (500 mg or 600 mg twice a day) for 6 months. Tolerance and efficacy were monitored at weeks 12 (month 3) and 24 (month 6). The primary endpoint was a complete virological response, as defined by the lack of detectable HCV RNA in serum. RESULTS: Baseline values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 121 +/- 72 IU/l and 75 +/- 67 IU/l, respectively. The total Knodell score was 10.4 +/- 2.4, with nine patients showing histological evidence of active cirrhosis (45%). All patients exhibited circulating HCV RNA. The treatment was well tolerated, with no impact on the course of HIV infection. After 6 months of combination therapy with IFN and ribavirin, 10 patients (50%) exhibited no further detectable HCV RNA viraemia, seven of whom achieved undetectable viraemia at month 3. Levels of ALT and AST decreased after 6 months of treatment from a mean of 121 +/- 72 to 51 +/- 40 IU/l and from a mean of 129 +/- 58 IU/l to 68 +/- 61 IU/l, respectively (P < 0.0002 and P < 0.0001). CONCLUSION: Our results indicate that combination therapy with IFN and ribavirin is effective in 50% of cases in clearing serum HCV RNA and may thus provide effective means of therapy in HIV-HCV-coinfected patients as initial treatment or in patients who have previously failed IFN monotherapy.

Adult↗

P-Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo.

The platelet plays a pivotal role in maintaining vascular integrity. In a manner similar to leukocytes, platelets interact with selectins expressed on activated endothelium. P-selectin glycoprotein ligand 1 (PSGL-1) is the main P-selectin ligand expressed on leukocytes. Searching for platelet ligand(s), we used a P-selectin-immunoglobulin G (IgG) chimera to affinity purify surface-biotinylated proteins from platelet lysates. P-selectin-bound ligands were eluted with ethylenediaminetetraacetic acid. An approximately 210-kD biotinylated protein was isolated from both human neutrophil and platelet preparations. A band of the same size was also immunopurified from human platelets using a monoclonal anti-human PSGL-1 antibody and could be blotted with P-selectin-IgG. Under reducing conditions, both the predicted PSGL-1 approximately 210-kD dimer and the approximately 120-kD monomer were isolated from platelets. Comparative immunoelectron microscopy and Western blotting experiments suggested that platelet PSGL-1 expression is 25-100-fold lower than that of leukocytes. However, patients with chronic idiopathic thrombocytopenic purpura who harbor predominantly young platelets displayed greater expression, indicating that PSGL-1 expression may be decreased during platelet aging. By flow cytometry, thrombin-activated platelets from normal individuals exhibited greater expression than those unstimulated. An inhibitory anti-PSGL-1 antibody significantly reduced platelet rolling in mesenteric venules, as observed by intravital microscopy. Our results indicate that functional PSGL-1 is expressed on platelets, and suggest an additional mechanism by which selectins and their ligands participate in inflammatory and/or hemostatic responses.

Animals↗