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Biomedical subjects

J Keck

Publications and source records attributed to J Keck.

At least 19 recordsLinked to original sources
PubMed2003

Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking.

Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.

Adolescent↗
PubMed2001

Cyclin D1 and p16 alterations in advanced premalignant lesions of the upper aerodigestive tract: role in response to chemoprevention and cancer development.

PURPOSE: To better understand the role of G(1)-S transition regulator abnormalities in the pathogenesis of advanced premalignant lesions of the upper aerodigestive tract and the biological effects of chemoprevention, we studied biopsies obtained sequentially from participants in a prospective trial using 13-cis retinoic acid, IFN-alpha, and alpha-tocopherol for 12 months. EXPERIMENTAL DESIGN: Cyclin D1 and p16 expression were analyzed by immunohistochemistry, loss of heterozygosity by polymerase chain reacting amplification, and then electrophoretic separation of the products, methylation of the p16 promoter by methylation-specific polymerase chain reacting, and cyclin D1 gene amplification by fluorescence in situ hybridization. RESULTS: Baseline dysregulation of cyclin D1 expression was found in 50% (14 of 28) and was reversed in 6 of 14 cases, whereas p16 expression was lost in 46% (13 of 28) and regained in 2 of 13 cases. Loss of heterozygosity at 9p21 occurred in 68% and p16(INK4a) promoter methylation occurred in 75% of cases, with increasing frequency from mild to severe dysplasia. Cyclin D1 gene amplification was identified in two cases. Cyclin D1 protein dysregulation at last follow-up alone and in combination with p16 loss was associated with histological progression and cancer development (P < 0.01). CONCLUSIONS: Additional study of these alterations in a larger sample and exploration of the upstream signaling partners of these cell cycle regulators in vivo is warranted to identify cancer risk profiles that would be meaningful targets for chemopreventive intervention.

Adult↗
PubMed1999

Intestinal sleeve anastomosis: a comparative study with end-to-end anastomosis.

This study examines the utility of a sleeve anastomosis with comparison to conventional end to end anastomosis. Thirty New Zealand white rabbits were randomized to sleeve (n = 15) or end-to-end (n = 15) small bowel anastomosis. Five rabbits of each group were sacrificed at 3 days, 7 days, and 6 weeks. Anastomoses were assessed for integrity, bursting strength, and stenosis and examined histologically. Ten control specimens of small bowel were tested for bursting pressure. Three rabbits died postoperatively (1 sleeve and 2 end-to-end). A fourth rabbit (sleeve) was sacrificed early at 3 weeks and had a total stenosis at the anastomosis. The remaining 26 rabbits were reoperated at the prescribed times. There was no evidence of infection or dehiscence in any of these rabbits. Both end-to-end and sleeve anastomoses were equivalent for bursting pressure at all times and, at 7 days and 6 weeks, were similar to controls. The stenotic index revealed no evidence of proximal dilation suggestive of obstruction in the 26 rabbits. For sleeve anastomoses the length of the projected bowel into the lumen persisted at the 6-week stage. Histologically there was good evidence of healing in both the sleeve and end-to-end anstomoses and the serosal surface of the sleeved bowel had epithelialized. Sleeve anastomosis has been demonstrated to heal well and to be as strong as conventional end-to-end anastomosis. Further studies are warranted to determine its role in intestinal anastomosis and potential as a valve.

Anastomosis, Surgical↗
PubMed1999

Total colectomy for Crohn's disease.

BACKGROUND: Total colectomy for Crohn's disease of the colon may be restorative with ileorectal anastomosis or with an ileostomy and rectal stump. The present paper retrospectively audits the results of total colectomy and in particular assesses the number of patients who had a permanent ileostomy and whether this was related to disease in the rectum at the time of the original operation. METHODS: A retrospective case note review was undertaken of patients operated upon between 1968 and 1994. RESULTS: Thirty-eight patients were identified (mean age 35 years; range 17-65 years). One patient died perioperatively from an anastomotic leak. Median follow-up for the remaining patients was 7 years (range 1-29 years). Ileorectal anastomosis was performed in 17 patients and total colectomy and ileostomy in 20 patients. Indications for surgery were failure of medical treatment (61%); toxic colitis (18%); abscess (8%); perforation (5%); large bowel obstruction (5%); and colovesical fistula (3%). Subsequent proctectomy (14 patients, 38%) was more likely with subtotal colectomy and ileostomy (nine patients, 45%) than ileorectal anastomosis (five patients, 29%). This was not statistically significant (P = 0.33). Additionally, seven patients had diversion of the rectum making 21 with an ileostomy (57%). Rectal involvement at the time of the original procedure significantly increased the likelihood of permanent ileostomy (P = 0.001). The presence of anal disease did not increase the prospect of ileostomy. One patient died with advanced adeno carcinoma in a defunctioned rectum. CONCLUSIONS: A permanent ileostomy after total colectomy for Crohn's disease is common and significantly more likely with rectal involvement.

