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M Hudson

Publications and source records attributed to M Hudson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Detection of herpesvirus DNA in cottontop tamarins: no association with colitis.

Colitis occurs spontaneously in the cottontop tamarin; it shares similar clinical, endoscopic and histological features with, and has a similar response to treatment as, human ulcerative colitis. An association between human ulcerative colitis and the presence of DNA from multiple herpesviruses (human herpesvirus 6 (HHV-6), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in the colon has been described. Intestinal herpesvirus infection may be involved in the pathogenesis of this condition. In a pilot study, coded full thickness colonic specimens from 27 cottontop tamarins were examined for the presence of HHV-6, CMV and EBV DNA using the nested polymerase chain reaction. The sections represented a spectrum of disease activity ranging from histologically normal bowel to severe colitis. A low prevalence of DNA from these viruses was found, which bore no relation to the presence of inflammation. Although these herpesviruses may have a pathogenetic role in human ulcerative colitis, they are not associated with colitis in this animal model.

Animals↗
PubMed1995

Grading of cellular rejection after orthotopic liver transplantation.

All 684 post-orthotopic liver transplantation (OLT) liver biopsies performed at the Royal Free Hospital (RFH) between 1988 and 1993, from 120 patients, were reviewed in order to try to define the relative importance of the histological features of immunosuppression-responsive cellular rejection. Twenty histological features considered to be possible contributors to the diagnosis of cellular rejection were documented in a binary (present/absent) fashion. These features in 106 biopsy specimens obtained 1 to 8 days after OLT were analyzed using stepwise logistic discriminant analysis. All clinical and treatment records were reviewed, and each biopsy specimen was assigned to a diagnostic category depending on these records and follow-up information. Important determinants of the histological diagnosis of cellular rejection (which occurred in 84 of the 106 cases) were moderate/severe mixed portal inflammation, eosinophils, endotheliitis, and bile duct damage. When these all occurred together, the odds of rejection increased 3.6-fold. The original histological diagnosis was recorded, and each biopsy specimen showing cellular rejection was regarded according to the specific criteria of Snover et al., Demetris et al., and a novel RFH scoring system. The latter consists of evaluating portal inflammation, endotheliitis, eosinophils, and bile duct damage, each on a 0 to 3 scale (none, mild, moderate, or severe, respectively) and summation. The resulting cellular rejection score thus can range from 0 to 12. The agreement between the different scoring systems was analyzed using K statistics, and there was good concordance (K, 0.64 to 0.78), despite different histological criteria being used to derive each score. Each system showed a similar degree of sensitivity (87% to 96%). The specificity ranged from 59% to 77%. We conclude that the histological diagnosis of cellular rejection relies mainly on the previously described features of mixed portal inflammation, endotheliitis, eosinophils, and duct damage. There is scope for unification and simplification of the existing grading systems, which depend on differing criteria, and we suggest one such scheme.

Biopsy↗
PubMed1994

Failure of granulocyte-macrophage colony-stimulating factor to reduce febrile neutropenia in children with recurrent solid tumors treated with ifosfamide, carboplatin, and etoposide chemotherapy.

Ifosfamide, carboplatin, and etoposide (ICE) chemotherapy has promising activity against various solid tumors but produces significant myelotoxicity that might be ameliorated by hematopoietic growth factors. Twelve patients with relapsed solid tumors were treated with ICE chemotherapy. Carboplatin was given on day 1 at a targeted area under the concentration-time curve (AUC) of 8 mg/mL x min (adjusted for each patient's glomerular filtration rate), followed by ifosfamide 2 g/m2 and etoposide 100 mg/m2 on days 2 through 4. Granulocyte-macrophage colony-stimulating factor (GM-CSF), 1,000 micrograms/m2/day, was started 24 hours after each course and given for 17 days or until the absolute neutrophil count (ANC) reached 10 x 10(9)/L. Myelotoxicity and responses in these patients were compared to those of eight patients who received the same therapy without GM-CSF. Patients received a median of three courses (range, 1-8). All 20 patients developed grade 4 neutropenia and grade 3 or 4 thrombocytopenia. The median duration of neutropenia was significantly shorter in patients who received GM-CSF (16.75 vs. 10 days, P = 0.005). However, the two groups did not differ in the proportion of courses associated with hospitalization for febrile neutropenia, the duration of hospitalization, or the median duration of thrombocytopenia. There were two complete, four partial, and three objective responses in the 12 patients treated with ICE plus GM-CSF, and two partial and three objective responses in the 8 patients treated with ICE only. GM-CSF did not reduce the occurrence of febrile neutropenia or the duration of thrombocytopenia associated with ICE chemotherapy. Studies of other hematopoietic growth factors in conjunction with this promising combination are merited.

