Diffusion-weighted signal patterns of intracranial haemorrhage.

The signal pattern of intracranial haemorrhage on diffusion-weighted imaging (DWI) as it evolves over time is rarely discussed due to the sensitivity of T2*-weighted sequences and the specificity of classic signal patterns on T1 and T2-weighted sequences. The DWI signal is strongly affected by the magnetic susceptibility of paramagnetic blood products and, therefore, is markedly hypointense in the same phases that demonstrate hypointensity on T2*-weighted sequences; however, hyperacute haemorrhage (oxyhaemoglobin-predominant clot) and late subacute haemorrhage (extracellular methaemoglobin) do not demonstrate T2* hypointensity. Moreover, T2*-weighted sequences are less sensitive to the presence of extra-axial haemorrhage than to intraparenchymal haemorrhage. At these stages of evolution, haemorrhage demonstrates high DWI signal in association with low ADC values, which may be more pronounced than even its corresponding fluid-attenuated inversion recovery (FLAIR) signal. DWI is useful for identifying hyperacute subarachnoid haemorrhage and as a problem-solving tool in challenging cases.

Perceived barriers to accessing physical therapy services in Florida among individuals with low back pain.

Background: Low back pain (LBP) affects up to 84% of adults and physical therapy (PT) has been reported to be an effective approach to conservative care. For those individuals with LBP referred to PT, the decision to initiate and follow through with care is influenced by numerous factors. Currently, a paucity of evidence exists to identify barriers for patients with LBP to access PT care. Thus, the purpose of this study was to investigate perceived barriers influencing the decision to pursue PT care in the state of Florida. Methods: A purposive survey was administered via Qualtrics ESOMAR. Screener questions ensured candidates had LBP, resided in Florida, and were referred to PT. Participants that met the screener questions were offered an opportunity to participate in the full survey. Once a participant completed the full survey, variables assessing LBP, access to PT services, and potential barriers were analyzed. A partial least squares structural equation model (PLS-SEM) via WarpPLS 7.0 was used to explore which of the perceived barriers had the greatest influence on whether an individual with LBP was able to pursue PT care. Results: The conceptual framework that demonstrated the best fit of direct effects of potential barriers to accessing care included six independent exogenous latent variables: (a) unaware of a PT clinic near their home or work, (b) had children but no childcare for them, (c) had long PT sessions (e.g., 60 min), (d) had more than one PT session per week, (e) had fewer days active per week, and (f) exercised fewer times per day. Together the six variables explained 19% of the variance related to following through with care (R 2 = 0.19). Conclusions: The ability of an individual with LBP to access PT care in the state of Florida is multifactorial. There appears to be three broad factors that are the primary barriers, which include (a) the logistic ability (location and access to childcare) to attend PT treatment, (b) how much time is dedicated to the PT treatment, and (c) activity frequency of the individual seeking care. These findings support previous conceptual frameworks for predicting PT treatment. Practitioners and policy makers should consider these barriers when developing plans for conservative management of LBP in Florida.

A systematic review of automated feeder detection software for locoregional treatment of hepatic tumors.

PURPOSE: The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using automated feeder detection (AFD) software. MATERIALS AND METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A structured search was performed in the PubMed, SCOPUS, and Embase databases of patients undergoing locoregional therapy of liver tumors utilizing AFD software. Demographic data, procedure data (including radiometrics) and tumor response rate were recorded. Where available, performance of AFD was compared to conventional digital subtraction angiography (DSA) and cone-beam CT (CBCT) without AFD. RESULTS: A total of 14 full-text manuscripts met inclusion criteria, comprising 1042 tumors in 604 patients (305 men, 156 women; mean age, 68.6±6.0 [SD] years), including 537 patients with hepatocellular carcinoma, 8 with metastases from neuroendocrine tumors, and 59 patients without reported etiology. Reported sensitivity of AFD ranged between 86% and 98.5%, compared to DSA alone (38% - 64%) or DSA in combination with CBCT (69% - 81%). Three studies reported tumor response by modified response evaluation criteria in solid tumors (mRECIST) guidelines, with complete response in the range of 60% - 69%. CONCLUSION: AFD is a promising new technology for the identification of intrahepatic and extrahepatic tumor-feeding arteries and should be considered a useful adjunct to conventional DSA and CBCT in the treatment of liver tumors.

Safety of early ambulation in patients undergoing ultrasound-guided femoral low angle arterial access technique (FLAT).