Adolescent↗
PubMed1996

Age-related assessment of central 5-HT1A receptors following irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).

Age-dependent differences in the ability of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to irreversibly inactivate 5-HT1A receptors were investigated in female Fischer 344 rats (ages 3 and 22 months). In the hippocampus, frontal cortex and amygdala, EEDQ reduced 5-HT1A receptor density (33-70%) and drug affinity (2.3-6.2 fold) as determined by Scatchard analyses using [3H]8-hydroxy-2-(di-N-propylamino)tetralin. In the frontal cortex, the reduction in Bmax values was significantly greater in 3 months vs. 22 months groups. These region-specific and age-dependent alterations in 5-HT1A receptors may be of pathophysiological significance in age-related cognitive decline and Alzheimer's disease.

Aging↗
PubMed1994

Treadmill stepping in infants born prematurely.

Premature infants stepped on a treadmill as early as 1-month corrected age and they performed more coordinated alternate steps than their full-term peers. Twelve low-risk premature infants were observed at 1-, 6- and 9-months corrected-age. The infants were supported on a treadmill for five 20-s trials at three speeds. The following data were analysed from the video records: (1) Leg postures in treadmill-moving and non-moving trials, (2) various parameters of limb position and movement during each step cycle, and (3) multiple anthropometric measures. Premature infants at all ages performed coordinated alternating steps which responded to changes in speed. The premature infants had more extended leg postures during non-stepping analysis than they did once the swing was initiated. Low-risk premature birth did not interfere with the neuromotor pathway. Experience out-of-utero may have facilitated stepping.

Anthropometry↗
PubMed1989

Preparation and biological activity of new substituted antimalarial diaminodiphenylsulfones.

Starting from 4,4'-diamino-diphenylsulfone (DDS) as a lead structure, new 2-substituted analogues as well as new 2-substituted 4-alkylamino-4'-amino diphenylsulfones have been designed and synthetized in different ways. This has led to compounds the inhibitory activity of which against 7,8-dihydropteroic acid synthase of plasmodia and mycobacteria is clearly superior to that of sulfadoxine and in most cases to that of DDS. Of special interest is 4'-amino-4-n-propylamino-2-methyl-diphenylsulfone. Together with inhibitors of 7,8-dihydrofolate reductase in vitro and in vivo it possesses a marked synergistic inhibitory activity against plasmodia. In contrast to DDS in doses up to 200 mg/kg p.o. (cat) no methemoglobin formation is observed. The compound has been selected for further studies.

Animals↗
PubMed1984

Synthesis of further amino-halogen-substituted phenyl-aminoethanols.

Starting from clenbuterol as a lead structure, new 4-amino-phenyl-aminoethanol analogues have been synthesized by different approaches. In these compounds one or both of the chlorine atoms of clenbuterol are replaced by other residues. This has led to compounds with high intrinsic beta 2-mimetic and/or beta 1-blocking activities. 1-(4-Amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) has been selected for clinical development. A detailed description is given also of the syntheses of intermediary new acetophenone derivatives as well as of the resolution of mabuterol into its enantiomers.

Adrenergic beta-Agonists↗
PubMed1977

The natural history of calcium urolithiasis.

The course of untreated calcium renal stones, derived from the retrospective study of 300 patients with defined metabolic disorders and from the analysis of two prospective, published studies, is complex and heterogeneous. Generally, stones provoke considerable morbidity; hyperuricosuria is associated with an unusually severe stone disease. Stone recurrence rates usually remain stable, or rise with successive stones; in a minority of patients, the reverse is true. A single stone is likely to be followed by a recurrence. The mean time to recurrence averages 6.78 years, with peaks at 1.56 and eight years. Because the disease is likely to be morbid and chronic and does not wane with age, diagnostic evaluation and treatment should be strongly considered for any patient with recurrent stones, and for those in whom recurrence is likely to pose more than the usual risk.

Adult↗