Costs and cost effectiveness of cardiovascular screening and intervention: the British family heart study.

OBJECTIVE--To measure costs and cost effectiveness of the British family heart study cardiovascular screening and intervention programme. DESIGN--Cost effectiveness analysis of randomised controlled trial. Clinical and resource use data taken from trial and unit cost data from external estimates. SETTING--13 general practices across Britain. SUBJECTS--4185 men aged 40-59 and their 2827 partners. INTERVENTION--Nurse led programme using a family centered approach, with follow up according to degree of risk. MAIN OUTCOME MEASURES--Cost of the programme it self; overall short term cost to NHS; cost per 1% reduction in coronary risk at one year. RESULTS--Estimated cost of putting the programme into practice for one year was 63 pounds per person (95% confidence interval 60 pounds to 65 pounds). The overall short term cost to the health service was 77 pounds per man (29 pounds to 124 pounds) but only 13 pounds per woman (-48 pounds to 74 pounds), owing to differences in utilisation of other health service resources. The cost per 1% reduction in risk was 5.08 pounds per man (5.92 pounds including broader health service costs) and 5.78 pounds per woman (1.28 pounds taking into account wider health service savings). CONCLUSIONS--The direct cost of the programme to a four partner practice of 7500 patients would be approximately 58,000 pounds. Annually, 8300 pounds would currently be paid to a practice of this size working to the maximum target on the health promotion bands, plus any additional reimbursement of practice staff salaries for which the practice qualified. The broader short term costs to the NHS may augment these costs for men but offset them considerably for women.     

Phospho-beta-glucosidase from Fusobacterium mortiferum: purification, cloning, and inactivation by 6-phosphoglucono-delta-lactone.

6-Phosphoryl-beta-D-glucopyranosyl:6-phosphoglucohydrolase (P-beta-glucosidase, EC 3.2.1.86) has been purified from Fusobacterium mortiferum. Assays for enzyme activity and results from Western immunoblots showed that P-beta-glucosidase (Mr, 53,000; pI, 4.5) was induced by growth of F. mortiferum on beta-glucosides. The novel chromogenic and fluorogenic substrates, p-nitrophenyl-beta-D-glucopyranoside-6-phosphate (pNPbetaGlc6P) and 4-methylumbelliferyl-beta-D-glucopyranoside-6-phosphate (4MUbetaGlc6P), respectively, were used for the assay of P-beta-glucosidase activity. The enzyme hydrolyzed several P-beta-glucosides, including the isomeric disaccharide phosphates cellobiose-6-phosphate, gentiobiose-6-phosphate, sophorose-6-phosphate, and laminaribiose-6-phosphate, to yield glucose-6-phosphate and appropriate aglycons. The kinetic parameters for each substrate are reported. P-beta-glucosidase from F. mortiferum was inactivated by 6-phosphoglucono-delta-lactone (P-glucono-delta-lactone) derived via oxidation of glucose 6-phosphate. The pbgA gene that encodes P-beta-glucosidase from F. mortiferum has been cloned and sequenced. The first 42 residues deduced from the nucleotide sequence matched those determined for the N terminus by automated Edman degradation of the purified enzyme. From the predicted sequence of 466 amino acids, two catalytically important glutamyl residues have been identified. Comparative alignment of the amino acid sequences of P-beta-glucosidase from Escherichia coli and F. mortiferum indicates potential binding sites for the inhibitory P-glucono-delta-lactone to the enzyme from F. mortiferum.     

beta-Bungarotoxin. Separation of two discrete proteins with different synaptic actions.

beta-Bungarotoxin, a specific presynaptic blocking agent, was prepared in two stages from the crude venom of Bungarus multicinctus by ion-exchange chromatography on the weakly acidic ion exchanger, CM-Sephadex, and on the strongly acidic ion exchanger, sulphopropyl-Sephadex. By these procedures it was purified to a single protein, which was shown by reduction to contain two polypeptide chains with mol.wts. of less than 15000. During purification of beta-bungarotoxin three other proteins were isolated. Two of these proteins have similar molecular weights, subunit structure and physiological properties to the major protein component. This latter is referred to as beta-bungarotoxin, since it has the same physiological properties as those described for unpurified beta-bungarotoxin by other workers. The first protein has very different physiological effects and biochemical properties from beta-bungarotoxin. This protein has a single class of polypeptide chains with an apparent molecular weight that is lower than the main beta-bungarotoxin protein, and appears to block synaptic transmission by a predominantly postsynaptic effect. It has been suggested [Oberg & Kelly (1976) J. Neurobiol. 7, 129-141] that the action of beta-bungarotoxin depends on its phospholipase A activity; however, in this preparation of the toxin less than 50 muunits of phospholipase A activity were detected (1 unit of activity is the amount of enzyme forming 1 mumol of L-alpha-phosphatidylcholine/min per mg of protein).     

