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.     

Cognitive learning during surgical residency. A model for curriculum evaluation.

The program summary of the American Board of Surgery In-Service Training Exam (ABSITE) can be used to quantitate cognitive learning during a surgical residency and to identify areas of curricular weakness in a residency program. Knowledge on each question is categorized as high (known) or low (unknown) depending on the percentage of residents who answered correctly. Knowledge of Level 1 (entry) residents is then compared with Level 5 (exit) residents. Each ABSITE question can thus be categorized on entry versus exit as known-known, unknown-unknown, unknown-known, and known-unknown. Only about half of unknown knowledge on entry appears to become known on exit. Very little knowledge known on entry becomes unknown on exit. Weaknesses in specific subject areas can be readily identified by ranking questions according to the number of exiting residents who answer incorrectly. Use of this technique to quantitate cognitive learning in a residency program may allow objective assessment of changes in curriculum.     

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.