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Biomedical subjects

M Fahey

Publications and source records attributed to M Fahey.

31 records · Page 2Linked to original sources

Acute hospital costs of trauma in the United States: implications for regionalized systems of care.

As part of a larger effort to determine total direct and indirect costs of injury in the United States, national estimates of the numbers and expenditures associated with acute hospitalization due to traumatic injury were derived using data from the 1984, 1985, and 1986 National Hospital Discharge Surveys (NHDS). Estimates of the numbers of hospital episodes and total expenditures are reported in this paper for subgroups of patients defined by age, sex, and body region and AIS severity of the injuries sustained. In 1985 2.1 million individuals sustained a traumatic injury which resulted in hospitalization. Hospital expenditures totaled $11.4 billion inclusive of professional fees. Adolescents and young adults aged 15-44 years accounted for nearly one half of all discharges and total hospital costs. The elderly, who represent only 12% of the population, accounted for an additional one quarter of total discharges and hospital costs. Nearly three quarters of the hospitalizations and one half of total expenditures were for minor (ICD/AIS = 1, 2) injuries. Moderate (ICD/AIS = 3) and severe (ICD/AIS = 4, 5), injuries respectively accounted for 23% and 3% of total episodes and 37% and 11% of total expenditures. Only 12% of patients and 25% of trauma care dollars involved injuries sufficiently severe to require treatment at a trauma center.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The distribution of GAWK-like immunoreactivity in neuroendocrine cells of the human gut, pancreas, adrenal and pituitary glands and its co-localisation with chromogranin B.

GAWK is a recently discovered peptide isolated from extracts of human pituitary gland and subsequently shown to be identical to sequence 420-493 of human chromogranin B. The distribution of this peptide was studied in human gut, pancreas, adrenal and pituitary glands using antisera to two portions of the 74 amino acid peptide (sequences 1-17 and 20-38). In addition, the co-existence of GAWK immunoreactivity with other peptides and chromogranin B was investigated using comparative immunocytochemistry. In the gut, GAWK was localised mainly to serotonin-containing cells of the mucosal epithelium, where electron microscopy showed it to be stored in typical electron-dense (250 nm diameter) granules, and to a moderate population of nerve fibres in the gut wall. Considerable quantities of GAWK-like immunoreactivity were measured in the gut, up to 36.3 +/- 18 pmol GAWK 1-17/g wet weight of tissue (mean +/- SEM) and 12.4 +/- 2.9 pmol GAWK 20-38/g. Chromatography of gut extracts revealed several GAWK-like immunoreactive peaks. GAWK-like immunoreactivity was also detected in endocrine cells of pancreas, pituitary gland and adrenal medulla, where the highest concentrations of GAWK-like immunoreactivity were measured (GAWK 1-17 2071.8 +/- 873.2 and GAWK 20-38 1292.7 +/- 542.7 pmol/g). Endocrine cells containing GAWK-like immunoreactivity were found also to be immunoreactive for chromogranin B. Our results define a discrete distribution of GAWK immunoreactivity in human endocrine cells and nerves and provide morphological support for the postulated precursor-product relationship between chromogranin B and GAWK. Details of the functions of this peptide are awaited.

Adrenal Glands↗

Occurrence and developmental pattern of neuromedin U-immunoreactive nerves in the gastrointestinal tract and brain of the rat.

Neuromedin U is a newly described regulatory peptide, found by radioimmunoassay in significant concentrations in both the brain and gut of the rat. The aim of the present study was to localize this peptide immunoreactivity to discrete structures of the gut and brain and to map its distribution using immunocytochemistry. In the gut, neuromedin U was confined to nerve fibres mainly in the myenteric and submucous plexuses and the mucosa of all areas except stomach. Immunoreactive ganglion cells were seen in both ganglionated plexuses and their number did not increase following colchicine administration. This observation and the finding that the population of neuromedin U-immunoreactive nerves in the ileum was not affected by complete extrinsic denervation indicated that the nerves are mostly intrinsic in origin. Colocalization studies revealed neuromedin U and calcitonin gene-related peptide were present in the same myenteric and submucosal ganglion cells. Transection experiments showed that, like calcitonin gene-related peptide-immunoreactive nerves, fibres containing neuromedin U project for very short distances in both an oral and anal direction. At the electron microscopic level, neuromedin U immunoreactivity, demonstrated using the immunogold technique, was localized to large granular vesicles. In the central nervous system, neuromedin U immunoreactivity was localized to fibres which were widespread throughout the brain, except in the cerebellum. The presence of neuromedin U-immunoreactive cell bodies was restricted to the rostrocaudal part of the arcuate nucleus. Colocalization studies showed that a proportion of the neuromedin U-immunoreactive cell bodies in the arcuate nucleus also contained pro-opiomelanocortin. Neuromedin U-immunoreactive fibres were first detected in the rat intestinal mucosa at day 1 after birth. In the brain, the arcuate nucleus showed neuromedin U-immunoreactive neuronal cell bodies at E16 but not at E14. In conclusion, neuromedin U is a new member of the group of molecules known as brain-gut peptides.

