Lessons for inflammatory bowel disease from rheumatology.

There are several areas of overlap between gastroenterology and rheumatology, some related to the side effects of drugs but others related to the similarities in probable pathogenic mechanisms and treatments. This is best illustrated by comparison between inflammatory bowel disease and rheumatoid arthritis-conditions of uncertain aetiology that are due to a combination of genetic and environmental factors and are associated with chronic inflammation in the absence of any clearly recognisable pathogen. Medical research is increasingly specialised but careful comparison of the relevant gastroenterological and rheumatological literatures suggests several common areas that are worthy of greater attention than they are currently receiving. These could include studies to address the following questions: (1) What are the functional and antigen-binding differences of the HLA class II alleles that are differently associated with rheumatoid arthritis and ulcerative colitis? (2) Why are both Crohn's disease and rheumatoid arthritis associated with smoking, yet, with one condition (Crohn's disease) increasing recently in incidence and the other (rheumatoid arthritis) becoming less common? (3) Which genetic and/or environmental factors distinguish the Turkish patients with HLA-B51-associated Behcet's disease who tend not to develop colitis and the Japanese patients with HLA-B51-associated Behcet's disease who develop colitis? (4) Is pANCA directly involved in the pathogenesis of ulcerative colitis-given evidence of its direct involvement in the pathogenesis of vasculitis? (5) Given the arguably greater similarity between rheumatoid arthritis and ulcerative colitis than with Crohn's disease, is etanercept effective in ulcerative colitis? (6) Do the very different risks of cancer in chronically inflamed colon and inflamed joints imply that cancer development requires both NFkappaB activation, to inhibit apoptosis, and the presence of agents, such as bacteria, to initiate DNA damage?     

Criteria for Selective Utilization of the Intensive Care Unit following Carotid Endarterectomy

n = 62, p < 0.05), emergent CEA (n= 2, p= 0.01), and need for postoperative anticoagulation (n= 2, p= 0.01). Only 56 (15%) of patients had indications for ICU admission, 57 (16%) would have been admitted to an EKG-monitored nursing unit, and 252 (69%) would have been admitted to a standard nursing unit. Immediate admission to the ICU after CEA is indicated for patients undergoing emergent CEA, those requiring anticoagulation postoperatively, those with intraoperative stroke or major cardiac complication, and possibly those with chronic renal failure. All other patients should be admitted to the RR. Patients experiencing stroke, major cardiac events, significant wound hemorrhage, or reintubation in the RR, and those requiring vasoactive medication more than 3 hours after surgery should be transferred to the ICU. Patients with indications of cardiac disease within 6 months prior to CEA but no indications for ICU admission may be discharged from the RR to an EKG monitored unit. All others may be discharged to a standard nursing unit.     

Peanut agglutinin in combination with CD19 monoclonal antibody has potential as a purging agent in myeloma.

Administration of high-dose chemotherapy to patients with myeloma, followed by rescue with autologous bone marrow transplantation (ABMT), sometimes induces complete disease remission but relapse is usual. We have attempted to reduce the risk of relapse by selective in vitro removal of myeloma cells from the autologous graft. A combination of the (gal-galNac)-binding lectin peanut agglutinin (PNA), which binds all plasma cells, and the pan-B monoclonal antibody CD19 was assessed for purging marrow of myeloma cells and their putative precursors using a magnetic bead method. Preliminary experiments performed on peripheral blood mononuclear cells spiked with fluorescent-labeled PNA+ Kirk tumor cells showed that a magnetic bead: target cell ratio of 40:1 resulted in a greater than 3-log reduction in PNA+ cells. This technique was then applied to 17 samples of myeloma bone marrow and to 18 samples of normal bone marrow spiked with PNA+ Kirk cells and CD19+ hairy cell leukemia cells. In each case all detectable plasma cells and CD19+ lymphocytes were effectively removed, and normal hemopoietic progenitor cell recovery was greater than 55%. This purging system deserves further study as a means of reducing relapse rates in myeloma patients treated by a combination of high-dose chemotherapy and ABMT.     

The Canadian Psychiatric Association practice profile survey: I. Methods and general sample characteristics.

OBJECTIVE: To describe the rationale, methodology, and general sample characteristics of the Canadian Psychiatric Association (CPA) practice profile survey, a national survey of psychiatrists and psychiatric practice. METHOD: Mail-in interviews were sent to all Canadian psychiatrists listed in their provincial registers and to all active CPA members (total = 3628). Respondents provided general information about their professional activities for one 24-hour day and detailed information for 1 randomly selected hour. Patient information--including sociodemographics, diagnostic profiles, functioning levels, risk of harm to self or others, and disposition--was elicited for 1 patient seen during the random hour as well as for the most seriously ill patient receiving clinical services that day. RESULTS: There was a 45.5% response rate. Questionnaires completed by nonpsychiatrists or with a large percentage of missing or incorrect data were eliminated (107 surveys), resulting in a final sample size of 1570. CPA members and those from Western Canada responded at a higher rate to the survey. The results suggest some cause for concern about future manpower shortages. Most psychiatrists practise eclectically, seeing patients across the life-span, and working in both community and institutional settings. The old and the young appear to be underserviced, compared with adults. CONCLUSIONS: This study represents an important step forward in evaluating the profile and activities of the profession.     

