PubMed Health⌕ Search

Biomedical subjects

R Hutchinson

Publications and source records attributed to R Hutchinson.

At least 19 recordsLinked to original sources
PubMed1992

Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with neutropenia.

The results of an open-label, randomized, Phase III trial of r-methionyl human granulocyte-colony-stimulating factor (r-metHuG-CSF) in 41 patients with severe chronic neutropenia (SCN) are reported. Patients with diagnoses of congenital, cyclic, and idiopathic neutropenia, with histories of recurrent infections, were evaluated. The primary objective of the trial was to evaluate the ability of r-metHuG-CSF to increase the ANC to greater than 1500/mm3. A secondary objective was to evaluate variables associated with infection-related morbidity in SCN. r-metHuG-CSF treatment consisted of 1 month of dose titration followed by 4 months of treatment at an optimal dose. Patients were randomized to either immediate treatment with r-metHuG-CSF (Group A) or four months of observation followed by r-metHuG-CSF treatment (Group B). r-metHuG-CSF was administered by daily, subcutaneous injection with initial doses of 3 to 10 micrograms/kg/day. Forty of 41 patients who received r-metHuG-CSF had a complete response (median ANC greater than 1500/mm3 during 4 months of r-metHuG-CSF treatment). All cases of gingivitis and severe mouth ulcers resolved upon treatment with r-metHuG-CSF. Serious infections were also eliminated. Only one patient failed to show clinical improvement in response to r-metHuG-CSF treatment. Adverse reactions during the first 5 months of treatment were mild. Splenomegaly (mild) was noted in some patients. The administration of r-metHuG-CSF in patients with SCN significantly increased the ANC (P less than 0.001) and was accompanied by a marked reduction in infectious complications.

Agranulocytosis↗
PubMed1992

Distal 8p deletion (8p23.1----8pter): a common deletion?

The clinical manifestations and cytogenetic details of five patients with a de novo deletion of the short arm of chromosome 8, del(8)(p23), are described. Of the four surviving children all had mild mental retardation and subtle facial anomalies; three of the five had cardiac abnormalities. The clinical features seen in these patients are compared with those of three previous single case reports with del(8)(p23), and with patients described as having the '8p-' syndrome associated with del(8)(p21). The findings in these patients suggest that major congenital anomalies, especially congenital heart defects, are frequent even in small distal 8p deletions, but facial dysmorphism may be subtle and mental retardation less severe than in those with deletions associated with more proximal breakpoints. The five patients were detected within a four year period, suggesting that this deletion syndrome is relatively frequent. The possible mechanisms for the formation of terminal deletions are discussed.

Abnormalities, Multiple↗
PubMed1992

Acute colonic pseudo-obstruction: a pharmacological approach.

Acute colonic pseudo-obstruction is a functional disorder that closely mimics mechanical large bowel obstruction, and in which inadvertent laparotomy carries a high mortality. Eleven such patients were treated by pharmacological manipulation of the autonomic innervation to the colon with guanethidine and neostigmine. Eight responded to treatment with passage of flatus and/or stool within 10 min with complete resolution of symptoms. In three patients the treatment failed. Postural hypotension occurred in only one patient and no other serious side-effect was apparent. This pharmacological approach to the management of acute colonic pseudo-obstruction is suggested as an alternative to the other treatment options of colonoscopic decompression or surgery, when conservative management has failed.

Acute Disease↗
PubMed1991

Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine.

Phaeochromocytomas and functioning paragangliomas are rare tumours in childhood and adolescence. We review our experience of 43 cases (24 men, 19 women) who were first diagnosed at the age of less than or equal to 18 years. All patients were evaluated at some point in their illness with iodine 131 metaiodobenzylguanidine (131I-mIBG) scintigraphy. Eight patients (19%) had bilateral adrenal tumours, 12 (28%) had solitary extra-adrenal tumours, and 8 (19%) had multiple tumours. In 10 patients (23%), the tumours were associated with a familial neurocristopathic syndrome. Thirteen of 24 (54%) unifocal tumours which were initially considered to be benign ultimately proved to be multi-focal and/or malignant. The final prevalence of malignancy was 60%--26 patients, of whom only 15 (57%) had obviously malignant tumours at the time of diagnosis. Primary tumour size greater than or equal to 5 cm was more commonly associated with a malignant course in adrenal but not extra-adrenal tumours. No other clinical, biochemical or morphological characteristic was significantly associated with malignancy. Although the high prevalence of malignancy in this series at least partly reflects referral bias, the need for lifelong follow-up of these patients is underscored. 131I-mIBG scintigraphy was positive in 36 patients (84%), with a somewhat lower false-negative rate (12%) than X-ray computed tomography (20%). Eight patients with malignant tumours received therapeutic doses of 131I-mIBG, with partial tumour responses in 3. Thus, 131I-mIBG is an efficacious, non-invasive, localising agent and may be considered as a palliative therapeutic agent when alternatives have failed.

