Global stability analysis of the disease-free equilibrium state of a mathematical model of trypanosomiasis

The global stability analysis represents a compound failure, mechanism which provides lower calculated factors of safety. In this research, the global stability analysis was used to propose a mathematically model of the transmission dynamics and control of Trypanosomiasis, known as African sleeping sickness. We obtained the Disease-free equilibrium state and present graphical profile of some of the compartments

Association of the immunohistochemical detection of gamma-glutamyl transferase expression with clinicopathological findings in postmenopausal women with endometrioid adenocarcinoma of the uterus.

Gamma-glutamyl transferase (GGT) is a membrane enzyme present not only in the liver but also in healthy endometrial epithelium. Its overexpression has been demonstrated in numerous malignancies, where it exerts an anti-apoptotic effect and causes drug resistance in response to oxidation stress. Aim of the study was investigation of GGT expression in postmenopausal patients with endometrioid adenocarcinoma of the uterus (EAC). The material comprised 98 paraffin-embedded post-operative tumour samples of EAC from postmenopausal patients and a control group of 60 normal human postmenopausal endometrium samples. For immunohistochemical specimen staining, polyclonal IgG anti-GGT was used; for GGT expression measurement, a semi-quantitative method was applied. In EAC patients, 16 (16.33%) were diagnosed as stage IA, 46 (46.93%) as stage IB, 14 (14.29%) as stage II, and 22 (22.45%) as stage IIIA-C, according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. Fifty-six (57.14%) patients were diagnosed with low- or moderate-grade (G1-2) disease, and 42 (42.86%) were diagnosed with high-grade (G3) disease. Cytoplasmic GGT staining was confirmed in all samples, while apical membrane GGT staining was observed only in G1-2 EAC specimens and the control group. In G3 EAC specimens, GGT cytoplasmic staining and high nuclear polymorphism areas were predominantly shown. Comparable high GGT median apical expression was confirmed in healthy endometrium (2.0, S.E.M. = 0.28) and in G1-2 EAC (2.0, S.E.M. = 0.27); however, in G3 tumours, GGT expression was significantly lower (0.0, S.E.M. = 0.07) than in healthy endometrium (P < 0.001 and P < 0.001, respectively). After stratification of the cancer cases according to FIGO staging, the lowest median apical GGT expression levels were in II EAC (0.0, S.E.M. = 0.64) tumours compared with IA (4.0, S.E.M. = 0.47) tumours, specimen and normal endometrium (2.0, S.E.M. = 2.8) (P < 0001). Stage IB EAC and IIIA-C EAC (1.0, S.E.M. = 0.16) cases showed only moderate median apical expression of GGT (1.0, S.E.M. = 0.24). We concluded that impaired GGT expression has the potential to become a valuable tool for stratifying EEC patients' prognosis and treatment planning.

Cross-priming amplification for detection of bovine viral diarrhoea virus species 1 and 2.

AIMS: The aim of the study was the development of cross-priming amplification for ubiquitous detection of bovine viral diarrhoea virus (BVDV) species 1 and 2. METHODS AND RESULTS: Three and five specific primers, respectively, for the detection of BVDV-1 and BVDV-2, were designed on the basis of the sequences of the 5'UTR region. Incubation temperature and reaction time were determined. The optimal incubation conditions using water bath were 63°C for 75 min. Reverse transcription step (RT) was not required. The results were visualized under UV-light as a bright yellow fluorescence in positive samples. Additional method for results interpretation was agarose gel electrophoresis. Positive samples showed the presence of ladder-like banding patterns, formed by harpin-like cross-priming amplification (CPA) products. Sensitivity of CPA was compared with conventional RT-PCR and real-time RT-PCR. The CPA detection limit was 3500 copies for BVDV-1 and 80000 copies for BVDV-2 per reaction. For RT-PCR it was 350 and 80 copies for BVDV-1 and BVDV-2, respectively, and for real-time RT-PCR it was 35 copies for BVDV-1 and 80 copies for BVDV-2. The sensitivity of the developed method is sufficient to detect persistently infected (PI) animals. Positive results were found in 24 of 25 BVDV isolates belonging to species 1 and 2. Additionally, one false-negative result for BVDV-2 was detected. There were no false-positive results in negative samples and in the negative control. Both sets of primers used for the detection of BVDV-1 and BVDV-2 were not able to detect atypical pestiviruses. CPA positive results were confirmed by RT-PCR and real-time RT-PCR. CONCLUSIONS: CPA is a rapid method for the detection of BVDV-1 and BVDV-2 in field samples from PI animals. SIGNIFICANCE AND IMPACT OF STUDY: This is the first report on the application of the CPA method for the detection of BVDV.

