Biomedical subjects
Publications and source records attributed to J Landman.
Laparoscopic adrenalectomy was performed early in the second trimester of pregnancy in a woman with an aldosteronoma causing hypertension (254/154 mm Hg). The patient was later delivered of a healthy baby. With suitable precautions and timing, major laparoscopic surgery can be performed safely during pregnancy.
PURPOSE: The indications for laparoscopic nephrectomy have grown to include renal malignancy. Although morcellation of these specimens has been described, to our knowledge we present the first systematic review of the feasibility and validity of pathological evaluation of these tumors with regard to grade and stage. MATERIALS AND METHODS: Nine formalin fixed and 5 fresh intact radical nephrectomy specimens were evaluated by 2 pathologists before and after high speed electrical tissue morcellation. The ability to distinguish tissue histology, and tumor size, stage and grade were compared. Impermeability of the laparoscopy sack after morcellation was also evaluated using indigo carmine stained normal saline placed in the used sack. RESULTS: The 9 preserved specimens included 7 renal cell carcinomas and 2 oncocytomas, while 4 of the 5 fresh specimens were renal cell carcinoma and 1 was oncocytoma. Overall tumor size was 2 to 7 cm. (mean 4.9). The 4 fresh renal cell carcinomas were of the clear cell type. Comparison of pathological evaluation after morcellation by another pathologist revealed identical histology, grade and stage for each tumor. Four cases of perinephric fat invasion (3 fixed and 1 fresh specimens) were identified after morcellation. Only tumor size was not assessed after morcellation. Laparoscopy sack integrity was confirmed in 13 of 14 cases. In 1 case involving a formalin fixed specimen a gross defect in the laparoscopy sack was demonstrated after morcellation. CONCLUSIONS: Morcellation of radical nephrectomy specimens in vitro did not alter the determination of histology, grade or local invasiveness of tumor. For all fresh tissue and remarkably for all but 1 formalin fixed tissue specimen the laparoscopy sack remained intact. Preliminary data from this in vitro model imply that limited in vivo morcellation of radical nephrectomy specimens may be performed without sacrificing staging information.
We describe our initial experience with the novel application of processed human cadaveric allograft skin in reconstruction of a damaged corpus cavernosum associated with distal extrusion of a penile prosthesis. The material was evaluated for ease of reconstruction, adequacy of repair, and outcome. Human processed dermis allograft requires no intraoperative harvesting, is technically easy to fashion, and offers adequate tensile strength in the reconstruction of damaged corpora cavernosa. This initial experience with processed human cadaveric dermis in reconstruction of damaged corpora cavernosa is encouraging. Further evaluation to define the long-term efficacy and scope of application of this material in urologic reconstructive procedures is warranted.
As disasters and conflict increase, a higher proportion of total food aid is given as humanitarian aid. Most food aid is in the form of cereals, primarily wheat. The main donors are the USA and the EU, but there is an increase in the numbers of donors, including non-governmental organizations, buying food rather than using surpluses. Alongside the greater diversity and complexity of food aid, there is more controversy about policy and practice. If disasters are development failures, emergency food aid must be a step in the continuum from relief to rehabilitation. Comparisons of the seventeen countries that were major recipients of food aid (> 10,000 t) in 1997, show diversity in social development, dietary pattern, number of refugees, relative food inadequacy and wasting (i.e. % standard weight-for-height > 2 SD). In the absence of information of consistent quality, what influences the scale of emergency aid is unclear and susceptible to politicization, so that need and supply may not be matched. Local considerations seem to be as important as external food aid for the nutrition of the recipients. Challenges for the future include assuring the nutritional quality of rations to solve deficiency problems. The implications for the professional public health nutritionist working on emergency food provision include continuing professional development to enhance the technical expertise necessary to design appropriate feeds or rations. These public health nutritionists, more than others, require a grounding in social science theories that underpin management, ethics of professionalism and the politics of food aid.
Two fractions of a three-day-old apheresis platelet collection from a known habitual donor were transfused to two children with thrombocytopenia and bleeding. Both patients developed evidence of severe infection during the transfusion. One died despite intensive care and antimicrobial therapy. The other, whose transfusion was cut short, recovered. A Klebsiella oxytoca strain was recovered from the two transfusion bags, from a third unused bag, and from blood samples from the patient who died. Genotyping results established that all these isolates were identical. Tests for K. oxytoca were negative on the batches of blood donation material, the bottle of antiseptic used, and throat and stool specimens from the donor and phlebotomists. The most likely hypothesis is that the donor developed transient asymptomatic bacteremia during the 136-minute-long collection procedure and that the organism subsequently grew in the platelet collections, which were kept at 20-24 degrees C with agitation for three days before being used.
