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Biomedical subjects

D R Cave

Publications and source records attributed to D R Cave.

At least 55 records · Page 3Linked to original sources

Pyoderma gangrenosum associated with ulcerative colitis: treatment with disodium cromoglycate.

Pyoderma gangrenosum is an uncommon skin disorder that is associated with ulcerative colitis, Crohn's disease, polyarthritis, and other conditions. Clinically it is usually characterized by painful ulceration of the skin and subcutaneous tissues, predominantly of the lower limbs. Treatment is empirical and often unsatisfactory. We report two cases of pyoderma gangrenosum associated with inflammatory bowel disease successfully treated with topical disodium cromoglycate.

Administration, Topical↗

Defective interfering virus particles modulate virulence.

To determine whether defective interfering (DI) particles modulate virulence by initiating a cyclic pattern of virus growth in vivo, adult mice were infected with vesicular stomatitis virus (VSV), both with and without DI particles. A total of 184 mice divided into groups were inoculated intranasally. A majority of mice inoculated only with standard VSV developed paralysis, most of them between days 7 and 9. The addition of DI particles altered the development of paralysis in several ways. When there was significant protection, a few still became paralyzed on days 7 and 9. When overall mortality was unaffected or even slightly increased, the majority of mice became paralyzed between days 7 and 9 as well. Protection could not be predicted based on a single ratio of standard VSV to DI particles or on the absolute amount of DI particles inoculated. Infectious virus recovered from mouse brains at the time of paralysis and incipient death showed considerable variation, although the titer in a majority of the animals was between 10(5) and 10(7) PFU/ml. When the brains of these paralyzed mice were examined for hybridizable VSV RNA, the detection of standard VSV RNA correlated well with infectivity. The amount of DI RNA in the coinfected mice was more variable and independent of the amount of 40S RNA, although DI RNA was usually found when standard RNA was present. Survivors examined between days 14 and 21 did not contain infectious virus or any detectable viral RNA in their brains. Because these results were consistent with the hypothesis of viral cycling in vivo, rather than a gradual accumulation of total infectious virus, mice were coinfected with 10(8) PFU of standard VSV and 10(5) PFU equivalents of DI particles and sacrificed daily thereafter, irrespective of whether they developed paralysis. Infectivity measurements indicated a reproducible cycling pattern of VSV in the mouse brains with a periodicity of about 5 days. This cycling and the detection of DI RNA in brains several days after intranasal inoculation suggest that there is a dynamic continuous interaction between standard VSV and its DI particle beyond the initial site of replication as the virus population spreads into the host animal. Such cycling of virus production before the full development of specific immune responses from the host may have important implications for viral diagnostics and disease transmission.

Animals↗

Histofluorescent and radioenzymatic analysis of colonic catecholamines in man.

Colonic tissues from patients with ulcerative colitis (UC), ileal tissue from patients with Crohn's disease (CD), and other ileocolonic disorders were radioenzymatically assayed for norepinephrine (NE) and dopamine (DA). These assays showed that the NE content of UC colon ranged from 3.2 to 4.3 ng/mg wet tissue, while in other colonic disorders it ranged from 3.0 to 5.3 ng/mg. Similarly, the DA content of UC colon ranged from 0.42 to 1.17 ng/mg wet tissue, while for other colonic disorders it ranged from 0.48 to 0.89 ng/mg. The same tissues were examined histochemically using glyoxylic acid condensation of catecholamines (CA) for the semi-quantitation of CA-containing structures. Examination of these structures revealed an apparent increase in their staining intensity in the myenteric plexus in ulcerative colitis as compared to other colonic disorders. Morphologically, the CA-containing structures of the colon appeared to be increased in UC, but determination of the NE and DA concentrations in colonic samples revealed no statistically significant differences in comparable regions of the colon.

Colitis, Ulcerative↗

Detection of vesicular stomatitis virus RNA and its defective-interfering particles in individual mouse brains.

To develop a highly sensitive and direct assay for defective interfering (DI) particles of vesicular stomatitis virus (VSV), we reverse transcribed RNA from DI particles and cloned the DNA in pBR322 and used it as hybridization probes. At the lower limit, cDNA of about 850 nucleotides detected 150 pg of VSV RNA. For differentiation of hybridizable sequences found in the RNA of DI particles from complementary or identical sequences in the L mRNA or standard genomic RNA of VSV, RNA obtained from mouse brains was first separated by size, blotted onto nitrocellulose, and then hybridized to in vitro-labeled cDNA probe. Genomic VSV, DI, or L mRNA sequences from one-half of the brain of an infected mouse were detectable, whereas uninfected mice failed to react with this specific probe. When mice were infected intranasally with 10(8) PFU of standard VSV, most of them died between days 6 and 7, and the detection of standard genomic RNA correlated with paralysis and death. DI RNA was not detected in these mice. When mice were infected with 10(8) PFU of standard VSV together with an equivalent amount of DI particles, similar results were obtained. When fewer DI particles were inoculated together with standard virus, significant protection of mice occurred together with the detection of DI RNA. These results indicate that DI particles are protective in vivo and that the details of the virus-host interaction may resemble the cyclic growth patterns in cell cultures for standard VSV and its DI particles.

