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Biomedical subjects

J Hamilton

Publications and source records attributed to J Hamilton.

At least 127 records · Page 7Linked to original sources

Pentoxifylline therapy for chronic claudication: are patients dependent on therapy?

BACKGROUND: The purpose of this study was to evaluate the efficacy of long-term pentoxifylline therapy. METHODS: Fifty consecutive patients on long-term pentoxifylline therapy entered a weaning program. The standard dose of 400 mg three times a day was reduced to 400 mg twice a day for 1 month, 400 mg daily for an additional month, and then withdrawn completely for 3 months. Subjective evaluation of each patient's symptoms and objective measurements (treadmill testing for initial claudication distance, maximum walking distance, and ankle/brachial indexes) were evaluated during treatment withdrawal. RESULTS: Twenty-seven patients tolerated withdrawal of therapy without symptomatic deterioration. Seven of nine patients who did not tolerate weaning had deterioration of treadmill ICD/MWD parameters; there was a significant absolute decrease (p = 0.016) in MWD from 430 +/- 78 to 221 +/- 23 feet. Patients with an initial low MWD were less likely to tolerate weaning. Sixty percent of the patients with successful weaning had clinically asymptomatic deterioration of treadmill ICD/MWD parameters. CONCLUSIONS: A substantial number of patients who have been on long-term successful pentoxifylline therapy for claudication can be weaned from the drug. Asymptomatic deterioration of treadmill test parameters is not an indication for resuming therapy.

Aged↗

Parathyroid hormone-like peptide and parathyroid hormone are secreted from bovine parathyroid via different pathways.

Parathyroid hormone-like peptide is a recently discovered protein which is thought to be responsible for the hypercalcemia of malignancy. Through the use of radioimmunoassay, Northern analysis and Western blot techniques this protein has been demonstrated to occur in a variety of tumor and normal cells. Its role in normal physiology is not established nor is there knowledge regarding its synthesis, secretion, and storage. We have investigated characteristics of the secretion of parathyroid hormone-like peptide in bovine parathyroid gland slices and cells to learn whether or not this protein is secreted in a manner similar to that of parathyroid hormone. We have used radioimmunoassays specific for PTH and PTH-rP to measure the secretion of each protein and have found that, unlike PTH, PTH-rP secretion was not influenced by the medium calcium concentration. Similarly, PTH-rP secretion was not influenced by other known PTH secretagogues such as c-AMP or isoproterenol. An examination of the subcellular distribution of PTH-rP revealed that 75-90% of it occurs in the soluble fraction of cell lysates. Analysis of isolated secretory granules demonstrated the presence of PTH while PTH-rP was undetectable in these organelles. We conclude that PTH-rP is not secreted from parathyroid cells via the regulated pathway utilizing PTH secretory granules.

Animals↗

Altered alpha 1-adrenoceptor binding in intact and adrenalectomized obese Zucker rats (fa/fa).

While many autonomic and metabolic defects associated with genetic obesity in the Zucker rat are corrected by adrenalectomy (Adx), brain adrenoceptor function has not been examined in this context. Here, 3 weeks after Adx or sham surgery, brains of 11 weeks old lean (Fa/Fa) and obese (fa/fa) male Zucker rats were assayed for alpha 1-([3H]prazosin; [3H]PRZ) and alpha 2-adrenoceptor ([3H]paraminoclonidine; [3H]PAC) binding by autoradiography. By genotype, obese rats had 19-256% higher [3H]PRZ binding than lean rats in the amygdala (central [ACN], basolateral [ABL], basomedial [ABM] and medial [MAN] nuclei [n.]), hypothalamus (dorsomedial n. [DMN] and lateral [LH]) and somatosensory cortex. In the ABL and ACN, increased maximal binding (Bmax) in obese rats was associated with decreased affinity (increased Kd). Three weeks after surgery, sham-operated obese rats gained 27% more weight than lean rats but lean and obese Adx rats gained the same amount of weight. Adx reduced [3H]PRZ binding in both lean and obese rats by 37-70% in the amygdala (ABM, ACN, MAN) compared to sham-operated rats. But, Adx selectively reduced [3H]PRZ binding only in lean rats in the ABL, DMN, ventromedial hypothalamic n. (VMN) and ventroposteromedial thalamic n. In most areas, decreases in maximal binding (Bmax) associated with Adx were accompanied by decreases in Kd. Unlike [3H]PRZ binding, there was no consistent genotype difference in [3H]PAC binding although Adx was followed by increased binding in obese and decreased binding in lean rats in the ABL. In only the VMN, obese rats had a 21% higher alpha 2- to alpha 1-adrenoceptor ratio than lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

A review of patients attending a preliminary cochlear implant assessment clinic.

