Influence of atipamezole on effects of midsacral subarachnoidally administered detomidine in mares

BACKGROUND: The reliable interpretation of the nasal provocation test in allergy diagnosis requires objective and measurable monitoring parameters for clinical practice. The clinical usefulness of the nasal provocation test has been limited by scanty knowledge of the specificity and sensitivity of the test and a lack of reference values. OBJECTIVE: To test and compare three objective monitoring parameters of a nasal provocation test in occupational allergic rhinitis. To evaluate the magnitude of the nasonasal effects in a unilateral allergen challenge. METHODS: The monitoring parameters of the nasal reaction were derived from the minimum cross-sectional area on acoustic rhinometry, the nasal resistance on active anterior rhinomanometry and the amount of nasal secretion measured at 15 min intervals for 60 min. Twenty-three bovine-allergic dairy and beef cattle farmers and 19 exposed, non-allergic control subjects were challenged first with a control solution and then with the cow allergen. RESULTS: All the three monitoring parameters showed high specificity and sensitivity in finding allergic and non-allergic subjects. The secretion parameter was found to be slightly superior to the acoustic rhinometry and rhinomanometry parameters. The side difference in the nasal response between the allergen-challenged and the contralateral diluent-challenged cavity was significant for all the parameters among the allergic subjects. The contralateral secretion amount was 1/3 of the ipsilateral secretion, indicating the magnitude of the contralateral nasonasal reflex. A nasonasal reflex was also noted in the nasal patency monitoring. The coefficient of variation was significantly lower for the acoustic rhinometry than for the rhinomanometry (P=0.0001). The optimal threshold values for a positive test were a secretion amount of 100 mg, a 15% decrease in the minimum cross-sectional area and a 50% increase in the resistance for the observation period of 30 min and correspondingly 210 mg, 30% and 100% for 60 min. CONCLUSION: The low-pressure aspiration of the nasal secretion from the anterior part of the nasal cavity was found to be a reliable and practical monitoring parameter to be used together with acoustic rhinometry or rhinomanometry in the nasal provocation test for clinical purposes. Although significant nasonasal effects took place in the unilateral allergen challenge, the response was more prominent in the allergen-challenged than in the contralateral diluent-challenged nasal cavity in most allergic subjects.     

Growth of infants and young children born small or large for gestational age: findings from the Third National Health and Nutrition Examination Survey

An allele-specific polymerase chain reaction (ASPCR) assay for prenatal genotyping of the Kidd antigen system in order to identify pregnancies at risk for haemolytic disease of the newborn (HDN) was developed. Oligonucleotide primers were designed for ASPCR of JKA and JKB. A validation study was performed using DNA isolated from 54 serotyped whole blood samples and 8 amniocentesis samples. A concordance rate of 100 per cent was observed between serotyping and ASPCR detection of the JKA and JKB alleles. Experiments were conducted to quantify the maternal contamination that could be tolerated in Kidd ASPCR assays. The sensitivity of this assay ranged from 0.2 per cent when detecting the presence of JKB and JKA background, to 2 per cent for detecting the presence of JKA in a JKB background. This sensitive assay is particularly useful for rapid genotyping of fetal amniotic cells to identify pregnancies at risk for HDN due to incompatibilities within the Kidd blood group system.     

Phase I and pharmacologic study of weekly doxorubicin and 1 h infusional paclitaxel in patients with advanced breast cancer

Doxorubicin and paclitaxel both display strong antitumor activity in the treatment of breast cancer. The optimal schedule of this combination, however, remains undefined. In this phase I and pharmacologic study, we administered weekly 12 mg/m2 doxorubicin as a bolus infusion immediately followed by a 1 h 80 mg/m2 paclitaxel infusion to patients with metastatic breast cancer. A total of 119 weekly courses were delivered to seven patients. Grade IV neutropenia was observed in two patients at the first dose level, thus already defining the maximum tolerated dose. Pronounced non-hematologic toxicities were mild neuropathy (grade I: 39%) and stomatitis (grade I: 19%, grade II: 8%). No signs of cardiac toxicity were observed with this dose schedule. Three partial responses were achieved in this group of heavily pretreated patients. The pharmacokinetics of paclitaxel, doxorubicin and Cremophor EL with this schedule were analyzed. Overall, the schedule was well tolerated and combined with its preliminary response rate justifies further evaluation in phase II studies.     

