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D Hollander

Publications and source records attributed to D Hollander.

At least 55 records · Page 3Linked to original sources
PubMed1995

Adhesion molecule expression and adhesion properties of murine intestinal intraepithelial lymphocyte hybridomas.

We used mouse intraepithelial lymphocyte hybridomas (IELH) to study the role of adhesion molecules, especially beta 7 integrins, in the adherence of IELH to intestinal epithelial cells. Unstimulated 9.1 gamma delta IELH cells expressed high levels of CD11a, CD11a/CD18, CD44, and CD45; medium levels of CD45RB and integrin alpha 4; low levels of alpha M290, beta 7, and 33D1; and very low levels of ICAM-1 and VCAM-1. PHA and TGF-beta stimulated IELH cells--but not control BW5147 cells (alpha 4/beta 7 integrin negative fusion partner)--to bind to IEC-18 and CMT-93 intestinal epithelial cells, but not to renal mesangial cells. The binding was partially blocked by mAbs to integrin alpha 4 and/or alpha M290. The two mAbs in combination did not completely block the binding, suggesting that epitopes not recognized by these two mAbs are also involved in binding. The adhesion of 9.1 gamma delta cells to IEC-18 cells was also partially inhibited by mAbs to VCAM-1, LFA-1, and CD44, but not by mAbs CD45 and a control rat IgG. Thus, IELH may be a useful model system with which to study the role of adhesion molecules in the interaction between IEL and intestinal epithelial cells.

Animals↗
PubMed1995

Mechanism of colonic permeation of inulin: is rat colon more permeable than small intestine?

BACKGROUND/AIMS: Colonic epithelium is considered to be relatively tight. The colonic "pore" diameter is 6 A; therefore, colonic epithelium has generally been considered to be impermeable to hydrophilic probes with a cross-sectional diameter of > 6 A. This study examined whether rat colon is permeable to inulin, a large hydrophilic macromolecule having a molecular weight of 5000 g/mol and a cross-sectional diameter of 15 A (hydration diameter, 20 A). METHODS: The colonic permeation of inulin (10 mumol/L) in vivo was investigated by perfusion of rat colonic segments. RESULTS: There was significant colonic permeation of inulin, but tissue retention of inulin was low. The net colonic flux of inulin was strongly dependent on net water flux, showing a strong solvent drag effect. Addition of 16,16-dimethyl prostaglandin E2 decreased water flux with a corresponding decrease in inulin flux; this process seemed to be mediated by 5'-cyclic adenosine monophosphate because both the phosphodiesterase inhibitor aminophylline and dibutyryl adenosine 5'-cyclic adenosine monophosphate decreased water and inulin flux in a parallel manner. Chenodeoxycholic and taurocholic acids decreased net mucosal-to-serosal water flux but increased inulin flux. The net colonic permeation rate of inulin was higher than the small intestinal permeation rate. CONCLUSIONS: Rat colon is permeable to inulin. The higher net colonic permeability may be caused by differences in mucosal surface, permselectivity, solvent drag effect, and differences in net water fluxes of the colon and small intestine.

16,16-Dimethylprostaglandin E2↗
PubMed1995

Intestinal permeability: an overview.

The noninvasive assessment of intestinal permeability in humans has a 20-year history. Because the tests are increasingly used in clinical practice and research and because there is much controversy, we reviewed the literature and outlined the potential and possible shortcomings of these procedures. Data was obtained from personal files and from a systemic search through MEDLINE and EMBASE. The principle of the differential urinary excretion of orally administered test markers is explained with reference to the desired physicochemical properties of the markers and how the principle can be exploited to allow assessment of various other gastrointestinal functions. The use of intestinal permeability tests for diagnostic screen for small bowel disease and assessment of responses to treatment, the pathogenesis of disease, normal intestinal physiology, and the effect of drugs and toxins on the intestine is described and reviewed. The controversy surrounding the anatomic location of the permeation pathways that the markers use is highlighted. Noninvasive tests of intestinal permeability have fulfilled early promises of usefulness in clinical practice and research. There is now a need for integrated research into the basic mechanisms of regulatory control of the intestinal barrier function.

Animals↗
PubMed1995

Crisis in admission beds. A four-year survey of the bed state of Greater London's acute psychiatric units.