BACKGROUND: In an attempt to find a more sensitive and specific noninvasive assay for the detection of bladder carcinoma, the authors assayed exfoliated cells from patients' voided urine for the presence of telomerase, an enzyme that maintains a cell's chromosomal length and is thought to be active in the transformation of normal somatic cells into immortal human tumor cells. METHODS: The authors used a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay to determine the presence of telomerase activity in voided urine samples from patients with known but yet untreated bladder carcinoma (n = 104) and from patients with hematuria of benign causes (n = 47). For 88 of the patients with bladder carcinoma, cytology was determined independently of the telomerase results or the pathology findings. RESULTS: Of the 104 bladder carcinoma specimens, 88 (85%) tested positive for the presence of telomerase. Seventy-nine percent (23 of 29) of the Grade 1 tumors, 84% (32 of 38) of the Grade 2 tumors, and 87.5% (28 of 32) of the Grade 3 tumors were positive for telomerase activity. Five patients with carcinoma in situ (100%) were also positive. Telomerase activity was not found in 31 of 47 patients with bladder calculi, benign urethral stricture, benign prostatic hyperplasia, or inflammation. In the 16 patients (34%) who did have a false-positive result when tested for telomerase, all had either chronic or severe inflammation, including 1 patient with an inverted papilloma, 1 patient with cystitis cystica, and 1 patient with cystitis glandularis. However, for 35 normal, healthy volunteers whose voided urine samples were also assayed for the presence of telomerase activity, none was found. By comparison, only 51% (45 of 88) of the cytology samples from patients with bladder carcinoma yielded positive findings, whereas 49% (43 of 88) resulted in false-negative readings for tumors. Only 13% (3 of 23) of the Grade 1 tumors, 44% (14 of 32) of the Grade 2 tumors, and 82% (23 of 28) of the Grade 3 tumors were diagnosed by cytology. All five patients with carcinoma in situ were positive for cytology as well as for telomerase activity. When cytology was compared with the PCR-based telomerase assay in determining the presence of bladder carcinoma, the difference in the overall detection rates (85% for telomerase vs. 51% for cytology) was significant (P < 0.001). Furthermore, when telomerase activity was compared with cytology for low grade lesions (Grades 1 and 2), the difference in the detection rates (82% for telomerase vs. 31% for cytology) was also significant (P < 0.001). CONCLUSIONS: Urinary cytology yields poor results for low grade tumors. This study shows the possible application of the telomerase assay in detecting bladder carcinoma, in particular low grade tumors, in voided urine samples.
OBJECTIVES: The recent introduction of novel molecular markers into clinical urology has created a need to evaluate the efficacy and utility of these potential markers. The ideal assay for bladder cancer should be noninvasive, sensitive, specific, and cost-effective. We compared the Matritech nuclear maxtrix protein (NMP)-22 assay, telomerase activity, and the Bard bladder tumor antigen (BTA) assay for the detection of human bladder cancer. METHODS: A single voided urine sample was obtained from patients with hematuria without bladder cancer and from patients with known bladder cancer before any treatment. Approximately 50 to 100 mL of voided urine sample was collected and aliquotted for the various assays. The results were compared to single cytologic results and ultimately to pathologic findings. RESULTS: In 47 patients with bladder cancer, the overall sensitivity was 81% for NMP-22, 80% for telomerase, 40% for BTA, and 40% for cytology. For Ta tumors (n = 31), sensitivity was 81% for NMP-22, 70% for telomerase, 32% for BTA, and 26% for cytology. For T1 or higher stage tumors (n = 13), sensitivity was 82% for NMP-22, 91% for telomerase, 64% for BTA, and 64% for cytology. The remaining 3 patients had carcinoma in situ (CIS). When tumors were stratified by tumor grade, grade I tumors (n = 16) were detected at 69% with NMP-22, 65% with telomerase, 13% with BTA, and 6% with cytology. Grade II tumors (n = 14) were detected at 86% with NMP-22, 72% with telomerase, 36% with BTA, and 36% with cytology. Grade III tumors (n = 14) were detected at 93% with NMP-22, 93% with telomerase, 79% with BTA, and 79% with cytology. Patients with CIS (n = 3) were detected at 67% with NMP-22, 100% with telomerase, 33% with BTA, and 67% with cytology. In 30 patients with hematuria but without bladder cancer, the overall specificity of the assays was 77% for NMP-22, 80% for telomerase, 73% for BTA, and 94% for cytology. CONCLUSIONS: In the population tested, NMP-22 and the telomerase assays gave similar sensitivity and specificity for the detection of bladder cancer, and appear to offer a greater sensitivity than the BTA assay and/or conventional cytology.