Laparoscopic hernia repair in Leicester General Hospital: a prospective audit of 94 patients

Conventional hernia repair is effective in terms of cure but is associated with considerable postoperative pain and delay in return to normal activity. Laparoscopic repair has the potential to reduce pain and speed return to normal activity, but there have been few published reports of the outcome of this operation in the UK. We present a prospective audit of 94 patients who underwent laparoscopic repair. Of the 94 patients, 87 (92.6%) were male and 7 (7.4%) were female. Thirteen of the repairs were bilateral and 12 were recurrent. Two had to be converted to open repair. The mean operating time for unilateral repair was 56 min and for bilateral repair 98 min. Sixty-three patients (67%) were discharged within 24 h and 21 (22.4%) were discharged within 48 h. There were minor complications in 20 patients (21%), eight of whom (8.5%) developed a haematoma. The other minor complications included seromas (2), bruising at the site of the entry port (2), hyperaesthesia in the groin (2), port hernia (1), shoulder tip pain after surgery (3) and postoperative urinary retention (2). Nine (9.5%) patients claimed to have had no pain or discomfort at all; 35 (37.2%) were pain and discomfort free in 2 weeks. Thirty-two (34%) patients returned to normal activities in 2 weeks. With a median follow-up of 8 months 3 (3.2%) recurrences were noted. It is emphasised that this series represents a learning curve and that the operation is developmental. We are now restricting laparoscopic repair to recurrent and bilateral hernias where the technique offers particular advantages.     

Clinical interpretations of transient otoacoustic emissions

The object was to study retrospectively the perioperative complications and results of the Bologna procedure for the treatment of stress urinary incontinence associated with cystocele grade 2 or more. In the study, 80 patients underwent a repair of all defects of pelvic support plus the Bologna procedure. Mean duration of follow-up was 40.2 months (range 3-127). The incidence of operative complications was 2.5% for inadvertent cystostomy and for hemorrhage. Mean hospital stay was 7.2 days (range 2-17). At 2-year follow-up 85% of the patients were completely free of incontinence symptoms (95% CI: 75-92) and 76% at 3-year follow-up (95% CI: 66-86). None of the parameters tested in a univariate analysis was independently linked with surgical failure. Further studies are needed to establish the place of this technique in the surgical management of urinary incontinence associated with genital prolapse.     

Antimicrobial activity of 12 broad-spectrum agents tested against 270 nosocomial blood stream infection isolates caused by non-enteric gram-negative bacilli: occurrence of resistance, molecular epidemiology, and screening for metallo-enzymes

From March 1989 to March 1993, six athletic patients were treated in our institution by thrombolytic therapy for acute effort axillary-subclavian vein thrombosis in thoracic outlet syndrome. Mean age of these patients was 20 (range 14 to 27). An in situ infusion with urokinase (2,500 U/kg/h) and Heparin (100 U/kg/12 hours) was given during 64 hours (Range 14 to 72). Phlebography showed a complete reperfusion in three cases (the treatment began within an average period of 5.6 days), partial reperfusion in two cases (the treatment began within an average period of 8.5 days). In one case there was no reperfusion on phlebography: treatment began within an average period of 15 days. For this patient, a venous axillo-jugular bypass graft was performed. In all cases, there was no bleeding complication. A trans-axillary first rib resection was done three months later. Mean follow up was 31 months (range: two to 51 months). All patients recovered their previous physical status. Echo-Doppler exam showed normal subclavian vein flow in four cases, partial occlusion in one case and a total occlusion of the subclavian vein flow in one case. In this last case, the thrombolytic therapy failed to restore the permeability of the subclavian vein. Bypassgraft was patent. Axillary-subclavian vein thrombosis seen within a period of seven days should be treated by local thrombolytic therapy using urokinase and heparin.     

