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Biomedical subjects

J L Shaffer

Publications and source records attributed to J L Shaffer.

At least 19 recordsLinked to original sources

Analytical performance of the Tandem-R free PSA immunoassay measuring free prostate-specific antigen.

The analytical performance of the Tandem-R free PSA assay available from Hybritech Inc. was evaluated. Comparison of recoveries of purified free (unbound) prostate-specific antigen (PSA) diluted in female serum in the Tandem-R free PSA assay and the Tandem-R (total) PSA assay demonstrated a link in calibration between the assays and an accurate determination of percent free PSA. The cross-reactivity of the assay to purified PSA-alpha 1-antichymotrypsin was determined to be < 1%. The minimum-detectable concentration was < 0.05 microgram/L. The within-run and between-day CVs were < or = 5% for samples with > 0.3 microgram/L free PSA. Dilution and recovery showed no significant deviations from linearity across the assay range. The assay was insensitive to interference from blood components. The Tandem-R free PSA kit was shown to be an accurate, precise, and reliable assay for the measurement of free PSA.

Calibration

Home parenteral nutrition: a systematic review.

OBJECTIVES: The objective of this Review was to locate, appraise and summarise evidence from scientific studies on home parenteral nutrition (HPN) in order to answer specific research questions on the effectiveness of this technology. The following questions were asked. What patients have received HPN? What has been the experience of patients on HPN programmes? How have HPN programmes been organised, and what techniques and equipment have been used, and to what effect? What comparative information is available on effectiveness? What evidence exists for the cost-effectiveness of HPN? What questions about the provision of HPN could be answered with additional research, and what studies would be most suitable? DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases (including MEDLINE, Embase, Science Citation Index, Uncover, Cinahl, Caredata, Food Science and Technology Abstracts, NTIS, Pascal, Psychlit, and Economic Literature Index), relevant journals (including Journal of Parenteral and Enteral Nutrition, Clinical Nutrition, American Journal of Clinical Nutrition, Nutrition, Clinical Gastroenterology, Nutrition Reviews, Annals of Nutrition and Metabolism, Nutrition and Cancer, Nutrition and Health, and Journal of Paediatric Nutrition and Metabolism), and scanning of reference lists, as well as other search strategies outlined in the protocol. STUDY SELECTION: Studies relevant to the questions were selected. The inclusion criteria were fairly broad because of the quality of the studies located. DATA EXTRACTION: Data extraction forms were used to collect data from studies included in the review. The data was checked by a second researcher to reduce error. DATA SYNTHESIS: Quantitative analysis was difficult owing to the type of studies located. The data is discussed in a qualitative manner. Where complication rates have been given, we have attempted to combine the results in a quantitative manner. RESULTS: The age and sex of patients on HPN varies according to the underlying disease but, on the whole, patients are young (see Tables 4a and 4b). There are trends showing an increased use of the technology at the extremes of the age range. There are marked differences between countries on the underlying diseases for which HPN is indicated. For example, many more patients with an underlying malignancy are treated in Italy and the USA than in the UK (40-67% versus 8%). Morbidity rates for the majority of patients are acceptable (see Table 8), the complications tend to be related to the central venous catheter. It is fairly clear that a minority of patients are susceptible to recurrent problems and that many patients have very few complications. The mortality rate for HPN patients (see Table 10) was good for those patients with benign underlying disease (for example, 5% of Crohn's HPN patients die per year), and there are very few reports of patients dying from complications of the technology. The survival of those with malignant disease and AIDS is poor, almost all having died from the underlying disease at one year; despite this, most programme growth worldwide is due to an increase in the numbers of patients with these diagnoses (see Table 5). Quality of life is reasonable for patients with benign disease (see Table 9); no studies were found that examined the quality of life of HPN patients with malignant disease. Economic analysis shows that the cost of HPN treatment is cheaper than the alternative of in-patient care (see Table 18). There is a paucity of comparative studies examining different aspects of the technology, and this accounted for the majority of gaps in the evidence. CONCLUSIONS: The use of HPN for benign intestinal failure is supported by evidence from the scientific studies located. There are, however, large gaps in the evidence, particularly relating to the use of HPN in malignant disease and AIDS. A programme of research is suggested at the end of this review.

Cost-Benefit Analysis

Ascorbic acid absorption in patients with systemic sclerosis.

OBJECTIVE: To investigate whether reduced circulating levels of ascorbic acid in patients with systemic sclerosis (SSc) are a result of malabsorption. METHODS: Eight patients with SSc, but with no evidence of bacterial overgrowth, and 8 healthy controls were recruited. On the first day of study, each subject was given orally an aliquot of [14C] ascorbic acid, which was then "flushed out" by oral intake of unlabeled ascorbic acid for the following 7 days. Plasma samples were collected at specified intervals and urine was collected continuously over the 8 day study period. [14C] content of plasma and urine were measured by scintillation counting. For each subject, a plasma [14C] decay curve was drawn. Each subject's ascorbic acid absorption was assessed using the area under the curve (AUC) and the apparent renal clearance (CLr[app]). Ascorbic acid intake was assessed using dietary history and food composition tables. RESULTS: There were no differences in the dietary intake of vitamin C (p = 0.16) and body mass indices (p = 0.91) between patients and controls. The plasma [14C] AUC and CLr(app) were similar between patients and controls [AUC patient mean (standard deviation, SD) = 37.1 (6.8), AUC control mean (SD) = 38.6 (9.9), p = 0.74; CLr(app) patient mean (SD) = 0.57 (0.24), CLr(app) control mean (SD) = 0.47 (0.27), p = 0.45]. CONCLUSION: There was no evidence of impaired absorption of ascorbic acid in patients with SSc without bacterial overgrowth compared to healthy controls.