Predominance of bovine viral diarrhea virus 1b and 1d subtypes during eight years of survey in Poland.

The genetic diversity of bovine viral diarrhea virus (BVDV) was determined from 65 animals persistently infected with BVDV and diagnosed between 2004 and 2011 in Poland. The samples originated from 28 herds in 12 provinces, where over 90% of the whole cattle population of Poland is reared. Phylogenetic analysis based on the fragments of two genomic regions of BVDV namely, 5'-untranslated region (5'-UTR) and N(pro) was performed. All the BVDV isolates belonged to BVDV-1 species and were further divided into four subtypes. There were 31 viruses of BVDV-1b subtype (47.6%) present in 12 herds, 24 of BVDV-1d subtype (36.9%) in 9 herds, 8 of BVDV-1f subtype (12.3%) in 5 herds and 2 BVDV-1g subtype (3.0%) in 2 herds. Neither BVDV-1a subtype, nor BVDV-2 species or any atypical bovine pestivirus were found among isolates tested. Despite increasing import of live cattle in the recent years, genetic diversity of Polish BVDV isolates was rather low.

A novel phenotype for the dynein heavy chain mutation Loa: altered dendritic morphology, organelle density, and reduced numbers of trigeminal motoneurons.

Dynein, the retrograde motor protein, is essential for the transport of cargo along axons and proximal dendrites in neurons. The dynein heavy chain mutation Loa has been reported to cause degeneration of spinal motor neurons, as well as defects of spinal sensory proprioceptive neurons, but cranial nerve nuclei have received little attention. Here, we examined the number and morphology of neurons in cranial nerve nuclei of young, adult, and aged heterozygous Loa mice, with a focus on the trigeminal, facial, and trochlear motor nuclei, as well as the proprioceptive mesencephalic trigeminal nucleus. By using stereological counting techniques, we report a slowly progressive and significant reduction, to 75% of wild-type controls, in the number of large trigeminal motoneurons, whereas normal numbers were found for sensory mesencephalic trigeminal, facial, and trochlear motoneurons. The morphology of many surviving large trigeminal motoneurons was substantially altered, in particular the size and length of perpendicularly extending primary dendrites, but not those of facial or trochlear motoneurons. At the ultrastructural level, proximal dendrites of large trigeminal motoneurons, but not other neurons, were significantly depleted in organelle content such as polyribosomes and showed abnormal (vesiculated) mitochondria. These data indicate primary defects in trigeminal α-motoneurons more than γ-motoneurons. Our findings expand the Loa heterozygote phenotype in two important ways: we reveal dendritic in addition to axonal defects or abnormalities, and we identify the Loa mutation as a mouse model for mixed motor-sensory loss when the entire neuraxis is considered, rather than a model primarily for sensory loss.

Early cerebral blood volume after severe traumatic brain injury in patients with early cerebral ischemia.

