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Biomedical subjects

D Hollander

Publications and source records attributed to D Hollander.

At least 19 recordsLinked to original sources
PubMed2005

Comparison of prostaglandin and cimetidine in protection of isolated gastric glands against indomethacin injury.

Prostaglandins can protect the in vivo gastric mucosa against necrosis produced by a variety noxious agents. Cimetidine has also been shown to have protective properties in humans and in some models of experimental injury. Whether prostaglandins or cimetidine may protect gastric mucosal cells directly in the absence of systemic factors remains controversial. In the present study, the potential protective actions of prostaglandin and cimetidine against indomethacin injury were assessed in isolated rat gastric glands. Gastric glands were pre-incubated in oxygenated medium with either placebo, 16,16 dimethyl prostaglandin E(2) (dm PGE(2)) or cimetidine and incubated at 37 degrees C in medium containing 0.5 mg/ml of indomethacin for 2, 4 and 6 hrs. Cell injury and protection was assessed by the Fast Green exclusion test (viability test), leakage of lactate dehydrogenase (LDH) into the medium, and by scanning and transmission electron microscopy. In addition, the generation of PGE(2) by the gland cells was determined using RIA assay. Indomethacin by itself significantly reduced the viability of gastric glands, increased LDH release into the medium and produced prominent ultrastructural damage. In contrast to cimetidine, co-incubation of gastric glands with dm PGE(2) added to indomethacin, significantly reduced indomethacin-induced injury, increased the number of viable cells, reduced LDH leakage and diminished the extent of ultrastructural damage. The dose of indomethacin (5 microg/ml) which significantly inhibited the generation of PGE(2) (up to 90% inhibition) had no effect on cell viability nor LDH release. We conclude that 1) exogenous PGE2 exerts a potent protective activity in vitro which is independent on neural, vascular and hormonal factors; 2) inhibition of endogenous PGs may not the primary mechanism in the deleterious action of indomethacin against damage to gastric glandular cells and 3) indomethacin can exert a direct cytotoxic effect on the mucosal cells in gastric glands.

16,16-Dimethylprostaglandin E2↗
PubMed2004

Restrictive use of immunosuppressive treatment in patients with idiopathic membranous nephropathy: high renal survival in a large patient cohort.

BACKGROUND: Immunosuppressive treatment initiated at an early stage in patients with idiopathic membranous nephropathy (iMN) improves renal survival. Treatment should ideally be restricted to high-risk patients. AIM: To evaluate the efficacy of a restrictive immunosuppressive treatment strategy for patients with iMN. DESIGN: Prospective cohort study evaluating a predefined treatment protocol. METHODS: From 1988, we adopted a restrictive treatment strategy: immunosuppressive treatment, mainly consisting of cyclophosphamide and steroids, was advised only in patients with renal insufficiency or severe intolerable nephrotic syndrome. We evaluated this strategy in a large patient cohort. To exclude any bias, we included all adult patients with iMN biopsied in the study period with a serum creatinine (Scr) < 135 micromol/l, a proteinuria > or = 3.0 g/day and/or a serum albumin (Salb) < or = 30 g/l at the time of biopsy. Analysis was according to the intention-to-treat principle. RESULTS: We studied 69 patients. At the time of biopsy, mean age was 51 years, Scr 90 micromol/l, Salb 23 g/l and proteinuria 6.7 g/day. Average follow-up was 5.5 years. Thus far 33 (48%) patients have received immunosuppressive therapy, mainly because of renal insufficiency (n = 24). Status at the end of follow-up was: complete remission n = 22 (32%), partial remission n = 24 (35%), nephrotic syndrome n = 15 (22%), persistent proteinuria n = 1 (1.4%), ESRD n = 6 (8.7%), death n = 1 (1.4%; due to bladder carcinoma after cyclophosphamide therapy). Patient survival was 100% at 5 and 7 years. Renal survival was 94% at 5 years and 88% at 7 years. DISCUSSION: In patients with iMN, a restrictive treatment policy assures a favourable prognosis, while preventing exposure to immunosuppressive therapy in >50% of the patients.

