Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).     

Central Sensitization Theory of Migraine: Clinical Implications

The clinical science of migraine headache continues to evolve. Theories of the pathophysiology of migraine have progressed from the early vascular basis of migraine to more complex current theories that emphasize the centrality of neuronal dysfunction. The most recently articulated theory of migraine is the central sensitization hypothesis, which proposes that altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis, could account for many of the temporal and symptomatic features of migraine, as well as its poor response to triptan therapy when such treatment is initiated hours after the onset of pain. Both preclinical and clinical data support the central sensitization theory. A critical clinical implication of this theory is that drugs that are capable of either aborting or arresting the process of central sensitization, most prominently dihydroergotamine, may have a unique role in the treatment of migraine. An additional, and highly practical, implication is based upon the finding that cutaneous allodynia—pain arising from innocuous stimulation of the skin, as in hair brushing or the application of cosmetics—is an easily identifiable marker of central sensitization. Thus, the presence or absence of cutaneous allodynia can be integrated into the routine clinical assessment of migraine and utilized as a determinant of treatment. Future basic and clinical research on central sensitization is likely to be of ongoing importance to the field.     

Changes in fetal presentation in twin pregnancies.

OBJECTIVE: The aim of the study was to describe the occurrence of spontaneous version in twins in the third trimester, as well as the correlation between antepartum and birth presentation. METHODS: Twin pregnancies were divided into four gestational age intervals: 20-23; 24-27; 28-31; and 32-36 weeks. Fetal presentation was categorized as cephalic (C) or non-cephalic (NC). Hospital records were reviewed to determine demographic factors, including mode of conception. Chi-square was used to compare distributions of presentations, and Cramer's V measure of association was used to correlate presentations in individual pregnancies between antepartum intervals and birth. RESULTS: A total of 207 pregnancies were included. The distribution of fetal presentations changed significantly through gestational age intervals (p < 0.001), although they were similar between 32-36 weeks and birth (p = 0.75). Correlation between antepartum and birth presentation in individual pregnancies strengthened throughout the four intervals. No correlation was seen between parity, gender, birthweight, or in vitro fertilization and fetal presentation or rate of spontaneous version.CONCLUSION: Many twins undergo spontaneous version in the third trimester, though there is excellent correlation between presentation at 32-36 weeks and birth. A cephalic presenting twin at > or = 28 weeks is highly likely to be in cephalic presentation at delivery.     

Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective survey of 150 patients.

One hundred and fifty patients presenting with small cell lung cancer (SCLC) to chest physicians, were assessed neurologically. Neuromuscular or autonomic deficits were common and occurred in up to 44% of cases. Weakness, dry mouth, and weight loss were not mutually independent and may represent the syndrome formerly described as carcinomatous neuromyopathy. By contrast, undoubted paraneoplastic syndromes were much less commonly detected. Two patients had the Lambert-Eaton myasthenic syndrome (LEMS) and one had subacute sensory neuropathy (SSN). In these patients, neurological symptoms antedated other manifestations of cancer, by between six and 17 months. The 95% confidence interval for the prevalence of LEMS or SSN among SCLC patients was 0-4%, consistent with the results of previous retrospective or smaller studies: summing these, the overall prevalence of LEMS among SCLC patients is close to 3%, which implies about 250 new cases per annum in England and Wales. If LEMS and SSN are the least uncommon neurological paraneoplastic syndromes in SCLC patients, this may reflect the accessibility of motor nerve terminals and dorsal root ganglia to cross-reactive anti-tumour cell antibodies.     

Early responses to chemotherapy of normal and malignant hematologic cells are prognostic in children with acute lymphoblastic leukemia.

PURPOSE: Improved cure rates for children with acute lymphoblastic leukemia (ALL) have resulted from better relapse prediction, using clinical and laboratory features at diagnosis, and more intensive therapy in high-risk patients. More recently, measurements of the variation in the response of malignant lymphoblasts to chemotherapy in vivo have further improved relapse prediction. It is unknown whether the variation in the response of nonmalignant hematologic cells after chemotherapy correlates with the response of lymphoblasts or risk of relapse. PATIENTS AND METHODS: We retrospectively evaluated myelosuppression during induction and consolidation chemotherapy in 227 children uniformly treated for ALL on consecutive Australian and New Zealand Children's Cancer Study Group protocols. The early response to treatment was assessed in a representative subset (n = 62) by determining minimal residual disease (MRD) level by molecular techniques on the end-of-induction bone marrow sample. RESULTS: We found that a slow rate of myeloid recovery at the end of induction chemotherapy, reflected in a low absolute neutrophil count (ANC), was highly predictive of relapse (P < .0001). Additionally, patients with a high end-of-induction MRD level had a high risk of relapse (P = .001). Multivariate analysis confirmed the independent prognostic significance of MRD and ANC at the end of induction chemotherapy (P < .05). There was no significant association between other measures of myelotoxicity and MRD or relapse. CONCLUSION: We conclude that the responses of normal myeloid cells and malignant lymphoblasts to chemotherapy predict outcome by distinct mechanisms. While these results are promising, their use in the clinical setting needs to be examined in a future randomized controlled trial.