Absorption

Total parenteral nutrition modifies the acute phase response to Crohn's disease.

Measurements of the acute phase proteins, C-reactive protein (CRP) and orosomucoid are widely used to monitor the activity of Crohn's disease. The effect of TPN upon the levels of acute phase proteins is unknown. Serum levels of CRP and orosomucoid were measured simultaneously over a four year period in 13 patients receiving TPN for Crohn's disease, nine patients with noninflammatory causes of intestinal failure, and 16 patients with Crohn's disease treated without TPN. An acute phase response was found with a similar frequency in both groups of patients with Crohn's disease (73.6% and 83.9% for Crohn's with and without TPN respectively), but was less prevalent in patients receiving TPN for non-inflammatory causes of intestinal failure (56.1%, P < 0.01). In this latter group, the acute phase response consisted primarily of an isolated elevation of orosomucoid (78.4%), compared with patients with Crohn's disease alone (21.1%, P < 0.001) and with Crohn's disease and TPN (46.6%, P < 0.05). Liver function abnormalities were seen on 68.8% of occasions in patients with noninflammatory causes of intestinal failure who had elevated levels of orosomucoid, compared with 34.9% of occasions on which orosomucoid levels were normal (P < 0.001). TPN may lead to isolated elevation of serum levels of orosomucoid, reducing the value of this acute phase protein in monitoring the activity of Crohn's disease in patients receiving TPN.

Acute-Phase Proteins

Hepatobiliary complications of total parenteral nutrition.

The relationships between various hepatobiliary disorders and the administration of total parenteral nutrition (TPN) were reviewed and, in particular, the role of TPN in their pathogenesis was critically evaluated. Several clinical and pathological entities including steatosis, steatohepatitis, cholestasis, and cholelithiasis have been commonly linked to TPN, and instances of chronic decompensated liver disease have been reported. However, it is concluded that it is often difficult to extricate the effects of TPN on hepatobiliary function from many other hepatotoxic factors that may be operative in these patients. Thus, whereas considerable evidence exists to support a role fro carbohydrate or calorie excess in TPN solutions in the pathogenesis of steatosis, a loss of enteric stimulation and not TPN per se may be the primary factor in the development of cholestasis, biliary sludge, and gallstones. The apparent predilection of infants to TPN-related cholestasis may be based on the relative immaturity of the neonatal biliary excretory system.

Adult

Spectrum of intestinal failure in a specialised unit.

300 consecutive admissions over 7 years to a purpose-built intestinal failure unit are reviewed. The commonest underlying condition was Crohn's disease (42%), and the commonest complication precipitating admission was intestinal fistula (42%). Total parenteral nutrition was used in 85% and surgery in 50%. A multidisciplinary approach to management gave a high success rate--90% of patients were discharged from hospital, although nearly 25% needed home parental nutrition. These results suggest that chronic intestinal failure should be managed in specialised units in the same manner as other types of organ failure.

Adolescent

Ascorbic acid absorption in Crohn's disease. Studies using L-[carboxyl-14C]ascorbic acid.

Total body pool and intestinal absorption of ascorbic acid were studied in 12 patients undergoing operation for Crohn's disease (six with fistulae and six without) and in six control patients undergoing operation for reasons other than Crohn's disease. L-[carboxyl-14C]Ascorbic acid, 0.19-0.40 megabecquerels (MBq), was given orally. After a period of equilibration, the labeled ascorbic acid was flushed out of the patient's body tissues using large doses of unlabeled ascorbic acid. Intestinal absorption of ascorbic acid, assessed from the total cumulative urinary 14C recovery, was found to be similar in patients with fistulizing Crohn's disease (73.9 +/- 8.45%), those without fistulas (72.8 +/- 11.53%), and in controls (80.3 +/- 8.11%). Total body pools of ascorbic acid, calculated using the plasma 14C decay curves, were similar in patients with Crohn's disease with fistulas (17.1 +/- 5.91 mg/kg), patients without fistulas (9.6 +/- 3.58 mg/kg), and in controls (13.3 +/- 4.28 mg/kg). The results indicate that ascorbic acid absorption is normal in patients with both fistulizing and nonfistulizing Crohn's disease. The results suggest that routine supplements of vitamin C are not necessary unless oral ascorbic acid intake is low.

Adult

Home parenteral nutrition: a review of 100 patient years of treatment in 76 consecutive cases.

