Search PubMed⌕ Search

Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 271 records · Page 15Linked to original sources

Nucleolar organizer regions and glycoprotein-hormone alpha-chain reaction as markers of malignancy in endocrine tumours of the pancreas.

The value of silver staining of nucleolar organizer regions (AgNORs) and human chorionic gonadotropin alpha-chain reaction (HCG-alpha) as markers of malignancy was investigated in 60 primary pancreatic endocrine tumours, 37 of which had metastasized at the time of surgery, and in one of which metastases developed 4 years after surgery. Assessment of AgNORs by digital image analysis revealed few but large AgNORs (mean number 2.5 +/- 1.1; mean area 0.32 +/- 0.1 microns 2) in the 22 benign tumours and many but small AgNORs (mean number 5.1 +/- 1.9, P < 0.05; mean area 0.18 +/- 0.09 microns 2, P < 0.01) in the malignant tumours. Quantification of the number of AgNORs per tumour cell nucleolus (AgNOR distribution score) showed that 96% (26/27) of tumours exhibiting at least 5% of cells with more than six AgNORs per nucleolus showed metastases either at the time of diagnosis or up to 4 years after surgery. HCG-alpha immunoreactive cells were present in 25/38 (66%) malignant tumours and in 4/22 (18%) benign tumours. Combined evaluation of AgNOR distribution and HCG-alpha scores showed a high positive predictive value of 96% in cases with a raised AgNOR distribution score irrespective of the HCG-alpha status. A good negative predictive value (81%) was, however, only obtained if both parameters, AgNOR distribution and HCG-alpha scores, were negative. Thus, investigation of AgNORs and HCG-alpha is helpful in predicting malignancy in a high percentage of pancreatic endocrine tumours.

Adolescent↗

Sub-gingival microflora in Macaca mulatta species of rhesus monkey.

The Macaca mulatta species of rhesus monkey is one of several non-human primate (nhp) models for periodontal disease. This report presents the bacteriology of the gingival sulci in M. mulatta monkeys. Three sub-gingival sites (maxillary right central incisor, the disto-buccal of the mandibular left second molar and mesio-buccal of the mandibular right second molar) of 9 monkeys were evaluated clinically before scaling and 7 days after scaling. Plaque samples were obtained from sub-gingival sites before clinical examination and studied bacteriologically by dark field microscopy, selective and non-selective culture, and by primary phenotypic characterizations of culture isolates. Several gingival sites presented with mild gingival inflammation. Anaerobic and facultatively anaerobic bacteria were the predominant flora colonizing the gingival sulci. The major microbial groups were Haemophilus species (100% of sites; percentage of total anaerobic count (TAC): 21-51), Peptostreptococcus micros (89%, 7.5-29.5), Actinomyces sp. (85%, 7-27), Fusobacterium nucleatum (90%, 5-8), Actinobacillus actinomycetemcomitans (73%, 1.3-12), black-pigmented anaerobic rods (BPAR) (80%, 0.6-6.5) and oral streptococci (80%, 0.2-1.0). Microbial groups detected less often were Wolinella sp. (66%, 0-2.6), Capnocytophaga sp. (30%), Eikenella corrodens (4.7%, 0), Campylobacter sp. (28%, 0-0.1) and spirochetes (4.7%, 0-0.07). Seven days after gingival sites were scaled, the plaque score and indices for gingival inflammation declined significantly. The gingival flora after scaling were characterized by lower proportions of the Actinomyces sp., P. micros and BPAR; and increased proportions of the oral streptococci, relative to pre-scaling levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinomyces↗

Effects of Listeria monocytogenes and Yersinia enterocolitica on cytokine gene expression and release from human polymorphonuclear granulocytes and epithelial (HEp-2) cells.

