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Biomedical subjects

G L Carlson

Publications and source records attributed to G L Carlson.

At least 37 records · Page 2Linked to original sources

Intestinal failure after surgery for complicated radiation enteritis.

Between 1983 and 1997, a total of 16 patients were referred to a tertiary Intestinal Failure Unit (IFU) following surgery elsewhere for complications of radiation enteritis. Eleven were female with a mean age of 43 years (range 21-71 years) and the most common primary site of malignancy was genitourinary (n = 13). Patients had undergone an average of two laparotomies (range 1-7 laparotomies) for complications of radiation enteritis prior to transfer to the IFU. On admission, the principal problem in eight patients was persisting intestinal fistulation, four patients had continuing intestinal obstruction and four had the short bowel syndrome after extensive intestinal resection. Only one patient had evidence of residual malignancy; this patient with short bowel syndrome was allowed home without invasive therapy. Of the remaining 15 patients, 12 required an abdominal surgical procedure, while three were discharged without further surgery after training for home parenteral nutrition (HPN). Following abdominal surgery, five patients died in hospital, but the remaining seven patients went home alive--including two further patients on HPN. Overall, of the 15 patients referred with intestinal failure after surgery for complications of radiation enteritis and actively treated, one-third died in hospital and a further third required institution of HPN before being able to be discharged home.

Adult↗

Nutritional status and assessment of patients on home parenteral nutrition: anthropometry, bioelectrical impedance, or clinical judgment?

The optimal method of assessing protein energy nutritional status in patients receiving home parenteral nutrition (HPN) is unknown. We evaluated protein energy nutritional status in 47 outpatients (23 male; 24 female) on HPN by measuring anthropometry, plasma proteins, and lymphocyte counts and compared these with the results of subjective clinical assessment and bioelectrical impedance measurements. Sixteen of the 47 patients (34%) were underweight (body mass index < 5th percentile of the reference) and 21 (45%) were below the 5th percentile of the reference for both triceps skinfold thickness and midarm muscle circumference. Plasma proteins were subnormal in 1-5 patients (2-11%). Lymphocyte counts were subnormal in 19 patients (40%). Clinical assessment classified 23 patients (49%) as well nourished and 24 (51%) as moderately malnourished. Moderately malnourished patients had a significantly lower body mass index than well-nourished patients (P = 0.02). Clinical assessment did not correlate with bioelectrical impedance analysis. Fat-free mass determined by bioelectrical impedance analysis resulted in values up to 9.4 kg lower and 8 kg higher than fat-free mass obtained by anthropometry. Weighing combined with a subjective clinical assessment is sufficient for evaluation of protein calorie nutritional status in patients on HPN.

Adult↗

Selective impairment of glucose storage in human sepsis.

BACKGROUND: Glucose utilization in sepsis is impaired but the mechanisms are unclear. This study examined the effect of sepsis on total glucose utilization, oxidation and storage, and the energetic costs of these metabolic processes. METHODS: Glucose infusion rate (GIR), glucose oxidation rate (GOR), non-oxidative disposal rate and the energetic cost of glucose storage were studied in 24 patients with abdominal sepsis and in 26 healthy controls, using indirect calorimetry and the euglycaemic hyperinsulinaemic clamp with insulin infusion rates of 40 and 240 mU m-2 min-1. RESULTS: Basal GOR was significantly lower in septic patients than in controls (1.5 versus 2.3 mg per kg fat-free mass (FFM) per min, P < 0.001). Septic patients had a significantly lower GIR at 40 mU m-2 min-1 (4.2 versus 9.1 mg per kg FFM per min) and at 240 mU m-2 min-1 (7.5 versus 11.8 mg per kg FFM per min), relative to controls (P < 0.001). GOR was similar in septic and control subjects at both rates of insulin infusion whereas non-oxidative disposal was significantly lower in septic patients (P < 0.001) and accounted entirely for the reduction in GIR. The energetic cost of glucose disposal was unaffected by sepsis. CONCLUSION: Sepsis is associated with selective impairment of glucose storage but the energetic cost of non-oxidative disposal is unaffected.

Blood Glucose↗

Serum leptin concentrations and their relation to metabolic abnormalities in human sepsis.