Pyrimidinoceptor-mediated potentiation of inducible nitric-oxide synthase induction in J774 macrophages. Role of intracellular calcium

We have shown that, in murine J774 macrophages, binding of UTP to pyrimidinoceptors stimulates phosphoinositide (PI) breakdown and an increase in [Ca2+]i. In this study, UTP modulation of the expression of inducible nitric-oxide synthase (iNOS) was investigated. Although UTP alone had no effect, stimulation of J774 cells with a combination of UTP (10-300 microM) and LPS (0.1-3 microgram/ml) resulted in a potentiated increase in nitrite levels. In parallel, the amount of iNOS protein induced by LPS was also potentiated by UTP treatment. The UTP potentiating effect was attenuated by U73122, suggesting involvement of the downstream signaling pathways of phosphatidylinositide turnover. The tyrosine kinase inhibitor genistein inhibited both the LPS-induced nitrite response and the UTP potentiation. Conversely, two protein kinase C inhibitors, Ro 31-8220 and Go 6976, and a phosphatidylcholine-specific phospholipase C inhibitor, D609, inhibited LPS-stimulated nitrite induction, but did not affect the potentiating effect of UTP, which was also unaffected by pretreatment with phorbol 12-myristate 13-acetate for 8 h. Furthermore, the UTP-induced potentiation was abolished by BAPTA/AM or KN-93 (a selective inhibitor of Ca2+/calmodulin-dependent protein kinase (CaMK)). Nitrite potentiation and iNOS induction were prominent when UTP was added simultaneously with LPS, with the potentiating effect being lost when UTP was added 3 h after treatment with LPS. Pyrrolidinedithiocarbamate (3-30 microM), an inhibitor of NF-kappaB, caused a concentration-dependent reduction in the nitrite response to LPS and UTP. In electrophoretic mobility shift assays, LPS produced marked activation of NF-kappaB and AP-1, which was potentiated by UTP. LPS-induced degradation of IkappaB-alpha as well as the phosphorylation of IkappaB-alpha were also increased by UTP. Moreover, the UTP-potentiated activation of NF-kappaB and AP-1 and the degradation and phosphorylation of IkappaB-alpha were inhibited by KN-93. Taken together, these data demonstrate that nucleotides, especially UTP, can potentiate the LPS-induced activation of NF-kappaB and AP-1 and of iNOS induction via a CaMK -dependent pathway and suggest that the UTP-dependent up-regulation of iNOS may constitute a novel element in the inflammatory process.     

Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies food-dependent Cushing's syndrome

Abnormal responsiveness of adrenocortical cells to gastric inhibitory polypeptide (GIP) in food-dependent Cushing's syndrome suggested that adrenal expression of ectopic, overexpressed, or mutated GIP receptor (GIPR) underlies this syndrome. The expression of GIPR was studied by RT-PCR in human adrenal tissues from two patients with GIP-dependent Cushing's syndrome (adenoma, bilateral hyperplasia), five fetal or adult controls, one patient with Cushing's disease, and four patients with non-food-dependent cortisol-secreting adenomas or bilateral hyperplasias and compared to that in normal pancreas. Hybridization of the RT-PCR-amplified ribonucleic acids with the human GIPR complementary DNA showed an overexpression of GIPR in the adrenals of the two GIP-dependent Cushing's syndrome patients compared to that in normal adrenal tissues (2-3 orders of magnitude) or pancreas (10-fold); no signal could be seen in adrenal adenomas or macronodular hyperplasia from cases of non-food-dependent Cushing's syndrome. No mutation of the GIPR was identified by sequencing the full-length receptor in GIP-dependent adrenal tissue. New alternative spliced isoforms of the GIPR were found, but are identical in GIP-dependent and normal adrenal tissues. Incubation of adrenal cells with GIP stimulates cortisol secretion in GIP-dependent, but not in normal fetal, adult, or non-food-dependent Cushing's syndrome, adrenals. We conclude that the GIPR overexpression and its coupling to steroidogenesis underlie GIP-dependent Cushing's syndrome.