Detection of intracranial aneurysms: multi-detector row CT angiography compared with DSA

PURPOSE: To prospectively compare the effectiveness of multi-detector row computed tomographic (CT) angiography with that of conventional intraarterial digital subtraction angiography (DSA) used to detect intracranial aneurysms in patients with nontraumatic acute subarachnoid hemorrhage. MATERIALS AND METHODS: Thirty-five consecutive adult patients with acute subarachnoid hemorrhage were recruited into the institutional review board-approved study and gave informed consent. All patients underwent both multi-detector row CT angiography and DSA no more than 12 hours apart. CT angiography was performed with a multi-detector row scanner (four detector rows) by using collimation of 1.25 mm and pitch of 3. Images were interpreted at computer workstations in a blinded fashion. Two radiologists independently reviewed the CT images, and two other radiologists independently reviewed the DSA images. The presence and location of aneurysms were rated on a five-point scale for certainty. Sensitivity and specificity were calculated independently for image interpretation performed by the two CT image readers and the second DSA image reader by using the first DSA reader's interpretation as the reference standard. RESULTS: A total of 26 aneurysms were detected at DSA in 21 patients, and no aneurysms were detected in 14 patients. Sensitivity and specificity for CT angiography were, respectively, 90% and 93% for reader 1 and 81% and 93% for reader 2. The mean diameter of aneurysms detected on CT angiographic images was 4.4 mm, and the smallest aneurysm detected was 2.2 mm in diameter. Aneurysms that were missed at initial interpretation of CT angiographic images were identified at retrospective reading. CONCLUSION: Multi-detector row CT angiography has high sensitivity and specificity for detection of intracranial aneurysms, including small aneurysms, in patients with nontraumatic acute subarachnoid hemorrhage.     

Development of ovine fetal ileal motility: role of muscarinic receptor subtypes

OBJECTIVE: In the preterm human fetus, immaturity of gastrointestinal (GI) motility contributes to impairment of oral feeding and an increased risk of necrotizing enterocolitis. In view of the limited knowledge of fetal GI motility development, and the primary role of the muscarinic system in adult GI motility, we examined the development of GI muscarinic receptor subtypes associated with ileal motility. STUDY DESIGN: Ovine term fetal, newborn, and pregnant adult ileal longitudinal muscle contractile responses to muscarinic agonists (bethanechol) and muscarinic nonspecific (atropine) and subtype specific-antagonists (M1-M4) were examined in organ baths. Immunohistochemical analysis of ileal muscle muscarinic receptor subtypes was correlated with contractile responses. RESULTS: Bethanechol induced a concentration-dependent ileal contraction at all 3 age groups. Adult ileal maximal tension was 2-fold higher than that of the fetus and newborn, while 50% effective concentration (EC(50)) was similar at all ages. Atropine (10(-6)mol/L) inhibited contractility in fetal (67%+/-7%), newborn (82%+/-5%), and adult (97%+/-2%) in an age-dependent manner. The M3 antagonist exhibited robust inhibition at all age groups while the M2 antagonist demonstrated enhanced inhibition in the fetus. Immunohistochemical analysis indicated coexpression of subtype receptors in fetal, newborn, and adult ileal smooth muscle with increasing expression with advancing age. CONCLUSION: These results demonstrate a specific developmental pattern of muscarinic receptor subtype expression. Knowledge and/or alterations of GI motility regulation may aid in the treatment of the preterm fetus or newborn.     

In vitro,pharmacokinetic, and pharmacodynamic interactions of ketoconazole and midazolam in the rat

Interactions of midazolam and ketoconazole were studied in vivo and in vitro in rats. Ketoconazole (total dose of 15 mg/kg intraperitoneally) reduced clearance of intravenous midazolam (5 mg/kg) from 79 to 55 ml/min/kg (p < 0.05) and clearance of intragastric midazolam (15 mg/kg) from 1051 to 237 ml/min/kg (p < 0.05), increasing absolute bioavailability from 0.11 to 0.36 (p < 0.05). Presystemic extraction occurred mainly across the liver as opposed to the gastrointestinal tract mucosa. Midazolam increased electroencephalographic (EEG) amplitude in the beta-frequency range. Ketoconazole shifted the concentration-EEG effect relationship rightward (increase in EC(50)), probably because ketoconazole is a neutral benzodiazepine receptor ligand. Ketoconazole competitively inhibited midazolam hydroxylation by rat liver and intestinal microsomes in vitro, with nanomolar K(i) values. At a total serum ketoconazole of 2 microg/ml (3.76 microM) in vivo, the predicted reduction in clearance of intragastric midazolam by ketoconazole (to 6% of control) was slightly greater than the observed reduction in vivo (to 15% of control). However, unbound serum ketoconazole greatly underpredicted the observed clearance reduction. Although the in vitro and in vivo characteristics of midazolam in rats incompletely parallel those in humans, the experimental model can be used to assess aspects of drug interactions having potential clinical importance.     

