PubMed Health⌕ Search

Biomedical subjects

K L Isaacs

Publications and source records attributed to K L Isaacs.

16 recordsLinked to original sources
PubMed2003

Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.

BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. AIM: To evaluate repifermin for the treatment of active ulcerative colitis. METHODS: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

Adult↗
PubMed1999

Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. North American Azathioprine Study Group.

BACKGROUND & AIMS: Azathioprine is effective for Crohn's disease but acts slowly. A loading dose may decrease the time to response. METHODS: A placebo-controlled study was conducted in patients with active Crohn's disease despite prednisone treatment. Patients were randomized to a 36-hour infusion of azathioprine, 40 mg/kg (51 patients), or placebo (45 patients) followed by oral azathioprine, 2 mg/kg, for 16 weeks. Prednisone was tapered over 5 weeks. The primary outcome measure was complete remission at week 8, defined by discontinuation of prednisone and a Crohn's Disease Activity Index of </=150 points. Erythrocyte concentrations of the azathioprine active metabolite, 6-thioguanine nucleotide, were measured. RESULTS: At week 8, 13 patients (25%) were in complete remission in the azathioprine-loaded group compared with 11 patients (24%) in the placebo group. The frequency of complete remission did not increase after 8 weeks in either group. Both groups achieved steady state of 6-thioguanine nucleotide by week 2, and no differences were found in mean concentrations between the groups. There were no significant differences in the frequency of adverse events between the groups. CONCLUSIONS: A loading dose does not decrease the time to response in patients with steroid-treated Crohn's disease beginning azathioprine therapy. Steady state of erythrocyte 6-thioguanine nucleotide and complete response occurred earlier than previously reported.

Administration, Oral↗
PubMed1999

Hyoscyamine as a pharmacological adjunct in colonoscopy: a randomized, double blinded, placebo-controlled trial.

OBJECTIVE: Investigators have assessed the utility of antispasmodic agents in colonoscopy, with conflicting results. The aim of this study is to determine the effects of premedication with hyoscyamine, an anticholinergic antispasmodic, on outcomes in colonoscopy. METHODS: A total of 165 patients undergoing elective colonoscopy were randomized in a double blinded fashion to one of three arms: intravenous hyoscyamine (0.25 mg), oral hyoscyamine (0.25 mg), or placebo, administered 20-40 min before colonoscopy. Primary outcome measures included insertion time to cecum, patient's assessment of pain, and physician assessment of spasm. Secondary outcome measures included amount of analgesic medications used, total procedure time, amount and type of pathology visualized, and physician assessment of patient's pain. RESULTS: Bivariate analysis showed no difference between the three groups in insertion time (13.8 min, 14.8 min, and 13.8 min for placebo, intravenous hyoscyamine, and oral hyocyamine, respectively), analgesic medication necessary, or any other primary or secondary outcome variable. Multivariate analysis controlling for potential confounders also failed to demonstrate any differences between the groups. Women had higher procedure duration and analgesic requirement, and reported more pain than did men. CONCLUSIONS: This randomized, double blinded, placebo-controlled trial did not demonstrate efficacy of either intravenous or oral hyoscyamine as a premedication for colonoscopy.

Administration, Oral↗
PubMed1998

Bioactive and immunoreactive FSH concentrations in ewe and ram lambs over the first year of life.

Several studies suggest that the concentration of immunoreactive (I) FSH measured in peripheral plasma by radioimmunoassay does not always reflect the level of bioactive (B) hormone capable of eliciting a biological response (e.g. oestradiol synthesis by Sertoli cells in vitro). The aim of this study was to measure both B-FSH and I-FSH concentrations in male and female sheep during the first year of life, and to relate this to pubertal development. The hypothesis being tested was that B-FSH is present in both male and female sheep during the prepubertal period and that discrete changes in B-FSH are associated with the onset of puberty. Eight ewe lambs and eight rams lambs were blood sampled fortnightly form 2 to 52 weeks of age. All samples were assayed for B-FSH content. Pubertal development was monitored in ewe lambs from behavioural oestrus and from plasma progesterone concentrations, and in ram lambs from penile and testicular development and from plasma testosterone concentrations. Mean I-FSH concentrations varied significantly with time after birth, in both females and males (P < 0.01). In contrast, B-FSH was found to vary with time in females only (P < 0.01). Around the expected time of puberty in ram lambs (i.e. at 30-40 weeks of age), and thereafter, I-FSH concentrations were undetectable (< 0.2 ng ml-1), whereas the B-FSH concentrations were measurable at concentrations up to twice the assay detection limit (0.8 ng ml-1) until 38 weeks of age. In ewe lambs, but not ram lambs, there was a significant linear relationship between B-FSH and I-FSH values (R = 0.595; P < 0.005). When standardised about the time of puberty, B-FSH (P < 0.05) but not I-FSH was significantly higher in ewe lambs that failed to reach puberty. No differences for either B-FSH or I-FSH between pubertal and non-pubertal ram lambs were noted. In summary, B-FSH was soften measurable in plasma throughout prepubertal development in sheep and the concentrations often differed from those of I-FSH, especially in ram lambs. However, there appeared to be no discrete change in B-FSH that could be directly related to specific pubertal events. It is concluded that although FSH may be a prerequisite for prepubertal testicular development and/or ovarian follicular growth, it is not a critical factor in determining whether puberty is attained during the first year of life in this seasonally breeding species.