Recent early cerebral blood flow (CBF) studies on severe head injury have revealed ischemia in a substantial number of patients with a variety of CT diagnoses. However, the underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathology. Therefore, acute CBF and CBV measurements were performed in 51 adult severely head injured patients within 24 hours after injury. For this purpose the stable Xenon-CT procedure was used for assessment of CBF, and a dynamic CT imaging technique was used for determining CBV. All ischemic patients were found among 35 subjects studied within 4 hours after injury (31%). Based on the occurrence of regional ischemia seven patients with varying anatomical lesions on CT were selected for comparison between CBF and CBV in ischemic and non-ischemic areas. Both CBF (p < 0.02) and CBV (p < 0.02) exhibited significantly lower values in the ischemic zones. Ten patients showing a subdural hematoma (SDH) were studied preceding surgery and seven were ischemic in at least one lobe or brainstem. Ipsilateral CBF was lower than CBF in the contralateral side (p < 0.1). CBV at the ipsilateral side was significantly reduced compared to the contralateral side (p < 0.05). Follow-up studies were performed in three ischemic patients and in one borderline ischemic patient immediately after removal of SDH showing a striking increase in both CBF and CBV. In the remaining 26 subjects follow-up studies were obtained between day 2 and day 8 and all patients showed CBF values within the normal range. These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels. This has implications for acute post-traumatic therapeutical strategies and management of the severely head injured patient and may lead to testing of new drugs that are effective in interfering with processes causing this ischemia.

Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia.

OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head injury have revealed ischemia in a substantial number of patients with a variety of computed tomographically demonstrated diagnoses. The underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathological abnormality. METHODS: For this purpose, stable xenon-enhanced computed tomography was used for assessment of CBF, and a dynamic computed tomographic imaging technique was used for determining CBV. Based on the occurrence of regional ischemia (CBF < 20 ml/100 g/min), seven patients with varying anatomic lesions revealed by computed tomography were identified for comparison between CBF and CBV in ischemic and nonischemic areas. RESULTS: Both CBF (15+/-4.3 versus 34+/-11 g/min, P < 0.002) and CBV (2.5+/-1.0 versus 4.9+/-1.9 ml/100 g) exhibited significantly lower values in the ischemic zones than in the nonischemic zones (means+/-standard deviations). Among 26 patients with or without ischemia observed during their initial follow-up studies, which were conducted between Days 2 and 8, all patients showed CBF and CBV values within the low-normal range. CONCLUSION: These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels.

Thresholds for cerebral ischemia after severe head injury: relationship with late CT findings and outcome.

Cerebral ischemic insults in at least 30% of severely head injured patients at a very early stage following trauma and are associated with early death. To date, the threshold for ischemia of 18 mL/100g/min used in human head injury studies has been adopted from animal studies (by temporary occlusion of the middle cerebral artery). Since the traumatized brain becomes more susceptible to irreversible damage if accompanied by ischemia one may question whether the threshold for ischemic vulnerability is higher than 18 mL/100 g/min. Cerebral ischemia can cause atrophy. Therefore, the authors obtained computerized tomography (CT) scans in 33 comatose head-injured patients (Glasgow Coma Score of 8 or less) at least 3 months following injury and compared ventricle sizes (as a reflection of atrophy) with cerebral blood flow (CBF) obtained within 4 h (average 2.3 +/- 0.8 h) after injury. Ventricular measurements were performed in three fashions: the third ventricular size (cm), the bicaudate cerebral ventricular index (BCVI), and the hemispheric ventricular index (HCVI). No significant correlation was found between early CBF and any of the ventricule sizes. Applying a multiple correlation analysis with four independent parameters [CBF, CBF/time postinjury, CBF/(time postinjury)2, age], only age emerged as a significant indicator for predicting ventricle size (p < 0.001). We also compared CBF data, obtained within 4 h after trauma, from survivors at 3 months after injury (mean CBF of 32 mL/100 g/min) with CBF data from non-survivors (CBF 20 mL/100 g/min). The difference in CBF between survivors and nonsurvivors was significant at p < 0.001 (Wilcoxon rank-sum test). The proportion of patients with CBF less than or equal to 20 mL/100 g/min was 56% in the nonsurvivors and only 5% in survivors. The difference in the proportions was significant at p < 0.001 (chi-square test). We conclude that a measure of atrophy does not correlate with ultra-early CBF. However, based on the clear distinction between survivors and nonsurvivors, we suggest the threshold for ischemia after head injury be redefined as a CBF of 20 mL/100 g/min.

Glutamate release and cerebral blood flow after severe human head injury.