The gene expression and cytokine release of the proinflammatory cytokines interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) after infection of human epithelial cells (HEp-2 cells) and polymorphonuclear granulocytes (PMNs) were investigated by using isogenic pairs of Listeria monocytogenes and Yersinia enterocolitica strains. By polymerase chain reaction-assisted mRNA amplification and RNA dot blot analysis, we showed that PMNs and HEp-2 cells expressed enhanced levels of mRNA encoding IL-1 beta, IL-6, and TNF-alpha after bacterial infection. Concomitant with the enhanced mRNA level, an increased secretion rate of IL-1 beta, IL-6, and TNF-alpha from PMNs as assessed by enzyme-linked immunosorbent assay was observed. HEp-2 cells after infection also released IL-6 and TNF-alpha into the cell supernatant, while no IL-1 beta release was detected. Cellular coincubation experiments were carried out with Transwell chambers. Our studies revealed that the coculture of PMNs and HEp-2 cells led to an increased IL-1 beta and IL-6 release. In contrast, after infection with the invasive bacteria, reduced levels of TNF-alpha were measured. Our data show that PMNs secrete the proinflammatory cytokines IL-1 beta, IL-6, and TNF-alpha within some hours after infection with L. monocytogenes and Y. enterocolitica and that cellular interactions with epithelial cells alone via soluble mediators influence the net amount of released proinflammatory cytokines.

Base Sequence↗

Prospective multicentre study of risk factors associated with delayed healing of recurrent duodenal ulcers (RUDER). RUDER Study Group.

Risk factors for delayed duodenal ulcer healing during treatment with ranitidine (300 mg daily) were examined in a multicentre German study of 1923 patients with endoscopically proved, recurrent duodenal ulceration. Healing rates, per protocol, were 39.5% at two weeks, 70.9% at four weeks, and 93.2% at eight weeks. Prospective testing of five, predefined risk factors indicated that smoking (p = 0.0039) was associated with a decreased healing rate at two weeks. Frequent prior recurrence (p = 0.464), a heavy physical workload (p = 0.145), and psychological stress (p = 0.062) were not associated with a decreased healing rate and there were too few patients at risk to allow assessment of the effect of regular NSAID intake. Exploratory analysis identified prior slow healing, a large ulcer, multiple ulcers, and prior ulcer complications, in addition to smoking, as markers of slow healing. In the absence of these risk factors, the mean healing time was 3.3 weeks (95% confidence interval 3.0, 3.5), rising to 3.7 weeks (3.5, 3.9) for one, 4.4 weeks (4.1, 4.7) for two, and 5.1 weeks (4.5, 5.6) for three to five risk factors. Delayed duodenal ulcer healing is associated with multiple factors whose effect is cumulative; for patients with two or more of five easily identified risk factors, more than four weeks' treatment with a histamine H2 receptor antagonist is required to achieve ulcer healing.

Adult↗

Incidence and prognosis of congenital aortic valve stenosis in Liverpool (1960-1990).

OBJECTIVE: To determine the incidence and prognosis of congenital aortic valve stenosis in the five Health Districts of Liverpool that make up the Merseyside area. DESIGN: The records of the Liverpool Congenital Malformations Registry and the Royal Liverpool Children's Hospital identified 239 patients (155 male, 84 female) born with aortic valve stenosis between 1960 and 1990. Patients were traced to assess the severity of stenosis at follow up. Information on the severity at presentation and all subsequent events was obtained. RESULTS: Congenital aortic valve stenosis occurred in 5.7% of patients with congenital heart disease born in the Merseyside area. The median age at presentation was 16 months (range 0-20 years). Stenosis was mild at presentation in 145 patients, moderate in 33, severe in one and critical in 21 and 39 had a bicuspid valve without stenosis. Additional cardiac lesions were significantly more common in children presenting under one year of age and in those with critical stenosis. The median duration of follow up was 9.2 years (range 1-28 years) and seven patients were lost to follow up. 81 operations were performed in 60 patients. The reoperation rate was 28.3% after a median duration of 8.7 years (range 2.5-18 years). 15% of patients who presented with mild stenosis subsequently required operation compared with 67% of those with moderate stenosis. There were no sudden unexpected deaths and no deaths after aortic valvotomy, except in those presenting with critical stenosis. Mortality was 16.7% but patients presenting with critical aortic stenosis had a much worse prognosis. Actuarial and hazard analysis showed that the survival and absence of serious events (aortic valve surgery or balloon dilatation, endocarditis, or death) were significantly better in patients who presented with mild aortic stenosis than in those who presented with moderate aortic stenosis. 75% of patients presenting with mild stenosis had not progressed to moderate stenosis after 10 years of follow up. CONCLUSIONS: Congenital aortic valve stenosis may be progressive even when it is mild at presentation. Patients presenting with mild stenosis, however, have a significantly better prognosis than those presenting with moderate stenosis. An accurate clinical and echocardiographic assessment of the severity of aortic valve stenosis at presentation provides a good guide to prognosis into early adult life.

