Prognostic significance of oestrogen and progestogen receptor activities in breast cancer

The prognostic significance of the tumour activities of 2 steroid receptors, those for oestrogen (ER) and for progestogen (PgR), has been studied in 372 patients with breast cancer, in whom follow-up was available for 2-6 years (median 41 months). Of 252 patients with operable disease, 75.8 per cent had ER-positive tumours and 46.4 per cent had PgR-positive tumours, though a small additional fraction (6.3 per cent) had an equivocal PgR assay result. For the 236 patients with unequivocal receptor status, the relationships between disease-free interval or overall survival and receptor activity and other factors were evaluated by univariate and multivariate analyses. The latter revealed that only tumour size, node status, menstrual status and ER status related significantly to both disease-free interval and survival, though adjuvant therapy also related to disease-free interval, and tumour grade related to survival. It is concluded that measurements of PgR activity do not add to the prognostic significance of ER status.     

Remodeling of B-50 (GAP-43)- and NSE-immunoreactive mucosal nerves in the intestines of rats infected with Nippostrongylus brasiliensis.

Intestinal mucosal mast cells (IMMCs) are closely apposed to nerves, which is consistent with other evidence suggesting that mast cells are innervated. Recent studies have indicated that coordinated changes in mast cell and nerve densities occur in the gut mucosa, during progressive fibrosis, but there is a lack of experimental evidence to support remodeling of intestinal nerve fibers as part of a disease process. Infection of rats with the nematode Nippostrongylus brasiliensis (Nb) results in an initial loss of stainable IMMCs, during an acute inflammatory phase, with subsequent mast cell hyperplasia. Accordingly, we employed the Nb model to look for structural neuroplasticity of intestinal mucosal nerves during inflammation. Immunocytochemical labeling of neurofilament subunits was very low in the jejunal mucosa of all animals, whereas neuron-specific enolase (NSE)-immunoreactive nerves were relatively abundant in control animals. The number of NSE-immunoreactive profiles increased approximately 2.5-fold by day 10 (d10) postinfection (p less than 0.01) and returned to near control values by d14. Immunoreactivity for B-50/GAP-43 was more extensive, labeling more than four times the number of nerves per villus, compared with NSE (p less than 0.0001). B-50 immunoreactivity decreased minimally (ca. 20%) by d7 postinfection, and then increased through control values between d10 and d21, to 30% greater than controls at d49 (p less than 0.05). Subclassification of the B-50-immunoreactive nerves according to cross-sectional area revealed a greater than twofold increase in the proportions of large fibers at d7 and d10. Subsequently, the proportions of small nerves were increased compared with controls. The fiber size changes were found to correlate with mast cell densities (r = -0.72 for large and r = 0.76 for small nerves). At d10, dilated B-50- and NSE-immunoreactive nerves predominated, and extraneuronal NSE was noted. Electron microscopy revealed that this was due to axonal dilation and degeneration. These data provide evidence for plasticity of intestinal mucosal nerve fibers during inflammation. This includes early degenerative and later regenerative phases that appear to correlate with mast cell densities. The phenotype of mucosal nerves in control animals suggests ongoing modeling of these fibers.     

Staircase bioassay: the up-and-down method

Experiments are conducted to estimate the threshold for an all-or-none response. Threshold is defined to be a point above which 50% of the subjects will respond and below which 50% of the subjects will not respond. Examples are death, death in a fixed time period, shock, fibrillation, emesis. Staircase designs, in particular up-and-down trials, produce median (ED50) estimates of given standard error with as few as one-fifth the number of subjects as the traditional designs with preset numbers of tests at each of several levels of stimulus. We discuss these estimates and their efficiency as well as procedures to estimate standard deviation and its use in designing up-and-down trails. The advantages in using several short series in factorial experiments are presented. Suggestions are given for minimizing the complications of sequential designs. Case studies indicate the efficiency of the design for various applications.     

The use of acyclovir in suspected encephalitis.