Over the last 10 years, the Nutrition Unit at Hope Hospital has trained and looked after 76 patients on home parenteral nutrition for a total of 100 patient years. Although 40 per cent of patients have required home parenteral nutrition for 6 months or less one patient has been on treatment for 7 years. The quality of life measured on a 4 point scale was good for the majority of patients. Sepsis and superior vena caval thrombosis are the main problems encountered. Overall mortality rate was 18 per cent and the sepsis rate was 0.14 episodes per patient per year. Home parenteral nutrition is an effective and safe treatment of intestinal failure.

Adolescent

Nutritional management of pregnancy in patients on home parenteral nutrition.

Three pregnancies are reported in two patients on home parenteral nutrition for intestinal failure. The nutritional regimen, 2300 kcal (9.63 MJ) (18% as lipid emulsion), 14 g amino acid nitrogen and electrolytes supplied daily in a 'big bag', was based on the measured resting energy expenditure and urinary nitrogen excretion during the third trimester in a 30-year-old woman on home parenteral nutrition. Commercial preparations of trace elements were added to the infusion as dictated by serum levels. Iron, iodine and fluoride were given orally, and vitamin B12 by monthly intramuscular injection. There were no serious deficiencies in trace elements and maternal weight-gain and fetal growth were satisfactory in all three pregnancies. The two pregnancies in one patient went to term and both infants had birthweights at the 50th centile for gestational age. The second patient who had had two spontaneous abortions went into premature labour at 30 weeks and gave birth to a baby with a minor facial deformity who subsequently developed the idiopathic respiratory distress syndrome. All three placentas were histologically normal. The growth and development of all three babies has been satisfactory. This nutritional regimen should be adequate for most pregnant patients who have attained a normal nutritional status on parenteral nutrition.

Adult

Disposition of metronidazole and its effects on sulphasalazine metabolism in patients with inflammatory bowel disease.

The pharmacokinetics of metronidazole were studied after oral and intravenous administration to seven patients with Crohn's disease and five patients with ulcerative colitis. The oral/intravenous availability ratio was 0.97 +/- 0.2 in the Crohn's patients and 0.90 +/- 0.1 in the colitics (mean +/- s.e. mean). Plasma clearance was 3.24 +/- 0.2 l h-1 and 4.1 +/- 0.5 l h-1, respectively. These differences were not statistically significant. Ten of the patients on long term sulphasalazine were studied to observe the effect of 2 weeks metronidazole therapy on plasma sulphapyridine concentration. The sulphapyridine concentration changed from 22.1 +/- 2.0 micrograms ml-1 to 15.95 +/- 4.5 micrograms ml-1 in the Crohn's patients and 26.0 +/- 6.0 micrograms ml-1 to 36.4 +/- 8.5 micrograms ml-1 in the colitis group, pre- and post-metronidazole. These differences were not statistically significant. These results suggest that metronidazole does not interfere with diazo-link splitting of sulphasalazine and that patients with Crohn's disease handle metronidazole in a similar manner to patients with colitis.

Administration, Oral

Controlled trial of rifampicin and ethambutol in Crohn's disease.

We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn's disease by carrying out a trial of treatment with antimycobacterial drugs. Twenty seven patients with Crohn's disease took part in a two year randomised double blind, crossover, controlled trial of rifampicin plus ethambutol against placebo. Fourteen patients completed the trial; four required an operation; five were withdrawn as poor compliers, and four because of adverse effects. There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn's disease activity index or any clinical indicator of disease activity. There was no suggestion that any subgroup of patients - for example, different regions of bowel affected or previous operation - were favourably affected by the drugs. There was no consistent pattern of change in prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period. A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy. The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn's disease.

Adult

QUEST--a package for processing questionnaire text and data.

An easy-to-use interactive program (QUEST) has been developed which facilitates the input, updating and checking of patient records from completed questionnaires possibly destined for statistical analysis by SPSS. Using the information about the data available in the SPSS control file, blank questionnaires can be generated, and up to date completed questionnaires printed. Selected cases can be printed out. QUEST is currently being used in four medical studies and one legal study. The program is written in standard Fortran-77 and makes full use of the new features of the language.

Computers

Nosocomial influenza B virus infection in the elderly.

A hospital-acquired outbreak of influenza-like illness that involved 29 patients during 4 weeks was detected in March 1980. The average age of the patients was 63 years. Eighteen of the 29 patients with symptoms had influenza B virus infection documented by virus isolations, fourfold or greater hemagglutination inhibition antibody increases, or both. The attack rate among all hospitalized inpatients was 20%. Absenteeism of the hospital staff because of influenza-like illnesses preceded the outbreak by several weeks, suggesting staff-to-patient transmission. The patients' sera during acute illness had low hemagglutination inhibition antibody titers (geometric mean titer of 1:21) against contemporary influenza B virus antigens, indicating that the patients were highly susceptible to influenza B virus. Only one patient had received trivalent influenza vaccine during the preceding year. The excess hospital cost resulting from the outbreak was +13 270 or +458 per patient. Our observations show that the elderly are at risk of developing nosocomial influenza B virus infection and that these illnesses are costly. Continued efforts to develop efficient influenza immunization programs for elderly persons and hospital staff are worthwhile.

Aged