PURPOSE: To evaluate the safety of early ambulation in patients undergoing transfemoral arterial interventions via ultrasound-guided femoral low angle arterial access technique (FLAT). MATERIALS AND METHODS: A total of 58 patients undergoing 72 transfemoral arterial procedures that underwent an attempt at FLAT for femoral artery cannulation at our institution from November 2014 to July 2015 were retrospectively identified. Technical success was defined as obtaining less than a 35-degree angle of entry through the anterior wall of the common femoral artery. Patients for which a low angle was achieved were ambulated after 2hours after hemostasis was achieved with manual compression. All patients received out-patient clinic follow-up which included ultrasound examination of the femoral artery. Chart review provided demographic data, pertinent past medical history, procedural information (type of procedure, size of femoral access sheath, time to ambulation), complications related to arterial access and follow up. RESULTS: Twelve patients were excluded from the study due to inability to analyze ultrasound images. A low angle was achieved in 37 patients (17 men, 20 women; mean age: 58.5 years±13.1 [SD]) undergoing 45 procedures who met inclusion criteria for the study, yielding technical success rate of 75%. There was a moderate positive correlation between the access angle and depth of the common femoral artery at the site of puncture (r=0.45; P<0.01). All patients were followed up within 2 weeks of the initial procedure in the outpatient clinic. No arterial access-related complications occurred. CONCLUSIONS: Femoral artery cannulation using FLAT followed by manual compression and ambulation after 2 hours appears to be a safe approach.

Quantitation of secretion by rat basophilic leukemia cells by measurements of quinacrine uptake.

A novel method for quantitating secretion is described based on measurements of the cellular uptake of the fluorescent aminoacridine dye quinacrine into low-pH secretory granules. The quinacrine fluorescence remaining in the medium was found to decrease after incubation with increasing numbers of the 2H3 rat basophilic leukemia line. This depletion of dye from the medium decreased after a secretory stimulus. Assuming that quinacrine partitions according to mass action, a quantitative model was derived to allow calculation of the percent secretion from dye uptake data. A good correlation was obtained when the values for the percent secretion determined by the quinacrine uptake method were compared with secretion measured by release of the granule enzyme beta-glucuronidase.

Measurement of cytotoxicity by target cell release and retention of the fluorescent dye bis-carboxyethyl-carboxyfluorescein (BCECF).

In order to utilize a newly available scanning microfluorimeter for lymphocyte-mediated cytotoxicity assays, a number of commercially available fluorescent dyes were compared for their suitability as target cell markers. One of them, bis-carboxyethyl-carboxyfluorescein (BCEFCF), was useful for assays with about 10(4) target cells and showed substantially less spontaneous leakage than other fluorescein derivatives, while still leaking more rapidly than 51Cr. For short cytotoxicity incubations (less than 2 h) with cytotoxic T lymphocytes (CTL), the corrected percentage BCECF release into the supernatant parallels that of 51Cr. For 4 h assays cytotoxicity could be quantitated by measuring the BCECF retained by target cells. Using human CTL and natural killer (NK) cells as effectors, with a variety of lymphoid cells and fibroblasts as targets in 4 h assays, the BCECF retention technique was found to give cytotoxicity values comparable to the 51Cr release assay. Cytotoxicity assays measuring BCECF fluorescence in microtiter wells with the scanning microfluorimeter offer advantages of safety, economy, and processing time compared with the 51Cr release assay.

Hantavirus pulmonary syndrome in Florida: association with the newly identified Black Creek Canal virus.

Hantavirus pulmonary syndrome (HPS) is a recently recognized viral zoonosis. The first recognized cases were caused by a newly described hantavirus. Sin Nombre virus (previously known as Muerto Canyon virus), isolated from Peromyscus maniculatus (deer mouse). We describe a 33-year-old Floridian man who resided outside the ecologic range of P maniculatus but was found to have serologic evidence of a hantavirus infection during evaluation of azotemia associated with adult respiratory distress syndrome. Small mammal trapping conducted around this patient's residence demonstrated the presence of antihantaviral antibodies in 13% of Sigmodon hispidus [cotton rat). Serologic testing using antigen derived from the Black Creek Canal hantavirus subsequently isolated from this rodent established that this patient was acutely infected with this new pathogenic American hantavirus. HPS is not confined to the geographical distribution of P maniculatus and should be suspected in individuals with febrile respiratory syndromes, perhaps associated with azotemia, throughout the continental United States.

Integrated RT-PCR/nested PCR diagnosis for differentiating between subgroups of plum pox virus.