Circulating leptin concentrations are raised in animal models of inflammation and sepsis. The purpose of this study was to determine the effect of sepsis on serum leptin concentration in humans and to examine the relationship between leptin and the metabolic consequences of sepsis. Resting energy expenditure, insulin sensitivity, and fasting serum leptin, plasma insulin, and cortisol concentrations were measured in 20 subjects with intra-abdominal sepsis and 20 healthy control subjects, before and during a 2-h period of euglycemic hyperinsulinemia. Fasting serum leptin concentrations were similar in septic and control subjects. In simple regression analysis, serum leptin concentrations correlated significantly with percent body fat in both septic patients (r = 0. 64, P < 0.005) and healthy subjects (r = 0.75, P < 0.0001). Multiple regression analyses additionally indicated that percent body fat, fasting plasma insulin, and plasma cortisol, but not sepsis, were significant and independent determinants of serum leptin concentration. No relationship between leptin and resting energy expenditure or insulin sensitivity was identifiable. A major metabolic role for leptin in human sepsis therefore appears unlikely.

Adipose Tissue↗

Indirect calorimetry--a review of recent clinical applications.

There has been a resurgence of interest in the information provided by indirect calorimetry. In the past calorimetry was considered a research technique, but technological advances have made it applicable in many clinical situations. Recent clinical applications of this technique have been examined in this review.

Acquired Immunodeficiency Syndrome↗

Induction of cytokines in cynomolgus monkeys by the immune response modifiers, imiquimod, S-27609 and S-28463.

Imiquimod, S-27609 and S-28463 are imidazoquinolines known to have antiviral and antitumour properties mediated by the induction of cytokines, in particular interferon alpha (IFN-alpha). This study evaluated these compounds for their ability to induce cytokines and cytokine specific messenger RNAs (mRNA) in cynomologus monkeys (Macaca fascicularis). Peripheral blood mononuclear cell (PBMC) cultures from monkeys produced IFN, interleukin 1beta (IL-1beta), IL-6 and IL-8 after treatment with imiquimod, S-27609 and S-28463. Tumour necrosis factor alpha (TNF-alpha) was also increased in cultures stimulated with S-27609 or S-28463. Monkey PBMCs stimulated with imiquimod, S-27609 and S-28463 showed increased mRNA levels of IFN-alpha, IL-1alpha, IL-6 and the IFN inducible protein, MxA above those seen in untreated cultures. S-27609 and S-28463 also had higher TNF-alpha mRNA expression than cultures not receiving drugs. When compared to lipopolysaccharide (LPS), S-27609 was less effective at inducing IL-1beta, IL-6, IL-8 and TNF-alpha but induced higher concentrations of IFN. Similar results were seen when evaluating cytokine mRNA levels. Upon oral administration to monkeys, S-28463 stimulated a dose-dependent increase in serum concentrations of IFN, TNF-alpha, IL-1 receptor antagonist (IL-1Ra) and IL-6, while imiquimod induced increases in IFN and IL-1Ra concentrations. Finally, skin biopsies from monkeys treated topically with S-28463 had increases over baseline in mRNA for IFN-alpha, IL-1alpha, IL-6 and MxA protein. The data show that imidazoquinolines induce cytokines and cytokine specific mRNA in cynomolgus monkeys. These results demonstrate the usefulness of human amplimers and human ELISAs in the detection of cytokine specific mRNAs and proteins in cynomolgus monkeys.

Adjuvants, Immunologic↗

Nutrient induced thermogenesis.

Although first described more than two centuries ago, the increase in energy expenditure associated with feeding (nutrient induced thermogenesis (NIT) is still incompletely understood. Although the magnitude of the response and the effect of varying the composition of the diet, route and rate of feeding is still the subject of controversy, the importance of taking into account NIT when designing an optimal feeding regimen is well recognised. What is currently unclear is the effect that injury or sepsis have on NIT. This is of clinical significance because it is precisely this group of patients in whom adequate nutritional support is most difficult to achieve yet most important. Despite significant differences in the metabolic response to feeding, NIT appears to be similar in septic patients and healthy subjects. Excessive use of intravenous glucose in such patients however may lead to marked increases in energy expenditure and stimulation of the sympathetic nervous system and should be avoided.

Body Temperature Regulation↗

Thermogenic, hormonal and metabolic effects of intravenous glucose infusion in human sepsis.

BACKGROUND: Sepsis is associated with alterations in glucose metabolism and the effect of intravenous feeding on energy expenditure is unclear. Many studies of glucose metabolism in humans with sepsis have employed techniques that are not relevant to the practice of intravenous feeding. METHODS: The thermogenic, hormonal and metabolic effects of glucose were evaluated in a prospective experimental study of septic (n = 6) and non-septic (n = 6) subjects, by administering glucose intravenously under conditions and at a rate similar to those used in total parenteral nutrition. RESULTS: Patients with sepsis had a higher fasting metabolic rate than control subjects (P < 0.001) and a lower fasting respiratory quotient (P < 0.03). The thermic effect of glucose in both groups was small and not statistically significant (median 3.2 and 0.4 per cent in septic and non-septic subjects respectively, P > 0.1). Patients with sepsis had an attenuated plasma insulin response to glucose administration compared with control subjects (P < 0.001) and less marked suppression of plasma fatty acid and glycerol concentrations (P < 0.001). Glucose administration was not associated with significant changes in plasma catecholamine concentrations in either group of patients. CONCLUSION: Intravenous infusion of glucose at clinically relevant rates is associated with a negligible thermogenic response, with no activation of the sympathetic nervous system.

