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Biomedical subjects

S Galandiuk

Publications and source records attributed to S Galandiuk.

At least 37 records · Page 2Linked to original sources
PubMed1999

Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.

BACKGROUND & AIMS: Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. METHODS: A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL-11 at doses of 5, 16, or 40 microgram. kg-1. wk-1 given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit. RESULTS: Subcutaneous injection of rhIL-11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhIL-11 40 microgram. kg-1. wk-1 as 2 or 5 weekly doses and 16 microgram. kg-1. week-1 as 5 weekly doses compared with patients receiving placebo (P < 0.05). Patients receiving 16 microgram. kg-1. wk-1 had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. CONCLUSIONS: Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 microgram. kg-1. wk-1 given in 2 equal doses.

Adult↗
PubMed1999

Limited utility of preoperative studies in preparation for colostomy closure.

Numerous diagnostic and therapeutic practices are used in an attempt to reduce the morbidity of colostomy closures. Our principal aim was to evaluate the role of preoperative studies, specifically barium enemas and endoscopic examinations, performed before colostomy closures. Additionally, we wished to identify other practices involved in the perioperative management of patients undergoing colostomy closure that influenced morbidity. The records of 100 consecutive patients who underwent elective colostomy closure at University of Louisville Hospital between January 1989 and July 1995 were reviewed. Wound infection was the most common complication (12%). Various bowel preparations were equivalent in efficacy and did not influence the complication rate. Intermittent wound irrigation with antibiotics for 3 days postoperatively, via subcutaneous drains, was associated with a low incidence of incision infection. Preoperative barium enema or sigmoidoscopy were often performed but rarely useful. Performing these examinations merely increased hospital cost without a corresponding decline in morbidity.

Adolescent↗
PubMed1998

Analysis of minocycline by high-performance liquid chromatography in tissue and serum.

A sensitive and rapid reversed-phase high-performance liquid chromatography assay can be used to accurately determine serum and tissue minocycline concentrations. Minocycline is a broad spectrum tetracycline derivative with many applications. Tissue and serum samples were obtained from guinea pigs that had received either topical or intravenous minocycline. Samples were extracted using a Sep-Pak C18 cartridge and were injected into a microBondapak C18 column with an isocratic methanol mobile phase. Samples were analyzed using UV detection and produced sharp peaks with a retention time of 2.5 min. The lower limit of detection was 100 ng and drug recovery was 61%. This method greatly facilitated the analysis of minocycline while allowing for sensitivity.

Administration, Topical↗
PubMed1998

Impact of sedation and resident teaching on complications of colonoscopy.

There is controversy regarding the frequency of sedation-related complications of colonoscopies and whether these procedures are safely performed by physicians-in-training. We retrospectively reviewed the safety of 1,004 consecutive outpatient colonoscopies. No perforations occurred. No patients were hospitalized for sedation-related complications. Seventeen percent of patients had significant changes in vital signs that lasted less than 5 min. These changes were less common in patients receiving </=3 mg midazolam intravenously without meperidine (p < 0.005). Complications were slightly more frequent in procedures performed by trainees (23%) than by gastroenterologists (12%) and by surgeons (18%) (p = 0.01). These data support the safety of colonoscopy under intravenous sedation, even when performed by trainees.

Adolescent↗
PubMed1997

Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer.

PURPOSE: Preoperative radiation with combined chemotherapy is effective in shrinking advanced rectal cancer locally and facilitating subsequent surgery. Suppository delivery of 5-fluorouracil is associated with less toxicity and higher rectal tissue concentrations than intravenous administration. This prompted us to evaluate suppository and intravenous administration of 5-fluorouracil and mitomycin C with concomitant radiation to determine associated toxicity. METHODS: Rectal, liver, lymph node, and lung tissue and systemic and portal blood were collected serially from male Sprague Dawley rats to determine drug concentrations following suppository or intravenous delivery of 5-fluorouracil or mitomycin C. Thirty-six animals were randomly assigned to treatment groups and received 5-fluorouracil suppositories, mitomycin C suppositories, or an equivalent intravenous dose of 5-fluorouracil or mitomycin C 30 minutes before radiation therapy. Before and 3, 6, 10, and 15 days following this treatment, blood was collected, colonoscopy was performed, and rectal tissue was harvested for histologic examination. RESULTS: Mitomycin C suppository was significantly less toxic compared with intravenous delivery, and higher rectal tissue concentrations were observed from 10 to 30 minutes (P < 0.05). Compared with intravenous 5-fluorouracil administration and radiation, 5-fluorouracil suppository and radiation resulted in additive myelosuppression at day 6 (P < 0.05) with rapid recovery. CONCLUSIONS: 5-Fluorouracil and mitomycin C suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration.