Aging↗

The occurrence of pancreastatin in tumours of the diffuse neuroendocrine system.

We have reported previously the localization of the 49 amino acid peptide pancreastatin to all identifiable endocrine cells of porcine gut, pancreas and adrenal, thyroid and pituitary glands. In this study, we have investigated the occurrence of pancreastatin in a series of human neuroendocrine tumours using an antibody to whole synthetic porcine pancreastatin. The most consistent immunostaining for pancreastatin was found in carcinoid tumours of ileum (four out of six), rectum (four out of six), ovary (two out of two) and lung (nine out of 10). Radioimmunoassay of tumour extracts showed that the concentrations of pancreastatin in ileal carcinoids were very high (mean 71.6, range 31.0-184.0 pmol g-1). The high rate of positivity in lung carcinoids contrasted sharply with the results of 10 pulmonary small cell carcinomas which displayed no immunoreactivity and contained minimal concentrations of pancreastatin (mean 2.0, range 0-6.0 pmol g-1). Extra-adrenal paragangliomas also contained pancreastatin (seven out of 10), but although radioimmunoassay detected peptide in phaeochromocytomas (mean 29.8, range 8.0-69.0 pmol g-1), immunocytochemistry did not. Porcine pancreastatin shows structural homology with bovine chromogranin A, an observation which has led to suggestions that chromogranin is a precursor for the peptide. More recently, a sequence homologous to porcine pancreastatin has been identified in the human chromogranin A molecule. In this study, immunostaining with an antiserum to human chromogranin gave positive results in most cases of each tumour type except the small cell carcinomas. The lack of consistent relationships between chromogranin and pancreastatin immunoreactivities may reflect the fact that the antiserum to pancreastatin was raised against the porcine peptide. When antibodies to human pancreastatin become available, the peptide may prove to be a more consistent marker for neuroendocrine tumours.

Adenocarcinoma↗

Immunohistochemical markers of small cell carcinoma and related neuroendocrine tumours of the lung.

A selected group of 263 pulmonary neuroendocrine tumours comprised 156 small cell carcinomas, five combined cell carcinomas, nine atypical carcinoid/small cell carcinomas, 32 atypical carcinoids, ten large cell/small cell carcinomas, and 51 carcinoid tumours. These were compared with a group of 109 non-small cell carcinomas, using four markers of neuroendocrine differentiation to determine differences in reactivity between the two groups and among the variants of neuroendocrine tumour. The antibodies used were neuron-specific enolase (NSE), protein gene product (PGP) 9.5, human bombesin, and the C-terminal flanking peptide of human bombesin (CTP). Most small cell carcinomas, carcinoid tumours, and atypical carcinoid variants showed immunoreactivity for both NSE and PGP 9.5 but a significant number of non-small cell carcinomas, mainly squamous cell carcinomas, were also positive (11 and 35 per cent, respectively). Bombesin was specific for neuroendocrine tumours, being demonstrable in 35 per cent carcinoids and 24 per cent small cell carcinomas, but staining was focal and often confined to scattered cells. Diffuse strongly positive immunoreactivity for CTP was seen in the majority of malignant neuroendocrine tumours, but only 12 per cent of carcinoid tumours were positive and non-small cell carcinomas were negative. CTP is therefore of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell-small cell carcinoma.

Biomarkers, Tumor↗

Effects of chronic estrogen treatment on water exchange in rats.

Intact female rats implanted subcutaneously with Silastic tubes containing estradiol benzoate (EB) (28.7 micrograms X kg-1 X day-1) for 28 wk had a significantly greater daily intake of water, a higher water-to-food intake ratio, and a greater urine output than untreated control rats. Ovariectomized (OVX) rats also implanted for 14 wk with EB tubes (15 and 36 micrograms X kg-1 X day-1) showed identical results. Dipsogenic responses of the EB-treated rats to isoproterenol (25 micrograms/kg sc), angiotensin II (200 micrograms/kg ip), and hypertonic saline (1 M, 1% of body wt ip) were significantly attenuated. Both intact and OVX rats were subjected to a 24-h dehydration to assess renal concentrating ability. EB-treated rats lost significantly more weight and excreted significantly more urine of lower osmolality than controls. Administration of vasopressin to volume-loaded, EB-treated rats revealed no abnormalities in the ability to concentrate urine to the level of controls. Thus, in spite of a reduced responsiveness to several dipsogenic stimuli, EB-treated rats have an increased daily water turnover apparently related to an inability to concentrate their urine. This in turn may be related to abnormalities in either synthesis or release of antidiuretic hormone or both.