Novel antagonists of the 5-HT3 receptor. Synthesis and structure-activity relationships of (2-alkoxybenzoyl)ureas.

A series of benzoylureas derived from bicycle amines were prepared and evaluated for 5-HT3 antagonist activity on the rat isolated vagus nerve. From among these compounds, those analogues which were ortho substituted by an alkoxy group on the benzoyl function were shown to be potent 5-HT3 antagonists with similar or greater potency than the standard agent ondansetron. NMR and X-ray crystallography studies showed these o-alkoxy compounds to exist as a planar, hydrogen-bonded, tricyclic ring system. In molecular modeling studies on endo-N-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl-amino] carbonyl]-2-(cyclopropylmethoxy)benzamide (30) the central hydrogen-bonded ring was able to mimic an aromatic ring present in previously reported 5-HT3 antagonists.     

Weapon involvement and injury outcomes in family and intimate assaults.

OBJECTIVE--To compare the risk of death and the risk of nonfatal injury during firearm-associated family and intimate assaults (FIAs) with the risks during non-firearm-associated FIAs. DESIGN--Records review of police incident reports of FIAs that occurred in 1984. Victim outcomes (death, nonfatal injury, no injury) and weapon involvement were examined for incidents involving only one perpetrator. SETTING--City of Atlanta, Ga, within Fulton County. PARTICIPANTS--Stratified sample (n = 142) of victims of nonfatal FIAs, drawn from seven nonfatal crime categories, plus all fatal victims (n = 23) of FIAs. MAIN OUTCOME MEASURES--Risk of death (vs nonfatal injury or no injury) during FIAs involving firearms, relative to other types of weapons; risk of nonfatal injury (vs all other outcomes, including death) during FIAs involving firearms, relative to other types of weapons. RESULTS--Firearm-associated FIAs were 3.0 times (95% confidence interval, 0.9 to 10.0) more likely to result in death than FIAs involving knives or other cutting instruments and 23.4 times (95% confidence interval, 7.0 to 78.6) more likely to result in death than FIAs involving other weapons or bodily force. Overall, firearm-associated FIAs were 12.0 times (95% confidence interval, 4.6 to 31.5) more likely to result in death than non-firearm-associated FIAs. CONCLUSIONS--Strategies for limiting the number of deaths and injuries resulting from FIAs include reducing the access of potential FIA assailants to firearms, modifying firearm lethality through redesign, and establishing programs for primary prevention of violence among intimates.     

Use of a synthetic peptide-based elisa for the diagnosis of infectious mononucleosis and other diseases

A simple enzyme immunoassay has been developed based on measuring antibodies to synthetic peptides corresponding to sequences in the Epstein-Barr nuclear antigen (EBNA). This assay, which is reproducible, quantitative, and simple to perform and interpret, can be an effective tool to aid in the diagnosis of infectious mononucleosis and nasopharyngeal carcinoma.     

The histology of anal skin tags in Crohn's disease: An aid to confirmation of the diagnosis

We have investigated excision biopsy of anal skin tags as an adjunct to rectal biopsy in the diagnosis of Crohn's disease. Twenty-six patients with proven Crohn's disease of the large and/or small bowel were studied. All had perianal skin tags removed under local anaesthesia as outpatients, when rectal biopsies were also obtained. Three sections from each skin tag and three from each rectal biopsy were examined for granulomas. The rectal biopsies were also examined for changes suggestive of Crohn's disease. Anal skin tags from 26 patients without Crohn's disease acted as controls. Of the patients with Crohn's disease, granulomas were found in both anal skin tags and rectal biopsies in five patients, in anal skin tags only in four, and in rectal biopsies only in three. When present, granulomas were more plentiful in anal skin tags than in rectal biopsies, being seen in all 3 sections in 7 of 9 positive tags (i. e.: in 31% of 78 sections), compared to only 1 of 8 positive rectal biopsies (i. e.: in 13% of 78 sections). No granulomas were seen in control anal skin tags. The procedure provides a simple technique which is complementary to rectal biopsy, by which histological confirmation of Crohn's disease may be obtained.This work was presented in part to the International Surgical Scientific Conference at the Bicentenary Meeting of the Royal College of Surgeons in Ireland, 1984     

Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin

Summary The highly lipophilic cyanomorpholinyl adriamycin (CMA) is the most potent antineoplastic anthracycline yet described. CNS distribution and toxicity were examined after i.v. administration of CMA to mice. At doses 0.1 mg/kg, a neurotoxic syndrome including ataxia, hypokinesia, and tremors appeared. At doses of 0.05 mg/kg, which have been reported to be antineoplastic, no neurotoxicity was observed. On histopathologic examination, no changes were observed in the brain, spinal cord, or dorsal root ganglia. Unlike adriamycin (ADR), which rapidly appears in the nuclei of several tissues, CMA showed no fluorescence, suggesting a different cellular microcompartmentalization. The i.d. injection of CMA disclosed a 200-fold increase in toxicity compared with that of adriamycin. In comparisons of CMA and ADR, neurotoxicity and cardiotoxicity occurred equally only at higher doses; however, the dermatotoxicity and antineoplastic activity of CMA were increased several hundred-fold.