Adenocarcinoma↗
PubMed1997

The natural resistance-associated macrophage protein gene is associated with Crohn's disease.

BACKGROUND: Identification of the genes causing inflammatory bowel disease (IBD) would enhance the understanding of and the treatment options for this disease. A hyperreactive immune response toward the intestinal flora has been implicated in the pathology of IBD. The natural resistance-associated macrophage protein (NRAMP) gene is believed to regulate macrophage function, especially the ability to fight intracellular pathogens. Genetic differences of NRAMP might, therefore, be associated with IBD. METHODS: Two DNA markers (D2S434 and D2S1323) near NRAMP were polymerase chain reaction (PCR) amplified and genotyped with DNA from 103 patients with Crohn's disease, 85 patients with ulcerative colitis, and 98 control subjects. Clinical data were obtained for all patients. Comparisons were made by chi-squared analysis. Disease association with significant haplotypes was expressed as odds ratio. RESULTS: Allele and genotype distributions were similar for both markers among all groups. Haplotype frequencies were different among Crohn's disease and control groups (p = 0.024). Two individual haplotypes of the patients with Crohn's disease were significant compared with control subjects: DA (p = 0.023; odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9) and EA (p = 0.001; odds ratio, 3.5; 95% confidence interval, 1.6 to 3.2). The haplotype distribution was different within three age-of-onset groups of patients with Crohn's disease (p = 0.05). CONCLUSIONS: This study is the first to report an association between the NRAMP gene and Crohn's disease.

Adolescent↗
PubMed1997

Crohn's disease and ulcerative colitis are associated with the DNA repair gene MLH1.

OBJECTIVE: The purpose of this study was to determine whether there is an association between Crohn's disease and ulcerative colitis with MLH1. SUMMARY BACKGROUND DATA: Identification of genes involved in the etiology of inflammatory bowel disease may lead to the development of markers that objectively can define disease and permit therapy. The treatment of Crohn's disease of the colon and ulcerative colitis also is complicated by difficulties in differentiating the two conditions. METHODS: The DNA and clinical data were obtained on 126 unrelated individuals (45 Crohn's disease, 36 ulcerative colitis, and 45 control subjects without intestinal disease). Polymerase chain reaction products were analyzed by single-strand conformation polymorphisms (MLH1 exons 9, 11, 14, 15, and 16) and polyacrylamide gel electrophoresis (markers D3S1611 and D3S1768). All comparisons were analyzed by chi square test. The association between single haplotypes and disease was expressed as relative odds. RESULTS: MLH1 exons 9, 11, 14, and 16 were monomorphic. Two, four, and six alleles were detected in MLH1 exon 15, D3S1611, and D3S1768, respectively. Significant associations were observed for MLH1 exon 15/D3S1611 haplotypes AB (OR = 5.5; p = 0.007) and BA (p = 0.002) with Crohn's disease and for haplotypes AB (OR = 4.0; p = 0.042), BA (p = 0.035), and BC (OR = 6.1; p = 0.016) with ulcerative colitis. Family history of inflammatory bowel disease was associated with D3S1768/D3S1611 (p = 0.05) and MLH1 exon 15/D3S1611 haplotypes (p = 0.03). D3S1611/D3S1768 haplotype CD (OR = 11.3; p = 0.03) was associated with disease, whereas MLH1 exon 15/D3S1611 haplotype AA (OR = 0.25; p = 0.02) was protective. Comparisons of MLH1 exon 15/D3S1611 haplotypes of Crohn's colitis and patients with ulcerative colitis were significant (p = 0.037). CONCLUSIONS: This study identifies a novel genetic and clinical association between MLH1 and inflammatory bowel disease.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Absorbable, delayed-release antibiotic beads reduce surgical wound infection.