The Cochlear Implant Programme at Manchester Royal Infirmary was established in 1988 and so far (January, 1992) 38 patients have been implanted with the Nucleus 22 channel intracochlear device and one with the Ineraid device. All patients who are referred for consideration for an implant are initially seen at a preliminary cochlear implant assessment clinic conducted by an ENT surgeon. One hundred and seventy three patients attended the initial outpatient screening clinic between 1987 and January 1992. Of these 112 patients (67.6 per cent) went on for further investigation regarding suitability for implantation. This paper details the aetiology and severity of deafness in these patients and explains how suitability for admission to the next stage of assessment was decided.

Adolescent↗

Merkel cell carcinoma of the eyelid.

The Merkel cell is part of the dendritic cell population of the epidermis, and studies suggest it has a role as a slowly adapting mechanoreceptor involved with mediating the sense of touch. Merkel cells can give rise to malignant neoplasms, one tenth of which occur in the eyelid and periocular area, and manifest as painless erythematous nodules, with overlying telangiectatic blood vessels. Merkel cell carcinoma can mimic other malignant lesions, and the diagnosis can be difficult. One third of the tumors recur, and there is a high rate of metastasis. The estimated 5-year survival rate is 38%. Initial treatment should be aggressive, including surgical resection, with consideration of postoperative radiation. Merkel cell carcinoma responds to chemotherapy, but routinely recurs on cessation of treatment. Two cases are presented to illustrate the typical presentation of Merkel cell carcinoma and the importance of electron microscopy and immunohistochemical studies.

Aged↗

A survey examining nurses' knowledge of pain control.

Three hundred and eighteen (318) nursing staff members at an acute care teaching hospital in Montreal, Canada, were surveyed to identify their knowledge of pain assessment and management. Two pain instruments were combined and adapted for use. The final instrument consisted primarily of true/false responses and took about 10 min to complete. The mean score was 63.9%. Overall results indicated that nurses lacked knowledge and understanding of opioid addiction, equivalent dosing, properties of opioids, and differences in acute and chronic pain. No statistically significant differences were found in the scores by level of educational preparation or by years of experience. Presentation of the results unit by unit demonstrated that the instrument is suitable as an educational tool as well as an effective strategy to introduce nursing staff to nursing research.

Adult↗

Distribution of cholecystokinin forms in intestinal secretory granule subtypes.

Peptides and proteins destined to be released in response to stimuli are found in the regulated secretory pathway. Substances in this pathway are packaged into secretory granules, wherein they are often rendered osmotically inactive by complexing to an oppositely charged molecule. The complexing mechanism employed by members of the cholecystokinin (CCK) peptide family is unknown, but the heterogenous charges of CCK peptides makes it possible that different CCK peptides have different abilities to form intragranular complexes. If the number of osmotically active intragranular CCK peptides varies, corresponding variations in secretory granule density should result, and when intestinal CCK secretory granules were purified on isotonic density gradients, four granule peaks were observed. Granules containing greater proportions of short CCK forms tended to have the lowest buoyant densities, suggesting that they contain a greater number of osmotically active molecules than granules of lower density and that short or all intragranular CCK forms are osmotically active. CCK secretory granules also contained novel CCK forms; in addition to previously characterized forms, granules contained a CCK form that appears to be CCK-6 and a form that could arise from cleavage of CCK-58 at position 4, 10, or 12. Because intragranular enzymes are responsible for peptide posttranslational processing, the intragranular CCK forms observed in the present study are likely to be authentic CCK-processing products. Finally, CCK sorting in intestine apparently differs from that in a rat medullary thyroid carcinoma cell line, in which CCK-22 and CCK-33 are not found in the regulated secretory pathway.

Animals↗

The effect of cytokines on the expression of MHC antigens and ICAM-1 by normal and transformed synoviocytes.

