Pharmacological evaluation of a selective bradykinin B1 antagonist in a canine model of arthritis.

The effects of a selective bradykinin 1 receptor antagonist, compound A, were evaluated in a canine model of acute inflammatory model of arthritis. Despite detection of the B1 receptor in canine type B synoviocytes using a fluorescent ligand, oral administration of compound A (9 and 27 mg/kg) did not improve weight bearing of dogs injected intra-articularly with IL-1ß in a force plate analysis. Analysis of the synovial fluid of IL-1ß-treated dogs indicated high levels of bradykinin postchallenge. Excellent exposure, coupled with evidence of the presence of the B1 receptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.

Assessing coughing-induced influenza droplet transmission and implications for infection risk control.

Indoor transmission of respiratory droplets bearing influenza within humans poses high risks to respiratory function deterioration and death. Therefore, we aimed to develop a framework for quantifying the influenza infection risk based on the relationships between inhaled/exhaled respiratory droplets and airborne transmission dynamics in a ventilated airspace. An experiment was conducted to measure the size distribution of influenza-containing droplets produced by coughing for a better understanding of potential influenza spread. Here we integrated influenza population transmission dynamics, a human respiratory tract model, and a control measure approach to examine the indoor environment-virus-host interactions. A probabilistic risk model was implemented to assess size-specific infection risk for potentially transmissible influenza droplets indoors. Our results found that there was a 50% probability of the basic reproduction number (R0) exceeding 1 for small-size influenza droplets of 0·3-0·4 µm, implicating a potentially high indoor infection risk to humans. However, a combination of public health interventions with enhanced ventilation could substantially contain indoor influenza infection. Moreover, the present dynamic simulation and control measure assessment provide insights into why indoor transmissible influenza droplet-induced infection is occurring not only in upper lung regions but also in the lower respiratory tract, not normally considered at infection risk.

Assessing dengue infection risk in the southern region of Taiwan: implications for control.

Dengue, one of the most important mosquito-borne diseases, is a major international public health concern. This study aimed to assess potential dengue infection risk from Aedes aegypti in Kaohsiung and the implications for vector control. Here we investigated the impact of dengue transmission on human infection risk using a well-established dengue-mosquito-human transmission dynamics model. A basic reproduction number (R 0)-based probabilistic risk model was also developed to estimate dengue infection risk. Our findings confirm that the effect of biting rate plays a crucial role in shaping R 0 estimates. We demonstrated that there was 50% risk probability for increased dengue incidence rates exceeding 0.5-0.8 wk-1 for temperatures ranging from 26°C to 32°C. We further demonstrated that the weekly increased dengue incidence rate can be decreased to zero if vector control efficiencies reach 30-80% at temperatures of 19-32°C. We conclude that our analysis on dengue infection risk and control implications in Kaohsiung provide crucial information for policy-making on disease control.

Using experimental human influenza infections to validate a viral dynamic model and the implications for prediction.

The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 10(3)-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection.

Understanding influenza virus-specific epidemiological properties by analysis of experimental human infections.

This study aimed to estimate the natural history and transmission parameters based on experimental viral shedding and symptom dynamics in order to understand the key epidemiological factors that characterize influenza (sub)type epidemics. A simple statistical algorithm was developed by combining a well-defined mathematical scheme of epidemiological determinants and experimental human influenza infection. Here we showed that (i) the observed viral shedding dynamics mapped successfully the estimated time-profile of infectiousness and (ii) the profile of asymptomatic probability was obtained based on observed temporal variation of symptom scores. Our derived estimates permitted evaluation of relationships between various model-derived and data-based estimations, allowing evaluation of trends proposed previously but not tested fully. As well as providing insights into the dynamics of viral shedding and symptom scores, a more profound understanding of influenza epidemiological parameters and determinants could enhance the viral kinetic studies of influenza during infection in the respiratory tracts of experimentally infected individuals.

Viral kinetics and exhaled droplet size affect indoor transmission dynamics of influenza infection.