Absorbable, polyglycolic acid (PGA) beads were evaluated as a new vehicle for local antibiotic delivery. Incisions on the dorsa of guinea pigs were contaminated with 1 x 10(8) Escherichia coli and 1 x 10(8) Staphylococcus aureus. PGA beads containing either minocycline, amikacin, or no antibiotic (placebo) were placed into these wounds and compared to animals treated with systemic minocycline or amikacin alone. The diameter of wound erythema was measured daily for 7 days. Serial blood and wound quantitative cultures were obtained, and serum and wound antibiotic concentrations were determined. Both minocycline-PGA and amikacin-PGA-treated wounds exhibited less erythema than placebo-PGA wounds (P < 0.05). All minocycline-PGA and amikacin-PGA-treated wounds healed primarily, whereas 67 per cent of placebo-PGA wounds developed purulence, dehisced, and healed secondarily. Local antibiotic delivery was more effective than systemic administration in reducing wound erythema and the number of bacteria in wound quantitative cultures. E. coli and S. aureus were quantitatively reduced (P < 0.05) in wounds of antibiotic PGA-treated animals compared to those in placebo-PGA-treated and systemic minocycline and systemic amikacin-treated animals. Measurable minocycline and amikacin concentrations were present in antibiotic-PGA-treated wounds through day 3, without detectable serum levels. Delayed-release, absorbable, antibiotic-containing PGA beads effectively prevent infection in contaminated wounds and have the advantage of not requiring vehicle removal.

Amikacin↗
PubMed1996

Suppository delivery of 5-fluorouracil in rectal cancer.

BACKGROUND: Preoperative radiotherapy with concomitant intravenous 5-fluorouracil (5-FU-i.v.) is effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Topical 5-FU application may enhance its radiosensitizing and cytotoxic effects. Suppository and intravenous 5-FU administration were compared with respect to myelo-suppression and tissue concentrations. METHODS: Rats received 120 mg/kg 5-FU-i.v. or via suppository (5-FU-S). White blood cell count, serum albumin, alkaline phosphatase, creatinine, and aspartate aminotransferase (AST) were determined before and serially after 5-FU administration. In a separate experiment, rats received 5-FU-S or 5-FU-i.v. as already described. Portal and systemic blood, rectal, iliac lymph node, liver, and lung tissue were harvested for high-performance liquid chromatography determination of 5-FU concentrations 30 min, 1, 3, 6, and 12 h after drug administration. RESULTS: No toxicity was observed in 5-FU-S animals, whereas 63% of 5-FU-IV animals had diarrhea. Weight loss and myelosuppression occurred only in 5-FU-i.v. animals. Rectal drug concentrations were significantly higher in the 5-FU-S animals compared with 5-FU-i.v. animals, 0.5-6 h after drug administration. Blood, liver, and lung 5-FU concentrations with 5-FU-S were comparable to those with 5-FU-i.v. CONCLUSIONS: 5-FU suppositories are associated with fewer systemic side effects and higher rectal 5-FU concentrations than with 5-FU-i.v. administration.

Administration, Rectal↗
PubMed1996

Constituent analysis may permit improved diagnosis of intra-abdominal abscess.