Elevations of extracellular glutamate have been found in patients with prolonged brain ischemia and focal cerebral contusions, following severe head injury. About 30% of severely head injured patients develop cerebral ischemia, defined as CBF < 18 ml/100g/min. Patients with both global and regional cerebral ischemia have the worst outcome. However, the relationship between CBF and EAA release is not well understood in head injured humans, and may differ from the findings in normal animals. To study the relationship between EAA release and CBF after severe head injury, we performed cerebral blood flow measurements using stable xenon enhanced computed tomography and correlated these with glutamate release in the extracellular fluid, measured by continuous microdialysis, in 25 severely head injured patients. Sustained cerebral blood flow reductions below the threshold for ischemic neuronal damage was closely related to massive excitatory amino acid release, as in previous animal studies. In patients without secondary ischemia, or focal contusions, delayed post-traumatic glutamate release appeared to be only transient or did not occur at all.

Central cementoossifying fibroma of the maxillary sinus: a review of six cases.

We present the radiographic findings of six patients with central cementoossifying fibromas of the maxilla. CT typically demonstrated large, spherical tumors in the maxillary alveolar ridge, filling and expanding the maxillary sinus and extending to involve the ipsilateral hard palate. The central tumors ranged from having soft-tissue density with scattered foci of high density to being heavily calcified.

Epilepsy surgery: removing the thorn from the lion's paw.

In the United States, 10,000 to 20,000 patients have epilepsy uncontrolled by medication. The addition of a second-line drug to the primary regimen has a 2% to 11% chance of controlling the seizures. We present a series of 35 patients with intractable epilepsy who had surgical resection of their seizure focus. Seventy-five percent of the patients with temporal lobe epilepsy were made seizure free, with an additional 14% sustaining a greater than 90% reduction in seizures (decrease in number and frequency). Seventy-one percent of the patients with extratemporal lobe epilepsy (seizures originating outside the temporal lobe) had a worthwhile reduction (> 90%) in their seizures. Two patients sustained permanent clinically significant deficits as a result of their presurgical evaluation or resection. There were no deaths. Epilepsy surgery offers a cure for the "incurable" patient with a morbidity of 5% to 6%.

MR angiography artifact due to metal joint of ventriculoperitoneal shunt mimicking severe carotid stenosis.

An artifact due to the metal joint of a ventriculoperitoneal shunt resulted in a diagnosis of severe internal carotid artery stenosis at magnetic resonance angiography. Conventional x-ray angiography showed the presence of the metal joint and revealed that the artery was not stenotic.

Documented reversal of global ischemia immediately after removal of an acute subdural hematoma. Report of two cases.

The authors report two cases of severe head injury with acute subdural hematoma, in which cerebral blood flow (CBF) and cerebral blood volume (CBV) measurements were obtained prior to evacuation of the subdural hematoma and again immediately after removal. The first patient, a 21-year-old man with a motor response localizing to pain, had a global CBF of 18.2 ml/100 gm/min and a decreased global CBV of 3.7 ml/100 gm at 2.3 hours after injury. Immediately after removal of the subdural hematoma (8.1 hours after injury), CBF and CBV measurements revealed increases to 35.5 ml/100 gm/min and 5.8 ml/100 gm, respectively. The second patient, a 49-year-old woman with a normal flexor motor response to pain, had preoperative global values of 15.8 ml/100 gm/min for CBF and 2.0 ml/100 gm for CBV at 3 hours after injury. Postoperatively (9.3 hours after injury), the CBF and CBV values increased to 41.6 ml/100 gm/min and 4.0 ml/100 gm, respectively. The first patient, with only borderline ischemia and removal of the subdural hematoma within 3 hours, made a good recovery, while the second patient, with prolonged lower levels of CBF, remained in a persistent vegetative state. The low values of preoperative CBV argue for compression of the microcirculation as the cause of ischemia.

Imaging the sphenoid bone and basiocciput: anatomic considerations.