BACKGROUND: This study was carried out to measure bed occupancy in Greater London's psychiatric units, in response to the apparent shortage of admission beds. METHOD: The bed occupancy of London's 54 National Health Service (NHS) acute psychiatric units within 29 districts was ascertained by telephone on 16 bank holidays covering the period 1990-93. RESULTS: The mean occupancy level for all London over the 4 years was 97.54% (95% CI- +/- 0.94%). The number of beds occupied in inner London was significantly greater (99.79 +/- 1.11%) than in outer London (95.1 +/- 1.49%) (t = 3.85, d.f. = 462, P < 0.001). Bed occupancy for inner London units was > or = 100% on over 49% of occasions. There has been a steady decline in the number of beds over the four-year period. There was a clear correlation between occupancy levels and the Jarman UPA8 Underprivilege Score (r = 0.504) and between bed provision and the UPA8 (r = 0.67). CONCLUSION. Occupancy rates have become unacceptably high and require careful monitoring. Corrective action may be required in order to prevent a breakdown in services.

Bed Occupancy↗
PubMed1994

High-dose dextromethorphan in amyotrophic lateral sclerosis: phase I safety and pharmacokinetic studies.

Much interest has focused on the role of glutamate-mediated excitotoxicity in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). We therefore conducted a phase I study of high-dose dextromethorphan (DM) in ALS. DM is a selective, noncompetitive antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor. Thirteen patients were given DM in an escalating dose fashion, to a target of 10 mg/kg/day or the maximum tolerable dose, and then maintained on this dose for up to 6 months. Total daily doses ranged from 4.8 to 10 mg/kg (median, 7 mg/kg). Side effects were dose limiting in most patients. The most common side effects were light-headedness, slurred speech, and fatigue. Detailed pharmacokinetic and neuropsychology studies were performed. This study demonstrates the feasibility of long-term administration of high-dose DM in ALS, as well as in other conditions associated with glutamate excitotoxicity.

Adult↗
PubMed1994

Mechanisms and sites of mannitol permeability of small and large intestine in the rat.

Mannitol is commonly used as an intestinal permeability probe, yet the mechanisms of its penetration of the intestinal barrier are not entirely clear. Therefore, we studied mannitol's permeability of different segments of the intestine and studied the kinetics and influence of intraluminal factors on mannitol permeability in vivo in perfused intestinal segments of rats. There was linear relationship between permeability rate of mannitol and its luminal concentration (y = 7.2x + 1.7; r = 0.98), indicating that passive diffusion is involved in mannitol's permeability. Increased luminal fluid osmolarity from 0.3 to 0.6 osmol/liter resulted in decreased net water flux with a corresponding decrease in mannitol permeability in both jejunum and colon (P < 0.01), indicating the prominent influence of solvent drag on net mannitol permeability. The relationship between mannitol permeability and water absorption at different osmolarities was linear in the jejunum and colon. At luminal osmolarity of 0.3 osmol/liter, 34.6% of mannitol permeability was mediated by passive diffusion and 65.4% was mediated by solvent drag in the jejunum. Mannitol permeability was much more dependent on solvent drag in the colon (88.9%) than in the small intestine (65.4%). The net permeability rate of mannitol was similar in the jejunum and ileum but was much higher in the colon (P < 0.01). Addition of chenodeoxycholate (5 mM) to the perfusate resulted in a significant decrease in absorption of water (P < 0.01) with a corresponding decrease in mannitol permeability (P < 0.01). These studies indicate that mannitol permeability of the intestinal barrier is mediated by passive diffusion and solvent drag, with the latter accounting for a greater fraction of the total permeability.

Animals↗
PubMed1994

Gastrointestinal complications of nonsteroidal anti-inflammatory drugs: prophylactic and therapeutic strategies.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used drugs in the Western world. Patients undergoing NSAID therapy often experience abdominal discomfort, and some of them develop serious complications, such as ulceration, perforation, or bleeding. Since serious complications of NSAID therapy can occur in relatively asymptomatic patients and abdominal symptoms do not serve as a signal of impending difficulties, there is a need for methods to identify those patients who may benefit from prophylactic therapy to prevent NSAID-induced injury. Therapy to prevent NSAID-associated gastrointestinal ulcerations is most effective when prostaglandins are used. H2-receptor antagonists prevent duodenal ulcerations but not gastric ulcerations. The role of omeprazole (hydrogen-potassium pump inhibitor) and sucralfate in the prevention of gastroduodenal ulcerations has not been firmly established. Healing of existing ulcerations in the face of continuing therapy with NSAIDs is marginally accelerated by H2-receptor antagonists, but the rate of healing in the presence of continued NSAID therapy is much slower than when NSAIDs are discontinued. Omeprazole may prove to accelerate the healing of NSAID-associated ulcerations even when NSAID therapy is continued, but more information is needed to substantiate this possibility. New methods are needed for early noninvasive detection of mucosal damage by NSAIDs and for the identification of individuals who should receive prophylactic therapy. New agents are also needed to provide cost-effective prophylaxis against the development of ulcerations and serious complications from NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives.