Adolescent↗
PubMed1994

Serum immunoglobulin G reactive with endothelial cells in inflammatory bowel disease.

Evidence of a humoral immune response to endothelium was sought in the sera of patients with inflammatory bowel disease. In an ELISA, IgG binding to human umbilical vein endothelial cells was found in 21% of Crohn's disease sera, 10% of ulcerative colitis sera, 6% of sera from patients with acute infective diarrhea, and 8% of normal control sera. The increased prevalence in Crohn's disease sera was significant (P < 0.05). IgG-endothelial cell binding was cell specific, was not Fc-mediated, and did not mediate complement-dependent cell lysis. It was not increased by pretreatment of cells with interleukin-1 or tumor necrosis factor. Endothelial cell binding was retained by IgG F(ab')2 fragments from one of three reactive Crohn's sera, but none of three nonreactive sera. The low prevalence of this interaction, even in patients with immunohistochemically confirmed vasculitis, makes it unlikely that Crohn's disease is determined by a humoral autoimmune response to endothelium.

Adult↗
PubMed1994

A vascular hypersensitivity model of acute multifocal gastrointestinal infarction.

We have investigated the hypothesis that submucosal vasculitis may account for the patchy transmural inflammation observed in Crohn's disease. Test ferrets (N = 11) were sensitized to human albumin. Five days after the last sensitization injection, human albumin microspheres (15-150 microns diameter) were injected intraarterially into the mesenteric circulation of a defined loop of mid-gut. Six control ferrets showed no histological abnormality at either 48 hr or two weeks after intraarterial injection. At 48 hr, five of six presensitized ferrets demonstrated submucosal vasculitis with fibrinoid necrosis. In two cases there was transmural inflammation and mucosal ulceration. A further five presensitized ferrets received weekly subcutaneous human albumin injections following the mesenteric intraarterial injection of albumin microspheres: after two weeks one animal demonstrated mild perivascular inflammatory changes and another demonstrated vasculitis. One of the two animals with transmural inflammation and mucosal ulceration at 48 hr, and the animal with vasculitis at two weeks, had precipitating antibodies to human serum albumin. This model demonstrates that an immune-mediated submucosal vasculitis can sometimes result in discontinuous transmural inflammation of the intestinal wall.

Animals↗
PubMed1994

Effects of ranitidine 150 mg four times a day on 24-hour intragastric acidity and 24-hour plasma gastrin concentration.

Twenty-four-hour integrated intragastric acidity and 24-hr integrated plasma gastrin concentration was measured twice in 23 healthy male volunteers on the seventh day of oral dosing with placebo or ranitidine 150 mg four times a day. The study was a randomized, double-blind, placebo-controlled, two-way crossover investigation. The mean integrated 24-hr intragastric acidity during dosing with ranitidine 150 mg four times a day decreased to 32% of the placebo value (placebo 825 mmol/hr/liter; ranitidine 265 mmol/hr/liter). The mean integrated 24-hr plasma gastrin concentration during dosing with ranitidine 150 mg four times a day was 904 pmol/hr/liter compared with placebo (410 pmol/hr/liter)--an increase of 122%. The median number of hours of pH > 3 during dosing with placebo and with ranitidine 150 mg four times a day were 5 and 11 hr, respectively. Ranitidine 150 mg four times a day caused a significant decrease of mean integrated intragastric acidity for each meal-related interval and also during the night.

Adult↗
PubMed1994

Acute indomethacin-induced jejunal injury in the rat: early morphological and biochemical changes.

