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Biomedical subjects

R Holmes

Publications and source records attributed to R Holmes.

At least 91 records · Page 5Linked to original sources

Evaluation of putative cytoprotective properties of antiulcer drugs using quantitative histological techniques.

The capacity for cytoprotection has been claimed for a number of drugs that may have a place in the treatment of peptic ulcer disease. In this study we have used quantitative histological criteria to evaluate the ability of these drugs to be cytoprotective and have compared their effects with that of natural prostaglandin E2 (PG). The standard rat model, with injury by instillation of 1 ml of absolute ethanol, has been used. Putative cytoprotective agents were administered 15 min prior to ethanol. Each animal was sacrificed 15 min after ethanol exposure. The stomach was removed and studied using an established quantitative histological technique. This technique provides a measure of the surface area of mucosa damaged and of the volume of mucosa damaged. Ethanol alone caused damage to 76% of the area of the rat stomach and 14% of the volume of the rat gastric mucosa. Pretreatment by PG (25 micrograms/ml) resulted in reduction of the area of damage to 45% and reduction of the percentage volume damage to 2.2%. The synthetic analog of PGE2, Enprostil (1 microgram/ml) achieved similar protective effects. With pretreatment with colloidal bismuth subcitrate (10 mg/kg) or sucralfate (25 mg/kg), no protection against the surface area damaged by ethanol was seen, but there was a marked reduction of the volume of mucosa damaged. Indomethacin pretreatment augmented the damage caused by ethanol. The protective effects of colloidal bismuth subcitrate and sucralfate were not blocked by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Simultaneous assessment of intestinal permeability and lactose tolerance with orally administered raffinose, lactose and L-arabinose.

1. In order to develop an improved differential sugar absorption test for simultaneously assessing intestinal permeability and lactose intolerance, methods were established for determining raffinose, lactose and L-arabinose in human urine. Using NAD(P)H-coupled enzymatic assays and fluorimetry, each sugar was measurable over a concentration range of approximately 3-300 mumol/l in diluted urine specimens. 2. After an overnight fast, 40 normal volunteers drank an iso-osmotic solution containing raffinose, lactose and L-arabinose. The median 5 h urinary sugar excretion was 0.26% of the ingested raffinose, 0.05% of lactose and 17.5% of L-arabinose. 3. In 143 patients with gastrointestinal disease, excretion of both ingested raffinose and lactose was significantly increased in coeliac disease in relapse or in partial remission and in Crohn's disease, but not in the irritable bowel syndrome, coeliac disease in remission or ulcerative colitis. Excretion of lactose, but not raffinose, was increased in patients with mucosal lactase deficiency, whereas excretion of L-arabinose was reduced in all disease groups except ulcerative colitis. 4. Discrimination between diseases was poor when based on individual sugar recoveries, but improved dramatically when excretion was expressed relative to that of L-arabinose. The raffinose/L-arabinose excretion ratio, an index of intestinal permeability, was greater than 0.08 in 15/15 untreated coeliac patients but less than 0.06 in all normal subjects and in 9/9 lactase-deficient patients, 15/16 recovered coeliac patients, 5/6 patients with ulcerative colitis, 13/16 patients with Crohn's disease and 61/62 patients with irritable bowel syndrome.

Adolescent↗

Treatment of severe chemomechanical erosion using castable ceramic restorations and a new dentin/enamel bonding system: a case report.

Six maxillary anterior teeth demonstrating severe chemomechanical erosion were restored using a minimal preparation design and a castable ceramic. Facial and lingual erosion prevented the development of the opposing wall retention and resistance form needed for traditionally cemented ceramic or porcelain-fused-to-metal crowns. Therefore, a dentin/enamel bonding system was used to condition the enamel and dentin simultaneously prior to cementation of an etched and silanated castable ceramic restoration. A resin cement was used as the luting agent.

Adult↗

Central nervous system lymphoma: primary lumbar nerve root infiltration.

Primary malignant lymphoma of the central nervous system (CNS) is rare and only infrequently involves the spinal cord, usually in association with multifocal CNS spread. We report a case of primary lymphoma infiltrating lumbar nerve roots without evidence of systemic lymphoma. There has been an excellent response to combined modality therapy, comprising radiotherapy with intrathecal and intravenous cytotoxics. The patient remains well and active 22 months after diagnosis. The literature regarding these rare tumors is reviewed.

Ganglia, Spinal↗

Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures.

