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Brain stem excitatory and inhibitory signaling pathways regulating bronchoconstrictive responses.

This review summarizes recent work on two basic processes of central nervous system (CNS) control of cholinergic outflow to the airways: 1) transmission of bronchoconstrictive signals from the airways to the airway-related vagal preganglionic neurons (AVPNs) and 2) regulation of AVPN responses to excitatory inputs by central GABAergic inhibitory pathways. In addition, the autocrine-paracrine modulation of AVPNs is briefly discussed. CNS influences on the tracheobronchopulmonary system are transmitted via AVPNs, whose discharge depends on the balance between excitatory and inhibitory impulses that they receive. Alterations in this equilibrium may lead to dramatic functional changes. Recent findings indicate that excitatory signals arising from bronchopulmonary afferents and/or the peripheral chemosensory system activate second-order neurons within the nucleus of the solitary tract (NTS), via a glutamate-AMPA signaling pathway. These neurons, using the same neurotransmitter-receptor unit, transmit information to the AVPNs, which in turn convey the central command to airway effector organs: smooth muscle, submucosal secretory glands, and the vasculature, through intramural ganglionic neurons. The strength and duration of reflex-induced bronchoconstriction is modulated by GABAergic-inhibitory inputs and autocrine-paracrine controlling mechanisms. Downregulation of GABAergic inhibitory influences may result in a shift from inhibitory to excitatory drive that may lead to increased excitability of AVPNs, heightened airway responsiveness, and sustained narrowing of the airways. Hence a better understanding of these normal and altered central neural circuits and mechanisms could potentially improve the design of therapeutic interventions and the treatment of airway obstructive diseases.

Animals↗

Aspergillus spinal epidural abscess.

Spinal abscess due to Aspergillus is rare. A young boy with chronic granulomatous disease and aspergillosis of the rib had been treated with antifungal treatment 3 months earlier. The patient presented with a brief history of progressive paraparesis. Imaging showed D9--11 vertebral involvement and destruction of the D10 vertebral body with angulation and a large dorsally placed, multiloculated epidural abscess extending from D6 to L2. There was also extensive granulation anterior to and on either side of the vertebrae. The patient underwent extensive laminectomy and decompression of all the loculi and partial removal of the granulation tissue. Aggressive medical treatment was started. The authors recommend an aggressive surgical and medical approach in such cases of disseminated invasive aspergillosis, even though the result may not be very satisfactory. This report discusses the full clinical profile and management of Aspergillus spinal epidural abscess and emphasizes the need to follow up these cases to detect recurrence and new lesions, even if the patients are on adequate medical treatment. In spite of all efforts, high morbidity and mortality is common in such patients.

Antifungal Agents↗

Efficacy of fluoride toothpaste in preventing demineralization of smooth dentin surfaces and narrow grooves in situ under frequent exposures to sucrose or bananas.

The use of models simulating fissures allows studying demineralization at sites that are most prone to caries in vivo. In practice, most in situ models use flat surfaces. Our objectives were: (1) to compare the demineralizing potential of sucrose solution with that of bananas and (2) to study the effect of fluoride toothpaste on demineralization in situ in an easily accessible site and a plaque stagnation site. Four volunteers wore bovine dentin specimens with narrow grooves and a smooth surface for two 1-week in situ periods, with eight 1-min sugar exposures daily: either by a rinse with 10% sucrose, or by consumption of a piece of banana. Twice daily, the appliance was dipped in toothpaste slurry of a control (fluoride-free) toothpaste at one side and a fluoride toothpaste at the contralateral side. Demineralization was assessed by transversal microradiography. We found no difference in dentin demineralization after frequent exposure to either sucrose solution or bananas. Fluoride toothpaste effectively protected dentin only at the smooth surface. In the grooves, fluoride affected the demineralization pattern; it drove lesions towards the bottom of the groove. We conclude that assessing only smooth surfaces in intraoral tests might lead to underestimated food cariogenicity and to overestimated efficacy of fluoride-containing toothpaste.

Adult↗

Characterisation of pararetrovirus-like sequences in the genome of potato (Solanum tuberosum).