BACKGROUND/AIMS: Gastrointestinal injury induced by nonsteroidal anti-inflammatory drugs includes smooth muscle contraction, endothelial cell injury, and neutrophil infiltration. The aim of this study was to correlate early morphological changes with those in the metabolism of arachidonic acid. METHODS: Rats administered a single oral dose of indomethacin (15 mg/kg) or vehicle were killed and their intestines perfusion-fixed at 1, 2, 3, 6, and 48 hours after dosage. Serial sections of affected small intestine were immunostained for neutrophils, macrophages, actin, and fibrinogen. In addition, rats receiving either indomethacin (15 mg/kg) or vehicle were killed at 1 and 6 hours after dosage; blood and small intestinal tissue were assayed for blood thromboxane B2, intestinal tissue prostaglandin E2, and the intestinal production of leukotriene B4. RESULTS: At 2-6 hours, both intravascular and extravascular fibrin deposition were evident at the villus tip, and vertical alignment of villus smooth muscle cells was prominent. Significant neutrophil infiltration associated with a significant increase in leukotriene production was observed 6 hours after dosage. The extracted prostaglandin E2 content that was suppressed at 1 hour had recovered by 6 hours, whereas the blood thromboxane B2 levels were suppressed throughout the experiment. CONCLUSIONS: This study identifies an early neutrophil-independent phase of indomethacin-induced enteropathy that involves rapid cyclooxygenase inhibition and both microvascular and smooth muscle changes.

Animals↗
PubMed1994

Measles virus induction of human endothelial cell tissue factor procoagulant activity in vitro.

Measles virus infection of microvascular endothelium in vivo and ensuing endothelial cell activation may be important in the pathogenesis of subsequent inflammation in target organs. This study investigated the capacity of measles virus to induce procoagulant activity, in vitro, in endothelial cells isolated from human umbilical cord veins. Endothelial cells were infected with a clinical isolate of measles virus propagated in Vero cells. Cells were also incubated with bacterial lipopolysaccharide (10 micrograms/ml), herpes simplex virus type 1, cytomegalovirus or culture medium alone as positive and negative controls, respectively. Endothelial cell procoagulant activity was measured in a one-stage clotting assay. Measles virus stimulated both a time and dose-dependent endothelial cell procoagulant response by the induction of tissue factor synthesis, confirmed by both immunocytochemistry and its dependence on factor VII for activity. This activity was reduced by u.v.-irradiation of the virus. Infected cells were analysed by double immunofluorescent staining for both tissue factor and measles virus N-protein, and examined using confocal scanning laser microscopy. Cells expressing tissue factor were also positive for the measles virus N-protein. Low levels of interleukin-1 were detected in some viral inocula derived from measles virus-infected Vero cells, however neutralising antibody to interleukin-1 failed to inhibit the endothelial cell procoagulant response to measles virus, whereas it significantly reduced procoagulant activity induced in endothelial cells by recombinant interleukin-1. The capacity of measles virus to induce endothelial tissue factor in vitro, may be relevant to the thrombotic vasculopathy associated with measles virus infection in vivo.

Animals↗
PubMed1994

Hepatic venular stenosis after orthotopic liver transplantation.

Fibrous stenosis of hepatic venules and other features of venous outflow obstruction, including zone 3 congestion and hemorrhage, are sometimes seen after orthotopic liver transplantation. similar changes associated with endothelial damage have recently been ascribed to azathioprine toxicity and may be forerunners of chronic rejection. Other potential causative agents such as viral hepatitis have yet to be considered. We reviewed 49 liver biopsy specimens from 21 consecutive patients after orthotopic liver transplantation, in whom full data including further follow-up biopsy samples were available. Hepatic venous stenosis was identified in seven patients who had received azathioprine and two additional patients in whom this change could not be ascribed to azathioprine. Stenosis was always associated with zone 3 hemorrhage and congestion and was first noted between 5 and 30 days after transplantation in all but two cases; in these two patients they were first noted after 72 and 133 days. Cellular rejection, including endotheliitis involving terminal hepatic venules, was found in five of the seven patients who had received azathioprine. Chronic (ductopenic) rejection was not seen during a follow-up period of between 97 and 540 days. In three of the nine patients with hepatic venular stenosis, zone 3 changes persisted, and in two of these azathioprine could not be held responsible. Of the 12 patients without hepatic venular stenosis, 10 had received azathioprine. Two of these 12 patients had peliosis-like foci but no other vascular abnormalities. Both also had moderate cellular rejection. Hepatic venular stenosis was found in 43% of patients after liver transplantation; this was usually associated with azathioprine administration and concomitant cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Serum intercellular adhesion molecule-1 in childhood malignancy.