Actuarial Analysis↗

Arterial duct angioplasty as an adjunct to dilatation of the valve for critical pulmonary stenosis.

OBJECTIVE: To assess the efficacy of arterial duct angioplasty in maintaining adequate ductal patency in neonates with critical pulmonary valve stenosis. PATIENTS: Two neonates presenting with cyanosis due to critical pulmonary valve stenosis with severe right ventricular hypoplasia underwent percutaneous balloon dilatation of the pulmonary valve. Despite successful dilatation, both remained cyanosed while receiving prostaglandin E2 infusions. RESULTS: Angioplasty of the arterial duct resulted in increased arterial oxygen saturations. Adequate arterial duct patency was maintained for three months during which time right ventricular dimensions increased enough to allow sufficient pulmonary circulation without the duct. CONCLUSIONS: Arterial duct angioplasty is an effective additional treatment for patients with critical pulmonary valve stenosis whose right ventricle is too small to provide adequate forward flow after balloon dilatation of the valve. Arterial duct angioplasty sustains adequate patency of the duct while the right ventricle grows sufficiently to undertake the pulmonary circulation.

Angioplasty, Balloon, Coronary↗

Gastroenteropancreatic endocrine tumours: effect of Sandostatin on tumour growth. The German Sandostatin Study Group.

One hundred and fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumours entered a prospective multicentre trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumours and 5 with other endocrine GEP tumours) to determine the efficacy of 200 micrograms Sandostatin t.i.d. in the control of tumour growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a 'negative' selection of patients included in the trial and suggesting that Sandostatin is unable to prevent disease progression when it is far advanced. In the evaluation of 68 patients followed up for at least 3 months, partial regression was observed in 4.4%, stable disease in 50% and tumour progression in 45%. An initially favourable response occurred frequently, however, it was followed by a decrease in response, from 54.4% at 3 months to 38% at 12 months, for the whole group of patients. Proven inhibition of tumour growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatin exerts a beneficial effect on tumour growth in patients with metastatic endocrine GEP tumours. This beneficial effect decreases with time and is as yet unpredictable in the individual patient.

Follow-Up Studies↗

[Receptor scintigraphy using 111In-pentetreotide in endocrine gastroenteropancreatic tumors].

Receptor scintigraphy with 111In-pentetreotide is a complementary imaging technique with a sensitivity of 88% for the localization of the primary tumor and its metastases in patients presenting with the clinical and biochemical symptoms of an endocrine tumor of the gastrointestinal tract or the pancreas. As a whole-body scintigraphic technique it covers all body regions and is also able to reveal small tumors which can only be detected with difficulty or not at all by the usual imaging methods. In 104 patients with GEP tumors or after operative removal of such tumors, receptor scintigraphy proved to be superior to ultrasound and computed tomography in 34%, equal in 52% and inferior in 14% of the cases.

Female↗

In vitro and in vivo depletion of T cells.

Transplant related mortality and relapse after bmt have a negative influence on the outcome of patients transplanted for acute leukaemia in first remission. Transplant related mortality includes graft-versus-host disease, infections and graft failure. To prevent gvhd and associated infections without increased graft rejection, a protocol of combined in vivo/ex vivo T-cell depletion (Campath IgG 20 mg i.v. for 5 days and Campath IgM T-cell depleted graft) with no further immunosuppression was initiated. Up to now 22 adult patients (median age 39 years, range 21 to 51) have been transplanted. One graft failure most probably due to persistent leukaemia, three acute gvhd (grade I) and no chronic gvhd occurred. Two patients relapsed after bmt and died. Two further patients died due to idiopathic interstitial pneumonitis and acute liver failure, respectively. Eighteen patients are alive in complete remission. With a median follow up of 13 months (1-30) the probability of survival is 78%, disease free survival is 80% and transplant related mortality is 10%. We compared these results with 3 historical control groups with different regimens of gvhd prophylaxis. 1. MTX group (n = 15): With a median follow up of 135 (115-147) months after bmt the probability of survival is 40%, disease free survival is 40% and transplant related mortality is 60% (mainly gvhd and infection). 2. Campath group (only ex vivo T-cell depletion n = 25): With a median follow up of 86 (62-102) months probability of survival is 52%, disease free survival is 43% and transplant related mortality is 36% (mainly rejection and infection).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Measurement of recipient-specific alloreactivity: is GVHD predictable?

Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. We determined the frequency with which host-specific interleukin-2 (IL-2) -secreting donor T lymphocyte precursors (Tl-p) occurred in 16 pairs of HLA-identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after BMT. We further analyzed the responding host (and donor) -specific Tl-p with respect to the cell surface phenotype, the influence of previous in vivo priming, and the MHC class restriction of minor histocompatibility (mH) antigen recognition. To investigate whether host-reactive Tl-p are involved in the induction of acute GVHD, we also examined the frequency of host-specific Tl-p at various time intervals after BMT in 14 patients with and without acute GVHD. High frequencies of host-specific Tl-p were detectable before BMT in 8 donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to 8 patients with mild (grade 0 or I) acute GVHD, low frequencies were found. Various T-cell subsets contributed to the responding Tl-p. The presence of host-specific Tl-p after BMT was significantly correlated with the development of serious (grade II or III) acute GVHD. We conclude that host-specific IL-2-secreting T cells are critically involved in the induction and maintenance of acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Graft rejection by a population of primed CDw52- host T cells after in vivo/ex vivo T-depleted bone marrow transplantation.

We investigated a case of graft rejection after in vivo/ex vivo T-depleted BMT in a patient who had received a HVG-matched, GVH one locus-mismatched, MLC-negative graft from his cousin. In vivo/ex vivo T cell depletion was performed with Campath 1G (CP1G) and Campath 1M (CP1M), respectively. We identified a failure of CP1G to eradicate a CDw52- (Campath-negative) host T cell population as the main cause of treatment failure. The analysis also suggests that significant host-versus-donor reactivity prior to transplant, as detected by limiting dilution analysis, also contributed to graft rejection. The rejecting T cells were bifunctional in that they showed cytotoxic activity and were capable of inhibiting haemopoietic progenitor growth by producing inhibitory lymphokines.

Adult↗

Immunoreactivity and expression of amylin in gastroenteropancreatic endocrine tumors.

Amylin was isolated from human insulinomas, but there has been only preliminary data regarding whether this peptide can also be detected in other types of gastroenteropancreatic endocrine tumors. In the present study, immunohistochemical staining of 87 gastroenteropancreatic endocrine tumors demonstrated amylin immunoreactivity in 21.8% of the neoplasmas. Thirteen of 15 insulinomas, three of 21 gastrinomas, two of 29 nonfunctioning tumors, and one of 18 carcinoids were amylin-immunoreactive. Seventeen of the 19 amylin-immunoreactive tumors were primarily located in the pancreas, but two tumors were found in the intestine. Measurements of amylin messenger RNA expression in a few tumors revealed amylin synthesis in these tumors. Amylin immunoreactivity did not correlate with invasion and metastasis. However, the rate of curative resections was significantly higher in amylin-immunoreactive tumors. These results demonstrate for the first time that amylin immunoreactivity is not restricted to insulinomas and can also occur rarely in endocrine tumors of the intestine.

Amyloid↗

[Colon diverticulitis: imaging diagnosis with ultrasound--a prospective study].

