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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 253 records · Page 14Linked to original sources

Differences in the procurement of organs and tissues by health care professionals.

BACKGROUND: The act of donating organs is familiar to most health care professionals (HCPs). However, the process of tissue and cornea donation is not nearly as well known. Most studies of the donation process have neglected the issue of tissue and cornea donation. This study offers some preliminary data concerning the differences between organ and tissue and cornea donation processes. As well, this is one of the first studies to report an eligibility rate for tissues among hospital deaths. METHODS: During a 5-month period in 1989, the charts of all patients (n = 233) who died in the study hospital were reviewed on a weekly basis to establish eligibility to donate organs, tissues and corneas. A case series of 50 eligible patients cases was selected for in-depth interviews. Cases were defined as those patients who were eligible to donate tissues or organs. The patient's attending physician, house officer, and primary nurse were interviewed using an open-ended interview format. These audiotaped interviews focused on the events surrounding the patient's death, focusing on the issue of donation. We also collected information concerning HCP knowledge of the medical criteria for donation and their attitudes toward donation. Consent was obtained from all HCPs before beginning the interview process. RESULTS: Of the 233 deaths, 4.3% were eligible to donate organs, 11.2% were eligible to donate tissues, and 18.9% were eligible to donate corneas. On the basis of our interview data we found that all eligible organ donors were identified and their families asked by at least one member of the patient's health care team to consider donation. HCPs were less successful identifying tissue patients: 30 of the 41 tissue donors (73.2%) were identified and only 65.9% of donor families were asked to donate. Rates of consent to donation were lower than might be expected based on public opinion polls. 33.3% of families consented to organ donation while only 29.6% consented to donate tissue and cornea. CONCLUSION: HCPs performed less efficiently in terms of the procurement process for tissues and corneas as compared to organs. They were also less knowledgeable about the donation criteria for tissues and corneas than organs. They generally exhibited more positive attitudes about corneal donation. More education of HCPs is necessary before we can optimally procure tissues for transplantation.

Aged↗

Effect of respiratory syncytial virus-antibody complexes on cytokine (IL-8, IL-6, TNF-alpha) release and respiratory burst in human granulocytes.

The release of interleukin-8 (IL-8), IL-6, and tumour necrosis factor-alpha (TNF-alpha) from human polymorphonuclear granulocytes (PMN) after exposure to infectious respiratory syncytial virus (RSV) particles was investigated. Our data showed that PMN secreted IL-8 and IL-6 in a time- and RSV-dose-dependent manner. During the RSV exposure, TNF-alpha was not detected in the cell supernatant of PMN. Similar amounts of IL-8 were secreted after either incubation with infectious or UV-inactivated RSV particles. Obviously, PMN bind and phagocytose the viral particles, which leads to the secretion of cytokines. The increased IL-8 secretion was accompanied with an enhanced cytoplasmic IL-8 mRNA steady state level, as shown by Northern blot analysis. The IL-8 secretion pattern from PMN was also studied after its interaction with RSV--antibody complexes. Non-neutralizing monoclonal antibodies (mAb) directed to the RSV fusion protein and glycoprotein were used to generate immune complexes. Only the mAb directed to the RSV fusion protein enhanced the IL-8 release from PMN significantly. In addition, the chemiluminescence response from PMN was analysed after exposure of the cells to RSV particles, RSV-mAb complexes, Ca-ionophore A23187 or N-formyl-methionyl-leucyl-phenylalanine (FMLP). The phagocytosis of RSV inhibited the oxygen radical production induced by the Ca-ionophore A23187 or FMLP. Only RSV-anti-fusion protein mAb complexes generated a chemiluminescence response from PMN. Thus, PMN play an important role in the control of RSV infection.

Antigen-Antibody Complex↗

High-titre interferon-alpha antibodies in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation.

In a patient undergoing allogeneic BMT for chronic phase CML, de novo chronic GVHD developed within 80 days after transplantation. Eighteen months post-BMT, high serum levels of neutralizing interferon-alpha (IFN-alpha) antibodies were detected, which persisted despite continuous immunosuppressive treatment. The antibodies were of oligoclonal or polyclonal origin, predominantly of the IgG1 type, and reacted broadly with various human IFN-alpha types, including the patients endogenous IFN-alpha, but failed to recognize natural IFN-beta and recombinant IFN-gamma. Pathogenesis and clinical impact of the IFN-alpha antibodies are unknown. Antibodies of cytokines are a novel class of autoantibodies that may develop after allogeneic BMT and interfere with cytokine homeostasis and immune regulation.