The metaphyseal defects in 40 patients with displaced tibial plateau fractures necessitating surgical repair were filled with either cancellous autograft or interporous hydroxyapatite. Roentgenographic and clinical assessments at follow-up periods averaging 15.4 months (autograft) and 34.5 months (hydroxyapatite) demonstrated no significant differences in the two groups. Interporous hydroxyapatite is a safe, effective alternative to autogenous cancellous bone for the filling of metaphyseal defects associated with tibial plateau fractures.

Adolescent↗

Porous hydroxyapatite as a bone graft substitute in maxillary augmentation. An histometric study.

A porous HA matrix, which is available for clinical use, was compared with split rib autografts after maxillary contour augmentation in 17 dogs. Specimens were retrieved at 3, 6, 12, 24 and 48 months and undecalcified sections were prepared for microscopy and histometry. The implant and graft cross sectional areas did not change with time, although mechanical trauma caused early changes in implant area in some specimens. In all implants, union with the maxillary cortex occurred along with substantial bone ingrowth. An area under the periosteum contained soft tissue ingrowth. In all grafts, except one, union also occurred. However, bone ingrowth into the cancellous spaces was not apparent, or minimal. The implant specimens were composed of 34.7% HA matrix, 23.9% bone and 41.3% soft tissue. The bone ingrowth remained permanent for the study duration. A 6.5% decrease in HA matrix occurred between the 24 and 48 month time intervals, suggesting the presence of microporous surface resorption. The graft specimens were composed of 55.8% bone and 44.2% non-mineralized tissue, without change over time. The similarity in mineralized tissue composition of the implants (58.6%) and grafts (55.8%) supported the thesis that a porous HA matrix can function as a bone graft substitute.

Animals↗

Changes in jejunal permeability and passive permeation of sugars in intestinal biopsies in coeliac disease and Crohn's disease.

1. The relative effects of changes in mucosal surface area and mucosal permeability on the passive uptakes of mannitol and raffinose have been studied in vitro using jejunal biopsies from 48 controls, 32 patients with coeliac disease and 11 patients with Crohn's disease. Total mucosal permeation was corrected for surface area measured morphometrically to provide an index of mucosal permeability. 2. In untreated coeliac disease, permeation of mannitol was reduced by 35% (P = 0.006) and that of raffinose was increased by 66% (P = 0.0095) compared with controls, whereas mucosal permeability to mannitol was increased twofold (P = 0.009) and to raffinose fivefold (P = 0.0001). Mucosal permeability was similar for each sugar. 3. In treated coeliac disease, permeation and permeability for mannitol were normal, but remained elevated for raffinose by 23% (P = 0.036) and 41% (P = 0.024), respectively. 4. In Crohn's disease, permeation of mannitol was reduced by 21%, but that of raffinose and mucosal permeability to both sugars were normal. 5. These findings suggest that surface area is quantitatively more important than mucosal permeability in determining the total permeation of mannitol, while the converse is true for raffinose. The findings are compatible with paracellular uptake of raffinose, but with both paracellular and transcellular uptake of mannitol. Both pathways are affected in coeliac disease, whereas only transcellular uptake is affected in Crohn's disease.

Adolescent↗

Treatment of hairy cell leukemia with increasing doses of recombinant alpha A interferon.

Since July 1984, eight patients with advanced hairy cell leukemia have received treatment with recombinant alpha A interferon. At commencement of interferon, seven patients had progressive cytopenia, and one was in leukemic phase (greater than 20 x 10(9)/L circulating hairy cells). All patients had had previous splenectomy. Interferon was administered subcutaneously. The initial dose was 3 x 10(6) U/day, continued until peripheral counts stabilised. Subsequently, patients received 6 x 10(6) U/day, 9 x 10(6) U/day, and finally 12 x 10(6) U/day. The dose increases proceeded every 8-12 weeks, as tolerated. Seven patients had an objective response. There were four complete remissions, two partial remissions, and one minor response. Complete remission was documented only in patients on at least 6 x 10(6) U/day for 12 weeks. The median time to complete remission was 40 weeks (range 35-53). Normalisation of peripheral blood counts preceded histologic marrow improvement. The median times for response (platelets greater than or equal to 100 x 10(9)/L, hemaglobin greater than or equal to 12 gm/dL, neutrophils greater than or equal to 1.5 x 10(9)/L), were six to eight and 17 weeks, respectively. Toxicity included myelosuppression during the first four weeks of therapy. With increasing doses of interferon, myelosuppression did not recur. A transient, mild, flu-like syndrome affected all patients. Two patients developed asymptomatic transaminitis at doses greater than 6 X 10(6) U/day. This resolved with dose reduction. In one case impotence was reported during the first four weeks of each interferon level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