Quantification of tissue plasma volume in the rat by contrast-enhanced magnetic resonance imaging

Magnetic resonance imaging enhanced with a macromolecular contrast medium (MMCM), albumin-Gd-DTPA, was used to estimate the plasma volume in vivo in the myocardium, lung, liver, and skeletal muscle of 10 normal rats. The plasma volumes of the same tissues in a parallel group of six rats were estimated in vitro by a conventional radioisotopic technique (¹¹¹In-transferrin). Plasma volumes of myocardium, lung, liver, and skeletal muscle estimated by the MR technique (μl plas. ia cc-¹ of tissue) were 101,109,163, and 11.0, respectively, while plasma volumes measured by the In-transferrin radioisotope technique (mg plasma g-¹ of tissue) were 78.6, 215,143, and 11-2, respectively. Assuming a ratio of densities of aerated lung to blood of 0.45 and of other tissues to blood of 1.0, correlation between the methods was excellent (R² = 0.99) indicating that MR imaging enhanced with MMCM permits reliable in vivo estimation of tissue plasma volume in the rat.     

Comparison of methods for identifying resistant herpes simplex virus and measuring antiviral susceptibility.

BACKGROUND: A number of in vitro assays are used to determine susceptibility of HSV to antiviral agents, but results from these in vitro assays do not necessarily correlate with treatment outcome. OBJECTIVES: A method with improved capability for identifying an isolate as acyclovir (ACV) or penciclovir (PCV) resistant when resistance is borderline could greatly improve the management of HSV disease. STUDY DESIGN: A comparative evaluation of four in vitro assays, plaque reduction (PRA), DNA hybridization, plating efficiency (PEA) and plaque autoradiography (PAR) was performed to accurately identify and measure resistance of a TK-altered clinical HSV isolate (HSV-1 N4) from a patient who was non-responsive to ACV treatment. Two established criteria for the prediction of antiviral resistance, IC(50)> or =2.0 microg/ml or an IC(50) greater than 10x above a sensitive virus IC(50), as well as testing in human (MRC-5) and nonhuman (Vero and CV-1 monkey kidney) cell lines were evaluated. RESULTS: The PRA and DNA hybridization assays accurately identified HSV-1 N4 as ACV(r) in human cells when using the 10x above sensitive virus IC(50) resistance criterion. Moreover, the PEA and PAR assays failed to classify HSV-1 N4 as drug resistant and indicate that these technologies alone are inadequate for identifying resistant virus. CONCLUSIONS: The data presented herein indicate that the PRA and DNA hybridization assays most accurately identified an otherwise borderline-resistant isolate as drug resistant: (i) when a sensitive virus is used within each individual assay as a control, (ii) when ACV and PCV susceptibility is evaluated in human cells, and (iii) when the 10x above sensitive IC(50) criterion is used to classify a virus as drug-resistant. Testing of additional clinical samples is warranted to further confirm these findings.     

Characterization of Wolbachia infections and interspecific crosses of Aedes (Stegomyia) polynesiensis and Ae. (Stegomyia) riversi (Diptera: Culicidae)

Prior studies have identified a complicated pattern of interspecific hybridization between members of the Aedes (Stegomyia) scutellaris (Walker) mosquito group, which includes medically important vectors of bancroftian filariasis and dengue. Here, we report that two members of the group, Aedes polynesiensis Marks and Aedes riversi Bohart & Ingram, are both infected with intracellular Wolbachia bacteria. Sequencing of the Wolbachia wsp gene demonstrates that the infections differ from each other and from Wolbachia infections previously reported in mosquitoes. Aedes polynesiensis is the first mosquito identified with a wMel Wolbachia type. Intraspecific crosses of infected and aposymbiotic lines generated via antibiotic treatment show that the Wolbachia infections in both species cause high levels of cytoplasmic incompatibility. Interspecific crosses show that the two species are reproductively isolated. However, repeating the interspecific crosses with aposymbiotic mosquito strains demonstrates that the Wolbachia infections play a role in preventing hybrid offspring. We discuss Wolbachia infections in relation to better defining the evolutionary relationships and causes of speciation within the group, understanding the basis for the observed east-to-west gradient in filarial refractoriness, and developing novel genetic control measures.     

Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.     

Airway obstruction due to massive lingual oedema following cleft palate surgery

The Pierre Robin syndrome consists of micrognathia, pseudo-macroglossia, glossoptosis and a high arched or cleft palate. Difficult intubation of the trachea and associated abnormalities such as congenital heart disease are well known complications of this syndrome. Intraoral surgery (such as cleft palate repair and palatoplasty) can also be technically difficult for the surgeon resulting in prolonged retraction on the tongue with a mouth gag to provide adequate surgical exposure. We report a case where massive lingual oedema following a cleft palate repair resulted in life-threatening airway obstruction.     

Insulin infusion protocol for critical care units.

PURPOSE: An insulin infusion protocol for critical care units is described. SUMMARY: Evidence that aggressive glycemic control improves outcomes led physicians, nurses, dietitians, and pharmacists at a trauma center to develop an insulin infusion protocol. Before the protocol, elevated blood glucose concentrations were often not treated until they reached 200 mg/dL or higher. Insulin infusions were underutilized and were often not started until capillary blood glucose concentrations were greater than 350 mg/dL for 12 or more hours. When orders for an insulin infusion were written, they did not include directions for dosage adjustment, and the goal blood glucose range varied. A preliminary protocol was drafted allowing adjustments in insulin administration to be based on changes in capillary blood glucose values since the previous blood glucose measurement. The protocol was presented to a multidisciplinary team and further refined. The targeted blood glucose concentration range was 80-130 mg/dL. After the targeted range was achieved for a patient, if the blood glucose level continued to decrease over three consecutive measurements, the infusion rate was decreased by 0.5 or 1 unit/hr, depending on the capillary blood glucose level. Data for the first 30 patients were collected from September 2003 to August 2004. It took 2-36 hours (mean, 12.6 hours) to bring the capillary blood glucose concentration to less than 130 mg/dL. Among 2,845 capillary blood glucose measurements, there were 15 cases of hypoglycemia (0.4%) requiring treatment with 50% dextrose injection. CONCLUSION: A multidisciplinary effort resulted in the development of an insulin infusion protocol for use in critical care units.     

Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study.

PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.