Management of myocardial infarction: the proper priorities

We calculated the rates for perioperative mortality and fatal pulmonary embolism (PE) after primary total hip replacement in a single UK health region, using a regional arthroplasty register and the tracing service of the Office of National Statistics. During 1990, there were 2111 consecutive primary replacements in 2090 separate procedures. Within 42 days of operation a total of 19 patients had died (0.91%, 95% CI 0.55 to 1.42). Postmortem examination showed that four deaths (0.19%, 95% CI 0.05 to 0.49) were definitely due to PE. The overall perioperative mortality and fatal PE rates are low and in our study did not appear to be altered by the use of chemical thromboprophylaxis (perioperative mortality rate: one-tailed Fisher's exact test, p = 0.39; fatal PE rate: one-tailed Fisher's exact test, p = 0.56). The routine use of chemical thromboprophylaxis for primary THR is still controversial. The issue should be addressed by an appropriate randomised, prospective study using overall mortality and fatal PE rate as the main outcome measures, but the feasibility of such a study is questioned.     

Basic fibroblast growth factor expression as a predictor of prognosis in pediatric high-grade gliomas

Clinical and histopathological factors fail to adequately predict outcomes in children with high-grade gliomas, indicating a need to identify relevant biological markers of tumor behavior to guide therapeutic decision-making. Basic fibroblast growth factor (bFGF) is a mitogenic and angiogenic factor that has been observed to be overexpressed in a significant percentage of malignant gliomas, although the prognostic significance of this expression is unknown. To address this issue, the expression status of bFGF was examined immunohistochemically in a series of 27 archival pediatric malignant non-brainstem gliomas treated consecutively at our institution between 1975 and 1992. Tumors were categorized based on expression levels, and the association between expression status and outcome was examined. Sixteen cases showed high levels of expression of bFGF, and 11 showed low levels. There was no correlation between expression status and either tumor histology, patient age, or tumor location. However, there was a significant difference in outcome between patients with high levels of bFGF immunoreactivity and those with low expression. Median progression-free survival was >66 months in the low bFGF group as compared to 6 months in the high bFGF group (P = 0.006). Median overall survival was >66 months in the low bFGF group as compared to 18 months in the high bFGF group (P = 0.03). Tumor bFGF expression seems to be strongly associated with outcome in children with high-grade gliomas and, consequently, may serve as a biological correlate of patient prognosis in conjunction with other prognostic variables.     

Optimized lens-sparing treatment of retinoblastoma with electron beams

PURPOSE: The ideal lens-sparing radiotherapy technique for retinoblastoma calls for 100% dose to the entire retina including the ora serrata and zero dose to the lens. Published techniques, most of which use photons, have not accomplished this ideal treatment. We describe here a technique that approaches this ideal configuration using electron beam therapy. METHODS AND MATERIALS: Dose-modeling calculations were made using a computer program built around a proprietary algorithm. This program calculates 3D dose distribution for electrons and photons and uses the Cimmino feasibility method for the inverse problem of beam weighting to achieve the prescribed dose. The algorithm has been verified in the ocular region by measurements in a RANDO phantom. To search for an ideal lens-sparing beam setup, a stylized phantom of an 8-month-old infant was generated with built-in inhomogeneities, and a phantom of a 5-year-old child was generated from a patient CT series. RESULTS: Of more than 100 different beam setups tested, two 9 MeV electron beams at gantry angles plus and minus 26 degrees from the optic nerve axis achieved the best distribution. Both fields have a lens block and an isocenter between the globe and origin of the optic nerve. When equal doses are given to both fields, the entire extent of the retina (including ora serrata) received 100%, while the lens received 10% or less. CONCLUSION: The two-oblique-electron-beam technique here described appears to meet most of the stringent dosimetry needed to treat retinoblastoma. It is suitable for a range of ages, from infancy to early childhood years.     

Prostate cancer masquerading as a zygomatic posttraumatic mass

INTRODUCTION: Idiopathic hypereosinophilic syndrome is an uncommon disease often associated with diverse non-specific skin manifestations. Mucosal ulcerations suggest a myeloproliferative from with poor prognosis due to possible progression to malignant hemopathy or visceral complications. CASE REPORT: A 28-year-old man presented idiopathic hypereosinophilia with isolated mucosal ulcerations involving the buccal and genital areas. Laboratory results (hematology, CD25) suggested a myeloproliferative form. Treatment with alpha interferon (18 months) led to regression of the mucosal lesions and a decrease in the markers of eosinophil toxicity. There was no visceral involvement. DISCUSSION: Immunosuppression with/without high-dose alpha interferon is usually used for the treatment of hypereosinophilic syndrome. In our case favorable outcome was obtained with lower doses of alpha interferon than those reported in the literature. There was objective decrease in eosinophil toxicity (regular counts of hypodense eosinophils, CD25 or interleukin 2 soluble receptor) and no progression (malignant hemopathy, mortal visceral involvement).     

Serum iron in catatonia and neuroleptic malignant syndrome

AIMS: The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment. METHODS: From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy. RESULTS: Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed. CONCLUSIONS: The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.     

Microchip device for performing enzyme assays

An automated enzyme assay was performed within a microfabricated channel network. Precise concentrations of substrate, enzyme, and inhibitor were mixed in nanoliter volumes using electrokinetic flow. Reagent dilution and mixing were controlled by regulating the applied potential at the terminus of each channel, using voltages derived from an equivalent circuit model of the microchip. The enzyme beta-galactosidase (beta-Gal) was assayed using resorufin beta-D-galactopyranoside (RBG), a substrate that is hydrolyzed to resorufin, a fluorescent product. Reaction kinetics were obtained by varying the concentration of substrate on-chip and monitoring the production of resorufin using laser-induced fluorescence. Derived Michaelis--Menten constants compared well between an on-chip and a conventional enzyme assay. Bias in the derived K(m) and kcat was primarily due to the limited solubility of RBG and the associated lack of measurements at substrate concentrations exceeding the K(m). A Ki of 8 microM for the inhibitor phenylethyl beta-D-thiogalactoside (PETG) was determined from plots of initial rate versus substrate concentration obtained at three concentrations of PETG. The relative inhibition of beta-Gal by lactose, p-hydroxymercuribenzoic acid, and PETG was determined by varying the inhibitor concentration with constant enzyme and substrate concentration. An enzyme assay performed on the microchip within a 20-min period required only 120 pg of enzyme and 7.5 ng of substrate, reducing the amount of reagent consumed by 4 orders of magnitude over a conventional assay.     

Heart tamponade: a life-threatening complication of a central venous catheter

A 57-year-old female patient initially admitted with acute pancreatitis became extremely hypotensive, with increased central venous pressure, a few hours after insertion of a central venous catheter into the right subclavian vein. Echocardiography revealed a large amount of pericardial fluid, which was removed by pericardiocentesis. A cardiac tamponade as a result of central venous cannulation is a rare but serious complication with a high mortality rate. The tamponade may be the result of perforation of the V. cava superior, the right atrium or the right ventricle (as in the patient described). Cardiac tamponade should be suspected in any patient with severe hemodynamic problems after insertion of a central venous line.