Aging↗
PubMed1998

Severe bone pain as an adverse effect of cyclosporin therapy for Crohn's disease.

A case of severe bone pain associated with cyclosporin therapy for Crohn's disease is reported. Severe leg pain developed in a 32-year-old man who was receiving cyclosporin for Crohn's disease that was refractory to medical management. Leg pain was related to the dose of cyclosporin, improved with calcium channel blockade, and resolved on discontinuation of cyclosporin. This syndrome has been described in the renal transplantation literature and may be related to vasoconstriction of bone vasculature.

Adult↗
PubMed1995

Plasma FSH, LH and immunoreactive inhibin concentrations in FecBB/FecBB and FecB+/FecB+ Booroola ewes and rams from birth to 12 months of age.

Endocrine and developmental changes were examined in Booroola FecBB/FecBB (BB, n = 16) and FecB+/FecB+ (++, n = 20) ewe lambs, and BB (n = 17) and ++ (n = 19) ram lambs from 2 to 53 weeks of age. Blood samples were taken weekly for the measurement of plasma concentrations of FSH, LH, immunoreactive inhibin, progesterone (ewe lambs) and testosterone (ram lambs). Behavioural oestrus in the ewe lambs and testicular volume and the breakdown of foreskin adhesions in ram lambs were recorded. Blood samples were taken from another flock of BB (n = 134) and ++ (n = 109) ram lambs at 20 weeks of age for the analysis of immunoreactive inhibin. In ewe and ram lambs, there appeared to be genotype differences for FSH, LH and immunoreactive inhibin at specific times during the neonatal period. In BB and ++ ewe lambs, respectively, mean FSH concentrations were 4.3 and 2.0 ng ml-1 (SED 0.54) between 4 and 6 weeks, 2.6 and 3.4 ng ml-1 (SED 0.33) between 12 and 28 weeks, and 1.8 and 1.9 ng ml-1 (SED 0.18) between 34 and 53 weeks of age. Mean plasma LH concentrations were lower in BB than in ++ ewe lambs from 26 to 53 weeks of age (P < 0.05) but not earlier. Mean concentrations of immunoreactive inhibin were also lower in BB than in ++ ewe lambs between 2 and 11 weeks (16.0 and 27.4 iu ml-1, respectively; P < 0.01), but thereafter no differences were apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Pituitary and plasma levels of growth hormone in Booroola sheep that are either homozygous carriers or non-carriers of the FecBB fecundity gene.

The aim of this study was to examine the effect of the FecBB fecundity gene on plasma concentrations and pituitary content of growth hormone (GH) in sheep. No differences were found between homozygous carriers (BB) and non carriers (++) of the FecBB gene with regard to pituitary GH contents in both ovariectomized and intact ewes. However, ovariectomized ewes had higher levels of pituitary GH than intact ewes (P < 0.01). There were no differences between FecBB genotypes with respect to plasma concentrations of GH in 6-year-old ovariectomized ewes bled every 10 min for 12 h or in ram lambs bled weekly during their first year of life. GH levels in the rams decreased until week 27, increased to a peak at week 31 then decreased before increasing again at week 43. Mean plasma GH concentrations in the ewe lambs bled weekly for a year decreased until week 19 then remained at approximately this level for the remainder of the year. Mean GH plasma concentrations in the ram lambs were higher than in the ewe lambs (P < 0.001). Ewe lambs that were homozygous for the FecBB gene had lower body weights (P < 0.05) and had higher levels of GH (P < 0.01) than non carrier ewe lambs during their first year. Before the average age of first behavioural oestrus (36 weeks) GH levels in the ewe lambs were negatively correlated with body weights (r = -0.69, P < 0.001, n = 22). When body weight was included as a covariate in analysis of variance the genotype difference in ewe lamb plasma GH concentrations was no longer significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Severe gastrointestinal bleeding.

Severe gastrointestinal bleeding is a common cause of admission of the elderly to intensive care units. Differentiation between upper and lower gastrointestinal bleeding is made on the basis of history, physical examination, and diagnostic tests. Therapy is based in part on the severity of the bleeding episode and on the cause of the hemorrhage. Therapeutic intervention may involve medical therapy, endoscopic therapy, angiographic therapy, and surgery. Patient outcome is often related to other underlying disease states.

Age Factors↗
PubMed1992

Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification.