Adult↗

Direct regulation of bile secretion by prostaglandins in perfused rat liver.

Prostaglandins have been postulated to act as mediators of intercellular communication between liver cell populations in the regulation of liver carbohydrate metabolism. Their role in the regulation of bile secretion is rather unclear. The action of prostaglandins on bile flow and bile acid secretion was studied in the in situ perfused rat liver. Infusion of prostaglandin F2 alpha resulted in reduction of bile flow and bile acid secretion. In addition, portal flow was diminished and glucose output was increased. The parameters were altered in a dose-dependent manner. The effects of prostaglandins D2 and E2 were similar but less potent than those of prostaglandin F2 alpha. To separate the effects on portal flow and bile flow, we used nitroprusside and nifedipine to suppress the hemodynamic changes induced by prostaglandins. In the presence of these substances, the alterations of bile flow and bile acid secretion were even more pronounced. Infusion of inhibitors of prostaglandin synthesis increased bile flow. In conclusion, prostaglandins F2 alpha, D2 and E2 reduce bile flow and bile acid secretion. These effects are independent of hemodynamic changes. Suppression of synthesis of endogenous prostaglandins by inhibitors of prostaglandin synthesis reversed these effects. Prostaglandins are involved in the regulation of bile flow and bile acid secretion.

Animals↗

[Leukocyte transfusion as therapy of recurrent CML after allogenic bone marrow transplantation].

Eight patients with relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with alpha-interferon and leukocyte transfusions of the bone marrow donor. Six patients responded with disappearance of leukemic cells (Ph1, BCR-ABL) and reestablished donor hemopoiesis. All six patients developed bone marrow hypoplasia and graft-versus-host disease (GvHD). Three of the six patients died of cerebral bleeding, infection and GvHD, respectively. The remaining three patients are alive and well at day 418, 677, 818 after leukocyte transfusions. Two patients relapsed with more advanced disease of CML after BMT and failed treatment. Donor leukocyte transfusions provide an effective therapy for patients with relapsed CML after BMT, but are associated with a high mortality due to bone marrow hypoplasia and GvHD.

Antigens, CD↗

The progression of mild congenital aortic valve stenosis from childhood into adult life.

UNLABELLED: We studied 187 patients who presented with mild congenital aortic valve stenosis or a bicuspid aortic valve without stenosis at presentation; 63% were males. Information on all clinical events was obtained, and patients were traced to assess current clinical status. RESULTS: The median age at presentation was 2 years (range, 0-15). Additional cardiac lesions occurred in 51 patients, more commonly in patients presenting under 1 year of age (P < 0.0001). The median duration of follow-up was 10 years (range, 1-28); seven patients were lost to follow-up. Thirty-two patients progressed to require intervention (28 surgical, five balloon valvuloplasty) at a median age of 10.5 years. No patient who presented with a bicuspid aortic valve required intervention. Two patients developed endocarditis. There were eight deaths; four after surgery for aortic stenosis and four due to other cardiac lesions. There were no sudden deaths. Actuarial and hazard analysis showed that progression beyond mild stenosis was closely related to duration of follow-up. CONCLUSIONS: Congenital aortic valve stenosis is most frequently mild at presentation. Progression is related to duration of follow-up. Fewer than 20% of patients are likely to still have mild stenosis after 30 years. Follow-up into adult life is essential.

Actuarial Analysis↗

[Palliative therapy of complex hilar biliary obstructions using self-expanding metal stents].

Implantation of self-expandable metal stents was planned for 21 patients (12 women, 9 men; mean age 64.7 +/- 11.6 [38-80] years) with malignant obstructive jaundice due to complex hilar biliary obstruction (Bismuth II: n = 5, Bismuth III: n = 13, Bismuth IV: n = 1, state after hepaticojejunostomy: n = 2). Stents were implanted bilaterally in 18 patients (one each on the right and left, n = 12; two stents on right, one stent on left, n = 6), one patient had three stents on one side, another had one unilateral stent. Thus there was a 93.3% success rate (46 of 49 planned stent implantations). The mean bilirubin level fell from 14.7 +/- 7.7 mg/dl before stent implantation to 3.9 +/- 5.4 mg/dl afterwards (P = 0.0001). One patient experienced late bleeding with haemorrhagic shock and consumption coagulopathy after a failed drainage attempt. She died despite superselective embolization, operative suturing of the puncture site, and wide-ranging intensive care measures. Procedure-related death rate was thus 4.8%, the 30-day death rate 9.5%. During the follow-up period, averaging 145 +/- 152 (16-529) days, jaundice recurred in six patients (30%) and was successfully treated by re-intervention in five. 13 patients died after a mean survival time of 98 +/- 119 (16-432) days. It is concluded from these data that self-expandable metal stents provide minimally invasive palliative treatment of complex biliary hilar obstruction in the type of case in which plastic stents are known to fail.