The purpose of this paper was to investigate the effects of viral kinetics and exhaled droplet size on indoor transmission dynamics of influenza infection. The target cell-limited model with delayed virus production was adopted to strengthen the inner mechanisms of virus infection on human epithelial cell. The particle number and volume involved in the viral kinetics were linked with Wells-Riley mathematical equation to quantify the infection risk. We investigated population dynamics in a specific elementary school by using the seasonal susceptible - exposed - infected - recovery (SEIR) model. We found that exhaled pulmonary bioaerosol of sneeze (particle diameter <10 microm) have 10(2)-fold estimate higher than that of cough. Sneeze and cough caused risk probabilities range from 0.075 to 0.30 and 0.076, respectively; whereas basic reproduction numbers (R(0)) estimates range from 4 to 17 for sneeze and nearly 4 for cough, indicating sneeze-posed higher infection risk. The viral kinetics and exhaled droplet size for sneeze affect indoor transmission dynamics of influenza infection since date post-infection 1-7. This study provides direct mechanistic support that indoor influenza virus transmission can be characterized by viral kinetics in human upper respiratory tracts that are modulated by exhaled droplet size. Practical Implications This paper provides a predictive model that can integrate the influenza viral kinetics (target cell-limited model), indoor aerosol transmission potential (Wells-Riley mathematical equation), and population dynamic model [susceptible - exposed - infected - recovery (SEIR) model] in a proposed susceptible population. Viral kinetics expresses the competed results of human immunity ability with influenza virus generation. By linking the viral kinetics and different exposure parameters and environmental factors in a proposed school setting with five age groups, the influenza infection risk can be estimated. On the other hand, we implicated a new simple means of inhaling to mitigate exhaled bioaerosols through an inhaled non-toxic aerosol. The proposed predictive model may serve as a tool for further investigation of specific control measure such as the personal protection masks to alter the particle size and number concentration characteristics and minimize the exhaled bioaerosol droplet to decrease the infection risk in indoor environment settings.

Characteristics of aerosols collected in central Taiwan during an Asian dust event in spring 2000.

Aerosol samples for PM(2.5) and PM(2.5-10) were collected at four locations in central Taiwan from 26 to 31 March 2000, a period that experienced exceedingly high PM levels from 29 to 30 March due to the passage of an Asian dust storm. The samples were analyzed for mass, metallic elements, ions, and carbon. The purpose of this paper is to investigate the influence of the dust storm on the characteristics of local ambient particulate matter. The results indicate that the concentrations of the crustal elements Ca, Mg, Al, Fe and the sea salt species Na+ and Cl- in PM(2.5-10) during the dust episode exceed the mean concentrations in the non-dust period by factors of 3.1, 2.9, 2.6, 2.2, 2.3 and 2.1 respectively. Enrichment factors of Ca, Fe, and Mg in PM(2.5-10) during the dust event are close to unity, indicating that these elements are from soil. Reconstruction of aerosol compositions revealed that soil of coarse particulates elevated approximately 50% in the dust event. It is noted that during the dust event, the ratio of Mg/Al in PM(2.5-10) ranged from 0.21 to 0.25 while that of Ca/Al ranged from 0.6 to 0.9, levels more constant than those obtained in non-dust period.

Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors.

Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propylamino-benzthiazole-dihydrochlor ide) is a potent dopamine autoreceptor agonist. We have carried out an analysis of the binding affinities of dopamine D2L, D2S, D3, and D4 receptors for pramipexole using both [3H]pramipexole and [3H]spiperone as radioligands at cloned and heterologously expressed receptors. Studies were carried out using rat and human D2L, D2S and D3 receptors with equivalent results. When the binding of pramipexole to the high affinity, guanine nucleotide-sensitive state of each receptor was analyzed, pramipexole is most selective for D3 compared to D2 and D4 receptors. These results indicate a 5-fold selectivity of pramipexole for D3 receptors, while quinpirole and bromocriptine are non-selective or more D2/D4 receptor selective. Two measurements of receptor activation for dopamine D2, D3, and D4 receptors also show that pramipexole is most potent for activation of D3 receptors. The dopamine D3 receptor selectivity of pramipexole may explain the previously described properties of this drug, including its potent autoreceptor preference.

Hypervolemic hemodilution may protect the rat's striatal neurons from ischemic injury by reducing the extracellular dopamine.

