From amaurosis fugax to asymptomatic bithalamic infarct

Bilateral paramedian thalamic infarctions are usually associated with impaired consciousness, oculomotor disturbances and neuropsychological changes. A 44-year-old healthy woman presented with amaurosis fugax of the right eye immediately after a Valsalva maneuver. Neurological examination, in particular visual acuity, vigilance and ocular movements, was normal. Blood pressure, ECG and angio-CT of the neck and head vessels were normal, but MRI/DWI and T2 sequences showed recent bi-thalamic ischemic lesions in the paramedian territories. Doppler sonography and transesophageal echocardiography showed a large right-to-left shunt due to an atrial communication, with septum aneurysm. Twenty-four-hours cardiac monitoring was normal but prior to an eventual closure of the cardiac defect she underwent an ambulatory 7-day ECG monitoring which revealed several paroxystic short lasting passages into atrial fibrillation, unnoticed by the patient. The interest in this case is threefold: (1) bilateral paramedian thalamic infarction which usually presents with a devastating clinical picture may occur clinically silent; (2) monocular amaurosis fugax which is usually associated with ipsilateral carotid disease may be the consequence of cardiac embolism, and (3) atrial fibrillation is never completely ruled out, here it was caught only in a 7-days ambulatory R-test, and consequently prevented closure of a possibly asymptomatic patent foramen oval

A defect-in-continuity in the canine femur: and in-vivo experimental model for the study of bone graft incorporation.

The in-vivo study of bone graft incorporation has traditionally used a segmental diaphyseal bone defect. This model reliably produces a nonunion, but is complicated by graft instability and altered limb loading stresses. The authors discuss the advantages of a defect-in-continuity canine femur model which produces a more consistent union with fewer mechanical complications despite the absence of fixation. This proposed model permits analysis of radiographic, histologic and biomechanical data which are more applicable to the usual clinical setting in which bone graft is required

Etoposide and adriamycin containing combination chemotherapy (HOPE-Bleo) for relapsed Hodgkin's disease.

Forty-four patients with relapsed or resistant Hodgkin's disease were treated with adriamycin 40 mg m-2 i.v. on day 1, vincristine 1.4 mg m-2 i.v. on days 1 and 8, prednisolone 40 mg m-2 orally daily for 8 days, etoposide 200 mg m-2 orally daily for 4 days according to the nadir white cell count, and bleomycin 10 mg m-2 i.v. days 1 and 8 (HOPE-Bleo). Median age was 27 (range 12-71). When stage was considered according to all sites currently or previously involved by Hodgkin's disease (cumulative stage) 26 patients (59%) had stage IV, 13 (29%) stage III and five (11%) stage II disease; 33 (75%) had B symptoms. All patients had received previous chemotherapy and 18 (41%) had received two or more regimens. Twenty-six patients (59%) achieved CR and 10 (23%) PR; the median duration of CR was 22 months and median survival for all patients was 48 months. Eight patients remain in continuous CR; none of these had received extensive previous chemotherapy. Among the 19 patients who had relapsed from CR achieved by a single previous chemotherapy regimen, six (32%) achieved long CR on HOPE-Bleo. The regimen was generally well tolerated but the principal toxicity was myelosuppression. There were two toxic deaths, one due to neutropenic sepsis and the other due to acute peritonitis. The HOPE-Bleo regimen is an effective treatment for relapsed or resistant Hodgkin's disease, with a low probability of carcinogenesis and infertility. These factors suggest that HOPE-Bleo deserves further evaluation as primary treatment for Hodgkin's disease and very careful selection of relapsed patients for high dose salvage chemotherapy with bone marrow transplants must be exercised

Hypoglycemia in response to glucose and glucagon in insulinoma patients with a negative prolonged fast: Functional and morphological properties

A negative 72-h fast is usually considered to preclude the diagnosis of insulinoma. The aim of this study was to describe the functional and morphological properties of two exceptional patients with an insulinoma who had exhibited pre-operatively a negative 72-h fast. Despite the ability of tumor cells to turn off insulin secretion in response to low plasma glucose during 72 h of fasting, hyperinsulinemic hypoglycemia occurred in both patients in response to stimulation by classical secretagogues. Pre-operatively, both patients underwent oral and iv glucose challenge tests and iv glucagon stimulation test. Insulin secretion was rapidly stimulated by these secretagogues to an exaggerated extent and thereby caused hypoglycemia due to an insulin mass effect. In contrast to the common functional features during suppression and stimulation tests, the tumors differed widely with regard to insulin and proinsulin response to calcium during ASVS tests and morphological properties. In patient 1, the immunohistochemical proinsulin distribution pattern resembled that of normal γ-cells, i.e. the staining was restricted to the perinuclear area; insulin and proinsulin were not stimulated by calcium during the ASVS test. In patient 2, the proinsulin staining pattern was abnormal, i.e. proinsulin was also found in the periphery of tumor cells; insulin and proinsulin were stimulated by calcium. We conclude that normal or exaggerated rather than defective glucose sensing may explain hypoglycemia in these exceptional insulinoma patients. Different functional characteristics of these tumors can be correlated with distinct morphological propertie