Three families of pararetrovirus-like sequences were isolated from the genome of potato using PCR of a characteristic fragment extending from the end of the transactivator domain. The potato pararetrovirus-like sequences are abundant in the nuclear genome of potato as demonstrated by their hybridisation to high-molecular weight DNA in Southern transfers and by fluorescence in situ hybridisation. Sequencing of cloned PCR products demonstrated that the potato pararetrovirus-like sequences were similar to other pararetroviral sequences and also to some expressed sequences from tobacco and tomato, notably from callus and Agrobacterium-infected tissue. It is possible that the potato pararetroviral sequences defend against viral genes via silencing mechanisms, although, as in Petunia or banana, their transcription and recombination may cause infection under stress conditions.

Base Sequence↗

Adult granulosa cell tumour of the testis and bony metastasis. A report of the first case of granulosa cell tumour of the testicle metastasising to bone.

Granulosa cell tumour is among the rarest forms of testicular cancer. Only 21 cases have been reported to date and only 4 have metastasised. All documented metastases are intra-abdominal. We present the first case of granulosa cell tumour of the testis metastasising to bone (tibia), presenting 6 years after orchidectomy. This highlights the need to maintain a high index of suspicion for extra-abdominal metastases during long-term follow-up in patients with previous testicular granulosa cell tumour.

Biopsy↗

Association between neopterin and carotid intima-media thickness in hemodialysis patients.

BACKGROUND: Atherosclerotic lesions are heavily infiltrated by macrophages. Neopterin can be used as a marker of the activity of macrophages. Serum neopterin levels were elevated in non-renal patients with atherosclerosis. The intima-media thickness (IMT) of the carotid arteries in hemodialysis patients was significantly higher than in control subjects. In this study, we measured serum neopterin levels in hemodialysis patients and evaluated a possible correlation between neopterin levels and carotid IMT. PATIENTS AND METHODS: Thirty-seven hemodialysis patients (26 male/11 female, mean age 47 +/- 15 years) and 12 healthy subjects (8 male/4 female, mean age 43 +/- 10 years) were included in this study. Serum neopterin levels were measured by using a commercial ELISA kit. Carotid IMT of the subjects were measured by high-resolution B-mode ultrasonography. RESULTS: Carotid IMT values were 1.04 +/- 0.29 and 0.77 +/- 0.25 mm in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 110.9 +/- 19.1 and 3.8 +/- 2.3 ng/ml in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 103.2 +/- 21.3 ng/ml in hemodialysis patients with IMT < 1 mm (n = 15), and 116.7 +/- 15.4 ng/ml in hemodialysis patients with IMT > or = 1 mm (n = 22) (p < 0.05). Moreover, there was a significant correlation between serum neopterin levels and carotid IMT (p < 0.05, r = 0.363). CONCLUSION: Our findings suggest that neopterin could be associated with the severity of carotid atherosclerosis in hemodialysis patients.

Adult↗

Utility of fiberoptic bronchoscopy for retrieval of aspirated headscarf pins.

BACKGROUND: Headscarf pin aspiration is a common and unique form of foreign body aspiration among young Moslem women. Rigid bronchoscopy (RB) is considered the standard procedure for retrieval. There are little data on the role of flexible fiberoptic bronchoscopy (FOB) in the retrieval of aspirated headscarf pins. OBJECTIVES: The aim of this study is to prospectively evaluate the utility of FOB for the retrieval of aspirated headscarf pins. METHODS: Patients with the diagnosis of headscarf pin aspiration admitted to King Abdullah University Hospital from December 2002 to December 2005 were included in the study. Standard FOB procedure under local anesthesia and conscious sedation was performed as the primary tool for retrieval. RESULTS: A total of 16 cases was admitted during the study period. The mean age was 19 years. The aspirated pin was successfully retrieved in 9/16 cases (56%) during the first attempt of FOB. In another 3 cases, although the pin was successfully retrieved from the bronchial tree, it was lost in the throat and swallowed, and then recovered by esophagogastroduodenoscopy. However, FOB was not successful in 4/16 cases. In 3 cases, the aspirated pins were successfully retrieved by RB under general anesthesia and the fourth case required thoracotomy. CONCLUSIONS: Headscarf pin aspiration is a relatively common form of foreign body aspiration among young Moslem Jordanian women. FOB under local anesthesia can be a useful first-step tool in retrieval, provided facilities for esophagogastroduodenoscopy and RB are readily available.

Adolescent↗

Morular metaplasia of the endometrium in a patient with polycystic ovary syndrome.

A 31-year-old women with polycystic ovary syndrome underwent dilatation and curettage (D&C) as part of her infertility workup. Pathologic examination revealed endometrial morular metaplasia without malignant potential. Follow-up D&C had no evidence of endometrial hyperplasia or carcinoma. The diagnostic difficulties and pathogenesis are discussed.

