The effect of outflow pressure upon thoracic duct lymph flow rate in fetal sheep.

Edema develops when lymph does not return to the venous circulation at a rate equal to the rate of capillary filtration. Fetal sheep develop edema as well as an increased central venous pressure while undergoing atrial pacing at 320 beats per min. We hypothesized that the increased central venous pressure augmented the appearance of fetal edema by impairing the return of thoracic duct lymph to the venous circulation. To investigate this hypothesis, we studied the effect of outflow pressure upon thoracic duct lymph flow in 10 unanesthetized fetal sheep who had low resistance lymph catheters placed in the cervical thoracic duct near its junction with the left jugular vein. After the ewe and fetus recovered for 5 d, we altered the outflow pressure of the lymph catheter by adjusting its height with respect to amniotic fluid pressure and measured the resultant change in thoracic duct lymph flow rate. We found that lymph flow rate was constant over the range of outflow pressures (central venous pressures) normally encountered but decreased in a linear fashion at pressures greater than 0.68 kPa (5.1 torr). Lymph flow stopped at an outflow pressure of 2.40 kPa (18 torr). The data points are best fit by two lines obtained by a piecewise linear regression rather than a single line obtained from a linear regression. We conclude that fetal thoracic duct lymph flow is sensitive to elevations in outflow pressure. Lymph flow begins to diminish at outflow pressures corresponding to central venous pressures commonly encountered in pathologic conditions and may augment the appearance of fetal edema.     

What some patients can eat during migraine attacks: therapeutic and conceptual implications

Although nausea and vomiting are diagnostic migraine symptoms, most patients can take tablets by mouth and a few say they can eat some food. This study was conducted to determine the proportion who could eat or drink, what was consumable and with what effect. One-hundred-and-nine migraineurs were asked what they could eat or drink at the beginning or height of their attacks; 59 could not take any food by mouth, but 50 could eat during the headache phase of their migraine attacks. Four ate normally, 5 took smaller amounts of their normal dietary intake, and 3 took lighter meals. Dry, carbohydrate foods were consumable by the remaining 38: a few had specific cravings, most stated the precise variety which, when eaten, reduced nausea, headache, other symptoms or length of attacks. Patients should therefore be encouraged to eat what they can tolerate, with their tablets taken as early as possible after the onset of attacks. Simultaneous nausea, tolerance or even craving for specific foods occur in other conditions, particularly high altitude headaches which share other features of migraine attacks. The observations in this paper support the notion that migraine is a central neuronal metabolic disturbance.     

An efficient multiple-exposure analysis of the toxicity of crisnatol,a DNA intercalator in phase II clinical trials

To investigate the toxicity and mechanism of action of crisnatol (CRS), a new DNA intercalator currently in phase II clinical trials, we analyzed cellular and nuclear flow cytometric (FCM) parameters of murine erythroleukemic cells (MELC) exposed to a range of CRS concentrations over three exposure conditions: short-term (4 h), long-term (24 h), and short-term with recovery (4 h⁺/19 h^–). At 0.5–1.0M CRS, 4 h exposure results in a reversible G₂-phase block, while 24 h exposure results in > G₂ polyploidy. At 5–10M CRS concentrations, cells exhibit persistent retardation of S-phase progression or irreversible G₂ and/or > G₂ blocks, depending on duration of exposure. Cells terminally blocked in G₂ exhibit increased nuclear/cellular volumes and increased nuclear fluorescein isothiocyanate (protein) staining, suggestive of unbalanced growth. At 25–50M CRS concentrations, MELC exhibit severe membrane perturbation (loss of viability) regardless of exposure. In contrast, following similar exposures to an inactive isomer of CRS, MELC exhibit minimal cell cycle effects, suggesting that cell cycle kinetics may be a useful criterion for assessing potential efficacy. Similar analyses with different classes of chemotherapeutic agents reveal that the range of induced cellular/nuclear perturbations varies with the class of compound used. Taken together, these results suggest that drug toxicity can vary with both concentration and duration of exposure and, as such, a selective multiple-exposure FCM analysis may better represent the spectrum of drug action for drug development and pharmacodynamic studies.Abbreviations m-AMSA amsacrine - ARA-C cytosine arabinoside - BrdU 5-bromodeoxyuridine - CF 5,6-carboxyfluorescein - CFDA 5,6-carboxyfluorescein diacetate - CRS crisnatol - FCM flow cytometry - FITC fluorescein isothiocyanate - 5-FU 5-fluorouracil - DMSO dimethylsulfoxide - MELC Friend murine erythroleukemic cell - MLP melphalan - PBS phosphate-buffered saline - PI propidium iodide - TAX taxol - topo topoisomerase - VBL vinblastine sulfate - cis-Pt cis-platinum     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.     

Complex fractures of the clivus: diagnosis with CT and clinical outcome in 11 patients

During a 20-month period, fractures of the clivus occurring after craniocerebral trauma were diagnosed with computed tomography (CT) in 11 patients. Five patients had longitudinally oriented fractures; these were fatal in four patients due to either vertebral-basilar artery occlusion, brain stem trauma, or both. Six other patients had transversely oriented fractures that extended through the carotid canal and petrous temporal bone. While less frequently contributing directly to mortality, transverse fractures were also associated with cerebrospinal fluid leaks (two patients) and a cavernous sinus-carotid fistula (one patient). They were not as frequently associated with Horner syndrome or cranial nerve deficits as suggested in the current literature. This retrospective evaluation reveals two distinct injury patterns that demonstrate a difference in related morbidity and mortality.