Phase II trial of trimelamol in refractory ovarian cancer

Trimelamol is an analogue of hexamethymelamine which exhibited activity against refractory ovarian cancer in phase I clinical trial. The dose limiting toxicity was leukopenia. In a phase II study, 42 patients with recurrent, or platinum-complex resistant, advanced ovarian cancer were treated using the dose schedule 800 mg m-2 i.v. daily for 3 days. There were one complete, three partial and five minor responses, objective response rate: 9.5%. The main toxicity observed was nausea and vomiting, myelosuppression was minor. The role of Trimelamol in the treatment of ovarian cancer remains to be defined, but its activity is limited in refractory disease

The value of computed tomographic (CT) scan surveillance in the detection and management of brain metastases in patients with small cell lung cancer.

One hundred and twenty-seven consecutive patients presenting with small cell lung cancer were entered into a whole-brain CT scan surveillance study, starting at presentation and repeating at 3-monthly intervals for 2 years as an alternative to prophylactic cranial irradiation (PCI). The aim of the study was to detect CNS metastases at an early asymptomatic stage in the hope that prompt CNS radiotherapy could achieve long-term control; at the same time unnecessary PCI with its potential long-term morbidity could be avoided. CNS metastases were found in 56 patients (44%) including 16 (13%) at diagnosis and 40 at a median of 4 months (range 1-27 months) after completing chemotherapy. No patient developed CNS disease while on chemotherapy. Thirty-six patients were asymptomatic at diagnosis (group A) but 20 developed clinical CNS relapse between scans (group B) (interval relapse). Despite prompt radiotherapy 56% of patients in group A and 60% of patients in group B died with active CNS disease. Likewise, there was no survival difference between patients in group A, group B or those who never developed CNS disease. Regular 3-month CT scan surveillance is therefore not an effective substitute for PCI

High dose melphalan, BCNU and etoposide with autologous bone marrow transplantation for Hodgkin's disease.

Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140 mg m-2 and the dose of BCNU from 300 to 600 mg m-2. The response rate was 76% with 53% complete remission. Forty-five per cent of the patients are free of disease at 4-20 months follow-up. There were eight (26%) treatment-related deaths due to lung damage (seven cases) and irreversible cardiac failure (one case). Fatal lung damage occurred only in patients receiving 600 mg m-2 of BCNU with high dose melphalan. The dose of BCNU given with high dose melphalan should not exceed 500 mg m-2. This treatment is effective against relapsed Hodgkin's disease but must be used cautiously. The best time for its use remains to be determined

Real-life data from standardized preanalytical coding (SPREC) in tissue biobanking and its dual use for sample characterization and process optimization.

The standardized preanalytical code (SPREC) aggregates warm ischemia (WIT), cold ischemia (CIT), and fixation times (FIT) in a precise format. Despite its growing importance underpinned by the European in vitro diagnostics regulation or broad preanalytical programs by the National Institutes of Health, little is known about its empirical occurrence in biobanked surgical specimen. In several steps, the Tissue Bank Bern achieved a fully informative SPREC code with insights from 10,555 CIT, 4,740 WIT, and 3,121 FIT values. During process optimization according to LEAN six sigma principles, we identified a dual role of the SPREC code as a sample characteristic and a traceable process parameter. With this preanalytical study, we outlined real-life data in a variety of organs with specific differences in WIT, CIT, and FIT values. Furthermore, our FIT data indicate the potential to adapt the SPREC fixation toward concrete paraffin-embedding time points and to extend its categories beyond 72 h due to weekend delays. Additionally, we identified dependencies of preanalytical variables from workload, daytime, and clinics that were actionable with LEAN process management. Thus, streamlined biobanking workflows during the day were significantly resilient to workload peaks, diminishing the turnaround times of native tissue processing (i.e. CIT) from 74.6 to 46.1 min under heavily stressed conditions. In conclusion, there are surgery-specific preanalytics that are surgico-pathologically limited even under process optimization, which might affect biomarker transfer from one entity to another. Beyond sample characteristics, SPREC coding is highly beneficial for tissue banks and Institutes of Pathology to track WIT, CIT, and FIT for process optimization and monitoring measurements