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Biomedical subjects

D Kaufman

Publications and source records attributed to D Kaufman.

At least 37 records · Page 2Linked to original sources

A novel approach to laryngeal suspension after partial laryngectomy.

OBJECTIVES: Supraglottic laryngectomy is a well-established surgical therapy for selected carcinomas of the larynx and hypopharynx. Most compromised by this procedure and its variations is the laryngeal mechanism that protects the lower respiratory tract from aspiration. Laryngeal suspension serves to compensate for the loss of the resected laryngeal elevator muscles by pulling the larynx upward and forward beneath the tongue base. In this study we describe a method of laryngeal suspension in supraglottic laryngectomy using a cartilage-anchored suture carrier device. STUDY DESIGN: Report of this novel approach to laryngeal suspension using seven suture anchors in two patients undergoing supraglottic laryngectomy. METHODS: Seven Mitek Micro anchors (Mitek, Westwood, MA) were used to perform laryngeal suspension in two patients undergoing supraglottic laryngectomy. Our technique is compared with traditional methods. Operative data as well as postoperative functional results are reviewed. RESULTS: Laryngeal suspension using suture anchors was successful, with failure of only one anchor. Oral alimentation was quickly reestablished in both patients. There were no perioperative or postoperative complications. CONCLUSIONS: We describe a novel approach to laryngeal suspension that overcomes some of the technical challenges inherent in traditional suturing techniques. This novel approach is technically easier and more efficient than traditional methods and accomplishes distribution of stress forces on the thyroid cartilage remnant.

Carcinoma, Squamous Cell↗

Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer.

PURPOSE: To assess the activity and toxicity of the combination of gemcitabine and cisplatin in the treatment of chemotherapy-naive patients with metastatic urothelial cancer. PATIENTS AND METHODS: Forty-six patients with measurable stage IV carcinoma of the urothelium were enrolled onto this trial. Gemcitabine 1,000 mg/m(2) was administered intravenously for 30 to 60 minutes on days 1, 8, and 15 of each 28-day cycle. Cisplatin was administered after gemcitabine on day 1 of each cycle. The first 11 patients received an initial cisplatin dose of 100 mg/m(2). Due to the hematologic toxicity observed in several of these patients, the dose was reduced to 75 mg/m(2) in the remaining 35 patients. Patients were treated with six cycles, unless disease progression or severe toxicity necessitated earlier discontinuation. RESULTS: Ten of the 46 patients achieved a complete response and nine showed a partial response. The overall response rate was 41%. The median time to treatment failure was 5.5 months. The median survival was 14.3 months, and the 1-year survival probability was 54%. Most of the toxicities were hematologic and, in general, easily manageable. CONCLUSION: Gemcitabine plus cisplatin is active in the treatment of metastatic urothelial cancer in chemotherapy-naive patients and has an acceptable clinical safety profile. Studies are under way to further define the place of gemcitabine in combination with other chemotherapeutic agents in the treatment of metastatic urothelial cancer.

Adult↗

Family Medicine residents' knowledge and attitudes about end-of-life care.

The medical management of end-of-life symptoms, and the psychosocial care of the dying and their families have not been a specific part of the curriculum for undergraduate medical students or residency training programs. The purpose of our research was to assess family medicine residents' knowledge of and attitudes toward care of the dying. All entering (PGY1) and exiting (PGY2) residents of the Dalhousie University Family Medicine Residency Program were given a 50-item survey on end-of-life care. They survey contains two 25-item subscales concerning attitudes/opinions toward end-of-life care, and knowledge about care. Thirty-one of the 33 entering PGY1s 94%) and 26 of the 30 exiting PGY2s (86%) completed the surveys. Overall attitude scores were felt to be high among both groups, with little difference between them. Areas of concern regarding the adequacy of knowledge were found in relation to managing opioid drugs and the symptom of dyspnea. Interventions are now in development to address these issues in the residency program. In an era of subspecialties, the challenge of integrating these areas into the curriculum without creating rotations in specialist palliative care is an issue faced by most family medicine residency programs.