In vivo voltammetry (IVV) was used in rats with transient brain ischemia to measure changes in extracellular concentrations of dopamine (DA) and its metabolites in the corpus striatum. Striatal neuronal damage were also rated on a scale of 0-3 (0 = no damage; 3 = maximum cell loss). The striatal extracellular levels of DA and its metabolites increased by 12-fold during the 30 min of brain ischemia and returned to control values at 30 min after reperfusion. In another group treated with 4-5 ml of 10% human albumin intravenously infused 30 min before brain ischemia, both augmented striatal DA (and its metabolites) levels and striatal neuronal damages were reduced as compared to the ischemic control group (P < 0.05, unpaired Student's t-test). These results suggest that hypervolemic hemodilution protects the striatal neurons from ischemic injury by reducing the extracellular striatal DA release in rats.

Complications in patients with palmar hyperhidrosis treated with transthoracic endoscopic sympathectomy.

OBJECTIVE: To assess the complications in a group of patients with palmar hyperhidrosis treated with transthoracic endoscopic sympathectomy. The extraordinarily high incidence of postoperative compensatory hyperhidrosis in our series is stressed and explained. METHODS: The retrospective study included chart reviews and outpatient assessments. Seventy-two patients underwent T2 or T2-T3 endoscopic sympathectomy for primary palmar hyperhidrosis. Patients' hyperhidrosis severity, precipitating factors, postoperative complications, surgical results, and satisfaction were assessed. Severity of palmar hyperhidrosis and compensatory hyperhidrosis was classified by two grading scales. RESULTS: The success rate of sympathectomy was 93%. All patients except one suffered from compensatory sweating, which was the main cause of patients' dissatisfaction postoperatively. Seventeen percent of the patients (12 of 72 patients) experienced new symptoms of gustatory sweating (facial sweating associated with eating). Twenty-one patients experienced other complications, including pneumothorax, Horner's syndrome, nasal obstruction, and intercostal neuralgia. CONCLUSION: Transthoracic endoscopic sympathectomy is an effective and simple modality to treat palmar hyperhidrosis. However, all patients need to be warned of the common complications, particularly compensatory hyperhidrosis, before surgery.

Selective blood-tumor barrier disruption by leukotrienes.

The authors have previously reported that intracarotid infusion of 5 micrograms leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 microgram to 50.0 micrograms (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 micrograms compared to vehicle alone (90.00 +/- 21.14, 92.68 +/- 15.04, and 80.17 +/- 16.15 vs. 39.37 +/- 6.45 microliters/gm/min, respectively; mean +/- standard deviation; p less than 0.01). No significant change in Ki within the tumors was observed at the 0.5-microgram LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 +/- 15.04 microliters/gm/min), but declined at 30 minutes (56.58 +/- 12.50 microliters/gm/min) and 60 minutes (55.40 +/- 8.10 microliters/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 3 1/2-fold compared with vehicle alone (139.86 +/- 23.95 vs. 39.37 +/- 6.45 microliters/gm/min).

The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors.

To determine if leukotrienes are important mediators of vascular permeability in brain tumors, the effect of 5-lipoxygenase inhibitors on blood-tumor barrier permeability in rats harboring HK Walker 256 brain tumors was examined using quantitative autoradiography with alpha-14C-aminoisobutyric acid. The 5-lipoxygenase enzyme converts arachidonic acid to leukotrienes. Three 5-lipoxygenase inhibitors were utilized: BW755C, nordihydroguaiaretic acid, and AA-861. All three 5-lipoxygenase inhibitors significantly decreased vascular permeability both within the tumors and in brain adjacent to tumor. This suggests that capillary permeability in and adjacent to tumors is influenced by endogenous leukotrienes and that leukotrienes play an important role in brain tumor edema.

Increased opening of blood-tumour barrier by leukotriene C4 is dependent on size of molecules.

Intracarotid injections of leukotriene C4 (LTC4) will increase blood-tumour barrier (BTB) permeability for 14C aminoisobutyric acid (AIB) in RG-2 tumours in rats. In this study, rats with RG-2 tumours were given 15 minute intracarotid infusions of LTC4 (5 micrograms total dose). Blood-tumour and BBB permeability were determined by quantitative autoradiography using different sized 14C tracers; AIB (103.1 daltons, radius = 2.8 A), Sucrose (342 daltons, radius = 5 A), Inulin (5000 daltons, radius = 15 A) and Dextran (70,000 daltons, radius = 60 A), respectively (n = 7 in each group). Permeability (Ki) within tumours for AIB, Sucrose and Inulin increased significantly after LTC4 infusion (92.7 +/- 15.0 vs 39.4 +/- 6.5, 47.8 +/- 5.2 vs 29.1 +/- 8.8, and 46.4 +/- 8.4 vs 26.4 +/- 4.8 microliters/gm/min, respectively, p < 0.01) (mean +/- SD). No significant change in Ki for 14C Dextran was observed. Increased permeability within tumours after LTC4 infusion is dependent on molecular size. This suggests that LTC4 opens tight junctions rather than increases vesicular transport through endothelial cells.