Increased intestinal permeability in patients with Crohn's disease and their first degree relatives has been proposed as an aetiological factor. The nine hour overnight urinary excretion of polyethyleneglycol-400 (PEG-400) and three inert sugars (lactulose, l-rhamnose, and mannitol) was used to test the permeation in 47 patients with Crohn's disease of whom 18 had at least one first degree relative with inflammatory bowel disease (2BD) and 52 patients with ulcerative colitis of whom 16 had at least one first degree relative with IBD. A total of 17 first degree relatives with IBD and 56 healthy first degree relatives were included. Thirty one healthy subjects not related to patients with IBD served as controls. No significant differences in PEG-400 permeation were found between the groups of patients, relatives, and controls, or between diseased and healthy relatives. The permeability to lactulose, rhamnose, and mannitol similarly did not differ between the three groups. This study challenges the previously reported findings of increased PEG-400 permeation in patients with Crohn's disease and in their healthy and diseased first degree relatives. There was no increase in permeability in a similar group of ulcerative colitis patients and their families.

Adolescent↗
PubMed1994

Respiratory dysfunction in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the voluntary motor system. Involvement of the respiratory system is inevitable and leads to the development of respiratory failure, the usual cause of death in this disorder. ALS at present is incurable, and only symptomatic treatment is available. This article presents guidelines for the recognition and management of respiratory failure.

Amyotrophic Lateral Sclerosis↗
PubMed1993

Uptake of riboflavin by intestinal basolateral membrane vesicles: a specialized carrier-mediated process.

The mechanism of riboflavin (RF) uptake by intestinal basolateral membrane vesicles (BLMV) was examined in this study. BLMV were isolated by an established Percoll-gradient methodology from rabbit small intestine. Uptake of riboflavin was mainly the result of transport of the substrate into an osmotically active intravesicular space with less binding to membrane surfaces. Uptake of RF with time was similar in the presence of a Na+ and a K+ gradient (out > in) and was not significantly influenced by changes in incubation buffer pH. The initial rate of uptake of riboflavin as a function of concentration was saturable in both jejunal and ileal BLMV and occurred with apparent Km values of 5.0 microM and 4.4 microM and Vmax values of 91.6 and 60.8 pmol/mg protein per 5 s, respectively. Unlabeled riboflavin and the structural analogues lumiflavin, isoriboflavin and 8-aminoriboflavin all caused significant inhibition (but to different degrees) in the uptake of [3H]riboflavin. On the other hand, 8-hydroxyriboflavin, lumichrome, lumazine and D-ribose failed to inhibit [3H]riboflavin uptake. Trans-stimulation of [3H]riboflavin efflux from preloaded BLMV by unlabeled riboflavin or lumiflavin was also observed. Altering transmembrane electrical potential by anion substitution and valinomycin-induced K+ diffusion did not affect the riboflavin uptake process. These results demonstrate the existence of a specialized carrier-mediated mechanism for riboflavin uptake by intestinal BLMV. Furthermore, the system appears to transport the vitamin by a process which is Na(+)- and pH-independent, and electroneutral in nature.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

The natural history of amyotrophic lateral sclerosis and the use of natural history controls in therapeutic trials.

We analyzed the natural history of amyotrophic lateral sclerosis in 277 patients. Our goal was to develop a better understanding of the clinical disease and thus improve the design of therapeutic trials. The Tufts Quantitative Neuromuscular Exam (TQNE) was used as the primary assessment instrument. Our analysis suggested that although more observations are desirable, six monthly TQNEs were adequate to establish the rate of disease progression. We observed a spectrum of deterioration rates without definable subgroups. The striking linearity of deterioration was confirmed. We found a high correlation between deterioration rates in arm and leg strength for individual patients, but a wide range between different patients. Sex and the age at clinical onset did not affect the deterioration rate. As compared with patients without a positive family history, those with other affected family members had a slower loss in arm but not leg strength. We propose that natural history controls can be used effectively in the design of ALS therapeutic trials.