Adult↗
PubMed2003

Inflammatory bowel diseases and brain-gut axis.

The influence of stress on inflammation in inflammatory bowel disease (IBD) is reviewed. In experimental forms of colitis in rats, stress reactivated the disease. A study of stable IBD patients who were followed for over five years explored the influence of stress on exacerbating the disease. Those patients with high prolonged stressful life events were found to have a 90% recurrence rate of their colitis as compared to only 40% recurrence in low stress patients. Some of the mediators of stress include VIP, TNFalpha, heat shock proteins, glucocorticoid and catecholamines. Stress was shown to increase intestinal permeability to markers such as Cr-EDTA, HRP and dextran 10,000 in rats. In addition, stress increases the permeability of intestinal M-cells. Finally, stress increased the permeability of Paneth cells to HRP. Since Paneth cells synthesize NOD2 mRNA and protein, stress may play a role in the genesis or reactivation of Crohn's disease involving the terminal ileum. Brain-gut interactions via neural, hormonal and cytokine signals can diminish the mucosal protective factors and increase the permeability of luminal antigens into the intestinal epithelial and immune cells. Stress appears to play a key role in exacerbating and accentuating the intestinal inflammation in IBD through brain-gut interactions.

Animals↗
PubMed2002

[Management of soft tissue injury in III B open tibial fractures: are local muscle flaps still up-to-date?].

Local muscle flaps for covering pretibial defects have been widely replaced due to the establishment of microsurgical procedures. The intention of the following study is to examine the results of soft tissue covering using local muscle flaps and to find out if its application is still indicated. At our level 1 trauma center 21 patients with III B open tibial fractures were treated with a local muscle flap to repair the soft tissue injury in the proximal and medial part of the lower leg. At the late follow-up after the average of 29 months all soft tissue defects and fractures were healed. Except of slight swelling under full weight stress no obstruction of blood circulation could be verified. 14 patients rated their functional outcome as good to excellent. In view of our results we consider local muscle flaps a suitable alternative to the free myoplasty for situations in which a more elaborate surgery is not feasible in due time, e. g. patients with acute brain edema, organ failure or lack of compliance.

Adolescent↗
PubMed2001

Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys.

BACKGROUND: Several studies have demonstrated that intrathymic injection of donor cells into adult rodents can result in long-term allograft survival. The rationale for using the intrathymic route of donor cell administration is that in the thymic environment immature T cells are educated to discriminate between self and non-self antigens. The validity of this approach was tested in non-human primates. METHODS: The effect of the intrathymic injection of allogeneic donor cells was investigated in rhesus monkeys and compared with IV and intracutaneous administration of donor cells. Intrathymic injections were carried out without and with antithymocyte globulin. All animals received subsequently an allogeneic skin graft of the same donor and no immunosuppression post transplantation. RESULTS: Skin graft survival was slightly shorter in animals treated with IC donor cell injections (mean survival time [MST]=8.9+/-0.52) than untreated control animals (MST=10.0+/-0.44), indicating that this route caused sensitisation. Intravenous donor cell injection showed prolongation of graft survival times (MST=11.6+/-1.69). Intrathymic donor cell injection resulted in a graft survival of 9.2+/-1.44 days although addition of antithymocyte globulin slightly prolonged graft survival to 10.3+/-2.84 (not significant). Whereas the cellular responses after intrathymic and intravenous donor cell injections increased, antithymocyte globulin treated animals did not show an increased cellular response. Recipients of intrathymic donor cells showed a significantly decreased humoral anti-donor response as compared to other groups. CONCLUSIONS: Donor cell pretreatment alters the subsequent response to an allogeneic skin graft in monkeys and is dependent on the route of donor cell administration. This is also reflected in the alloantibody response and the in vitro cellular reactivity. Intrathymic administration of donor cells does not lead to prolonged skin graft acceptance.

Animals↗
PubMed2001

Serum insulin-like growth factor-I (IGF-I) does not correlate positively with isometric strength, fatigue, and quality of life in post-polio syndrome.