The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is essential. However, rapid diagnostic tests are not freely available. Hence, all patients with suspected encephalitis may need to be commenced on acyclovir. In our study, of 34 patients with suspected encephalitis, only two eventually had HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non-encephalitis illness was finally diagnosed. Guidelines for the use of acyclovir in suspected encephalitis are given aimed at minimizing the drug cost whilst still protecting all cases of presumed HSE.     

Sex, Enterobius vermicularis and the appendix

Examination of 182 appendices containing Enterobius vermicularis demonstrated that male pinworms are seen more commonly than female. There was no association between the sex of pinworms and inflammation in the appendix but inflammation was frequently seen in association with luminal ova. Ova release from female pinworms may be a feature of appendiceal obstruction.     

Primary care referrals for lumbar spine radiography: diagnostic yield and clinical guidelines.

BACKGROUND: Primary care requests for radiographs of the lumbar spine have come under increasing scrutiny. Guidelines aiming to reduce unnecessary radiographs by limiting referrals to patients at high risk of serious disease have been widely distributed. Trial evidence suggests that guidelines can reduce radiography referrals. It is not clear whether this reduction has been achieved in routine practice. AIM: This study, using routine data, was conducted to measure trends in pnmary care referrals for lumbar spine radiography at two hospitals between 1994 and 1999. DESIGN OF STUDY: Analysis of primary care requests for lumbar spine radiography from computerised records. SETTING: Addenbrooke's Hospital, Cambridge (1 July 1994 to 30 June 1999), and Ipswich General Hospital (1 July 1995 to 30 June 1999), United Kingdom. METHOD: All primary care requests for lumbar radiography were identified electronically from computerised information systems. A random sample of 2100 radiography reports were classified according to clinical importance. These classifications were used to examine whether the proportion of radiographs demonstrating potentially more serious findings had increased between 1994 and 1999. RESULTS: There was no evidence that primary care referrals for radiography of the lumbar spine had decreased between 1994 and 1999 at either hospital. General practitioners did not progressively refer more high-risk patients for lumbar radiography. Only a small proportion of patients had important radiographic findings that might warrant specialist referral or specific therapy. CONCLUSION: The implementation of diagnostic guidelines offers much to the NHS. However in these two hospitals, the reduction in radiograph utilisation evident in trials was not achieved. Guideline development is a resource intensive process; distribution must be supported by more effective implementation strategies.     

Potential for cost economies in guiding therapy in patients with metastatic breast cancer.

Therapeutic response in patients with advanced breast cancer is conventionally assessed with reference to criteria devised by the International Union Against Cancer. Evidence to date suggests, however, that assessments of equivalent quality may be obtained at lower cost from the use of serum markers. The paper presents estimates of potential cost savings resulting from the use of serum markers in place of conventional assessment and argues that the size of these savings merits the establishment of a randomised controlled trial.     

Computed tomography in blunt abdominal trauma: an analysis of clinical management and radiological findings.

We have retrospectively assessed the computed tomography (CT) findings in 92 patients suffering severe blunt abdominal trauma. Surgical findings and clinical follow-up were correlated with the CT findings. In nine patients CT was first used after emergency surgery and provided baseline data which was useful for further management. In two patients CT did not demonstrate small hepatic lacerations seen during previous surgery. No deaths were recorded. In 16 patients surgery followed CT within 24 h; there was good correlation between the CT and operative findings in 10 patients. However, CT failed to detect significant solid organ injury in five patients and was misleading (false positive) in another patient. There were two deaths amongst these 16 patients. Sixty-seven haemodynamically stable patients were initially managed non-operatively. Fifteen of these 67 patients had normal CT examinations; only one had subsequent laparotomy (for reasons unconnected with the trauma) where no injury was detected; there were no deaths. Of the 52 patients with an abnormal CT examination, 43 were successfully managed non-operatively. There were three deaths, including one where an injury missed at CT contributed to the demise of the patient. After an initial trial of non-operative management, the remaining six patients went to surgery where there was good concordance with the CT findings except for one missed renal injury. Active non-operative management of blunt abdominal trauma is widely accepted in haemodynamically stable patients and this report shows how CT supports this policy of surgical restraint in such cases. However, on review CT missed 13 injuries in nine patients overall; stricter attention to technique and better equipment may lead to improved results in the future.