Adult↗
PubMed1993

Nonvasculitic, steroid-responsive mononeuritis multiplex.

We report two patients with mononeuritis multiplex, both of whom had focal inflammation of the perineurium and endoneurium on sural nerve biopsy without necrosis of blood vessel walls, histologic evidence of lymphoid malignancy, or mycobacterial infection. The predominant early sensory symptoms were asymmetric pain and paresthesias; subsequently, muscle weakness developed. Electrophysiologic studies showed an asymmetric sensorimotor axon loss radiculoneuropathy with denervation of limb and paraspinal muscles. Spinal fluid protein was elevated in one patient. There was no cause or underlying systemic disease. Marked improvement occurred with steroid therapy.

Action Potentials↗
PubMed1993

Autoradiographic determination of permeation pathway of permeability probes across intestinal and tracheal epithelia.

Mucosal permeability studies are used to assess intestinal and respiratory barrier functions. Our ability to interpret results of permeability studies are hampered by our lack of understanding of absorptive pathways of permeability markers. The aim of this study was to visually trace the pathway of permeability probes across the small intestinal and tracheal epithelia by using electron microscopic autoradiography and cytochemistry. We saw a constant rate of mucosal to serosal permeation of intestinal permeability probes polyethylene glycol 400 (PEG-400) and mannitol across the everted small intestinal sac and of the pulmonary permeability probe bovine serum albumin (BSA) across the tracheal epithelia. Electron microscopic tracing of the permeation pathways of tritiated PEG-400 and tritiated mannitol revealed that the majority of the probes traversed the intestinal epithelium paracellularly within 1 half distance (1650 A) of the intercellular space. It is interesting that we also found a small but significant transcellular transport of permeability probes. Goblet cells also absorbed permeability probes transcellularly, but in an "all or none" fashion. Similar pathways were identified in studies utilizing the commonly used pulmonary permeability probes iodine 125-labeled BSA and horseradish peroxidase to determine the routes of transfer in the airway epithelia. In the normal unperturbed trachea, these large permeability probes traversed the pulmonary epithelia transcellularly via endocytosis. On barrier disruption by cytochalasin D, the probes permeated predominantly via the paracellular pathway. This study also demonstrates some of the similarities and differences in transmucosal pathways shared by intestinal and pulmonary epithelia.

Animals↗
PubMed1993

[Potassium substitution during coronary surgery: K(+)-Mg+(+)-aspartate-complex (Inzolen) versus potassium chloride].

Potassium loss may cause arrhythmias and cardiac injury in patients undergoing heart surgery with cardiopulmonary bypass (CPB). In a prospective, randomized trial two different methods of potassium substitution were investigated regarding their influence on cardiac rhythm following reperfusion. Patients received either potassium chloride (Group I, n = 102) or potassium magnesium aspartate (Inzolen, group II, n = 105) to achieve intraoperative serum potassium concentrations of 4.5 mmol/l. St. Thomas cardioplegic solution was used. CPB was performed in moderate hypothermia (28-32 degrees C) with a non-pulsatile pump flow, a membrane oxygenator and a single two-stage venous catheter. The two study groups were comparable with regard to biometric data, preoperative state, duration of operation, ischemia and clinical outcome. In 6 patients in group I and in 3 patients in group II perioperative myocardial infarction was diagnosed based on ECG and CK-MB findings. One patient in each group died during the postoperative hospital stay. At the time of declamping mean serum potassium concentration was 4.9 +/- 0.7 mmol/l in group I and 4.8 +/- 0.5 mmol/l in group II (n.s.). The concentration of magnesium was significantly lower in the potassium chloride substitution group (1.48 mmol/l) compared to the other group (2.33 mmol/l) (p < 0.05). No significant differences in cardiac electric activity were observed between the two groups. The incidence of ventricular fibrillation in the early reperfusion period was 37% versus 45% (n. s.). In both groups patients with a potassium value of < 4.5 mmol/l showed a significantly higher incidence of ventricular fibrillation. Five percent of the patients had bradycardia requiring temporary pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid↗