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Biomedical subjects

M Hudson

Publications and source records attributed to M Hudson.

At least 109 records · Page 6Linked to original sources
PubMed1993

Immunohistochemical study of tissue factor expression in normal intestine and idiopathic inflammatory bowel disease.

AIMS: To investigate the localisation of tissue factor expression in normal and inflamed intestine. METHODS: Serial cryostat sections of tissue taken from patients with Crohn's disease (n = 8), ulcerative colitis (n = 5), and from controls (n = 5) were stained with haematoxylin and eosin and immunostained for tissue factor, collagen type IV, fibrinogen and platelet glycoprotein IIIa. RESULTS: In control tissues tissue factor was present as a continuous layer along the epithelial basal lamina: sections from controls did not immunostain for fibrinogen or platelets. In non-ulcerated inflamed mucosa, tissue factor staining intensified in cases of Crohn's disease and was associated with fibrin deposition. Staining for tissue factor was either patchy or absent in cases of ulcerative colitis and there was no fibrin deposition. This change accompanied the early destruction of the epithelial basal lamina in ulcerative colitis that was not seen in Crohn's disease. In both diseases tissue factor expression in severely inflamed and ulcerated mucosa was present on lamina propria macrophages and vascular endothelium and was associated with fibrin or platelet thrombi. In three of eight cases of Crohn's disease tissue factor expression and thrombi were evident in areas of submucosal vasculitis. These were not seen in adjacent normal vessels. CONCLUSIONS: These observations are consistent with a tissue factor haemostatic barrier in the intestine: this barrier seems to be incomplete or defective in ulcerative colitis. Tissue factor expression by macrophages and endothelial cells may be important, particularly in the microvascular thrombosis and induration which are characteristic of Crohn's disease.

Adult↗
PubMed1993

Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors.

PURPOSE: The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors. PATIENTS AND METHODS: To reduce interpatient variability in carboplatin systemic exposure, 45 children were treated with doses individualized to a target area under the serum concentration versus time curve (AUC) based on renal function, using technetium 99-diethyl-enetriamine pentaacetic acid (99mTc-DTPA) clearance to estimate glomerular filtration rate (GFR). Cohorts of at least three patients received carboplatin at an initial target AUC of 2 mg/mL x min, with escalations of 1 mg/mL x min in subsequent cohorts. Courses consisted of carboplatin on day 1 followed by IFOS 2 g/m2 plus VP-16 100 mg/m2 on days 2 and 3. Patients received at least two courses, with a maximum of eight courses possible in the absence of progressive disease. When only moderate toxicity occurred after escalation to 5 mg/mL x min, a third dose of IFOS plus VP-16 was added. After three patients were treated at this level, carboplatin escalation proceeded. RESULTS: Neutropenia and thrombocytopenia were the dominant toxicities in the 43 assessable patients. At the target AUC of 8 mg/mL x min, 13 of 20 cycles were associated with febrile neutropenia. For phase II trials, we recommend a carboplatin target AUC of 6 mg/mL x min with three doses of IFOS and VP-16 for patients with prior craniospinal irradiation or high-dose cisplatin (CDDP)/VP-16, or 7 mg/mL x min for patients without such histories. There were two complete responses (CRs), 13 partial responses (PRs), and 17 objective responses (ORs). CONCLUSION: The ICE regimen shows promising activity in pediatric solid tumors. The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy.

Adolescent↗
PubMed1993

The inappropriate use of acute hospital beds in an inner London District Health Authority.

