Discrepancies in central review re-testing of patients with ER-positive and HER2-negative breast cancer in the OPTIMA prelim randomised clinical trial.

BACKGROUND: There is limited data on results of central re-testing of samples from patients with invasive breast cancer categorised in their local hospital laboratories as oestrogen receptor (ER) positive and human epidermal growth factor receptor homologue 2 (HER2) negative. METHODS: The Optimal Personalised Treatment of early breast cancer usIng Multiparameter Analysis preliminary study (OPTIMA prelim) was the feasibility phase of a randomised controlled trial to validate the use of multiparameter assay-directed chemotherapy decisions in the UK National Health Service (NHS). Eligibility criteria included ER positivity and HER2 negativity. Central re-testing of receptor status was mandatory. RESULTS: Of the 431 patients tested centrally, discrepant results between central and local laboratory results were identified in only 19 (4.4%; 95% confidence interval 2.5-6.3%) patients (with 21 tumours). On central review, seven patients had cancers that were ER-negative (1.6%) and 13 (3.0%) patients with 15 tumours had HER2-positive disease, including one tumour discrepant for both biomarkers. CONCLUSIONS: Central re-testing of receptor status of invasive breast cancers in the UK NHS setting shows a high level of reproducibility in categorising tumours as ER-positive and HER2-negative, and raises questions regarding the cost effectiveness and clinical value of central re-testing in this sub-group of breast cancers in this setting.

Subcutaneous ancrod in prevention of deep vein thrombosis after hip replacement surgery.

In a randomised double-blind controlled trial we have assessed the use of ancrod ('Arvin') in the prophylaxis of deep vein thrombosis (DVT) in patients undergoing hip replacement surgery. Thirty-five patients received daily subcutaneous injections of ancrod and 38 patients received saline injections. DVT was detected by bilateral ascending venography (67 patients) 7-19 days after surgery. The frequency of major femoral DVT (greater than or equal to 5 cm long) was significantly reduced from 18 thrombi in the limbs of the placebo group to 5 in the ancrod group (p less than 0.01). The overall frequency of thrombi including calf DVT was not significantly different between the two groups. Four patients within the ancrod group had evidence of wound bleeding, compared with 2 placebo patients. One patient had a bleeding event which was considered severe enough to require cessation of ancrod injections.

A simple, microcomputer-based transcription system for radiology reports.

A simple, computerized system for radiology transcriptions at a small military medical treatment facility is described. This system can be implemented in any department having access to an MS-DOS-based microcomputer, and can be used by anyone with little or no computer experience or typing skills. Through the use of standard text, this method can expedite considerably the transcription of routine radiographic reports at a nominal cost.

Automated radiographic report generation using barcode technology.

Barcode reporting is a method of automated report preparation made possible by advancing computer technology, which may improve radiographic services and reduce their costs. This reporting method for normal examinations in a hospital-based radiology practice has been well accepted by radiology staff and has encouraged further applications. A free-text barcode system for reporting mammographic examinations subsequently has been developed and has further reduced dependency on transcription services, with little or no increase in radiologist's workload. Most radiologists in the department with the system believe it has had a positive impact on radiographic services, and almost two-thirds of them would consider using this kind of reporting system in a private-practice setting.

Recombinant chymotrypsin inhibitor 2: expression, kinetic analysis of inhibition with alpha-chymotrypsin and wild-type and mutant subtilisin BPN', and protein engineering to investigate inhibitory specificity and mechanism.