Animals↗

Crohn's ileitis and ileocolitis: a study of the anatomical distribution of recurrence.

The records were reviewed of 56 consecutive patients with Crohn's disease (CD) who had had an ileocolonic anastomosis formed during surgical resection for Crohn's ileitis or ileocolitis. Twenty-seven patients (48%) were found to have radiological, pathological, or surgical evidence of recurrent CD. Of 24 patients with a diagnosis of Crohn's ileitis at initial surgery, 9 were found to have recurrent disease proximal to the anastomotic site. Of 32 patients with ileocolitis, 11 had recurrent disease proximal and distal to the anastomosis. Contrary to many prior reports, recurrent CD is not always located proximally to a surgical anastomosis. The distribution of recurrent CD tends to be a statistically significant function of the initial anatomical location with proximal recurrence found most often in Crohn's ileitis, while proximal and distal recurrence is associated with Crohn's ileocolitis (X2 = 4.5 P less than 0.05).

Adolescent↗

Induction of granulomas in mice by Crohn's disease tissue.

Normal and immunodeficient CBA and A2G strain mice were inoculated with crude (100 to 20 to 30 micrometer), cell-free (0.2 micrometer) filtrates of Crohn's or noninflammatory bowel disease tissue homogenates, which were either fresh or frozen to -70 degree C. Mice of each strain developed epithelioid and giant cell granulomas both locally at the site of injection and systemically in response to crude and cell-free filtrates of Crohn's tissues. Control mice did not develop such changes. The granulomas evolved slowly, predominantly between 9 and 27 months. The granuloma-inciting agent has been shown to be present in ileum, colon, and mesenteric lymph nodes of patients with Crohn's disease and it withstands freezing to -70 degree C. The use of Crohn's tissues common to this study and one in rabbits previously reported, suggests that the induction of granulomas by this agent is not strain- or species-specific, and is independent of the immune status of CBA mice.

Animals↗

Evidence of an agent transmissible from ulcerative colitis tissue.

Five New Zealand White rabbits were injected intracolonically with homogenates (100 mum) of ulcerative-colitis tissue. Histological changes closely similar to those seen in the human donors were present in the mucosa and submucosa of the large intestine of four of these rabbits 3-12 months later. Similar changes were seen in the large intestine of three of four rabbits 6-13 months after intravenous or intracolonic inoculation of homogenates of rabbit mesenteric lymph-nodes after passage of human ulcerative colitis tissue (100 mum or 0.2 mum). Three of thirty A2G strain mice injected with similar tissue homogenates (100 mum or 0.2 mum) from patients with ulcerative colitis into the footpad or intraperitoneally, had granulomatous changes in footpad, bowel, liver and/or spleen 3-22 months later. Such changes did not develop in rabbits or mice inoculated with tissue from normal controls. The results of these experiments suggest that a transmissible factor is involved in the aetiology of ulcerative colitis.

Animals↗

Place of azathioprine for Crohn's disease.

The clinical effects of azathioprine have been compared with those of corticosteroids in a group of 112 patients who have come under the care of a single unit between 1963 and 1975. There is no clear evidence that azathioprine alters the course of the disease in the long term; it is of value in obtaining a remission, particularly when the disease affects the large intestine.

Adrenal Cortex Hormones↗

Experimental animal studies of the etiology and pathogenesis of Crohn's disease.

Nineteen New Zealand White Rabbits were inoculated intramurally into the intestine with a 100- or 0.2-mu filtrate of homogenate of fresh ileum or colon from each of 6 patients with histologically confirmed Crohn's disease and compared with 22 animals injected with homogenates of normal ileum or colon from each of 5 patients; 4 sham controls were also included. The animals receiving Crohn's homogenates put on less weight than the controls; mucosal ulceration, ileal thickening, and abscess formation were seen in 8 animals and granulomatous changes evolved in 9. No significant macroscopic abnormalities or granulomatous changes were present in any of the 22 control inoculated rabbits. Successful first passage was achieved from 6 of 11 rabbits. The results of these experiments therefore confirm and extend those of our earlier reports and demonstrate that the transmissible agent or agents responsible must approximate to the size of a virus or be capable of being deformed to pass through a 0.2-mu filter.

Animals↗

Endoscopic pulsed dye laser lithotripsy of gallbladder calculi in vivo.

We have evaluated the efficacy and safety of pulsed dye laser lithotripsy of gallbladder calculi using a percutaneous endoscopic technique in a porcine model. Fragmentation was readily achieved in vivo. Using a combination of laser lithotripsy and saline lavage, complete removal of all stone debris was feasible through a 24 F tract (N = 3). However, the degree of fragmentation required rendered removal through a smaller tract inefficient, a mean 53% of stone mass being retrievable through a 16 F tract (N = 11). Repeated laser activation at 1 mm from the gallbladder mucosa produced minimal injury, regardless of pulse energy. When the laser fiber was pressed against the mucosa, perforation of the gallbladder was possible at therapeutic pulse energy, but this did not lead to clinical sequelae. We conclude that the pulsed dye laser is a safe and effective means of fragmenting gallbladder calculi in vivo.

Animals↗