Attitude of Health Personnel↗

Protective role of beta-chemokines associated with HIV-specific Th responses against perinatal HIV transmission.

To examine the protective role of cellular immunity in the vertical transmission of HIV, we analyzed HIV-specific IL-2 and CTL responses, as well as beta-chemokine expression in HIV-infected and uninfected infants of HIV+ mothers. Our results showed that HIV envelope (env) peptide-specific IL-2 responses associated with beta-chemokine production were detectable at birth in the majority of uninfected infants of HIV+ mothers. The responses falling to background before the infants were 1 yr old were rarely associated with HIV-specific CTL activity. Conversely, HIV-specific Th and CTL cellular responses were absent at birth in HIV-infected infants. Infants with AIDS-related symptoms exhibited undetectable or very low levels of HIV-specific cellular immunity during the first year of life, whereas those with a slowly progressive disease showed evidence of such immunity between their second and ninth month. The latter group of infected infants tested negative for plasma HIV RNA levels shortly after birth, suggesting lack of intrauterine exposure to HIV. The presence of HIV-specific Th responses at birth in uninfected newborns of HIV+ mothers, but absence of such activities in HIV-infected infants without evidence of intrauterine HIV infection, suggests that in utero development of HIV-specific Th responses associated with beta-chemokines could mediate nonlytic inhibition of infection during vertical transmission of HIV.

Alleles↗

Low bioavailability of cyclosporine microemulsion and tacrolimus in a small bowel transplant recipient: possible relationship to intestinal P-glycoprotein activity.

With intestine transplants the allograft is dependent on itself for maintenance of adequate immunosuppression. We evaluated an intestinal transplant recipient who required very large doses of either tacrolimus or cyclosporine emulsion to achieve acceptable blood concentrations. Pharmacokinetic studies revealed bioavailabilities of 2% and 6% respectively, while D-xylose and B12 absorption were found to be within normal limits and fecal fat was only slightly increased, suggesting that there was a selective absorptive defect for these drugs. Biopsies of the allograft ileum revealed a high P-glycoprotein activity compared to the jejunum or to intestinal biopsies from other normal subjects. This may be a contributing factor to poor immunosuppressive drug absorption in this patient and others.

Biological Availability↗

Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group.

BACKGROUND: Postoperative infections remain common after high-risk gastrointestinal procedures. PGG-glucan (Betafectin; Alpha Beta Technology Inc, Worcester, Mass), derived from yeast cell walls, promotes phagocytosis and intracellular killing of bacterial pathogens by leukocytes, prevents infection in an animal model of wound infection, and acts synergistically with antibiotics to reduce mortality in rat peritonitis. HYPOTHESIS: We hypothesized that infectious complications in these patients might be reduced by the administration of a nonspecific immune-enhancing agent. DESIGN: Multicenter, prospective, randomized, double-blind, placebo-controlled trial of 1249 patients prospectively stratified into colorectal or noncolorectal strata. SETTING: Thirty-nine medical centers throughout the United States. PATIENTS: Aged 18 years or older, scheduled for gastrointestinal procedure lasting 2 to 8 hours, with 2 or more defined risk factors. INTERVENTIONS: PGG-glucan, 0.5 mg/kg or 1.0 mg/kg, or placebo once preoperatively and 3 times postoperatively. All patients received standardized antibiotic prophylaxis. MAIN OUTCOME MEASURES: Serious infection or death within 30 days. RESULTS: All randomized patients revealed no difference in serious infections and deaths in the treated groups compared with placebo groups (15% vs 14%, P>.90). In the prospectively defined noncolorectal stratum (n = 391), PGG-glucan administration was associated with a statistically significant relative reduction (39%) in serious infections and death (placebo, 46 [36%] of 129 vs either PGG-glucan group, 29 [21%] of 132 and 28 [22%] of 130, P<.02). PGG-glucan reduced postoperative infection or death in malnourished patients having noncolorectal procedures (31 [44%] of 70, placebo group; 16 [24%] of 68, 0.5-mg/kg PGG-glucan group; 12 [17%] of 72, 1.0-mg/kg PGG-glucan group; P<.001). Study drug was stopped owing to adverse effects more frequently for patients receiving PGG-glucan than placebo (2%, 4%, and 7% for the placebo group, 0.5-mg/kg PGG-glucan group, and 1.0-mg/kg PGG-glucan group, respectively, P<.003). CONCLUSION: Perioperative administration of PGG-glucan reduced serious postoperative infections or death by 39% after high-risk noncolorectal operations.