Immunoregulatory properties of cytokines may mediate disordered inflammatory events in ulcerative colitis (UC) and Crohn's disease (CD). In the present study, profiles of cytokines produced by activated macrophages were studied in colonic tissue from 43 patients with and without inflammatory bowel disease (IBD). Cytokine messenger RNA (mRNA) extracted from mucosal biopsy specimens was studied using polymerase chain reaction assay techniques. A greater percentage of active UC samples had detectable levels of mRNA for interleukins (IL) 1, 6, and 8 and gro than samples in inactive UC and noninflammatory controls. These cytokines were comparable in active UC and inflammatory controls. Expression of gro mRNA in active UC tissue was significantly higher than in active CD. Tumor necrosis factor was detected in only 7 of 43 samples with no difference between groups. Active and inactive CD did not differ in percentage of cytokine mRNA expression. IL-1 receptor antagonist (IL-1ra) was detected in more inflammatory controls than in CD and was expressed in fewer IBD patients than IL-1. Expression of proinflammatory cytokines in grossly inactive CD and possible defective production of IL-1ra may explain disease reactivation and chronicity.

Actins↗
PubMed1992

Mucocele of the appendix: computed tomographic, endoscopic, and pathologic correlation.

Mucoceles of the appendix are a rare group of lesions thought to occur as a sequelae of luminal obstruction as well as certain benign and malignant neoplasms of the appendix. Early, preoperative diagnosis is rare. We report a case of an appendiceal mucocele in which the diagnosis was suggested by computed tomographic imaging and colonoscopy, and confirmed at surgery. Radiologic, endoscopic, and pathologic correlations of this rare entity are discussed.

Aged↗
PubMed1991

Special diagnostic and therapeutic considerations in elderly patients with upper gastrointestinal disease.

Special diagnostic and therapeutic considerations apply to older patients with upper gastrointestinal disease. Age-related anatomical and physiologic changes occur in the major organ systems, affecting functions as diverse as swallowing and hepatic and renal clearance of therapeutic drugs. Because of these factors, and because older patients are more likely to be receiving multiple drugs for concomitant illness, they are more prone to drug-drug interactions and to medication-induced injury of the esophagus and stomach. In addition, several gastrointestinal disorders, notably gastroesophageal reflux and peptic ulcer disease, are commonly seen in the elderly. This report reviews those age-related system changes that affect the gastrointestinal tract, and also reviews the esophageal and gastric disorders that are common and/or particularly problematic in the elderly. Diagnostic techniques to evaluate gastrointestinal disease in older patients and approaches to therapy for this population are described as well.

Aged↗
PubMed1990

Pancreatitis after rectal administration of 5-aminosalicylic acid.

A patient treated with sulfasalazine for new-onset ulcerative colitis developed self-limited pancreatitis. Rechallenge with 5-aminosalicylic acid (5-ASA) in enema form (Rowasa) again induced pancreatitis. Recent case reports suggest that the salicylate component of sulfasalazine can lead to the development of pancreatitis with oral 5-ASA administration. This patient's course demonstrates further that rechallenge with 5-ASA in a rectal form may also lead to pancreatitis.

Administration, Rectal↗
PubMed1990

Esophageal obstruction with a dietary fiber product designed for weight reduction.

Supplements consisting primarily of dietary fibers are marketed as aids to weight reduction. Of uncertain efficacy, they have generally been regarded as safe when used according to directions. We report two cases of acute esophageal obstruction by a guar gum product in patients with preexisting esophageal abnormalities and review similar reports from other centers.

Adult↗
PubMed1983

Antigen size and charge in immune complex glomerulonephritis. II. Passive induction of immune deposits with dextran-anti-dextran immune complexes.

Utilizing dextrans of restricted sizes (10,000, 70,000, 500,000 daltons), modified with regard to charge (neutral, polycationic, polyanionic) and an anti-dextran murine IgA myeloma, W3129, the authors have examined a model that may be used in the study of the combined effect of size and charge on renal deposition of immune complexes. Polycationic DEAE dextran complexes, using the 10,000 dalton antigen, showed a mesangiocapillary pattern of deposition. The other antigens showed focal to diffuse mesangial localization of varying degree. This indicates the potential usefulness of this system in examining the factors important in glomerular immune injury. The relevance to other observations, importance of polysaccharide antigens, and role in circulating versus in situ or "planted" immune complex models are considered.

Animals↗
PubMed1982

Role of antigen size and charge in immune complex glomerulonephritis.

To explore the role of size and charge in immune complex glomerulonephritis, a series of sized (10,000-, 70,000-, 500,000-dalton) dextrans was modified by the addition of charged groups (diethylaminoethyl dextran, neutral dextran, dextran sulfate) and administered to mice. The animals developed glomerulonephritis characterized by the deposition of IgA with lesser amounts of IgM and C3. The pattern of glomerular response was charge dependent with neutral antigens eliciting a focal, segmental proliferative response with mesangial deposition in scant amounts. The anionic dextran sulfate led to a diffuse mesangial proliferative picture with heavy deposition. The cationic, diethylaminoethyl-dextran-treated animals showed a marked increase in mesangial matrix with much less proliferation. The importance of this model to mechanisms of complex deposition, i.e., circulating versus in situ, and the potential importance of polysaccharide antigens (this study representing the first active induction of nephritis with this class of substances) is discussed.

Animals↗