Adult↗

[Risk for developing tumors in therapy with the proton pump inhibitor omeprazole].

The experience received hitherto with the treatment of omeprazole proves this drug as absolutely save and poor of side effects. ECL-cell hyperplasia and carcinoids which occur during application of very high doses of omeprazole in rats are not caused by a direct effect of omeprazole. These changes are induced by extremely elevated serum gastrin levels due to achlorhydria. However, these high doses of omeprazole are not applicated in man. Therefore, the results from animal studies can not be applied on humans. During long-term treatment with omeprazole in most patients only slight increases of serum gastrin levels and ECL-cell densities occur. Only a very few patients exhibit a progressive and marked increase of serum gastrin levels. These patients should be carefully monitored by endoscopy in regularly intervals. There is no current evidence to support the contention that omeprazole is genotoxic. Results from Burlinson on the potential of omeprazole to induce DNA damage proved to be unsounded and of no clinical relevance. Omeprazole produced negative results in all well established genotoxicity tests. The incidence of neoplasias in the stomach is not increased after long-term acid suppression as indicated by 15 years application of H2-blockers and even a longer period of experience with vagotomy. Hitherto, there is also no evidence that acid inhibition induced by omeprazole causes an increased rate of carcinoma of the stomach. The risk for promoting carcinomas of the colon by the mild hypergastrinaemia during treatment with omeprazole seems to be inferior. In addition the correlation between development of carcinomas of the colon respective rectum and hypergastrinaemia is discussed controversly.

Animals↗

[Standardized surgical concept for the diagnosis and therapy of Zollinger-Ellison syndrome].

Between 1987 and 1991, 16 patients (13 females, three males; mean age 52.4 [33-73] years) with Zollinger-Ellison syndrome (ZES) were treated according to a standardized surgical concept. The diagnostic work-up consisted of measuring serum gastrin levels, pre-operative localization by ultrasound and abdominal computed tomography, as well as extensive staging by laparotomy. As complete a tumour resection as possible was the aim of treatment in 15 patients, while in one patient it was to reduce the tumour mass. In six patients who had resection of a solitary tumour there was no evidence of recurrence after 6-42 months of follow-up. Exploration of the duodenum made it possible to identify and then remove a small gastrinoma of the duodenal wall in three patients. No gastrinoma was found in one patient despite extensive exploration. In a further four patients the laparotomy was purely exploratory, because diffuse metastasization was found. In four patients the primary tumour and, where present, the regional lymph nodes were removed, but the signs of ZES persisted, i.e. the intervention was merely palliative. In one female patient, reduction of tumour mass was necessary because the symptoms could not be controlled by conservative measures: she died postoperatively from toxic hepatitis. This experience indicates that standardized surgical intervention achieves potentially curative results in nearly 40% of patients. Including the duodenum in the surgical exploration allows the identification of even small gastrinomas of the duodenal wall. It is concluded that all patients with ZES but no evidence of diffuse metastases should undergo surgical treatment.

Adult↗

Quantitative assessment of posttransplant host-specific interleukin-2-secreting T-helper cell precursors in patients with and without acute graft-versus-host disease after allogeneic HLA-identical sibling bone marrow transplantation.