The sphenoid bone is a complex structure with an intricate embryologic origin. It is centrally located within the skull base and articulates with almost every structure in the skull and face. The sphenoid bone contains multiple foramina and fissures accommodating numerous vessels and nerves. This report reviews the embryology of the sphenoid bone and its normal postnatal changes, and describes the normal anatomy of the sphenoid bone and its numerous foramina and fissures. Computed tomography (CT) and magnetic resonance (MR) are used to illustrate developmental changes and normal anatomy.

Imaging the sphenoid bone and basiocciput: pathological considerations.

Many diverse pathologic processes can involve the sphenoid bone because of its complex embryologic origin. In addition to primary neoplasia, the central location of the sphenoid predisposes it to involvement by many intracranial and extracranial lesions. The presence of multiple foramina and fissures offer "paths of least resistance" that allow the spread of pathology across the skull base. Sphenoid sinus disease also accounts for a number of pathologic entities occurring in this vicinity. This article reviews the more common lesions affecting the sphenoid bone as well as their CT and MR appearance.

Characterization of non-lytic cytolysin-membrane intermediates.

In order to understand the nature of cytolysin-membrane interactions, the characteristics of stable, non-lytic cytolysin-target cell intermediates formed at low ionic strength, neutral pH, and at physiological ionic strength, pH 6.0, were examined. Protease treatment of cytolysin-RBC intermediates formed at low ionic strength inhibited subsequent hemolysis when the intermediates were exposed to physiological ionic strength and pH. Similarly, when such intermediates were treated with anti-granule and anti-cytolysin antibodies a significant dose-dependent inhibition of hemolysis was observed. These results suggested that in this non-lytic state the cytolysin molecule was exposed on the RBC surface. If low ionic strength or pH 6.0 generated intermediates were washed in 0.5 M NaCl, hemolytic activity was greatly reduced and cytolysin activity could be recovered from the medium. In addition to RBC, both murine (Yac-1 and Lettre ascites) and human (K562) tumor targets formed cytolysin-target cell intermediates at low ionic strength and at low pH. Multilamellar vesicles composed of either phosphatidylcholine, sphingomyelin or phosphatidylserine inhibited the binding of cytolysin to RBC at both low ionic strength and pH 6.0 indicating a lack of polar head group specificity for cytolysin binding.

Analysis of rat natural killer cytotoxic factor (NKCF): mechanism of action and relationship to other cytotoxic/cytostatic factors.

Natural killer cytotoxic factor (NKCF) has been proposed as one of the factors that mediates lysis induced by natural killer (NK) cells. Recently, an excellent source of NKCF has been found to be the rat large granular lymphocyte (LGL) tumor (RNK) cell line. In this study, the kinetics of lysis of the NK-sensitive, tumor target YAC-1 by the RNK-NKCF was analyzed and found to parallel that seen with NK cell-mediated killing. RNK-NKCF was also capable of killing the NK-resistant target cell, MBL-2, over a longer time period. This study utilized monoclonal antibodies (mAbs) prepared against granule protein, previously termed "anti-NKCF mAbs." These mAbs established the nature of RNK-NKCF as compared to other known cytotoxic factors in combination with studies that show that RNK-NKCF causes both 51Cr release and nuclear degradation. Antibody inhibition experiments have verified that RNK-NKCF is unique from tumor necrosis factor (TNF), leukoregulin, or complement. Anti-NKCF mAbs were capable, however, of neutralizing the RNK cell granule activity against YAC-1 tumor target cells. Based on these results, the ability of anti-NKCF mAbs to neutralize the cytolytic function of pore-forming protein (PFP), a component of these granules, was analyzed. In these experiments, the antibodies were found to inhibit the hemolytic activity of granules. Interestingly, the antibodies were effective in inhibiting the activity of unbound granule proteins as well as those bound to sheep red blood cell (SRBC) targets. Further studies to examine the target lysis requirements demonstrated that in contrast to PFP, the RNK-NKCF was able to lyse the tumor target in the absence of calcium. In addition, treatment of targets with RNA and protein synthesis inhibitors indicated that the mechanism of lysis of NKCF is quite unique from other defined cytotoxic moieties.