Adult↗

Aspergillus wound infection following laparostomy.

Wound infections with Aspergillus are surprisingly rare given the quantity of spores in hospital air. We report the first case of infection of abdominal viscera due to Aspergillus in a patient with a laparostomy for Crohn's disease. Amphotericin B effected a cure. Sampling of air from the patient's environment yielded one isolated of Aspergillus fumigatus that matched the patient's isolates. Other examples of surgical wounds being contaminated by Aspergillus are reviewed.

Adult↗

Quality of life on home parenteral nutrition: a single centre study of 37 patients.

Quality of life was assessed in 37 patients receiving home parenteral nutrition (HPN) for intestinal failure. A questionnaire was developed specifically for this purpose and the results were compared with those obtained by subjective assessment using a simple linear scale. The majority of patients (n = 26, 70.3%) had a good objective quality of life and most (n = 16, 53.3%) of those eligible (n = 30, 81.1%) did not express an interest in intestinal transplantation. Despite the apparent good quality of life enjoyed by patients receiving HPN, there were numerous areas in which patients with intestinal failure felt that their quality of life left much to be desired: many patients reported significant psychological symptoms (n = 15, 40.5%) sexual (n = 10, 27.0%) and social dysfunction (n = 19, 51.3%) and most patients with intestinal failure were unable to return to work (n = 24, 88.9%). Detailed quality of life assessment reveals that there is much still to be done to ensure that provision of care for patients with intestinal failure involves not only prolongation of life but also an improvement in quality of life.

Journal Article↗

Incidence and management of catheter-related sepsis in patients receiving home parenteral nutrition.

Fifty patients, comprising 24 male and 26 female of median age 43 (range 15-67) years, received a total of 2620 patient-months of home parenteral nutrition (median 48 (range 2-130) months). There were 13 episodes of bacterial catheter sepsis (of which the catheter was successfully salvaged by an antibiotic-fibrinolytic 'lock' technique in four cases) and ten of exit-site sepsis (all managed by elective catheter replacement), representing an incidence of 1 septic complication per 113 patient-months of parenteral nutrition. This low incidence of catheter-related sepsis was achieved by strict adherence to established protocols of catheter management.

Adolescent↗

Which nutritional measurements assess protein-energy nutritional status in patients receiving home parenteral nutrition?

Weight, midarm circumference, triceps skinfold thickness, arm muscle circumference, albumin, prealbumin, transferrin and total lymphocyte count were measured at each outpatient visit in patients reveiving home parenteral nutrition from September 1987 to November 1991. Each nutritional variable was analysed for individuals and for the whole group. Group data were expressed using the actual values obtained and successive differences (the change between clinic attendances). Nutritional variables were evaluated using a correlation matrix. Identical analysis of individual and group data demonstrates that laboratory investigations are of little value in the assessment of nutritional status in patients receiving home parenteral nutrition. Anthropometry detected changes in body weight secondary to changes in muscle and/or fat in 80% of patients. Pooling anthropometric data distors the relationship between variables owing to inter-individual variability when actual values are used. The method of successive differences is the preferred method of analysis for group anthropometric data.

Journal Article↗

Change in bioelectrical impedance following laparoscopic and open abdominal surgery.

The effect of surgery, and in particular, the relative effects of open and laparoscopic abdominal surgery on whole body bioelectrical impedance (BI) has been investigated. Repeated measurements of BI were performed over a 60 h period in 12 patients undergoing laparoscopic surgery (group A) and in 12 patients undergoing elective open abdominal surgery for benign conditions (group B). Control measurements were performed upon 4 healthy adult subjects over the same time period. Attempts were made to relate postoperative changes in BI in group A and group B to changes in net postoperative fluid balance. The postoperative disturbance in BI was significantly greater in group B than group A (P < 0.001 Mann-Whitney-U test) and differed significantly from the minor fluctuations of BI observed in the control group (P < 0.001 Mann-Whitney-U test). The fluctuations in BI observed after laparoscopic surgery were not significantly greater than those seen in the control group (P = 0.1 Mann- Whitney U test). Changes in BI in both group A and B did not correlate with changes in net postoperative fluid balance, which suggests that the effect of surgery upon BI was related to changes of body water distribution rather than changes in total body water volume.

Journal Article↗