Adjuvants, Immunologic↗

Evaluation of the patient with extremity trauma: an evidence based approach.

This article reviews relevant literature to provide evidence based guidelines for the evaluation of patients with extremity trauma in the emergency department. The development of clinical decision rules for extremity trauma in the ankle and knee, and guidelines for obtaining postreduction radiographs of shoulder dislocations and nursemaid's elbows are discussed.

Ankle Injuries↗

IgY antiporcine endothelial cell antibodies effectively block human antiporcine xenoantibody binding.

Avian IgY antibodies are structurally different from mammalian IgGs and do not fix mammalian complement components or bind human Fc receptors. As these antibody-mediated interactions are believed to play significant roles in both hyperacute rejection (HAR) and acute vascular xenograft rejection (AVXR), IgY antibodies to xenoantigen target epitopes may inhibit these rejection processes. In this report, we show that chicken IgY antibodies to alpha-Gal antigen epitopes and to other porcine aortic endothelial cell (PAEC) antigens block human xenoreactive natural antibody binding to both porcine and rat cardiac tissues and porcine kidney tissues. Chicken IgY antibodies blocked complement-mediated lysis of PAECs by human serum, and inhibited antibody-dependent cell-mediated lysis of PAECs by heat-inactivated human serum plus peripheral blood leukocytes. Binding of IgY to porcine endothelial cells did not affect cell morphology nor expression of E-selectin. These results suggest that avian IgYs could be of potential use in inhibiting pig-to-human xenograft rejection.

Animals↗

The effect of waitresses' touch on alcohol consumption in dyads.

A total of 96 men and 48 women participated in a study on the effect of touch in the natural setting of public taverns in the United States. Participants in the same-gender (men-men) or mixed-gender dyads were either touched or not touched by waitress confederates. Regardless of dyad type, participants who were touched consumed more alcohol than participants who were not touched. Men in the mixed-gender dyads consumed more alcohol when the women was touched. Same-gender (men-men) dyads aggregately consumed more alcohol than mixed-gender dyads. The results are interpreted in terms of the environmental cues and the dynamics of the group.

Adult↗

Long-term follow-up of patients with rectal cancer managed by local excision with and without adjuvant irradiation.

OBJECTIVE: The long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation after local excision of T1 and T2 rectal cancers. METHODS: Ninety-nine patients with T1 or T2 rectal cancers underwent local excision with or without adjuvant irradiation at Massachusetts General Hospital and Emory University Hospital between January 1966 and January 1997. Of these, 52 patients were treated by local excision alone and 47 patients by local excision plus adjuvant irradiation. Twenty-six of these 47 patients were treated by irradiation in combination with 5-fluorouracil chemotherapy. The outcomes of these groups were compared. RESULTS: The 5-year actuarial local control and recurrence-free survival rates were 72% and 66%, respectively, for the local excision alone group and 90% and 74%, respectively, for the adjuvant irradiation group. This improvement in outcome was evident despite the presence of a higher-risk patient population in the adjuvant irradiation group. Adverse pathologic features such as poorly differentiated histology and lymphatic or blood vessel invasion decreased local control and recurrence-free survival rates in the local excision only group. Adjuvant irradiation significantly improved 5-year outcomes in patients with high-risk pathologic features. Four cases of late local recurrence were seen at 64, 72, 86, and 91 months in the adjuvant irradiation group. CONCLUSIONS: The authors recommend adjuvant chemoradiation for all patients undergoing local excision for T2 tumors, and for T1 tumors with high-risk pathologic features. The four cases of late local failures beyond 5 years in the adjuvant irradiation group underscores the need for careful long-term follow-up in these patients.