The serine protease inhibitor chymotrypsin inhibitor 2 (CI2 or BSPI2) has been expressed in Escherichia coli with the pINIIIompA3 expression vector to produce 20-40 mg/L of culture. Recombinant CI2 purified from this system has been characterized and found to be identical with CI2 from barley. Slow-binding kinetics were observed for the interaction between CI2 and subtilisin BPN', with Ki = 2.9 x 10(-12) M. Analysis of slow-binding data indicates that binding of the inhibitor follows the simplest model of E + I = EI with no kinetically detectable intermediate steps or proteolytic cleavage of the reactive site bond in CI2 (Met-59-Glu-60). This, in agreement with crystallographic data, indicates that the enzyme-inhibitor adduct is the Michaelis complex, which is not chemically processed by the enzyme. Three mutant CI2 molecules with new P1 residues have also been examined with a range of serine proteases, including a mutant subtilisin. In agreement with earlier studies, we find the P1 amino acid an important determinant of specificity. CI2 Met----Lys-59 was found to be a temporary inhibitor of subtilisin BPN' but an effective inhibitor of subtilisin Carlsberg and subtilisin BPN'(Glu----Ser-156). The structural reasons for this are discussed in relation to mechanisms of inhibition of serine proteases.

Subcutaneous ancrod in prevention of deep-vein thrombosis after operation for fractured neck of femur.

In a randomised double-blind controlled trial 53 patients received 5 daily subcutaneous injections of ancrod ('Arvin') after operation for fractured neck of femur, and 52 patients received saline fractured neck of femur, and 52 patients received saline injections. Deep-vein thrombosis (D.V.T.) was detected by bilateral ascending venography or necropsy 6--16 days after surgery. The frequency of D.V.T. and bilateral D.V.T. was significantly lower in the ancrod group (P less than 0.01). The frequency of major D.V.T. (thrombi in veins proximal to the calf, or calf-vein thrombi more than 3 cm long) was also significantly lower in the ancrod group (P less than 0.001). No complications of ancrod prophylaxis occurred. Ancrod reduced plasma-fibrinogen, and hence plasma and blood viscosity, during the first week after surgery; preoperative levels of fibrinogen and viscosity were not associated with post-operative D.V.T. Subcutaneous ancrod is a simple and effective alternative to oral anticoagulants for the reduction of the frequency of D.V.T. after operation for hip fracture, and merits assessment in other high-risk groups of patients.

A trial of minocycline given after exposure to prevent gonorrhea.

In a prospective evaluation of antibiotic prophylaxis against gonorrhea, 1080 men were given 200 mg of oral minocycline or placebo after sexual intercourse with prostitutes in a Far Eastern port. Later, at sea, gonococcal infection was detected in 57 of 565 men given placebo and 24 of 515 men given minocycline (P less than 0.001). Minocycline prophylaxis completely prevented infection by gonococci susceptible to 0.75 microgram or less of tetracycline per milliliter, reduced the risk of infection or prolonged the incubation period in men exposed to gonococci susceptible to 1.0 to 2.0 micrograms per milliliter, but did not prevent infection or prolong incubation in men exposed to gonococci resistant to 2.0 micrograms. Minocycline did not increase the proportion of asymptomatic infections. Minocycline prophylaxis would probably have limited effectiveness as a public-health measure because of the tendency to select resistant gonococci.

Cohort study of venereal disease. I: the risk of gonorrhea transmission from infected women to men.

Reliable data on the risk of transmission of N. gonorrhoeae would enhance our understanding of the importance of host defenses against gonorrhea and would aid in the evaluation of prophylactic measures. This paper examines the risk of transmission of gonorrhea from infected female to male and the role that variables such as race, prophylaxis and amount of exposure play in the development of gonococcal urethritis. Volunteer crew members of a large naval vessel were followed prospectively as a cohort to study their risk of acquiring gonococcal infection during a four-day liberty period in the Far East. At the same time the prevalence of N. gonorrhoeae was determined in a population of females to whom the sailors were exposed. The calculated risk of transmission per exposure with an infected partner was .19 for whites and .53 for blacks. A statistically significant relationship was noted between the risk of transmission of gonorrhea and both the number of partners and the frequency of sexual intercourse. Further, the increasing infection rate with increasing numbers of exposures in men who had a single sex partner suggests that the majority of men are in fact susceptible to gonorrhea if the quantity of exposure is sufficient.