An RT-PCR/nested PCR technique was developed for the simultaneous detection and typing of plum pox virus (PPV) and its major types--Dideron (D), Marcus (M), El-Amar (EA) and Cherry (C). Degenerated oligonucleotides were synthesized for the general detection of PPV, flanking the coding sequence for the N-terminal portion of the coat protein (CP), within which strain-specific differences were identified. On the basis of these characteristic differences, degenerated primer pairs were designed to differentiate between the four major subgroups of the virus in nested PCR reactions. The validity of the technique was tested on viral strains and cloned cDNAs overlapping the CP region. High specificity was observed with no detectable cross-reactions. The results of general PPV detection with the new primers and those of the PCR-based detection of the 3' non-coding region of the viral genome correlated with complete coincidence. The PCR typing results correlated well with those of the RsaI-RFLP and serological typing and revealed a surprisingly high incidence of PPV-D in Hungary.

Vincristine potentiates cytochalasin B-induced DNA fragmentation in vitro.

The cytochalasins are fungal metabolites that have previously been shown to have some chemotherapeutic potential. When various cell types are treated in vitro with both cytochalasin B and vincristine, the resultant DNA fragmentation is greater than the sum of that caused by each agent alone. The levels necessary to achieve this potentiation are obtainable in vivo. DNA fragmentation induced by cytochalasin E, an actin-specific agent, is potentiated by vincristine. Pretreatment of the mastocytoma line P815 with vincristine results in an enhancement of the ability of cytochalasin B to fragment DNA. These results indicate that cytochalasin B might be effective as a chemotherapeutic agent in the presence of vincristine.

Wernicke's encephalopathy in AIDS: a preventable cause of fatal neurological deficit.

Wernicke's encephalopathy is commonly associated with chronic alcohol abuse, but may also occur in patients with poor nutritional status. We report a case of acute Wernicke's encephalopathy in a patient with AIDS without any predisposing risk factors for thiamine deficiency. In developing countries, without vitamin supplementation, this disorder may play a role in the morbidity and mortality associated with AIDS. We believe that thiamine supplementation should be considered in cachetic AIDS patients, especially where access to antiretroviral therapy is limited.

The safety and efficacy of indinavir and ritonavir (400/400 mg BID) in HIV-1-infected individuals from an inner-city minority population: a pilot study.

We evaluated the safety and efficacy of indinavir 400 mg and ritonavir 400 mg twice daily (RIT/IND 400/400) in HIV-1-infected individuals, using an open label, proof of concept study. All patients received indinavir 400 mg and ritonavir 400 mg twice daily. Patients were followed up to 48 weeks. Nineteen subjects were enrolled, 11 (58%) men and eight (42%) women. The majority were American Black (nine; 47%) or Haitian (eight; 42%). The median baseline plasma HIV-1 viral load (VL) was 5.13 log10 copies/mL and the median CD4 cell count was 112 cells/mm(3). The proportion of compliant patients with VL <400 copies/mL at week 24 was 60% compared with 0% for non-compliant patients (P=0.011 [intent-to-treat] or P=0.085 [on-treatment]). VL at week 4 predicted week 24 VL response. Compliant patients had a median average CD4 cell count increase of 83.2 cells/mm(3) compared with 42.0 cells/mm(3) for non-compliant patients (P=0.010). The median average changes in triglycerides and cholesterol were significantly higher in compliant patients. This is a potent, safe combination for the treatment of HIV-1. VL at week 4 is predictive of viral outcome at week 24. Fasting serum cholesterol and triglycerides were significantly elevated during the study.

Cell-secreted Gp96-Ig-peptide complexes induce lamina propria and intraepithelial CD8+ cytotoxic T lymphocytes in the intestinal mucosa.

Induction of mucosal immunity is critical for protection from enteric pathogens. Heat shock protein gp96 is one of the primary peptide and protein chaperones located in the endoplasmic reticulum. We reported previously that a cell-secreted gp96-Ig fusion protein (gp96-Ig) mediated strong systemic, antigen-specific CD8-CTL expansion in vivo. We now evaluate the mucosal immune response to stimulation by secreted gp96 using allogeneic NIH-3T3 transfected with ovalbumin (OVA) and gp96-Ig. A single intraperitoneal NIH-3T3-OVA-gp96-Ig immunization caused significant homing of OVA-specific TCR transgenic CD8 cells (OT-I) to Peyer's patches, to the intraepithelial compartment and to the lamina propria. Intraperitoneal immunization with cells secreting gp96-Ig provided stronger mucosal immunity than the same dose instilled vaginally or rectally or injected subcutaneously or intradermally. Our results provide the first evidence that cell-based gp96-Ig-secreting vaccines may serve as a potent modality to induce mucosal immunity.