BACKGROUND: Intra-abdominal abscesses (IAA) often fail to resolve with intravenous antibiotics alone and frequently require drainage. Diagnosis of IAA in postoperative patients with other likely sources of infection is very difficult. PATIENTS AND METHODS: In order to characterize IAA and identify parameters that might facilitate diagnosis, we prospectively examined peripheral blood and pus of 15 consecutive patients with IAA and compared them to samples from 34 consecutive patients with soft-tissue abscesses (STA). RESULTS: Serum interleukin (IL)-10 was elevated in IAA patients, while abnormally detectable serum IL-4 was demonstrated in the pus of both IAA and STA patients. IL-10 in IAA pus was more than 11-fold higher than in STA, whereas IL-4 in pus was similar in both types of abscesses. Both IL-4 and IL-10 were 4- to 10-fold higher in IAA and STA pus than in corresponding patient serum. Serum lysozyme was, however, significantly elevated in all abscess patients. CONCLUSIONS: The presence of IL-4 and IL-10 may indicate a T-helper 2 lymphocyte response in the etiology of abscess formation and persistence, although precise determination of T-helper 1-related cytokines is needed to verify this. Serum lysozyme and IL-10 may be reliable and relatively inexpensive diagnostic aids.

Abdominal Abscess↗
PubMed1995

HPLC analysis of 5-FU and FdUMP in tissue and serum.

Tissue and serum concentrations of 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine 5' monophosphate (FdUMP) can be determined using a simple and sensitive reverse phase HPLC technique. Samples are extracted with ethyl acetate, evaporated to dryness, resuspended in the mobile phase (water/methanol [85:15]), and injected into a C18 muBondapack column (250 mm x 30 mm) with a flow rate of 1 ml/min. Both fluorescence (266 lambda Excitation and 350 lambda Emission) and UV (250 nm) are used for detection. Standard solutions of 5-FU and FdUMP produce a linear relationship (r2 = 0.985) with a detection sensitivity of 50 pg. Recovery following this extraction procedure is 78%. This analytical method is simple and convenient to use for the simultaneous detection of 5-FU and FdUMP.

Animals↗
PubMed1995

A surgical subspecialist enhances general surgical operative experience.

OBJECTIVE: To examine the impact of a surgical subspecialist on residents' operative experience in a mature general surgery training program. METHODS: American Board of Surgery operative experience records were used to examine the impact of a surgical subspecialist on surgical training in a stable residency program. Operations performed as surgeon by residents in their chief and junior years were analyzed 4 years before and 4 years after the addition of this subspecialist to the faculty. Hospital admissions for Crohn's disease and ulcerative colitis during these periods were analyzed as well. RESULTS: There was a statistically significant increase in the number of ileal pouch anal anastomoses, ileostomies, small-bowel resections, partial colectomies, and coloanal anastomoses performed by surgical residents after the addition of a colorectal surgical subspecialist. CONCLUSIONS: Subspecialty faculty may favorably influence general surgical training by increasing resident operative experience and patient management skills with procedures characteristic of the subspecialty.

Anastomosis, Surgical↗
PubMed1995

Expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in colon disease.

Surveillance colonoscopy and biopsy are inaccurate methods of predicting the likelihood of ulcerative colitis patients to develop colon carcinoma. We examined uPA and PAI-1 as potential markers for assessing these patients and those with familial polyposis who are at risk of developing colon cancer. For comparison, biopsies of normal colon and Crohn's disease were evaluated. We examined 77 colonic mucosa specimens taken from patients undergoing elective resection for benign and malignant colonic disease. uPA and PAI-1 were measured using a monoclonal antibody-based ELISA kit (American Diagnostica, Greenwich, CT) and expressed as ng/mg extract protein. Intra- and interassay controls of uPA gave CV = 3-4% and CV = 8-9%, respectively, while those for PAI-1 were 6-7% and 10-11%, respectively. The Mann-Whitney test showed that both uPA and PAI-1 expression were significantly higher in colon cancer, chronic ulcerative colitis, and Crohn's disease than in normal colon. uPA in familial polyposis samples was similar to that of normal colon, while PAI-1 was much lower than in normal colon. Neither patient age nor sex appeared to influence the expression of these potential markers in any tissue. The pattern of uPA and PAI-1 expression in normal, benign and malignant colon suggests these proteins deserve further consideration as markers for assessing colon carcinoma risk.

Adenomatous Polyposis Coli↗