OBJECTIVES: To describe how the Nutrition Society developed public health nutrition as a profession between 1992 and 1997, and to analyse the influences propelling on this professionalization. DESIGN: Qualitative case study. SETTING: Britain. RESULTS: The Nutrition Society of Britain consulted with various stakeholders (such as dietitians, researchers, professionals and practitioners and educators from the UK, and latterly from mainland Europe) to build a consensus about the definition, roles and functions of public health nutritionists and the need for, and scope of, this new profession. Building on this consensus, the Society developed a curriculum in line with British national nutrition policy. Analysis shows that the design and philosophy of the curriculum is explicitly international and European in orientation, in keeping with the tradition of the discipline and the Society. The curriculum is designed in terms of specialist competencies in public health nutrition, defining competency so that registered public health nutritionists are advanced practitioners or leaders: this is in keeping with contemporary trends in professional education generally and as expressed by the UNU/IUNS and at Bellagio, in nutrition in particular. CONCLUSIONS: Despite a unique relationship with British state and policy, this case of professionalization contributes to contemporary international inter- and intraprofessional debates about the nature of public health nutrition and is consistent with professional educational theory.
Voided urine from patients with bladder cancer and from control patients with either hematuria or with no urologic conditions were examined for telomerase activity in order to explore the possibility that this activity could be used as a marker for the detection of bladder cancer. This assay was found to have an overall sensitivity in detecting bladder cancer of 85% (88/104) with 79% (23/29) grade 1 tumors, 84% (32/38) grade 2 tumors, 87.5% (28/32) grade 3 tumors, and 100% (5/5) carcinoma in situ testing positive. This compared favorably with urinary cytology which had an overall sensitivity of 51% and sensitivities of 13%, 44%, 82%, and 100% for grades 1, 2, 3 tumors and carcinoma in situ, respectively. The specificity of telomerase in patients with benign causes of hematuria was 66%, and in normal volunteers without urologic conditions, it was 100%. Assessment of nuclear matrix protein suggested comparable sensitivity and specificity. Evaluation of bladder tumor antigen showed less sensitivity for low-grade disease and less specificity, as it was influenced by inflammation and instrumentation. Telomerase thus seems to be a means whereby low-grade tumors may be detected in examination of voided urine and may offer an advantage in monitoring for recurrent disease.
Bladder cancer has classically been associated with exogenous risk factors, and a large literature has identified risk factors associated with the genesis of transitional cell carcinoma. Only recently have efforts been made to identify host factors and to evaluate possible changes in tumour presentation and biology, including grade and stage, in association with these risk factors. The available literature appears to demonstrate alterations in tumour biology associated with environmental carcinogens. Various studies have suggested a consistent upgrading of bladder cancer stage and grade as a result of cigarette smoking and high risk occupational exposures. It is important, however, that all factors associated with increased risk for bladder cancer be more extensively evaluated in assessing the validity of this concept.
We report on six cases of unrelated UCB transplant in adult patients with hematological malignancies: three chronic myelocytic leukemias and three acute leukemias. Their median age and body weight were respectively: 28 years (range 15.5-40) and 55.5 kg (range 46-90). The cord blood units were from the New York Blood Center. The median number of nuclear cells provided, evaluated before thawing, was 2.1 x 10(7)/kg (range 1 x 10(7)/kg-4.7 x 10(7)/kg). The degree of HLA disparity was 1/6: two patients, 2/6: three patients, 3/6: one patient. The patients received a pretransplant regimen including total body irradiation. They were given graft-versus-host disease prophylaxis which consisted of cyclosporin A and corticosteroids. They were all given a combination of G-CSF and erythropoietin. The median time of white blood cell and platelet reconstitution were respectively 24 days (range 12-43) and 60 days (range 23-90). All the patients had a full chimerism. A grade I acute GVHD was observed in four patients and two patients do not have any GVHD. No chronic GVHD has been observed yet. Three patients died from toxicity. Three patients are alive and well in complete remission at 2 years, 1 year and 11 months post-graft.