Angiotensin II↗

Management of pneumonia in the prospective payment era. A need for more clinician and support service interaction.

We compared the diagnostic and therapeutic management of pneumonia during 1970 and 1971 with that during 1979 and 1980 in clinically similar populations at The Johns Hopkins Hospital, Baltimore. More patients received aminoglycoside and cephalosporin therapy during 1979 and 1980. Guidelines for the use of chest roentgenograms and cultures were exceeded in 14% to 24% of cases. Patients whose cases were judged to be suboptimally managed had significantly higher charges and length of stay. Aged patients and those requiring thoracentesis also used resources more intensively. Given the technologic explosion, clinicians cannot know the performance characteristics of all tests and medications they can order. To minimize inefficient and ineffective practices, it is essential that clinicians and support service directors develop guidelines for testing and antibiotic use. Deviations should trigger timely interventions. Management under prospective payment will also require identifying specific patient subgroups to verify appropriate utilization and to assure equitable reimbursement.

Aminoglycosides↗

Pre-hospital trauma management.

Pre-hospital trauma care and management in the United Kingdom, West Germany, Denmark, the United States of America, Australia and New Zealand, are briefly compared. An analysis is presented of 738 serious motor vehicle accidents attended in Canterbury from November 1972 until February 1977, showing that the accidents with life threatening conditions commonly occurred more than 20km from the base hospital.

Accidents, Traffic↗

Pancreastatin distribution and plasma levels in the pig.

Pancreastatin is a peptide isolated from porcine pancreas which has insulin-suppressive actions in vitro and sequence homology with chromogranin A. Using radioimmunoassay and immunocytochemistry we investigated whether pancreastatin has a more widespread distribution and a possible endocrine role in the pig. Pancreastatin immunoreactivity was found in plasma, adrenal gland, pancreas, anterior pituitary and throughout the gastrointestinal tract. The immunoreactivity was colocalized with chromogranin immunoreactivity in endocrine cells and ultrastructurally (in the pancreas) to storage granules. Characterization of pancreastatin-like immunoreactivity, using gel permeation and high performance liquid chromatography, separated 3 different pancreastatin-like immunoreactive forms: one molecular form, indistinguishable from synthetic pancreastatin 1-49, was predominant in pancreas and thyroid and released into the circulation postprandially. However, a high dose (greater than 1 nmol/l) infusion of pancreastatin 33-49 (the biologically active moiety in vitro) into conscious pigs had no effect on either basal or glucose-stimulated insulin secretion.

Adrenal Glands↗

Bone tunnel enlargement after anterior cruciate ligament replacement.

Radiographic increase in the size of tibial and femoral tunnels has been observed. This retrospective study compared tibial tunnel diameter in 56 autograft and 87 allograft patellar tendon bone-tendon-bone anterior cruciate ligament replacements whose observed tunnel changes were correlated with clinical results at 1 year postoperatively. Tibial tunnel sclerotic margins were measured approximately 1 cm below the joint line. Exact tunnel dimension was calculated by using a magnification factor determined by the interference screw of known diameter within the same tunnel. Average allograft tunnel enlargement was 1.2 mm (-2.5 to 6.0) compared with the autograft tunnel enlargement of 0.26 mm (-2.5 to 2.7); the difference was significant (P > 0.0002). No significant difference was seen in KT-1000 arthrometer measurements between autograft or allograft groups, and no correlation was seen between increased tunnel size and clinical outcome as determined by the modified Hughston knee evaluation system. Tunnel measurement reproducibility was confirmed by independent repeated measurements. The significance of this tunnel enlargement is unknown and does not appear to adversely affect clinical outcome of allograft utilization. Possible explanations include an immune response with resorption, stress shielding proximal to the interference screw resulting in resorption, or an inflammatory response by synovium in the tunnel.

Adolescent↗

What causes p53 mutations in patients with lung cancer?

We studied the association between occurrence of p53 mutations and both smoking history and family history of cancer (FH) in 109 lung cancer patients using the logistic regression model. A dose-response relationship between smoking defined as pack-years smoked (PY) and p53 mutations was clearly demonstrated [Odds ratio (OR) for PY 30-59: 1.92 (0.55-7.94); OR for PY 60: 4.21 (1.09-19.0); trend P=0. 04], but no association between p53 mutations and FH was obtained in male patients. In females, smoking habit [OR: 3.23 (0.48-25.4)] and FH [OR: 4.17 (0.84-25.0)] might both be associated with p53 mutations.

Adenocarcinoma↗