Actuarial Analysis↗

Decreased superoxide production, degranulation, tumor necrosis factor alpha secretion, and CD11b/CD18 receptor expression by adherent monocytes from preterm infants.

Preterm infants have an increased incidence of infection, which is principally due to deficiencies in neonatal host defense mechanisms. Monocyte adherence is important in localizing cells at sites of infection and is associated with enhanced antimicrobial functions. We isolated cord blood monocytes from preterm and full-term infants to study their adhesion and immune functions, including superoxide (O2-) generation, degranulation, and cytokine secretion and their adhesion receptors. O2- production and degranulation were significantly diminished, by 28 and 37%, respectively, in adherent monocytes from preterm infants compared to full-term infants (P < 0. 05); however, these differences were not seen in freshly isolated cells. We also observed a significant decrease of 35% in tumor necrosis factor alpha secretion by lipopolysaccharide-stimulated adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, this difference was not observed in interleukin-1beta or interleukin-6 production by the monocytes. The cell surface expression of the CD11b/CD18 adhesion receptor subunits was significantly decreased (by 60 and 52%, respectively) in monocytes from preterm infants compared to full-term infants (P < 0. 01). The cascade of the immune response to infection involves monocyte upregulation and adherence via CD11b/CD18 receptors followed by cell activation and the release of cytokines and bactericidal products. We speculate that monocyte adherence factors may be important in the modulation of immune responses in preterm infants.

Birth Weight↗

LeIF: a recombinant Leishmania protein that induces an IL-12-mediated Th1 cytokine profile.

We have evaluated the ability of the Leishmania protein LeIF to influence the Th1/Th2 cytokine responses and the generation of LeIF-specific T cell clones in the absence of adjuvant. We characterized LeIF-specific T cell responses in Leishmania major-infected and uninfected BALB/c mice. These mice develop a strong Th2 response during infection with L. major. When lymph node cells from infected BALB/c mice were stimulated in vitro with LeIF, only IFN-gamma (and no detectable IL-4) was found in the culture supernatant. In addition, LeIF down-regulated Leishmania Ag-specific IL-4 production by lymph node cells from infected BALB/c mice. Subsequently, Th responses were evaluated in naive BALB/c mice following immunization with LeIF. T cell clones derived from mice immunized with LeIF preferentially secreted IFN-gamma. Finally, to understand the basis for the preferential Th1 cytokine bias observed with LeIF, the ability of LeIF to influence the early cytokine profile was evaluated in splenocytes of SCID mice. We found that LeIF stimulated fresh spleen cells from naive SCID mice to secrete IFN-gamma by IL-12/IL-18-dependent mechanisms. The N-terminal half of the molecule (amino acid residues 1-226) maintained the ability to stimulate IFN-gamma from splenocytes of SCID mice. Finally, we also demonstrated that LeIF was able to provide partial protection of BALB/c mice against L. major. Thus, our results suggest the potential of LeIF as a Th1-type adjuvant and as a therapeutic and prophylactic vaccine Ag for leishmaniasis when used with other leishmanial Ags.

Adjuvants, Immunologic↗

Antibiotic susceptibility in the surgical intensive care unit compared with the hospital-wide antibiogram.