Adenocarcinoma↗

Pregnancy following transvaginal sonographic guided aspiration of endometrioma.

A 30-year-old infertile women with stage IV endometriosis was treated initially with endoscopic surgery, danazol and intrauterine insemination to no avail. Before starting ovulation induction for in vitro fertilization, transvaginal sonographic guided aspiration of endometrioma was performed. One month after the procedure the patient became pregnant and delivered a normal child at term.

Adult↗

Ultrasonographic measurement of fetal lung.

Fetal lung measurements were obtained by ultrasonographic examination on 103 normal pregnancies between 18 and 41 weeks' gestation. A linear relationship between right, left and total lung circumference and gestational age was observed. The chest and heart circumference correlated well with gestational age (p less than 0.001). The ratio of left lung circumference to right lung circumference remained virtually constant throughout gestation. However, the ratios of total lung circumference to chest circumference and heart circumference to chest circumference increased significantly (p less than 0.001) with gestational age.

Embryonic and Fetal Development↗

Serum CA-125 and 17 beta-estradiol in patients with external endometriosis on danazol.

Serum concentration of CA-125 and 17 beta-estradiol (E2) were measured by radioimmunoassay in 40 patients with stage III or IV endometriosis to evaluate their usefulness in assessing the outcome of disease. Patients were categorized into good responders and poor responders depending on the result of the second-look laparoscopy 8 weeks after danazol therapy. CA-125 decreased significantly in all subjects after initiation of treatment. However, after 12 weeks of treatment a significant increase (p less than 0.05) in serum CA-125 was noted in the poor-response subjects as compared to the good-response subjects. In addition, 8 weeks after treatment CA-125 levels in the poor-response group were significantly higher (p less than 0.001) than in the good-response group. On the other hand, in the good-response group, E2 levels decreased for 8 weeks during danazol therapy to return to almost basal levels after 12 weeks, while in the poor-response group E2 levels did not change as compared to pretreatment levels. We conclude that the determination of CA-125 and E2 may be helpful in assessing the response of patients with advanced endometriosis on danazol treatment.

Antigens, Tumor-Associated, Carbohydrate↗

Effect of serum from patients with endometriosis on the development of mouse embryos.

The effect of serum from patients with endometriosis on the in vitro development of 2-cell mouse embryos was evaluated in the present study. Embryos were cultured for 72 h in 5% serum supplement from patients with endometriosis, infertile patients with no evidence of endometriosis, and Ham's F-10 medium with no serum supplement. Significantly less embryos developed to the blastocyst stage at 72 h in the endometriosis group as compared with the nonendometriosis groups and Ham's F-10 medium (p less than 0.05). These results suggest the presence of one or more serum factors that are toxic to early embryonic development and thus may play a role in the infertility associated with endometriosis, especially with respect to early embryonic loss.

Animals↗

Intraoperative cytologic crush preparation findings in craniopharyngioma: a study of 72 cases.

OBJECTIVE: To describe the intraoperative crush preparation and the cytologic features of craniopharyngioma and the differential diagnosis. STUDY DESIGN: Twelve cases of craniopharyngioma were diagnosed by crush preparation cytology in the Department of Pathology, Shiraz Medical School, and formed the basis of this study. The patients' ages ranged from 7 to 43 years; 3 were female and 9 male. The cytologic findings together with the histologic findings were studied. RESULTS: All cases had a high yield of cells, consisting of honeycomb sheets of epithelial cells with and without palisading rows of cells, papillary clusters, squamous cell clusters, anucleated squames, calcification, multinucleated giant cells, cholesterol crystals, glandular or rosettelike structures, ciliated columnar cells and spindle cells. The smears were diagnosed as suggestive of craniopharyngioma. Histologic sections confirmed the cytologic diagnoses. CONCLUSION: Intraoperative cytologic crush preparation findings are helpful in the diagnosis of craniopharyngioma, when combined with clinical information. Crush preparation cytology is important in the diagnosis of central nervous system tumors.

Adolescent↗

Functional characterization of connexin43 mutations found in patients with oculodentodigital dysplasia.

