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J L McCall

Publications and source records attributed to J L McCall.

45 records · Page 3Linked to original sources

Serum tumour necrosis factor alpha and insulin resistance in gastrointestinal cancer.

Cancer cachexia may be mediated by endogenous peptides such as tumour necrosis factor alpha (TNF-alpha). Insulin resistance occurs in these patients, and is also seen experimentally with TNF-alpha administration. In this study, insulin sensitivity and energy metabolism were measured in 11 patients with gastrointestinal cancer and ten controls, using the euglycaemic glucose clamp and indirect calorimetry. Patients with cancer were significantly more insulin resistant than controls (P < 0.01) and in such patients insulin resistance correlated with serum TNF-alpha level (rs = 0.74, P < 0.01). Fasting insulin levels also correlated inversely with insulin sensitivity (rs = -0.62, P = 0.003). These results suggest a possible association between endogenous TNF-alpha production and insulin resistance in patients with gastrointestinal cancer.

Aged↗

Methylxanthines in surgery: a bright future?

Methylxanthines have been used in clinical practice for over 100 years, and although understanding of their mechanisms of action is growing their effects are not fully understood. Nevertheless the knowledge to date has brought about a general upsurge of interest in methylxanthines and the development of novel derivatives. Methylxanthines are poised to escape the confines of their traditional role as these agents are applied in novel ways to surgical illnesses such as septic shock, the adult respiratory distress syndrome, cancer cachexia and functional neutrophil disorders. Methylxanthines, alone or in combination with other compounds, may well become part of the surgeon's future stock-in-trade.

Humans↗

Tumour necrosis factor-alpha immunodetection in blood monocytes and serum: preliminary findings in weight-losing cancer patients.

The peptide tumour necrosis factor-alpha (TNF-alpha) is a central mediator of the host response. Identifying where and when TNF-alpha is produced may give insights into its potential role in various pathophysiological states. This paper describes a quantitative analysis of TNF-alpha expression in peripheral blood monocytes (PBM) at the single cell level. A pilot study has been undertaken, using this method to assess TNF-alpha expression in PBM from healthy volunteers and cancer patients. We also report mildly elevated serum TNF-alpha levels in the cancer patients, using an immunoradiometric assay (IRMA) sensitive to 1 pg/mL of recombinant TNF-alpha. The results of this preliminary investigation suggest that TNF-alpha production may be altered in cancer patients.

Humans↗

Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs.

Achieving nitrogen accretion in patients with critical surgical illness or cancer cachexia is often not possible by the simple provision of calories and nitrogen. Cachexia may result from the metabolic derangements caused by release of inflammatory mediators such as tumor necrosis factor (TNF). We wished to determine whether recombinant human insulin-like growth factor I (rhIGF-I) preserves its protein-sparing effects in the face of high plasma TNF concentrations. Primed constant infusions of [15N]urea and [6-3H]glucose tracers were used to measure protein and glucose kinetics in fasted lambs. The lambs were divided into four groups: two groups received normal saline infusions of 480 min, and two groups received recombinant TNF (rTNF) infusions of 1 microgram.kg-1.h-1. During the last 300 min, one of the normal saline and one of the rTNF-infused groups were infused with rhIGF-I at a dose of 50 micrograms.kg-1.h-1. rTNF infusion resulted in the lambs becoming febrile and significantly increased plasma cortisol, glucagon, and insulin levels. rhIGF-I infusion in the control animals reduced the rate of loss of protein by 15% (P less than 0.01) and increased the rate of peripheral glucose clearance by 55% (P less than 0.01). rhIGF-I infusion in the rTNF-treated animals reduced the rate of net protein loss by 15% (P less than 0.01) and caused similar changes in glucose kinetics, as were observed in the control animals. We conclude that as rhIGF-I preserves its protein anabolic action in the face of high rTNF levels, further investigation into a possible clinical role for rhIGF-I in severe surgical illness is warranted.

Animals↗

Tumour necrosis factor in surgical illness.

TNF is a multipurpose molecule which works alongside other cytokines to stimulate and coordinate immune and inflammatory responses to antigenic challenges. It is extremely well conserved throughout all mammal species, and obviously confers considerable survival advantage. There are circumstances, however, in which TNF itself can be a source of tissue injury. This occurs in septic shock when the magnitude of the host response is overwhelming. TNF also initiates the energy substrate mobilization required to meet the heightened fuel demands associated with immunological, inflammatory and wound-healing activities. In chronic infection and malignancy this may lead to severe depletion of host tissues with its own attendant morbidity and mortality. At present our understanding of the host response is expanding rapidly. The challenge for the future will be to manipulate this response selectively, to maximize its influence on the disease while minimizing its negative impact on the host.

Animals↗

In vivo immunohistochemical identification of tumor necrosis factor/cachectin in human lymphoid tissue.

To find an alternative approach to the in vivo detection of tumor necrosis factor/cachectin (TNF alpha), an immunohistochemical method to identify TNF alpha in histologic sections was developed. This method employs the streptavidin-biotin immunoperoxidase technique, and TNF alpha-specific monoclonal and polyclonal antibodies, on cryostat sections of fresh frozen human lymphoid tissue. Staining was evident in most specimens displaying follicular hyperplasia, but was absent from histologically normal tissue. Both tingible body macrophages and follicular dendritic reticulum cells appeared from phenotype analysis in serial sections and by double staining experiments to constitute the main source of TNF alpha. This technique complements other systemically oriented assays that may fail to detect significant in vivo TNF alpha production and activity at a cellular level.

Humans↗

Prospective randomized comparison of open versus laparoscopic appendectomy in men.

A prospective, randomized trial was performed to compare open appendectomy with laparoscopic appendectomy in men with a clinical diagnosis of acute appendicitis. Sixty-four patients with a median age of 25 years (range 18-84 years) were randomized to open appendectomy (n = 31) or laparoscopic (n = 33) appendectomy. Of the 64 men, 56 (87.5%) had appendicitis (27 open, 29 laparoscopic procedures). The mean operating times were 50.6 +/- 3.7 minutes (+/- SEM) for open and 58.9 +/- 4.0 minutes for laparoscopic appendectomy (p = 0.13). Five (15%) patients randomized to laparoscopic appendectomy had an open operation. The mean postoperative hospital stay was significantly longer for open appendectomy (3.8 +/- 0.4 days) than for laparoscopic appendectomy (2.9 +/- 0.3 days) (t = 2. 05,df = 62,p = 0.045). The complication rate after open appendectomy (25.8%) was not significantly different from that after laparoscopic appendectomy (12.1%). There was a single postoperative death due to a pulmonary embolus in the laparoscopic group and a single death due to cardiac and renal failure in the open group. The mean time to return to normal activities was significantly longer following open appendectomy (19.7 +/- 2.4 days) than after laparoscopic appendectomy (10.4 +/- 0.9 days), (t = 3.75,df = 49,p = 0.001). In conclusion, laparoscopic appendectomy in men has significant advantages in terms of a more rapid recovery compared to open appendectomy. There were no significant disadvantages to laparoscopic appendectomy compared to open appendectomy.

Adolescent↗

Hepatic cryotherapy for metastatic liver tumours.

Liver resection is the treatment of choice for resectable hepatic metastases; however, most patients have unresectable disease when diagnosed. Hepatic cryotherapy has been advocated to treat unresectable tumours in the liver although its precise role is still being evaluated. This article discusses mechanisms of action, technical considerations, current indications and the early results of cryotherapy in treating metastatic liver disease.

Colorectal Neoplasms↗