DNA probe technology: implications for service planning in Britain

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.     

Human metabolism of arsenobetaine ingested with fish

1. Six volunteers ingested 74As-labelled arsenobetaine with a fish meal. The retention and distribution of the tracer were studied by body radioactivity measurements. 2. The tracer became rapidly dispersed in soft tissues, with no major concentration in any localized organ or region. 3. In all subjects less than 1% of the ingested activity remained in the body after 24 days. 4. Any losses from the skin were minor in relation to those by other routes of excretion.     

Use of fibronectin and somatomedin-C as markers of enteral nutrition support in traumatized patients using a modified amino acid formula

The purpose of this study was to evaluate the use of serum fibronectin and serum somatomedin-C as nutritional markers during enteral nutrition support (ENS) of critically ill, traumatized patients using an enteral product containing high concentrations of branched-chain amino acids. Twelve critically injured patients received a standard enteral formula with 30 g of a 44% branched-chain amino acid supplement added to each liter of formula. Fibronectin concentration, somatomedin-C concentration, and nitrogen balance were measured on study days 1, 4, 7, 14, 21, 28 or until adequate oral intake began. Both fibronectin and somatomedin-C concentrations increased significantly from baseline by day 7 of ENS. Nitrogen balance increased significantly from baseline by day 4. On days 14 and 21, only somatomedin-C and nitrogen balance increased significantly from baseline. Nitrogen balance was significantly correlated with somatomedin-C concentration (r = 0.53, p less than 0.01), cumulative caloric intake (r = 0.68, p less than 0.01), and cumulative nitrogen intake (r = 0.72, p less than 0.01). The results of this study suggest that serum somatomedin-C is useful and serum fibronectin has potential in monitoring nutrition support response in critically ill, traumatized patients.     

Factors causing interrupted delivery of enteral nutrition in trauma intensive care unit patients.

BACKGROUND: The intent of this study was to ascertain the adequacy of delivery of enteral nutrition (EN) to critically ill adult multiple trauma patients and to identify potential detrimental factors that affect EN delivery. METHODS: Retrospective observational study. Trauma intensive care unit (TICU) in a university-affiliated hospital. Adult patients (>/=18 years of age) admitted to the TICU who received enteral feeding. RESULTS: Fifty-six adult patients were enrolled for study. Patients received, on average, 67% +/- 19% of what was prescribed for 5.7 +/- 2.0 days. A total of 222 occurrences for temporary discontinuation of tube feeding were identified. Gastrointestinal intolerance, as defined by a gastric residual volume of >150 mL, abdominal pain, or >3 liquid stools per day, accounted for only 11% of the occurrences for discontinuation of feeding. Surgery (27%) and diagnostic procedures (15%) represented the majority of reasons for inadequate nutrient delivery. Minor factors for EN interruptions were mechanical feeding tube problems (8%), pharmacy delivery delay (4%), and miscellaneous factors (3%). Multiple and unknown reasons contributed to 14% and 18% of the occurrences, respectively. CONCLUSIONS: Surgery and diagnostic procedures accounted for the largest factor in enteral feeding discontinuations in our critically ill trauma patients. Gastrointestinal intolerance contributed a minor role in the temporary discontinuation of enteral feeding.     

Lipoprotein (a) levels in those with high molecular weight apo (a) isoforms may remain low in a significant proportion of patients with end-stage renal disease.

BACKGROUND: Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. METHODS: A total of 239 patients at end-stage renal failure (ESRF) were studied prior to the initiation of dialysis. Blood was taken for Lp (a) levels and apo (a) isoforms. Clinical vascular disease (CVD) was assessed on the basis of clinical history and Rose questionnaire. The control group for Lp (a) levels consisted of 228 healthy volunteers. RESULTS: Despite a higher median Lp (a) level in those with HMW isoforms, 30% of patients had Lp (a) levels <10 mg/dl. Overall, 49% patients were identified as having CVD. Diabetes, smoking history and Lp (a) levels were significantly associated with CVD in logistic regression analysis, although when patients with low molecular weight (LMW) and HMW isoforms were analysed separately, Lp (a) levels were not significantly associated with CVD in those with LMW isoforms. The rates of CVD in those with HMW isoform and low Lp (a) levels were significantly lower than those with HMW isoforms and elevated Lp (a) levels, 34 vs 57% (P < 0.01). CONCLUSIONS: Although median Lp (a) levels in those patients at ESRF with HMW isoforms are higher than controls, in a third of such patients Lp (a) levels remain relatively low. These patients have lower rates of CVD than those with high levels of Lp (a).     

Constancy and variability of gallbladder ejection fraction: impact on diagnosis and therapy.

The main objective of this study was to test the constancy and variability of gallbladder (GB) ejection fraction (EF) in long-term studies to (a) determine whether EF ever becomes normal once it is low, (b) determine how long it takes for the EF to become abnormal once it is found to be normal, (c) explore the cause of low EF, and (d) define objective parameters for biliary and nonbiliary abdominal pain. METHODS: Fifty-two patients (42 women, 10 men) who underwent quantitative cholescintigraphy twice (total studies, 104), over a mean period of 38.54 mo between studies, were chosen for retrospective analysis. They were divided into the following groups: control (n = 13; nonbiliary abdominal pain), chronic acalculous cholecystitis (CAC) (n = 27; biliary abdominal pain), chronic calculous cholecystitis (CCC) (n = 6; biliary abdominal pain), and opioid (n = 6; nonbiliary abdominal pain). The last group had received an opioid before cholecystokinin-8 (CCK-8) infusion in one study but not in the other study. A GBEF value of > or =35% was considered normal with a 3-min infusion and > or =50% as normal with a 10-min infusion of CCK-8. RESULTS: The mean GBEF value was reproducible between the 2 sequential studies in the control group (66.0% +/- 20.5% vs. 73.9% +/- 17.7%), CAC group (24.4% +/- 22.3% vs. 16.9% +/- 10.9%), and CCC group (20.8% +/- 20.9% vs. 27.5% +/- 34.5%) but not in the opioid group (14.8% +/- 14.6% vs. 56.5% +/- 31.7%). The severity of GBEF reduction in CAC increased with time: 7.2% +/- 8.1% within 12 mo, 16.1% +/- 14.9% in 13-47 mo, and 23.5% +/- 21.3% in 48-168 mo. None of the 27 patients with CAC developed a gallstone as detected by ultrasound during the study period. In 5 patients with CAC, a mean period of 52.6 +/- 28.9 mo was required for conversion from normal to a low EF. CCK-induced cystic duct spasm is the etiology for low EF in both CAC and CCC. CONCLUSION: Normal and low GBEF values are reproducible in long-term studies. Once the EF reaches a low value, it does not return to normal, and a normal value requires many years to become abnormal. CCK-induced cystic duct spasm is the cause of low GBEF in CAC and CCC, and the severity of EF reduction is similar for both. Exclusion of opioid intake immediately before the study is critical before attributing a low GBEF value to an irreversible GB motor dysfunction.     

RBE and w(R) values of Auger emitters and low-range beta emitters with particular reference to tritium.

An apparent disparity exists between RBE (relative biological effectiveness) values for low-range beta and Auger emitters, and the current value for their radiation weighting factor (w(R)). This paper presents evidence that the current w(R) value of unity for these nuclides is inconsistent with most RBE evidence and should be increased by a factor of two to three. It recommends that the ICRP should clearly state that the most appropriate RBE value for these nuclides, and not the w(R) value, should be used in specific dose calculations, retrospective dose estimations and epidemiological studies. The ICRP should also publish guidance as to the methods and data sources that could be used for these RBE values.