Specific mutations in GJA1, the gene encoding the gap junction protein connexin43 (Cx43), cause an autosomal dominant disorder called oculodentodigital dysplasia (ODDD). Here, we characterize the effects of 8 of these mutations on Cx43 function. Immunochemical studies have shown that most of the mutant proteins formed gap junction plaques at the sites of cell-cell apposition. However, 2 of the mutations (a codon duplication in the first extracellular loop, F52dup, and a missense mutation in the second extracellular loop, R202H, produced full-length connexins that failed to properly form gap junction plaques. Cx43 proteins containing ODDD mutations found in the N-terminus (Y17S), first transmembrane domain (G21R, A40V), second transmembrane domain (L90V), and cytoplasmic loop (I130T, K134E) do form gap junction plaques but show compromised channel function. L90V, I130T, and K134E demonstrated a significant decrease in junctional conductance relative to Cx43WT. Mutations Y17S, G21R, and A40V demonstrated a complete lack of functional electrical coupling even in the presence of significant plaque formation between paired cells. Heterologous channels formed by coexpression of Cx43WT and mutation R202H resulted in electrically functional gap junctions that were not permeable to Lucifer yellow. Therefore, the mutations found in ODDD not only cause phenotypic variability, but also result in various functional consequences. Overall, our data show an extensive range of molecular phenotypes, consistent with the pleiotropic nature of the clinical syndrome as a whole.

Abnormalities, Multiple↗

Comparative overview of brain perfusion imaging techniques.

BACKGROUND AND PURPOSE: Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. SUMMARY OF REVIEW: This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview established by consensus among specialists of the various techniques. CONCLUSIONS: For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting.

Aged↗

Pulmonary function and exercise-associated changes with chronic low-level paraquat exposure.

The present study was undertaken to test the hypothesis that chronic, low-level paraquat exposure causes restrictive lung function with gas transfer impairment. Three hundred thirty-eight Costa Rican farm workers from banana, coffee, and palm oil farms completed a questionnaire, spirometry, and a test of single-breath carbon monoxide diffusing capacity. Subjects 40 years of age or older, without other medical risk factors, completed maximal cardiopulmonary exercise tests. Most (66.6%) were paraquat handlers; 24.8% of handlers and 27.3% of nonhandlers reported current cigarette smoking. In linear regression models, cumulative paraquat exposure was not an independent predictor of VA, carbon monoxide diffusing capacity, peak oxygen uptake, FVC, or oxygen pulse peak. However, the ventilatory equivalent for CO(2), although within normal range, was significantly higher with increased cumulative paraquat exposure. Oxygen desaturation greater than 5% from rest to peak exercise had an odds ratio of 1.7 (95% confidence interval = 0.9-3.0) with the cumulative paraquat exposure index in models adjusted for age, weight, and smoking status. The association of paraquat exposure with ventilatory equivalent and oxygen desaturation suggests that paraquat may be associated with subclinical gas exchange abnormalities, but overall these findings are consistent with no clinically significant increases in interstitial thickening or restrictive lung disease among this population.

Adolescent↗

Catalytic activation of extracellular signal-regulated kinases induces cyclin D1 expression in primary tracheal myocytes.

We have demonstrated that extracellular signal-regulated kinases (ERKs) and cyclin D1 are required for bovine tracheal myocyte DNA synthesis. We hypothesized that catalytic activation by ERKs may regulate cyclin D1 expression in these cells. To test this hypothesis, we examined the effects of two inhibitors of ERKs and two reagents that increase the level of activated ERKs on cyclin D1 protein abundance and promoter activity. ERK activity was inhibited either by PD98059, a synthetic inhibitor of mitogen-activated protein kinase (MAPK)/ERK kinase (MEK), the upstream signaling intermediate required and sufficient for ERK activation, or by transient transfection with a dominant-negative mutant of MEK1 (MEK-2A). The level of activated ERKs was increased by transient transfection with either a constitutively active form of MEK1 (MEK-2E) or wild-type ERK2 (MAPKwt). Cyclin D1 expression was assessed either by immunoblot or cotransfection with the full-length cyclin D1 promoter subcloned into a luciferase reporter. We found that pretreatment of bovine tracheal myocytes with PD98059 significantly attenuated platelet- derived growth factor (PDGF)-induced cyclin D1 protein abundance. Furthermore, transfection with MEK-2A reduced PDGF-induced cyclin D1 promoter activity. Finally, transfection with either MEK-2E or MAPKwt induced cyclin D1 promoter activity in the absence of growth factor treatment. We conclude that catalytic activation of ERKs regulates cyclin D1 expression in airway smooth-muscle cells.

Animals↗