Recent studies in mice and humans have emphasized an important contribution of host-reactive minor histocompatibility antigen (mH)-specific lymphokine-secreting donor T-helper cells (Th) for the induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). By using limiting dilution (LD) and clonal specificity analyses, we investigated in 14 patients with and without acute GVHD after non-T-depleted HLA-identical sibling BMT whether posttransplant host-reactive mH-specific interleukin-2 (IL-2)-secreting Th are involved in the development of clinically significant acute GVHD and the establishment of tolerance. At different time intervals posttransplant (I, days 0 through 45; II, days 45 through 90; III, days 90 through 180), host-specific IL-2-secreting Th-precursors (Th-p) were quantitatively assessed in six patients during clinically apparent grade II-III acute GVHD. Frequencies of responding Th-p ranged from 1/13,000 to 1 4,000. The presence of host-specific Th-p was significantly correlated with the development of grade II-III acute GVHD (P = .0003 by Fisher's exact test). The detectability of host-specific Th-p preceded the clinical onset of grade II-III acute GVHD. Host-specific Th-p were no longer detectable after the clinical resolution of grade II-III acute GVHD. No subsequent chronic GVHD was observed in these patients. However, prolonged occurrence of host-specific Th-p was accompanied by clinically persisting acute GVHD and the onset of secondary chronic GVHD. In patients with no acute GVHD (grade 0) (n = 7) and grade I (n = 1) acute GVHD, host-specific Th-p were not detectable at all. We conclude that host-reactive Th are critically involved in the development and maintenance of acute GVHD and may contribute to the establishment of tolerance after genotypically HLA-identical sibling BMT.

Acute Disease↗

Patient, family, and staff perceptions of coercion in mental hospital admission: an exploratory study.

Little is known about the coercive pressures brought to bear on psychiatric patients in the hospitalization process. Significant methodological hurdles stand in the way of this research. Most notably, reliable and valid methods of ascertaining and quantifying perceptions of coercion have not been developed. This report summarizes the findings of an exploratory study designed to gather data needed to refine the conceptualization and measurement of coercion. Multiple perspectives on admission incidents for forty-three patients (26% of whom were involuntarily hospitalized) were obtained. Patients were administered research interviews and completed a self-administered inventory shortly after the admission decision. The admitting clinician and a family member involved in the admission were administered parallel interviews. In addition, focus groups comprised of outpatients, former patients, family members, and clinical staff were conducted to uncover the terminology and description of coercion commonly used. The implications of these preliminary quantitative and qualitative findings for future research are discussed.

Adult↗

Gastric argyrophil (enterochromaffin-like), gastrin, and somatostatin cells after proximal selective vagotomy in man.

The number, size, and volume density of endocrine cells was determined in biopsies obtained endoscopically in patients after proximal selective vagotomy (PSV; N = 31), antrectomy (N = 9), untreated duodenal ulcer (DU) disease (N = 11), and in controls (N = 15). Serum gastrin was significantly elevated after PSV (mean 60 pg/ml) compared to DU patients (29 pg/ml), controls (26 pg/ml), and after antrectomy (11 pg/ml). Volume density of fundic argyrophil (largely enterochromaffin-like) cells after PSV (0.74%) and in DU disease (0.63%) were significantly (P < 0.001) higher when compared with controls (0.37%) but lower after antrectomy (0.24%; P < 0.02). The density of argyrophil cells was not influenced by the interval following PSV or the magnitude of hypergastrinemia. Antral gastrin cells were increased after vagotomy, whereas the antral and fundic somatostatin cell numbers were reduced after PSV. It is concluded that: (1) a major role of the vagal nerve as a trophic factor for enterochromaffin-like cells could not be demonstrated after PSV, and (2) moderate hypergastrinemia after PSV did not induce proliferation of ECL cells.

Adult↗

Pseudoreticulocytosis in a patient with myelodysplasia.

A patient with a myelodysplastic syndrome (MDS) and reticulocytosis of > 50% in the absence of a correspondingly increased erythrocyte turnover is reported. Evaluation of the kinetics of erythrocyte turnover revealed a decreased erythrocyte life span of 44 days. From these data a prolongation of the reticulocyte maturation time to > 20 days can be concluded. The patient's erythrocytes lacked the increase of mean corpuscular volume and a significant increase of erythrocyte enzymes that would be expected in marked reticulocytosis. This finding suggests that the reticulocytes represented not newly formed red blood cells, but "pseudoreticulocytes", i.e., mature erythrocytes that retained their substantia reticulofilamentosa.

Humans↗

Preoperative localization of gastrointestinal endocrine tumors using somatostatin-receptor scintigraphy.

