Validation of diffuse correlation spectroscopy against 15O-water PET for regional cerebral blood flow measurement in neonatal piglets

Diffuse correlation spectroscopy (DCS) can non-invasively and continuously asses regional cerebral blood flow (rCBF) at the cot-side by measuring a blood flow index (BFI) in non-traditional units of cm²/s. We have validated DCS against positron emission tomography using ¹⁵O-labeled water (¹⁵O-water PET) in a piglet model allowing us to derive a conversion formula for BFI to rCBF in conventional units (ml/100g/min). Neonatal piglets were continuously monitored by the BabyLux device integrating DCS and time resolved near infrared spectroscopy (TRS) while acquiring ¹⁵O-water PET scans at baseline, after injection of acetazolamide and during induced hypoxic episodes. BFI by DCS was highly correlated with rCBF (R = 0.94, p < 0.001) by PET. A scaling factor of 0.89 (limits of agreement for individual measurement: 0.56, 1.39)×10⁹× (ml/100g/min)/(cm²/s) was used to derive baseline rCBF from baseline BFI measurements of another group of piglets and of healthy newborn infants showing an agreement with expected values. These results pave the way towards non-invasive, cot-side absolute CBF measurements by DCS on neonates.     

The pathophysiology of chronic subdural hematoma revisited: emphasis on aging processes as key factor

GeroScience - Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural collections of...     

Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells

Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Symptoms at presentation to the emergency department: Predicting outcomes and changing clinical practice?

Background

The type and number of symptoms in emergency patients differ widely. It remains unclear, if outcomes can be predicted by the number of symptoms. Furthermore, it is unknown, whether clinical practice could be influenced by presenting symptoms.

Methods

Prospective observational study, performed in the emergency department of the University Hospital Basel, a tertiary hospital. A consecutive sample of patients was interviewed at presentation for a predefined set of 35 symptoms. The number of symptoms was correlated with outcomes using linear and logistic regression models. Clinical practice was observed using prospective data on disease severity ratings, triage category, use of resources, length‐of‐stay and follow‐up presentations.

Results

Data of 3472 patients were analysed. The number of symptoms ranged between 1 and 25, the mean being 2.74. Women reported more symptoms than men. Age and comorbidity indices were not associated with the number of symptoms. After adjusting for age and gender, there was no correlation between the number of symptoms and adverse outcomes, such as ICU‐admission or in‐hospital mortality (OR: 1.03, CI: 0.88‐1.18, P = .68). The number of symptoms at presentation was associated with hospitalisation, disease severity rating by patients and emergency physicians, triage categories, use of resources, length‐of‐stay and follow‐up presentations.

Conclusion

The number of symptoms did not correlate with the main adverse outcomes (ICU‐admission and in‐hospital mortality). However, clinical practice was influenced by the nature and number of symptoms. This was shown by associations with hospitalisation, length‐of‐stay, use of resources and follow‐up presentations. Furthermore, the number of symptoms correlated with the caregivers’ disease severity ratings and the attributed triage categories. This may indicate that caregivers respond to the number of symptoms by a higher investment in their immediate work‐ups and later follow‐ups.     

Liver resection for breast cancer metastases

BACKGROUND/AIMS: The prognosis of patients with hepatic metastases (HM) from breast cancer receiving no treatment is extremely poor. Results of systemic and regional chemotherapy as well as other treatment modalities, such as immunotherapy or hormonal therapy, are disappointing in this group of patients, with median survival rates hardly exceeding 1 year. METHODOLOGY: We performed a retrospective analysis of patients undergoing resection of isolated HM from breast cancer to determine the morbidity, mortality and prognosis following this procedure. RESULTS: Fifteen female patients underwent liver resection between September 1985 and April 1997. Two patients had synchronous and 13 patients had metachronous HM. The mean number of HM was 3.3 (1-9) (bilobar in 6 patients) with a mean diameter of 5.3 cm (2-11 cm). The following resections were performed: wedge resection (4), left lateral segmentectomy (2), right hemihepatectomy (3), left hemihepatectomy (1), extended right hemihepatectomy (3) and extended left hemihepatectomy (2). There was no hospital mortality. Morbidity (transient hepatic failure (n=2) and intra-operative hemorrhage necessitating splenectomy (n=1)) occurred in 3 patients. Median follow-up was 12 (1-88) months. Six patients developed recurrent liver disease; 2 relapsed elsewhere. Six of these 8 patients died. Overall median survival following liver resection was 57 months with 1-, 2- and 3-year survival rates of 100%, 71.4% and 53.6% respectively. CONCLUSIONS: Liver resection is a viable treatment option for selected patients with isolated HM from breast cancer that can be performed safely. It should be considered in individual patients if the operative risk is low, if no extrahepatic disease is present and provided a complete resection with clear margins is technically feasible.     

Anemia of the Belgrade rat: evidence for defective membrane transport of iron

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.