OBJECTIVE: To compare the antibiotic susceptibility of bacterial isolates from patients in the surgical intensive care unit (SICU) with hospital-wide bacterial susceptibility. DESIGN: Retrospective cohort analytic study. SETTING: Eight-bed SICU in a university-affiliated teaching hospital. PATIENTS: All hospitalized patients with culture results positive for microorganisms. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Antibiotic susceptibility data were collected retrospectively for all bacterial isolates from SICU patients during July 1, 1994, to June 30, 1995. All duplicate and surveillance cultures were eliminated from the data set. Susceptibility testing was conducted using our standard laboratory methods. Results were compared with the hospital-wide antibiogram (HWA) for the same time period. Comparisons were made using the chi(2) test with Yates correction or the Fisher exact test, as appropriate. Staphylococcus aureus (HWA, n=494; SICU, n=71) was significantly less susceptible to oxacillin (51% vs 28%; P<.001), ciprofloxacin (50% vs 25%; P<.001), erythromycin (46% vs 23%; P<.001), and clindamycin (51% vs 27%; P<.001) in the SICU. Coagulase-negative staphylococci (HWA, n=339; SICU, n=37) were significantly less susceptible to oxacillin (33% vs 16%; P=.04) and clindamycin (57% vs 34%; P=.02). Pseudomonas aeruginosa (HWA, n=513; SICU, n=96) was less susceptible to imipenem (85% vs 74%, P=.01) and more susceptible to ticarcillin-clavulanic acid (88% vs 100%, P<.001) in the SICU. Escherichia coli (HWA, n=474; SICU, n=36) was more susceptible to most penicillin-derivative antibiotics in the SICU (ampicillin [68% vs 83%, P=.06], ticarcillin [65% vs 86%, P=.01], mezlocillin [76% vs 95%, P=.01], and ticarcillin-clavulanic acid [88% vs 100%, P=.02]). CONCLUSIONS: The 2 most commonly isolated bacterial pathogens in the SICU (S aureus and P aeruginosa) had significantly different susceptibility patterns compared with the HWA. Surprisingly, E coli isolated in the SICU tended to be more susceptible to penicillin-derivative antibiotics. These data indicate that empiric antibiotic choices in the SICU may be better guided by unit-specific antibiograms.

Cohort Studies↗

Drug-induced ocular cicatricial pemphigoid: a series of clinico-pathological reports.

Ocular cicatricial pemphigoid is a slowly progressive disease of mucous membranes and skin of unknown but presumed autoimmune aetiology. We describe eight cases of presumed drug-induced cicatrising conjunctival changes simulating ocular cicatricial pemphigoid, following the chronic use of topical glaucoma medication. In three of four patients who underwent conjunctival biopsy of the inferior fornix, this revealed histopathological changes similar to ocular cicatricial pemphigoid.

Aged↗

Comparison of primary and reoperative surgery in patients with Crohns disease.

OBJECTIVE: This study was performed to determine the clinical results of patients with Crohns disease who require surgical resection. The outcome of patients undergoing initial surgery was compared with those having reoperation. METHODS: One hundred sixty-four patients undergoing intestinal resection for Crohns disease at The Mount Sinai Hospital from 1976 to 1989 were studied prospectively. The mean duration of follow-up was 72 months. RESULTS: Ninety patients (55%) underwent initial intestinal resection whereas 74 patients (45%) underwent reoperation for recurrent disease. Patients undergoing reoperation were older (33.4 vs. 38.7 years), had longer durations of disease (8.7 vs. 15.2 years), had shorter resections (60 vs. 46 cm), and were more likely to require ileostomy. Forty-seven percent of the patients with multiple previous resections required an ileostomy. This group also received a mean of 2.3 U blood in the perioperative period and showed a trend to increased symptomatic recurrence (49% vs. 71% at 5 years). CONCLUSIONS: Patients with Crohns disease undergoing first and second reoperation have outcomes similar to those in patients undergoing primary resection. Patients requiring multiple reoperations are more likely to require blood transfusions and permanent ileostomy and to show a greater trend to early symptomatic recurrence.

Adult↗