We report the expression on synovial cells of cell surface molecules known to be involved in T cell activation by antigen presenting cells. Normal human synovial fibroblasts and a human synovial cell line transformed with the SV40 large T antigen were used for in vitro stimulation studies with recombinant cytokines. We demonstrate an increase in MHC-A, B, C expression in normal synovial cells in response to recombinant interferon gamma (r gamma IFN), tumour necrosis factor alpha and beta (rTNF alpha and beta) and interleukin-1 (rIL-1 alpha). Intercellular adhesion molecular-1 (ICAM-1) expression was increased in parallel with MHC Class I. The combination of r gamma IFN and rTNF alpha was additive in its effect on ICAM-1 expression. Northern blot analysis suggests that ICAM-1 expression in synovial cells is controlled at the level of transcription. In contrast, MHC Class II (HLA-DR) was only significantly induced by r gamma IFN. Other stimuli including interleukin-4 (IL-4), interleukin 6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF) and prostaglandin E2 (PGE2) did not affect the expression of ICAM-1 or MHC Class I and II. Leucocyte function antigen 3 (LFA-3) expression was not affected by any of the stimuli tested. Immunoperoxidase staining of rheumatoid synovial tissue confirmed enhanced in vivo expression of ICAM-1 in rheumatoid arthritis. These changes are discussed in the context of T cell activation in inflammatory arthritis.

Arthritis, Rheumatoid↗

Preparation and crystallization of human transthyretin (prealbumin) variants.

Naturally occurring variants of human serum transthyretin (prealbumin) have been prepared by recombinant DNA methods and crystallized from ammonium sulfate solutions to give crystals suitable for x-ray crystallographic analysis. Included are variants which are known to be associated with familial amyloidotic polyneuropathy. Dyes which have been used as histochemical stains to identify amyloid tissue deposits: Congo Red, Methylene Blue and Bromophenol Blue, have been co-crystallized with the transthyretin variants. Congo Red was found to be very selective while Methylene Blue actually assisted in the formation of crystals. All crystal forms which were examined were isomorphous to the structure of normal transthyretin.

Base Sequence↗

On the relationship between self-focused attention and psychological disorder: a critical reappraisal.

A recent review of the literature on the role of self-focused attention in psychological dysfunction (Ingram, 1990) is critically examined. This article (a) reexamines the evidence relevant to Ingram's proposal that self-awareness is a nonspecific factor involved in virtually all forms of psychopathology and argues that this conclusion is not warranted by the existing evidence; (b) takes issue with his premise that the fact that self-awareness is associated with a variety of psychological dysfunctions poses a conceptual dilemma; (c) corrects several important inaccuracies and mischaracterizations in his presentation of Carver and Scheier's (1981) cybernetic control theory and Pyszczynski and Greenberg's (1987) self-regulatory perseveration theory; and (d) critiques the "self-absorption" model that he proposed as an alternative to extant theories and concludes that this conceptualization does not add to the understanding of either self-awareness processes or psychopathology.

Attention↗

Equine neural angiostrongylosis.

Verminous encephalomyelitis due to Angiostrongylus cantonensis larvae was diagnosed in 2 foals at necropsy. The principal clinical feature was tetraparesis, although history and neurological examination revealed progressive and multifocal neurological disease. At presentation, a tentative diagnosis of parasitic larval migration involving the central nervous system (CNS), presumably due to Strongylus vulgaris, was proposed. Dissection of the spinal cord in one case resulted in recovery of intact larvae of both sexes of A. cantonensis. In both foals, histopathology of the brain and spinal cord revealed nematode sections which were consistent with A. cantonensis larvae.

Angiostrongylus↗

Measuring the efficiency of an artificial lung: 1. Carbon dioxide transfer.

The performance of a hollow fibre artificial lung ('Capiox E') was analysed by measurement of the 'parallel deadspace' of the device under varying conditions in 21 patients. The efficiency with which carbon dioxide was exchanged was determined by the time available for equilibration between the blood and gas phases. When this equilibration coefficient was less than 12 seconds per litre of blood flow per litre of gas flow, there was a marked reduction in the efficiency of gas exchange. Under certain conditions, the 'counter-current' design of the device apparently permitted the clearance of carbon dioxide at a partial pressure greater than that which was found in the mixed venous blood. This anomalous behaviour may represent in vivo confirmation of the Haldane effect.

Adult↗