The requirement for District Health Authorities to assess the health care needs of their population implies that they must consider how well acute hospital care meets these identified needs. This study, which was conducted in an inner London health district, identified that 123 (14.6%) patients were perceived by medical and/or nursing staff to be inappropriately located in an acute bed. This group was dominated by patients aged 65 years or above, those in general and geriatric medicine, those with a length of stay of 30 days or more, and those with high levels of physical and mental dependency. The main reasons for patients being labelled as 'inappropriate' were the need for non-acute health services (eg rehabilitation, terminal care etc), a need for nursing home places or because of social or housing problems. Five months after identification, the notes of 100 of the 123 inappropriate patients were traced. Retrospective classification of these notes using the more 'objective' Oxford Bed Study Instrument showed that 97 patients were still defined as inappropriate. Details of the length of inappropriate stay were available for 74 patients who accrued 7,519 inappropriate bed days at a cost of 836,547 pounds. These patients are an illustration of the potential failings of current health and social care systems and highlight the need for imaginative care solutions which bridge this divide.

Adult↗
PubMed1993

Serum interleukin-2 receptor levels in Hodgkin disease and other solid tumors of childhood.

Serum levels of interleukin-2 receptor (IL2R) were determined in children with newly diagnosed Hodgkin disease (n = 68), Wilms tumor (n = 20), osteosarcoma (n = 18), rhabdomyosarcoma (n = 18), or Ewing sarcoma (n = 15). Measurements of soluble IL2R were positively correlated with disease stage in Hodgkin disease but not in other tumors. Very high levels of soluble IL2R (> or = 5000 U/ml) were significantly associated with a poorer treatment outcome in Hodgkin disease (p = 0.006) and retained significance in a multivariate analysis (p = 0.03). The addition of soluble IL2R measurements to existing prognostic models may improve risk assignment in children with Hodgkin disease.

Child↗
PubMed1993

Ranitidine has no effect on postbreakfast ethanol absorption.

The effect of ranitidine, the H2-receptor antagonist, on the systemic bioavailability of ethanol (0.3 g/kg body weight) taken orally 1 h after breakfast, was investigated in a randomized, placebo-controlled, double-blind cross-over study. Twenty normal male subjects (age, 19-26 yr) were studied on the morning of the 8th day of twice-daily dosing with either 150 mg ranitidine or placebo. Plasma ethanol concentration was measured by the alcohol dehydrogenase method from 0 to 240 min after oral ingestion of ethanol (100% ethanol made up to 200 ml orange juice). Compared with placebo, dosing with ranitidine resulted in nonsignificant changes in either the mean integrated 4-h plasma ethanol concentration (27.8 vs. 32.4 mg.h/dl), the peak plasma ethanol concentration (18.0 vs. 21.1 mg/dl), or the time to peak (43 vs. 40 min). There is no clinically important interaction between ranitidine and a low dose of ethanol taken orally 1 h after breakfast.

Administration, Oral↗
PubMed1992

Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction.

The prevalence of herpesvirus DNA was examined in inflammatory bowel disease tissue. DNA was extracted from resection and biopsy specimens of the large intestine from patients with ulcerative colitis (n = 21), patients with Crohn's disease (n = 29), and patients with noninflammatory bowel disease (controls) (n = 21). The nested polymerase chain reaction was used to detect viral DNA using primer pairs specific for either cytomegalovirus (CMV), herpes simplex virus 1 (HSV1), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), or Epstein Barr virus (EBV). HSV1 and VZV DNA were not detected in any of tissue samples. There was a high prevalence of CMV (81%), HHV6 (76%), and EBV (76%) DNA in ulcerative colitis tissue compared to Crohn's disease tissues (CMV 66%, HHV6 45%, EBV 55%). Control tissue had a relatively low frequency of CMV (29%) and EBV (19%) DNA but a prevalence of HHV6 DNA similar to that of ulcerative colitis (86%). However, the simultaneous presence of HHV6 and CMV and/or EBV DNA in ulcerative colitis tissue (76%) was much greater than in either Crohn's disease tissues (38%) or control tissue (29%) (P < 0.05). There was a low prevalence of CMV, HHV6, and EBV DNA in peripheral blood mononuclear cells from all patient groups. CMV and EBV are capable of reactivating HHV6: the high prevalence of coexistent HHV6 infection with either or both of these two viruses in ulcerative colitis tissue suggests that they may play a synergistic role in the pathogenesis of this disease.