3-Iodobenzylguanidine↗
PubMed1991

Intra-arterial blood sampling for clotting studies. Effects of heparin contamination.

Prothrombin time and activated partial thromboplastin time were measured in two groups of 30 patients each. Blood sampled from an arterial line after various discard volumes and from a central venous line were compared with direct venipuncture control samples. The arterial line flushing solution contained 1 unit of heparin per ml in group 1 and 2 units per ml in group 2. Our results confirmed that clotting studies carried out on blood samples from an arterial line or central venous line correlate well with those obtained from a venipuncture sample. The only exception was activated partial thromboplastin time in group 2 patients when the discard volume from the arterial line is only 2.5 ml above the deadspace volume of the connecting line. At least 5 ml of discard volume must be withdrawn before sampling, to obtain reliable results.

Blood Coagulation Tests↗
PubMed1991

Diverticulum of the rectum due to a rectal leiomyosarcoma.

A 78 year old woman with a rectal leiomyosarcoma is presented. The case is of interest because of very unusual radiological and operative features of a large rectal diverticulum. As a result of the difficulty in making the correct diagnosis pre- or intraoperatively, a simple, but possibly suboptimal, resection was performed. Although the patient has done well, the long-term outlook is uncertain. The problems of optimum management and prediction of outcome in this uncommon condition are discussed.

Aged↗
PubMed1991

Severe congenital neutropenia: clinical effects and neutrophil function during treatment with granulocyte colony-stimulating factor.

We studied neutrophil function and clinical responses in seven patients with severe congenital neutropenia (SCN) after they received treatment with recombinant human granulocyte colony stimulating factor (rhG-CSF). Two subpopulations of patients with SCN were defined by their pattern of absolute neutrophil response, superoxide production, and cytochrome b559 levels. One group had an oscillating absolute neutrophil count and reduced ability to produce superoxide and cytochrome b559 (n = 4), and the second group had a relatively constant absolute neutrophil count response with normal superoxide and cytochrome levels (n = 3). Neutrophils from both groups had decreased surface expression of FcRIII and abnormal upregulation of the C3bi receptor (CR3). All patient neutrophils, however, had normal contents of the primary granule constituent, beta-glucuronidase, and the specific granule constituent, vitamin B 12 binding protein. The clinical response to rhG-CSF was evident by marked improvement in the degree of periodontitis and reduction in the number of oral ulcers in both groups of patients. Although neutrophil function is not completely normal in patients with SCN, it is likely that enough redundancy exists in neutrophil bactericidal capacity to promote normal host response to inflammation.

CD18 Antigens↗
PubMed1990

Peptide-amine interactions in the hypothalamic paraventricular nucleus: analysis of galanin and neuropeptide Y in relation to feeding.

The neuropeptide galanin (GAL) has been found to elicit feeding after injection into the paraventricular hypothalamic nucleus (PVN), where it coexists with norepinephrine (NE), a neurotransmitter believed to be important in the control of natural feeding behavior. Using pharmacological tools, this study investigated the possibility that PVN GAL influences food intake via its direct interaction with the noradrenergic system localized in this nucleus. Tests with alpha-adrenergic receptor blockers demonstrated that GAL-induced feeding, similar to NE-stimulated feeding, depends specifically upon functional alpha 2-receptor sites. Further, experimentation with the catecholamine synthesis inhibitors, alpha-methyl-p-tyrosine and Fla-63, suggested that GAL's action also depends upon the release of endogenous NE. This is in contrast to another hypothalamic peptide, neuropeptide Y, which is also a strong stimulant of food intake and coexists with NE in the PVN. Neuropeptide Y remains effective in eliciting feeding in the presence of alpha 2-receptor antagonists and catecholamine-synthesis inhibitors, suggesting that, unlike GAL, it can act independently of endogenous NE.

Adrenergic alpha-Antagonists↗
PubMed1990

Preferential biliary elimination of FPL 63547, a novel inhibitor of angiotensin-converting enzyme, in the rat.