OBJECTIVES AND BACKGROUND: To determine if serum insulin-like growth factor-I (IGF-I) levels are associated with strength, body mass index (BMI), fatigue, or quality of life in post-poliomyelitis syndrome (PPS). PPS is likely due to a distal disintegration of enlarged post-polio motor units as a result of terminal axonal sprouting. Age-related decline in growth hormone and IGF-I (which support terminal axonal sprouts) is proposed as a contributing factor. METHODS: As part of the North American Post-Poliomyelitis Pyridostigmine Study (NAPPS), baseline data on maximum voluntary isometric contraction (MVIC), BMI, subjective fatigue (fatigue severity scale, Hare fatigue symptom scale), health-related quality of life (short form health survey-36; SF-36), and serum IGF-I levels were gathered on 112 PPS patients. Pearson correlation coefficients were calculated to evaluate the association between serum IGF-I and MVIC in 12 muscles, BMI, two fatigue scales, and SF-36 scale scores. RESULTS: There is a significant inverse correlation of IGF-I levels with MVIC in left ankle dorsiflexors (r=-0.30, P<0.01), and left and right knee extensors (r=-0.22, -0.25, P=<0.01, 0.01), but no significant correlations in other muscles. When men and women were evaluated separately, inverse correlations of IGF-I levels with MVIC were found only in men. IGF-I correlated inversely with BMI (r=-0.32, P=0006) and age (r=-0.32, P=0.0005). IGF-I did not correlate with the fatigue or SF-36 scales. CONCLUSIONS: In this exploratory study, we found that contrary to our expectations, IGF-I did not correlate positively with strength. IGF-I correlated negatively with strength in several lower extremity muscles, BMI, and age. IGF-I is likely not an important factor in the pathogenesis of fatigue and in determining quality of life in PPS, but its role on strength should be studied further.

Adult↗
PubMed2001

Influence of laparoscopy and laparotomy on systemic and peritoneal T lymphocytes in a rat model.

Little is known about the local influence of pneumoperitoneum on components of the peritoneal immune defense mechanisms. We investigated CD25, CD4, CD8 expression and CD4/CD8 ratio of systemic and peritoneal T lymphocytes in a rat model. Fifty male Sprague Dawley rats underwent laparotomy, CO2 pneumoperitoneum, helium pneumoperitoneum, gasless laparoscopy, or anesthesia only. After 24 h venous blood was drawn, and peritoneal lavage was performed to harvest CD25+, CD4+, and CD8+ cells. CD4+, CD8+, and CD25+ T lymphocytes were determined. A significantly lower peritoneal CD4/CD8 ratio was found after CO2 and helium laparoscopy than in controls (P<0.05). However, no significant differences in systemic CD4/CD8 ratio or peritoneal or systemic CD25 expression were found between the different operative groups. Pneumoperitomeum independently of the insufflation gas (CO2 or helium) leads to comparable postoperative immunmodulations of peritoneal CD4+ and CD8+ T-lymphocytes. The mechanical pressure of the pneumoperitoneum seems to aggravate peritoneal T lymphocytes.

Animals↗
PubMed2001

Microbiological, molecular biological and stable isotopic evidence for nitrogen fixation in the open waters of Lake Michigan.

We have used a combination of microbiological, molecular biological and stable isotope methods to relate specific microbial populations to elemental cycling at an offshore site in Lake Michigan. Several lines of evidence suggest that atmospheric N2 may be a significant source of nitrogen to the lake. Particulate organic nitrogen (PON) at approximately equals 10-15m depth in July and October had a delta15N of 0.5-1.5%o. These values closely reflect the 15N composition of atmospheric N2, suggesting biological nitrogen fixation. Historical data show a developing late-summer N:P minimum at approximately equals 15 m; low abundance of inorganic nitrogen relative to phosphorus favours species able to acquire atmospheric nitrogen. Microscopic examination of October water samples revealed abundant heterocystous cyanobacteria, including Nodularia sp. Potentially nitrogen-fixing Anabaena spp. have been found in Lake Michigan before but, to our knowledge, this is the first report of Nodularia. Finally, we have amplified both cyanobacterial and non-cyanobacterial nifH sequences (encoding the nitrogenase iron protein) from lakewater samples, evidence for the presence of bacteria capable of nitrogen fixation. The surface waters of Lake Michigan are considered to be phosphate limited in the stratified season and, under these conditions, energetically expensive nitrogen fixation is expected to be uncompetitive with assimilation of combined nitrogen. Our results suggest that, from both microbiological and biogeochemical perspectives, this may be an oversimplification.