Race and ethnicity impact on the maximum proliferative response in peripheral blood lymphocytes from HIV-seropositive individuals.

The effects of race and ethnicity on immunological function have not been fully studied in patients infected with HIV-1. To study such differences, 54 patients on virally suppressive highly active antiretroviral therapy (HAART) with CD4 counts >200 cells/microL had their peripheral blood lymphocytes (PBL) evaluated for response to recall antigen. Significant differences were found in the maximum responses for PBL from black individuals compared with those from white individuals, and the differences were highly significant when responses for African-Americans were compared with those for white-Hispanics. These findings support work delineating ethnicity and race as significant variables to be taken into account when looking at vaccination strategies and responsiveness to therapeutic pharmacological interventions.

Human cytotoxic T lymphocytes and activated peripheral blood lymphocytes enhance cytochalasin B-induced DNA fragmentation of indicator bystander cells.

The cytochalasins are known to have multiple effects on cellular function. Not only do they induce secretion from granule compartments but they can induce DNA fragmentation in numerous cells. Evidence is presented which shows that treatment of human cytotoxic T lymphocytes and activated peripheral blood lymphocytes with cytochalasin B induces release of a factor capable of enhancing DNA fragmentation in cytochalasin-susceptible target cells. This activity can be transferred in the supernatants of cytochalasin B-activated CTL.

Enhancement of redirected target cell lysis by cytotoxic T lymphocytes in the presence of cytochalasin B.

The cytochalasins are known secretogogues. Their function as such is examined in light of the granule exocytosis model for lymphocyte-mediated cytotoxicity. Cytochalasin B is found to enhance target cell lysis by cytotoxic T lymphocytes when antibody-coated polystyrene beads are used to bridge the cells. The pattern of lysis is found to be biphasic in its dependence on cytochalasin B. Secretion of the enzyme BLT-esterase from the effector cells parallels the cytochalasin concentration-dependent pattern of lysis. Cytochalasin D is also able to enhance lysis but at concentrations less than cytochalasin B. Cytochalasin B does not inhibit binding of breads to the effector cell. This is shown by the ability of fluorescent beads coated with antibody to bind with an appropriate specificity to cells. These studies indicate that cytochalasin B is not strictly inhibitory for the induction of target cell lysis but can enhance lymphocyte-mediated lysis at low drug concentrations. These results are compatible with the interpretation that target cell lysis is mediated through a secretion process from cytotoxic T lymphocytes.

Enhancement of antigen driven lymphocyte proliferation secondary to GP41-induced B7 expression on adherent monocytes.

HIV-1 viral proteins are known to have immune regulatory effects. The interplay between these molecules and the host immune cells is complex. In this study the immune regulatory effects of gp41 on lymphocyte proliferation were evaluated as a function of the state of the monocyte. It is shown that monocyte adherence to tissue culture plates prevents suppression of lymphocyte proliferation to recall antigen in the presence of gp41. In addition, gp41 can enhance proliferation to low concentrations of Casta antigen when PBL are permitted time to adhere. It is shown that these effects are in part mediated through enhanced expression of the costimulatory molecules B7 and CD40. Cyclosporin A was not able to fully abrogate gp41-enhanced proliferation, indicating participation of a calcium-independent pathway. In addition, concentrations of anti-IL2 receptor antibody sufficient to inhibit maximal proliferation to antigen did not fully inhibit PBL proliferation to antigen that is augmented with gp41. Taken together these results suggest that modification of the monocyte state of activation or differentiation could mediate a response to gp41 that is immune enhancing.

The generation of cytotoxic T lymphocytes against acetaldehyde-modified syngeneic cells.

The major metabolic product of ethanol is acetaldehyde. It is highly reactive with proteins. In situ this modification is significant enough to generate an antibody response. Whether an effector cellular immune response can be generated against these acetaldehyde modified adducts on syngeneic cells is not known. In this paper we have demonstrated in the murine system that acetaldehyde modified splenic cells can generate cytotoxic T lymphocytes (CTL). These CTL are specific for the acetaldehyde modified syngeneic cells, and not acetaldehyde modified allogeneic cells. The ability of the CTL to lyse-specific targets is dependent on the formation of stable acetaldehyde adducts. Cold target inhibition studies reveal that modified syngeneic cells can inhibit lysis as effectively as unmodified cells. Therefore, the present study lends support to the hypothesis that acetaldehyde modified cells can generate a cellular immune response and may do so in pathologic states.