Levels of soluble intercellular adhesion molecule-1 (ICAM-1) were measured in serum samples taken at diagnosis from pediatric patients with Hodgkin's disease (n = 69), acute lymphoblastic leukemia (n = 28), Wilms' tumor (n = 20), osteosarcoma (n = 17), rhabdomyosarcoma (n = 18), or Ewing's sarcoma (n = 15). Median levels of serum ICAM-1 were significantly higher in acute lymphoblastic leukemia and Hodgkin's disease than in controls and other malignancies. Levels were positively correlated with disease stage for patients with Hodgkin's disease, Ewing's sarcoma or Wilms' tumor, and with the frequency of relapse in Hodgkin's disease (P = .016). Serum levels were normal in all of 76 patients tested in remission. It remains to be determined whether increased serum ICAM-1 levels simply reflect a greater tumor burden or whether this molecule contributes directly to the progression of childhood malignancies.

Adolescent↗
PubMed1993

Crohn's disease and anastomotic recurrence: microvascular ischaemia and anastomotic healing in an animal model.

Microvascular injury and ischaemia may be factors in anastomotic recurrence after resection for Crohn's disease. This hypothesis was explored in a ferret model of multifocal intestinal infarction. At laparotomy, isolated loops of small intestine were injected intraarterially with styrene microspheres (test loop) or saline (control). At a second laparotomy 72 h later, test and control loops were divided and an end-to-end anastomosis performed between test loops (n = 2), test and control loops (n = 9) or control loops (n = 2). Abnormalities including chronic transmural inflammation, ulceration and granuloma formation were identified 2 weeks after the second operation in ten of the 11 surviving animals; changes were confined to the test loops and were more prominent adjacent to the anastomosis. No abnormalities were seen in control loops. The combination of two self-limiting ischaemic insults can produce a pattern of intestinal inflammation similar to that seen in anastomotic recurrence in Crohn's disease.

Anastomosis, Surgical↗
PubMed1993

Whose responsibility is it anyway? Hospital admission and discharge of older people in an inner-London District Health Authority.

The division of responsibilities that exists between primary and secondary health care services and health and social care services may create problems in the provision of care to patients whose needs mean that a number of different agencies are involved in their care. The objective of all the agencies involved is the smooth transfer of clients between different sectors of care provision. One client group thought to be particularly vulnerable to dislocations in the continuous pattern of care provision is older people. Problems over the division of responsibility between professional groups are particularly evident on admission to and discharge from hospital. It is the latter rather than the former aspect that has been the focus of research. An extensive multi-methods study of the admission and discharge of older people from hospital in an inter-city District Health Authority was undertaken. This paper examines the transfer of older people between different elements of the health and social care systems. Our study illustrates that on neither admission nor on discharge was there a clearly defined mechanism for affecting liaison between hospital and community. Clearly, the responsibility for this task must be delegated to a specific group. However, such responsibility must be given within a properly resourced and managed system, otherwise the current position of blurred responsibilities will remain. It is unclear as to how the reform of the National Health Service and the introduction of the internal market and the purchaser/provider division will aid the improved co-ordination which this study has identified as being required.

Aged↗
PubMed1993

Early histological features of small intestinal injury induced by indomethacin.