OBJECTIVE: The purpose of this study was to determine the value of somatostatin-receptor scintigraphy (SRS) in the preoperative localization of gastrointestinal endocrine tumors. The authors report their preliminary experiences with this new technique as compared to conventional imaging studies like computed tomography (CT) and ultrasonography (US). SUMMARY BACKGROUND DATA: Most endocrine tumors possess high-affinity somatostatin-receptors. Using the stable, 111Indium labelled somatostatin analogue pentatreotid, which binds to these receptors, it is possible to detect somatostatin-receptor-positive tumors scintigraphically. METHODS: In nine patients with various gastrointestinal endocrine tumors, SRS, CT, and US were performed before surgical exploration. The preoperative imaging studies and intraoperative ultrasound (IOUS) were then compared to findings on surgical exploration. RESULTS: Twelve primary tumors were found in 8 patients at surgical exploration. These primary tumors were correctly identified with SRS in five patients, with US in four patients, and with CT in three patients. In one patient with the Zollinger-Ellison syndrome, scintigraphy suggested a tumor in the area of the hepatoduodenal ligament, while CT and US had negative results. The underlying gastrinoma could not be identified despite extensive surgical exploration. Scintigraphy, CT, and US showed comparable results in the detection of metastases in four patients. CONCLUSIONS: The data from this small series suggest that SRS is helpful in the preoperative localization of gastrointestinal endocrine tumors.

Adult↗

Interferon-alpha and donor buffy coat transfusions for treatment of relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation.

Eight patients with chronic myeloid leukemia relapse after allogeneic BMT were treated with IFN-alpha and buffy coat transfusions (BC) of the bone marrow donor. The antileukemic effect of this treatment was directly demonstrated in 4 patients by the disappearance of Philadelphia chromosome-positive metaphases or the loss of detectable BCR-ABL transcripts by polymerase chain reaction. In 2 patients in whom cytogenetic or polymerase chain reaction analysis was not performed, a change in hemopoietic chimerism with recurrence of donor-type hemopoiesis was demonstrated. Two patients, both treated in advanced stages of hematological relapse after BMT, did not respond. However, severe side effects of the treatment were observed: graft-versus-host disease (GVHD) occurred in 5 patients. Two of these patients progressed to severe chronic GVHD and 1 patient ultimately died of this complication. GVHD occurred in 5 of the 6 responding patients; one patient responded without developing clinical symptoms of GVHD. Six patients developed bone marrow hypoplasia after IFN/BC treatment, and pancytopenia occurred in 4 patients. None of these 4 patients recovered spontaneously and 2 patients died of complications of pancytopenia (cerebral bleeding, infection). Our results demonstrate that treatment of chronic myeloid leukemia relapse with IFN and BC transfusions is highly effective in patients with relapse in chronic phase. The occurrence of GVHD and pancytopenia, however, resulted in a high treatment-associated morbidity and mortality. Whereas a response to treatment was observed in 1 patient without GVHD, indicating that GVHD and a graft-versus-leukemia effect may be clinically separable, bone marrow hypoplasia occurred in all responding patients.

Adult↗

An open trial of long-term therapy with lansoprazole in patients with peptic ulceration resistant to extended high-dose ranitidine treatment.

Forty-two patients with peptic ulceration of the duodenum, stomach or oesophagus, who had not responded to 3 or more months of high-dose treatment with ranitidine (450 or 600 mg/day), were treated with oral lansoprazole at 30-60 mg daily. In 40 patients (95.2%) the ulcers healed within 2-12 weeks. In the remaining 2 patients healing took several months but eventually all ulcers healed. After healing, 40 patients underwent long-term maintenance treatment with 30-60 mg lansoprazole daily for 1-3 years (continuing). During maintenance therapy with lansoprazole, no endoscopically verified relapses occurred when the drug was taken regularly. In 1 patient treatment had to be discontinued because of a drug-related colitis that disappeared soon after treatment had been stopped. There were no significant changes in routine laboratory tests in any patient. Basal serum gastrin concentrations, which were already elevated by the previous high-dose ranitidine treatment (125 +/- 25 pg/ml), rose to four times the normal values after 4 weeks of treatment with lansoprazole (255 +/- 65 pg/ml). Thereafter no further increases in basal serum gastrin concentrations were observed, even after 3 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased slightly during lansoprazole treatment; until now no dysplasia of the enterochromaffin-like cells has been observed. In conclusion, 30-60 mg lansoprazole daily healed ranitidine-resistant peptic ulcers, and subsequent maintenance therapy with 30-60 mg lansoprazole daily was found to be highly effective and safe over the time observed.

2-Pyridinylmethylsulfinylbenzimidazoles↗