Risk factor of complications requiring neurosurgical intervention in infants with bacterial meningitis.

Among 50 consecutive cases of bacterial meningitis in infants aged 6 months or less, 9 (Group I) were confirmed to have complications requiring neurosurgery during the first 2 weeks of antibiotic treatment. Neurosurgery was performed in 40, 33, and 30% of cases caused by Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, respectively. There were 5 cases of subdural empyema, 1 case of brain abscess, 1 case of subdural empyema and brain abscess, and 2 cases of ventriculitis with severe hydrocephalus. All complications requiring neurosurgery were initially detected by cranial ultrasonography. The other 41 patients who did not undergo neurosurgery were classified as Group II. Comparison of clinical presentations and laboratory findings between the two groups showed that Group 1 contained more patients with a history of inadequate treatment, and longer duration of illness before diagnosis. Except for prolonged disturbance of consciousness, there was no difference between the two groups in clinical and laboratory data on admission or in clinical course during therapy. Due to the high incidence of complications requiring neurosurgical treatment, cost-effective cranial ultrasound is recommended for screening every young infant with bacterial meningitis, especially in cases caused by S. pneumoniae.

Primary cerebral anaplastic large cell lymphoma containing abundant reactive histiocytes and eosinophils. A case report and literature review.

Primary cerebral anaplastic large cell lymphoma (ALCL) is very rare. We report on our experience with such a case and review the literature. A 46-year-old Taiwanese woman presented with headache, weakness of her right extremity, and limited eye movement. A solid mass (5 cm x 4 cm) at the left occipital lobe was almost completely removed. The neoplastic cells, some of which had reniform or embryo-like nuclei, were large and were admixed with abundant eosinophils, histiocytes, and some small lymphocytes. These neoplastic cells expressed CD30, CD43, granzyme B and T-cell intracellular antigen-1, but not ALK1, CD3, CD20, CD45, CD79a, cytokeratin, and EMA. They were positive for Epstein-Barr virus-encoded mRNA by in situ hybridization. Polymerase chain reaction study of formalin-fixed tissue showed a clonal gene arrangement of the T-cell receptor-gamma chain. ALCL of T-cell lineage with cytotoxic phenotype was diagnosed. The patient received cranial irradiation and has remained with no evidence of disease for 25 months of follow-up.

Aggressive temporal lobectomy for uncal herniation in traumatic subdural hematoma.

Over a period of 28 months, 29 patients who sustained uncal herniation originating from fronto-temporal acute subdural hematoma with major contusion and swelling of the temporal lobe were treated surgically. These 29 patients were divided into two groups according to whether or not they underwent aggressive temporal resection in two study periods. During the initial 16 months, from February 1991 to June 1992, 16 of the 29 (group A) underwent classic surgery (subtemporal decompression for evacuation of the hematoma and debridement of the contused brain). In the 12 months from July 1992 to June 1993, the remaining 13 patients (group B) underwent an aggressive temporal lobectomy in addition to the afore-mentioned procedures, including 10 complete temporal lobectomies and three anterior temporal lobectomies. In group A, there were nine operative deaths, with a mortality of 56%, and the mean Glasgow Outcome Scale (GOS) score was 2.2 +/- 0.4 (mean +/- SEM) after 24 to 36 months of follow-up. In group B, one patient died after operation, and the mean GOS score was 4.0 +/- 0.4 in a follow-up period of 12 to 24 months. Compared with group A, group B showed a better survival rate and more favorable functional outcome. Favorable recovery in group B was noted only after a complete temporal lobectomy (good in seven and moderate disability in three). The three patients who underwent an anterior temporal lobectomy had unfavorable recoveries (two vegetative states and one death).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytogenetic study of twenty-two intracranial tumors.