The early histological features of indomethacin-induced jejunal injury in the rat are described in tissues preserved by perfusion-fixation with 10% formol-saline. After an oral dose of indomethacin (15 mg/kg, known to cause severe multifocal ulceration of the rat jejunum), groups of rats were anaesthetized with subsequent perfusion-fixation of the gastrointestinal tract at 1, 2, 3, 6 and 48 h after dosing. Using routine light microscopic techniques, we have observed a sequence of four distinct stages, in time, of small intestinal injury. The earliest histological features were shortening of the villi, epithelial stratification, basal lamina degeneration, eosinophil degranulation and infiltration of the epithelium prior to infiltration of the mucosa by neutrophils. We consider that these earliest changes, seen at 1, 2 and 3 h, represent a distinct histological entity termed Type 1 change or villous 'tufting'. Type 2 change includes all of the features of Type 1 change plus the subsequent infiltration of the mucosa by neutrophils at 2, 3 and 6 h. Type 3 change includes necrosis of the upper-third of the villi and was mainly seen at 3 and 6 h. Type 4 change describes extreme injury to more than one-third of the mucosa with severe, acute inflammation and perforation of the bowel wall by 48 h. Although a small number of neutrophils had appeared to infiltrate the mucosa as early as 2 h after dosing, they were only significantly increased at 3, 6 and 48 h. Possible pathogenic mechanisms involved in shortening of villi as a result of smooth muscle contraction and the role of mucosal eosinophils in NSAID-induced jejunal injury in the rat are discussed.

Animals↗
PubMed1993

Short report: the absorption of fluconazole and itraconazole under conditions of low intragastric acidity.

The study investigated the oral absorption of two antifungal agents, fluconazole and itraconazole, under conditions of low intragastric acidity. Twelve healthy male volunteers received each of 4 dosing regimens: 200 mg itraconazole alone, 200 mg itraconazole and famotidine, 100 mg fluconazole alone, and 100 mg fluconazole and famotidine. Two oral doses of 40 mg famotidine were used to induce hypochlorhydria. Serum drug concentrations were measured (by high pressure liquid chromatography) for 48 h after a single dose of each anti-fungal agent. When dosed with famotidine, there was a significant 52.9% decrease of the peak intraconazole concentration (P < 0.011), and a significant 51.1% decrease of the 48-h integrated serum intraconazole concentration (P = 0.005). Famotidine-induced hypochlorhydria did not affect the absorption of fluconazole.

Adult↗
PubMed1993

Factor XIIIA subunit and Crohn's disease.

Factor XIIIA is the active subunit of plasma factor XIII that is responsible for cross linking fibrin into a stable clot. Sixteen patients with Crohn's disease were studied prospectively from relapse (Crohn's disease activity index > 150) into remission. Plasma factor XIIIA concentrations were significantly lower in active disease (median 63 (95% CI 46-72) U/dl) than remission (median 90 (95% CI 60-112) U/dl; p = 0.002). Plasma factor XIIIA concentrations correlated positively with the activity index (p = 0.005) and platelet count (p = 0.003), and negatively with serum albumin (p = 0.006). In five patients with persistent aggressive disease, the factor XIIIA concentration remained below the lower range of normal despite apparent clinical improvement in response to medical treatment. Tissues from three patients who underwent surgical resection during the study were immunostained for factor XIIIA. Gut mucosal and submucosal macrophages stained strongly for factor XIIIA. In one patient, capillary thrombi near superficial mucosal erosions immunostained for factor XIIIA in macroscopically normal mucosa. Similar changes were identified in more severely inflamed sections of intestine from the other two patients. The demonstration of significantly low plasma factor XIIIA concentrations in active Crohn's disease, and the immunostaining of factor XIIIA in capillary thrombi in the bowel wall, suggest that activation of coagulation may be involved in the pathogenesis of Crohn's disease. The plasma factor XIIIA concentration may prove a useful laboratory marker of disease activity.

Adolescent↗
PubMed1993

Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens.

Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate.

Adult↗
PubMed1993

Early mucosal changes in Crohn's disease.

Aphthoid ulceration has been regarded as an early macroscopic feature of Crohn's disease, yet the cause of this mucosal lesion is unknown. Examination of areas of apparently normal and non-inflamed bowel in Crohn's disease has allowed the identification of mucosal changes which occur before macroscopic and microscopic ulceration. Thirty five resection specimens from patients with Crohn's disease were compared with 12 specimens from patients with ulcerative colitis and 13 controls. Specimens were fixed either by immersion in formalin in the routine way or by perfusion fixation with formalin at mean arterial pressure. Immunostaining for macrophages, vessel wall, and blood constituents allowed identification of small mucosal capillaries which were not apparent otherwise. In Crohn's disease damage and rupture of these small capillaries occurred before infiltration of the lamina propria by inflammatory cells. Loss of the overlying epithelium seemed to follow this vascular damage.

Capillaries↗