Vertebrates have special structures at the ends of their chromosomes, known as telomeres, which are composed of 5- to 15-kb pairs of a guanine-rich hexameric repeat (TTAGGG)n. In normal somatic cells there is a progressive degradation of telomeres with aging. The cell can afford to lose only a finite number of these telomeres before significant sequences of the parent DNA are lost, resulting in chromosomal instability and cell death. However, germ-cell telomeres are maintained despite multiple rounds of replication. This suggests that they produce an enzyme that maintains their telomere length. This enzyme, a ribonucleoprotein, is called telomerase. In this review, we discuss the presence of telomerase activity in various human cancers and, in particular, in urologic tumors. We describe the potential clinical utility of detection of the presence of telomerase activity in cells from voided urine samples of patients with bladder cancer.
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In vitro determination of brain glucose metabolism in the temporal cortex from patients with Alzheimer's disease showed a marked decrease when compared with nondemented, age-matched control subjects. Additional determinations on normal human temporal cortex obtained at autopsy demonstrated an age-dependent decline in the rate of glucose use. These data provide an in vitro correlate for positron emission tomography studies that suggest decreased brain glucose use in Alzheimer's disease.
RATIONALE AND OBJECTIVES: Iopromide is a nonionic monomeric contrast agent. Initial laboratory and clinical data have shown that it is relatively safe. Efficacy for excretory urography has been shown to be good, comparable with other low-osmolality agents. The authors attempted to confirm these impressions in a randomized, double-blind comparison with equivalent doses of ioversol and iopamidol. METHODS: Two hundred adult patients undergoing excretory urography were studied. One hundred received iopromide, 40 received ioversol, and 60 received iopamidol (300 mg I/kg) as an intravenous bolus. Urographic films (obtained 1, 5, 15, and 20 minutes after the bolus, and postvoid) were interpreted by an observer blinded to contrast type. Visualization of renal parenchyma, pelvis and calyces, ureters, and bladder was independently assessed as excellent, good, poor, or nonvisualized. Vital signs were recorded before, 30 to 60 minutes after, and 24 hours after injection. Adverse reactions were sought, physical examinations were performed, and standard hematology and serum chemistry values were measured before and 1 day after injection; a 72-hour serum creatinine level was also measured. RESULTS: Ninety-eight percent of visualization scores were good or excellent; no significant differences among iopromide, iopamidol, and ioversol were found, nor were there any significant differences among groups in vital signs. Only one patient experienced a contrast-related physical examination change (subcutaneous extravasation). No significant changes with regard to hematology or serum chemistry values were observed; there was no contrast-induced nephropathy. Mild adverse reactions were experienced by 10% of patients; there were no significant differences in reaction rates among contrast agents. CONCLUSIONS: Iopromide at a dose of approximately 300 mg I/kg is safe and effective as an excretory urographic agent and is comparable in performance with ioversol and iopamidol.
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Since 1976, patients grafted at the Hôpital Saint-Louis for Fanconi anemia (FA) without evidence of leukemic transformation have been given a uniform conditioning regimen that consisted of low-dose cyclophosphamide (Cy) and thoracoabdominal irradiation (TAI). The use of low-dose Cy raised the question of whether it is sufficient for the establishment of a complete hematopoietic chimerism in all patients. We therefore initiated a study of chimerism early during hematopoietic reconstitution after bone marrow transplantation (BMT) and thereafter in transplanted FA patients. Minisatellite probes were used after DNA amplification by the polymerase chain reaction (PCR). From July 1989 to October 1992, 24 consecutive patients underwent BMT for FA, 19 of whom were assessable for chimerism. Our results using this sensitive technique showed that, among these 19 patients, all but one successfully engrafted. Engraftment was complete early after BMT in 12. The persistence of a small proportion of recipient's cells was detected in six. This partial hematopoietic chimerism was demonstrated to be only transient in at least five of the six patients. The one patient who failed to engraft showed a recipient-type profile for circulating cells early posttransplantation, indicating autologous bone marrow recovery. A second graft in this patient was also rejected. For both transplantations, the patient was grafted from a matched, unrelated donor. Therefore, 17 of 17 patients successfully grafted and with complete follow up data presented complete hematopoietic chimerism, within the sensitivity limit of the method used. In conclusion, lowering the Cy dose in the conditioning regimen of patients with FA could still allow complete engraftment to occur, at least in patients with an identical sibling donor.