In a prospective study, we investigated the value of high resolution sonography for the imaging diagnosis of colonic diverticulitis. A total of 161 patients with abdominal complaints on account of which acute diverticulitis entered into differential diagnosis were included in the study. 74 of these finally had proven colonic diverticulitis (prevalence, 46%). The results of intestinal sonography and the working diagnoses on admission were evaluated on the basis of final diagnoses. According to history, symptoms, and clinical findings on admission, the working diagnosis of diverticulitis was graded as being "highly suspect" in 26 (35.1%) of these 74 diverticulitis patients, as being "possible/equivocal" in 36 (48.6%), and as being "very unlikely" in in 12 (16.2%). In 7 (9.5%) patients with diverticulitis, the diagnosis was clinically unsuspected and primarily established by ultrasound. Overall accuracy, sensitivity, and specificity of intestinal sonography with regard to the diagnosis of diverticulitis were 97.5%, 98.6%, and 96.5%, respectively. There were three false positive ultrasonic diagnoses of diverticulitis which were made in two patients with perforated carcinoma of the sigmoid and in one case of sigmoid volvulus (positive predictive value, 96%). Ultrasound failed to visualize sigmoid diverticulitis with perforation in one patient (negative predictive value, 98%). In 19 out of 20 patients with abdominal abscesses (prevalence, 12.4%), the diagnoses were established by means of sonography. Nine of these patients with abscesses initially were treated by ultrasound guided percutaneous drainage enabling elective surgery. In 26 (70%) of 36 patients with morphological disorders other than diverticulitis, ultrasound findings substantially added for the definite diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Receptor scintigraphy with 111In-pentetreotide for endocrine gastroenteropancreatic tumors.

Receptor scintigraphy with 111In-pentetreotide is a simple method with a sensitivity of 86% for the localization of the primary tumor and its metastases in patients presenting with the clinical and biochemical symptoms of an endocrine tumor of the gastrointestinal tract or the pancreas. As a whole-body scintigraphic technique it covers all body regions and is also able to reveal small tumors which either cannot be detected or can only be detected with difficulty by the usual imaging methods. In 85 patients with GEP tumors or after operative removal of such tumors, receptor scintigraphy proved to be superior to ultrasound and computed tomography in 34%, equal in 52%, and inferior in 14% of the cases.

Aged↗

Single-drug oral antibacterial prophylaxis with ofloxacin in BMT recipients.

We evaluated the efficacy and safety of a new oral fluoroquinolone, ofloxacin (200 mg twice daily), as antibacterial prophylaxis after BMT in a non-comparative prospective study of patients nursed in either LAF plastic isolators or HEPA filtered single rooms. Of the 101 evaluable patients who were neutropenic (< 500 x 10(6)/l) for a median duration of 20 days, 92 (91%) had febrile episodes of varying length and causes. Infections were documented in 34 patients, of whom 14 had proven bacterial infection (13 with bacteremia and one with pneumonia). Mortality rate within 6 weeks after transplant was 6%. Only one patient died from bacterial infection. Univariate analysis using an array of potentially prognostic factors including the type of isolation was not helpful in identifying significant variables for predicting the development of documented infection. Tolerance was excellent. Oral ofloxacin was associated with a relatively low incidence of documented bacterial infection and related mortality, although it did not obviate the need for frequent empiric antimicrobial therapy due to a high incidence of febrile episodes.

Administration, Oral↗

Influence of graft-versus-host disease on the eradication of minimal residual leukemia detected by polymerase chain reaction in chronic myeloid leukemia patients after bone marrow transplantation.

To evaluate the remission quality of Philadelphia chromosome (Ph)-positive, BCR/ABL-positive CML patients after allogeneic bone marrow transplantation (BMT) we used the polymerase chain reaction (PCR) to detect BCR-ABL specific RNA in addition to Southern blotting, cytogenetic, and hematological investigation. Fifty-five bone marrow samples of 27 patients in clinical remission were studied by PCR, 0.5 to 99 months (median 8 months) after BMT. The median clinical follow-up of this cohort of patients is 24 months (1-109) after BMT. BCR-ABL transcripts could be detected in 16 out of 27 patients (59%). Risk factors for minimal residual leukemia (MRD) as defined by PCR were the kind of graft-versus-host disease (GvHD) prophylaxis (patients with T-cell-depleted grafts had a higher rate of MRD in comparison to patients treated with methotrexate/cyclosporin A) and the presence or absence of GvHD after BMT (patients without GvHD had a higher incidence of MRD than patients with GvHD). Moreover, the detection of minimal residual leukemia had prognostic significance. Out of 16 patients with minimal residual leukemia as detected by PCR, four patients relapsed clinically and two further cases relapsed cytogenetically. In contrast none of the patients lacking evidence of minimal residual leukemia relapsed. Serial PCR analysis may prove helpful in deciding about further therapeutic interventions (e.g. interferon therapy or adoptive immunotherapy) before leukaemic relapse becomes manifest after BMT.

Adult↗