Adolescent↗
PubMed1992

A ferret model of acute multifocal gastrointestinal infarction.

Based on the demonstration of mural granulomatous vasculitis in Crohn's disease, it was hypothesized that this vasculitis may account for the discontinuous pattern of lesions in this condition. Accordingly, the present study investigated the histological changes produced by interruption of the submucosal and mucosal microcirculation in the ferret midgut. Two techniques were used. First, up to 30 adjacent vasa recta were ligated using microsurgical techniques; this produced no evidence of ischemic damage. Second, interruption of the submucosal collateral plexus by the intra-arterial injection of styrene microspheres (27-, 50-, or 90-microns diameter) produced acute intestinal mucosal damage. A combination of 27- and 90-microns spheres resulted in focal mucosal inflammation, necrosis, and ulceration. "Summit" lesions with normal adjacent mucosa were observed 48 hours after embolization, with evidence of regeneration of the mucosa overlying the occluded vessels at 72 hours. This model shows that focal gastrointestinal infarction with normal adjacent mucosa can be produced by acute occlusion of submucosal and mucosal arteries.

Acute Disease↗
PubMed1992

Transmucosal penetration of bismuth particles in the human stomach.

Electron microscopic examination of upper gastrointestinal biopsies with x-ray microanalysis was used to detect electron-dense particles of bismuth in the mucosa of the upper gastrointestinal tract, 30-60 minutes after oral dosing with either tripotassium dicitrato bismuthate [De-Noltab; Brocades (Great Britain) Ltd., Weybridge, UK; five patients] or bismuth salicylate (Pepto-Bismol; Richardson Vicks Ltd., Egham, UK; five patients), or without dosing (two patients). Transmucosal penetration of bismuth particles was observed in the gastric antral mucosa of all patients who had been dosed with tripotassium dicitrato bismuthate, but there was no penetration after oral dosing with bismuth salicylate. Persorption of bismuth particles through the gastric mucosa to the vascular endothelium provides an explanation for the rapid rise of plasma bismuth concentration observed only after oral dosing with tripotassium dicitrato bismuthate.

Adult↗
PubMed1992

Evaluation of mean transit time in children as an indicator of airways obstruction.

Mean transit time was evaluated as a test of pulmonary function in normal and asthmatic children. It was found to be independent of body size and negatively correlated with PEFR, FEV1 and FVC in normal children. Mean transit time was less sensitive in detecting the effects of bronchodilator therapy in asthmatic children than other simpler tests of lung function. The range of normal was so wide that there was no clear demarcation between normal and abnormal. The degree of overlap makes isolated tests of mean transit time of little diagnostic value. It is therefore concluded that mean transit time though it theoretically offers the attractive advantage of being a sensitive indicator of both large and small airways obstruction, is unlikely to play a major part in the routine evaluation of lung function in asthmatic children.

Adolescent↗
PubMed1992

Evidence for activation of coagulation in Crohn's disease.

Haemostatic changes in 16 patients with Crohn's disease were studied from active disease into clinical remission and beyond. Elevated concentrations of fibrinopeptide A (FpA) and prothrombin fragments F1 + 2 (F1 + 2) were found at times of both active (FpA median 3.2, range [0.3-40] ng/ml and F1 + 2 median 2.3, range [0.3-18] nm/l) and inactive disease (FpA median 2, range [0.4-40] ng/ml and F1 + 2 median 1.3, range [0.2-20) nm/l]. We also measured the physiological inhibitors of coagulation and fibrinolysis; there was no significant difference in the levels of antithrombin III, protein C or the Exner ratio between active and inactive disease. Free protein S levels were significantly lower in active disease (median 34, range 9-54 U/dl) than in remission (median 40, range 12-65 U/dl). Plasminogen activator inhibitor type 1 (PAI-1) was significantly raised in remission (median 11, range 3-32 ng/ml) when compared to active disease (median 7, range 3-42 ng/ml). The D-dimer correlated significantly with fibrinopeptide A (P < 0.001), suggesting reactive fibrinolysis in some patients. Most (35/52, 67%) samples showed evidence of persistent haemostatic activation (elevated FpA and/or F1 + 2) during phases of apparent clinical remission in Crohn's disease, a factor that is not reflected by clinical activity scores. This study supports the hypothesis that coagulation is activated in the mesenteric vasculature of patients with Crohn's disease.