G-banded chromosomal analysis was performed on primary cultures of 22 intracranial tumors, including eight astrocytomas, nine meningiomas, two dermoid cysts, one acoustic neuroma, one pineal teratoma and one eosinophilic granuloma. One or more chromosomally abnormal clones were observed in 6 (75%) gliomas and 5 (56%) meningiomas. There was no chromosomal abnormality found in one of the dermoid cysts, the acoustic neuroma or the eosinophilic granuloma. A teratoma and a grade IV glioma had heterogeneous hyperdiploid karyotypes. Furthermore, astrocytomas displayed nonrandom loss of chromosomes #19, #21, #22 and Y. In meningiomas, characteristic changes involving chromosome 22 were found in 5 tumors. One meningioma had a ring chromosome in addition to chromosomal loss. With our culture and harvesting techniques, cytogenetic studies can be successfully performed on nearly all intracranial tumor explants, including those derived from small biopsy specimens. Also, in our study, specific nonrandom chromosomal anomalies were found.

Prognostic significance of altered cerebral blood flow velocity in acute head trauma.

From July 1992 to January 1993, 31 patients with acute closed head injuries underwent blood flow velocity (BFV) measurement in the middle cerebral artery by transcranial Doppler ultrasound. Eighteen patients had abnormal changes of BFV (group A) and 13 patients had normal BFV (group B). In group A, there were eight deaths (44%) and the Glasgow Outcome Scale score was 2.6 +/- 0.4 (mean +/- SEM). On admission, 14 group A patients had decreased BFV, including nine patients with evidence of early cerebral circulatory arrest (CCA). During hospitalization, eight group. A patients were diagnosed with global hyperemia, including two patients who had early CCA. Another six in group A had ultrasound recordings consistent with vasospasm, and three of these six also experienced early CCA. The renaming four patients in group A had persistently low BFV, progressing from early CCA. In group B there were two deaths (15%) and the mean Glasgow Outcome Scale score was 4.0 +/- 0.5. Group A had higher mortality (Fisher's exact test, p = 0.128) and a significantly higher rate of unfavorable functional outcome than group B. To evaluate the prognostic significance of these BFV changes, group A was subdivided into global hyperemia, vasopasm and early CCA subgroups. Both the vasospasm and early CCA subgroups had significantly lower Glasgow Coma Scale scores on admission and a higher rate of unfavorable functional outcomes than group B. All five survivors with vasospasm and/or early CCA showed ischemic morbidity on follow-up cranial computed tomography; though those with global hyperemia did not. There were no significant differences in the Glasgow Coma Scale score on admission, mortality or functional outcome between global hyperemia patients and group B patients. Global hyperemia may represent a recovery stage of impaired cerebral hemodynamics. This stage may occur transiently and has no major impact on morbidity or mortality. Vasospasm and early CCA may be closely related to ischemic complications, and may provide clinical information for selecting appropriate therapy in acute head trauma.

[Telethermography of the soles of the feet. Theory in relation to muscle tension of the back]. / Teletermografia delle piante dei piedi. Ipotesi in relazione alle tensioni muscolari del dorso.

The Authors take into consideration the telethermography of the soles of the feet in fifty-four patients suffering from troubles of the rachis and document the thermic asymmetries of the foot at rest: a static and dynamic load. We can find the above mentioned asymmetries also in patients with normal feet and traditional and normal podographies. If we assume a reflex arch parting from the propioceptors of the muscles of the plantar arch, we can make a type of sole that applied to the patients, normalize the muscular tensions of the back. We illustrate two cases treated with different methods but that have given good results both subjectively and objectively.

[Acupuncture in breast diseases. How, when and why]. / L'agopuntura nelle malattie della mammella. Come, quando e perché.

We can value the therapeutic result reached by acupuncture in 43 female patients suffering from mastodinies, compared with other similar groups treated with antinflammatories and polyvitaminics. Before and after treatment every patient went through a complete--clinical--instrumental examination in which we also valued with telethermography the condition of mastosic vascular congestion. Positive considerations are made about the therapeutic validity of acupunture that has reached the highest percentage of success (over 95%) in comparison with other traditional methods, and patients really appreciated that. We nevertheless emphasize the need of always associating a correct, objective and instrumental study before starting any mastalgies therapy, to exclude coexistence of a sort of productive or surgical pathology.