1. The route of elimination of FPL 63547, a novel inhibitor of angiotensin-converting enzyme (ACE), has been investigated in the anaesthetized rat. Comparisons have been made with other ACE inhibitors. 2. Bile and urine samples were collected over a 5 hour period following a single i.v. dose of ACE inhibitor (2 mumol kg-1). Samples were bioassayed for ACE inhibitory activity using affinity-purified rabbit lung ACE and the amounts of the active form of inhibitor present in each sample were calculated by comparison with a standard curve. 3. FPL 63547 was rapidly and extensively excreted as the diacid in the bile but appeared in the urine in negligible amounts. The bile:urine ratio was 21.4:1 indicating a marked preference for the biliary route. A similar elimination profile was observed when the compound was dosed in its active form (FPL 63547 diacid), 87.9% of which was found in the bile over the 5 h collection period, with a bile: urine ratio of 14.6:1. 4. The marked preference of FPL 63547 for biliary elimination was not shared by the other ACE inhibitors tested in this study. Lisinopril demonstrated the opposite pattern, being excreted almost exclusively by the kidney (bile:urine ratio 0.06:1). Enalapril was eliminated in approximately equal amounts in bile and urine (ratio 0.7:1) while spirapril diacid showed a slight preference for the bile (ratio 2.6:1). 5. The physical chemical properties of FPL 63547 diacid may be responsible for its unusual preference for biliary elimination. In particular, the amphipathic character and strong acid functionality of the compound are thought to favour transport into the bile. 6. Elimination by the biliary route will be preferred in patients whose renal function is impaired as a result of disease or age. In such patients the elimination of renally-excreted ACE inhibitors is known to be compromised, resulting in compound accumulation and the need for closer monitoring. Therefore, the elimination profile of FPL 63547, if confirmed in man, may prove to be clinically advantageous.

Anesthesia↗
PubMed1989

Attachment of neuroblastoma cells to extracellular matrix: correlation with metastatic capacity.

Extracellular matrix (ECM) serves important attachment functions during organogenesis in mammalian species. When layered on a plastic surface, ECM extracted from the rat lung, liver, or kidney enhances the attachment of C1300 murine neuroblastoma cells to that surface. Enhanced attachment to ECM by these cells correlates with their potential to form metastatic deposits in vivo. Conversely, neuroblastoma cells selected for increased metastatic potential by in vivo passaging demonstrate enhanced attachment to organ-derived ECM. However, although ECM provides attachment sites for these murine neuroblastoma cells, the attachment is not preferential for any of the organ ECMs tested (lung, liver, kidney). Histopathologic examination of the murine liver, lungs, and kidneys performed 20 to 22 days after intravenous inoculation of C1300 cells reveals notable metastatic seeding in each of these organs, but the liver clearly exhibits a greater degree of replacement by tumor metastases than the lungs or the kidneys. Therefore, the data from the attachment assays, coupled with the histopathologic findings obtained after tumor inoculation, suggest that although the ability to attach to ECM correlates with metastatic potential, additional factors are important in determining the preferential pattern of metastatic disease observed in murine neuroblastoma.

Animals↗
PubMed1988

Nasopharyngeal oxygen in children.

Hypoxia caused by pneumonia or bronchiolitis is a common cause of death in children in developing countries. Oxygen is very expensive in developing countries, and it is important that the limited supplies available be used as efficiently as possible. This study evaluated the administration of oxygen through an 8 FG catheter inserted into the nose to a depth equal to the distance from the side of the nose to the front of the ear, so that the tip of the catheter was just visible in the pharynx below the soft palate. A flow rate of 150 ml/kg/min gave an inspired oxygen concentration of about 50% in children less than 2 years old. Thus, newborn infants with pneumonia can usually be treated with 0.5 l/min and infants up to 12 months old with 1.0 l/min of nasopharyngeal oxygen.

Blood Gas Monitoring, Transcutaneous↗
PubMed1988

Gastrointestinal iodine-131-meta-iodobenzylguanidine activity.

Radioactivity in the colon during 131-I-meta-iodobenzylguanidine (MIBG) scintigraphy may obscure or be mistaken for tumor uptake. Fecal excretion of radioactivity was examined in eight patients following therapeutic 131-I-MIBG administration (123-218 mCi, 4.551-8.066 GBq) and was found to be 0.02-1.93% of the administered dose. Semiquantitative grading of colonic activity on scintigraphy was inversely related to fecal excretion. An additional patient with marked colonic activity was studied before and after an enema: all visible gut activity was evacuated. We conclude that radioactivity in the colon seen in 131-I-MIBG scintigraphy is due largely to gut excretion of 131-I and is not due to 131-I-MIBG uptake in the autonomic innervation of the gut. Laxatives and enemas are suggested for patients in which such gut radioactivity may lead to difficulties in interpretation.

3-Iodobenzylguanidine↗
PubMed1987

Isolated testicular leukemic relapse. Response to radiation therapy.

Between January, 1975, and December, 1984, at the University of Michigan Medical Center, 17 boys with leukemia presented with overt or occult isolated testicular relapse. Diagnosis was obtained by bilateral open-wedge biopsies of the testes. All the patients were treated with combined local testicular irradiation and systemic chemotherapy. In only 1 of the 17 patients (6%) testicular leukemia developed as the only site of relapse. It appears that doses in the range of 2,000 to 2,400 cGy in 10 to 12 fractions achieve optimum control of leukemic infiltration of the testes.

Adolescent↗