Adolescent↗
PubMed1992

Short report: the effect of ranitidine on the post-prandial absorption of a low dose of alcohol.

Twenty healthy male subjects were studied twice using a double-blind, randomized placebo controlled, cross-over study design. Alcohol absorption (integrated 2-h plasma alcohol concentration, peak plasma alcohol concentration, and time to reach peak concentration) was measured after 8 daily doses of either placebo or 300 mg ranitidine. They were given alcohol, 0.15 g/kg of body weight by month after an evening meal. Compared with placebo, there was a trend towards higher integrated 2-h plasma alcohol concentrations (3.17 and 3.89 mg. h/dL, respectively, P = 0.07), and a statistically significant increase in mean peak plasma alcohol concentration after dosing with ranitidine (4.92 and 6.47 mg/dL, respectively, P = 0.05).

Adult↗
PubMed1992

Ranitidine, cimetidine, famotidine have no effect on post-prandial absorption of ethanol 0.8 g/kg taken after an evening meal.

Forty-seven healthy male subjects were studied twice using a randomized, placebo-controlled design. Each subject took an 8-day course of two of the following four regimens; 300 mg ranitidine, 800 mg cimetidine, 40 mg famotidine or placebo (identical either to 300 mg ranitidine or 800 mg cimetidine). The systemic bioavailability of ethanol (integrated 6-h plasma ethanol concentration, peak plasma ethanol concentration, and the time to peak plasma ethanol concentration) was measured after the oral ingestion of 0.8 g of ethanol per kg body weight, given one hour after an evening meal on Day 8 of each regimen. There was no significant difference of integrated 6-h plasma ethanol concentration, peak ethanol concentration, or time to reach peak ethanol concentration after dosing with either ranitidine, cimetidine or famotidine or placebo.

Absorption↗
PubMed1992

Pyoderma faciale in a patient with Crohn's disease.

We wish to report the progress of a patient with pyoderma faciale and Crohn's disease. The patient is interesting in that on two occasions the relapse in her skin condition coincided with the introduction of non-steroidal anti-inflammatory drugs. Therapy with isotretinoin was effective and well tolerated.

Adult↗
PubMed1992

Mucosal capillary thrombi in rectal biopsies.

We studied the initial rectal biopsy from 46 patients in whom subsequent follow-up established the diagnosis of either self-limited colitis or inflammatory bowel disease. An additional 12 non-inflamed rectal biopsies were also studied. There was between 2 and 8 years of follow-up in each of these cases. Staining for fibrin (MSB, fibrinogen), platelets (factor XIIIA, Y2/51), and capillary basement membrane (reticulin, collagen 4) was performed to identify thrombotic material within capillaries. Mucosal capillary thrombi were best identified by staining for factor XIIIA; thrombi were observed in 8/13 cases of ulcerative colitis, 4/10 cases of Crohn's disease, 1/3 cases of unspecified inflammatory bowel disease and 5/20 cases of self-limited colitis. The presence of capillary thrombi was not related to the severity of inflammation, but none of the control biopsies showed capillary thrombi. Their presence seems of little diagnostic value in distinguishing inflammatory bowel disease from self-limited colitis. The pathogenetic significance of these mucosal capillary thrombi is uncertain.

Adult↗