Diagnosis of pseudomembranous colitis.

Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections not requiring operations; the other 22 cases all occurred after major surgery. All the patients had diarrhoea; six patients also had fever with clinical signs of sepsis, and three had abdominal pain thought to be due to anastomotic dehiscence after colonic resection. Pseudomembranous colitis was associated with white blood counts over 15 000/mm3 in 17 patients and albumin concentrations of less than 30 g/1 in 18. Pseudomembranous colitis was an incidental finding at necropsy in two of six patients who had not had an operation. Of the 22 patients who had had major surgery, nine died from this complication; in all except two of these cases the diagnosis was made only at necropsy. If pseudomembranous colitis is suspected on clinical grounds or if there is an unexplained complication after colorectal surgery repeat sigmoidoscopy and testing for faecal toxins should be carried out to establish the diagnosis so that prompt supportive treatment can be given.     

Linkage analysis and the inheritance of arches in a Habbanite isolate.

A pedigree and linkage analysis was performed on a corrected version of the Habbanite pedigree 2 of Slatis et al. [1]. The trait "arch on any digit" was examined for major gene inheritance and possible linkage to several blood and serum group markers. The results confirm the proposed dominant major gene inheritance of this trait with almost complete penetrance. In addition, the analysis suggests linkage with the haptoglobin locus with evidence against linkage with Pl and Rhesus. These results are of particular interest in view of recently reported dermatoglyphic associations with haptoglobin.     

Studies on the size,location and turnover of calcium pools accessible to growing Tetrahymena cells

Tetrahymena pyriformis cells in the logarithmic phase of growth accumulate 2.5–3.75 times as much calcium per unit volume as is present in the growth medium. It appears that most of this calcium is stored in a non-ionic form, with approximately 30% existing in the cilia, near its site of action in effecting ciliary reversal. The exchange of extracellular ⁴⁵Ca²⁺ with the major internal pools is extremely rapid, exhibiting a $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ of less than 0.5 h. Sites located on the cilia are responsible for 35–50% of Ca²⁺ influx, with the remainder entering through other positions on the cell surface.     

Evaluation of antibody inhibition assays of melanoma antigens in sera to monitor tumor growth in melanoma patients

Summary It was reported previously that melanoma leukocyte-dependent antibody (LDA) in the sera of melanoma patients was inhibited by small-molecular-weight (small-mol.-wt.) glycoproteins which were similar to cell surface antigens identified in cell membrane extracts of melanoma cells. The present study was to determine whether measurement of the levels of these factors in sera may be a useful monitor of tumor growth in melanoma patients. Small-mol.-wt. fractions were obtained by gel filtration or membrane chromatography of acidified sera and tested for their ability to inhibit LDA in ⁵¹Cr release cytotoxic assays. A panel of LDA was used, consisting of three antisera from melanoma patients, which appeared relatively specific for melanoma, and three non-melanoma antisera against carcinoembryonic antigen, ₂ microglobulin, and fetal antigens. The results showed that in patients with melanoma, approximately 70% had melanoma LDA-inhibitory activity detected in the small-mol.-wt. fractions of their sera when these were tested against the panel of melanoma LDA. The specificity of the inhibitory activity for melanoma LDA was shown by failure of the serum fractions to inhibit non-melanoma LDA and by absence of inhibitory activity in equivalent serum fractions from non-melanoma carcinoma patients for melanoma LDA. The levels of melanoma LDA-inhibitory activity in the serum fractions appeared to correlate with tumor growth, as shown by clearance of the inhibitory activity after surgical removal of melanoma and reappearance in the serum of patients who subsequently developed recurrent melanoma. The 30% false-negative rate indicated that the assays could not be used to reliably exclude melanoma, but the close correlation with tumor growth and the low number of false-positive results suggested that in 70% of patients detection of these small-mol.-wt. antigens would be of value to detect recurrence from melanoma and to monitor the effectiveness of therapy.