Animals↗
PubMed2000

CO2 environment influences the growth of cultured human cancer cells dependent on insufflation pressure.

BACKGROUND: Experimental and clinical studies, have suggested that the CO2 pneumoperitoneum influences the development of intraabdominal tumor dissemination and port site metastases. Previous experiments performed both in vitro and in vivo have proved that CO2 insufflation stimulates malignant cell growth. Therefore, we designed a study to investigate the influence of CO2 insufflation administered at different pressures on the growth of cultured human tumor cells. METHODS: Two human tumor cell lines (CX-2 colon adenocarcinoma, DAN-G pancreas adenocarcinoma) were exposed to a CO2 environment maintained at different pressures (0 mmHg, 6 mmHg, 12 mmHg). Tumor growth was determined at different times after exposure to CO2 using fluorescence photometry. Cytotoxity of the CO2 environment different pressures was investigated using flow cytometry. RESULTS: At 1-4 days after exposure to CO2 insufflation, CX-2 and DAN-G tumor cell growth was decreased significantly (p < 0.01). Proliferation of pancreatic adenocarcinoma DAN-G increased significantly from day 5 to day 15 independent of the insufflation pressure (p < 0.01). Proliferation of colon adenocarcinoma CX-2 increased significantly from day 5 to day 15 but was found to be dependent on the insufflation pressure. CX-2 growth increased significantly with higher pressures (p < 0.05). CONCLUSION: CO2 insufflation influences the growth of cultured human tumor cells. After a short period of suppression, the CO2 environment stimulates malignant cell growth. The insufflation pressure may also have additional effects in promoting tumor growth.

Adenocarcinoma↗
PubMed1999

A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome.

BACKGROUND: Postpoliomyelitis syndrome (PPS) is likely due to degeneration and dysfunction of terminal axons of enlarged postpolio motor units. Age-related decline in growth hormone and insulin-like growth factor (IGF-I) may be a contributing factor. Neuromuscular junction abnormalities and decreased IGF-I levels may respond to the anticholinesterase pyridostigmine, with consequent improvement in strength, fatigue, and quality of life. OBJECTIVES: To determine the effect of pyridostigmine in PPS on health-related quality of life, isometric muscle strength, fatigue, and serum IGF-I levels; and to assess the safety of pyridostigmine in PPS. METHODS: The study was a multicenter, randomized, double-blinded, placebo-controlled trial of a 6-month course of pyridostigmine 60 mg three times per day in 126 PPS patients. The primary data analysis compared mean changes of outcomes between treatment and control groups at 6 months using an intention to treat approach. Secondary analyses included a comparison of outcomes at 6 and 10 weeks, and in compliant patients. RESULTS: The study showed no significant differences in pyridostigmine and placebo-treated patients with regard to changes in quality of life, isometric strength, fatigue, and IGF-I serum levels at 6 months in the primary analysis and in compliant patients. There were no differences in outcomes at 6 and 10 weeks between groups. However, very weak muscles (1 to 25% predicted normal at baseline) were somewhat stronger (p = 0.10, 95% CI of difference -9.5 to 73.3%), and in compliant patients IGF-I was somewhat increased (p = 0.15, 95% CI of difference -6.4 to 44.8 ng/mL) at 6 months with the medication. Pyridostigmine was generally well tolerated. CONCLUSIONS: This study showed no significant differences between pyridostigmine and placebo-treated PPS patients on measures of quality of life, isometric strength, fatigue, and serum IGF-I.

Aged↗