Effects of estrogenic (o,p'-DDT; octylphenol) and anti-androgenic (p,p'-DDE) chemicals on indicators of endocrine status in juvenile male summer flounder (Paralichthys dentatus)

Laboratory experiments were conducted with male summer flounder to assess the value of selected measures of endocrine status in fish as indicators of exposure to endocrine-disrupting contaminants. Effects of 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethane (o,p'-DDT), octylphenol and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE) on hepatosomatic and gonadosomatic indices, plasma steroid hormone levels, vitellogenin production, and gonadal development were evaluated in laboratory-raised, juvenile male summer flounder. Flounder were injected twice with test chemical in a coconut oil carrier. Each chemical was tested at three different concentrations. Estrogenic (o,p'-DDT; octylphenol) and anti-androgenic (p,p'-DDE) chemicals were evaluated alone and in combination (octylphenol plus o,p'-DDT or p,p'-DDE). Additionally, some fish were treated with the natural ligand for the estrogen receptor, 17beta-estradiol. Blood and tissues from different fish in each treatment were sampled 4, 6 and 8 weeks after the first injection. Fish exposed to a combination of o,p'-DDT plus octylphenol were also sampled after 15 weeks. In all cases, responses of fish exposed to a test chemical were compared to control fish sampled at the same time. The following significant differences, relative to controls, were observed in at least one sampling time or at least one concentration of chemical. 17beta-Estradiol-treated flounder exhibited decreased gonadosomatic index (GSI), altered hepatosomatic index (HSI), elevated plasma estradiol, reduced plasma testosterone, and high levels of plasma vitellogenin. Fish treated with o,p'-DDT showed lower GSI, no change in HSI or plasma estradiol, depression of plasma testosterone, and induction of vitellogenesis. Octylphenol treatment resulted in lower GSI, no change in HSI, initially increased plasma estradiol and decreased testosterone, and no vitellogenin production. p,p'-DDE treatment did not significantly alter any indicator relative to controls. In experiments using combinations of chemicals, flounder receiving o,p'-DDT plus octylphenol had lower GSI after 8 weeks and elevated plasma estradiol after 15 weeks exposure. Fish treated with p,p'-DDE plus octylphenol for 8 weeks exhibited a significantly lower GSI. Overall, lower GSI and plasma testosterone levels, relative to controls, were consistent indicators of exposure to estrogenic chemicals in juvenile male flounder. No indicators were found that would identify exposure to the mammalian anti-androgen p,p'-DDE.     

Stored retinoids in populations of the estuarine fish Fundulus heteroclitus indigenous to PCB-contaminated and reference sites

Concentrations of retinoids, derivatives of vitamin A, were measured in populations of the nonmigratory estuarine fish Fundulus heteroclitus, indigenous to a reference site and a site highly contaminated with polychlorinated biphenyls (PCBs) to address the hypothesis that contaminant exposure causes depletion of stored retinoids in native fish populations. To assess differences related to chemical exposure, as well as season and diet, hepatic retinoid analyses were conducted using fish collected early and late in the natural spawning season and after laboratory holding. Though hepatic retinoid composition was generally similar among groups, hepatic retinoid concentrations differed. Laboratory-held fish had higher hepatic retinyl ester concentrations than field-collected fish. Among field-collected fish, those collected early in the spawning season had higher hepatic retinyl ester concentrations than those collected later in the spawning season. Although there was no evidence of the dramatic retinoid depletions that have been reported in highly exposed populations of other fish species, hepatic retinoid stores were consistently lower in F. heteroclitus indigenous to the highly PCB-contaminated site. These results are consistent with prior findings that fish from this contaminated site are relatively insensitive to some of the toxic effects of PCB exposures, including retinoid depletion. Received: 28 July 2000/Accepted: November 2000     

Relationships among total lipid, lipid classes, and polychlorinated biphenyl concentrations in two indigenous populations of ribbed mussels (Geukensia demissa) over an annual cycle

Two indigenous ribbed mussel (Geukensia demissa) populations were sampled approximately every four weeks during 1997 to investigate the relationships among concentrations of total lipid, lipid classes, and polychlorinated biphenyls (PCBs). One population was located in a highly contaminated area near a Superfund site (New Bedford Harbor, MA, USA), while the other population was located at a relatively clean site (West Island, Fairhaven, MA, USA). Mussel tissue total PCB concentrations (quantified as the sum of 18 congeners) from the contaminated site were two orders of magnitude greater than those at the clean site. Total lipid and triacylglycerol (TG) also were higher at the contaminated site. No significant relationship (p > 0.05) was observed between total PCBs and total lipid at either location; however, the correlations at both sites increased when total PCBs were compared with total TG or, to a lesser extent, total nonpolar lipid. Principal component analysis and linear discriminatory analysis indicated that the two mussel populations could be distinguished by the proportions of their lipid classes, particularly the concentration of nonpolar lipids, which consisted mainly of TG. These results suggest that the standard method of normalizing organism PCB concentrations to total lipid may not be appropriate as a routine practice, especially when the organism has a relatively low total lipid content (<6% dry wt in this study).     

Recurrent Carpal Tunnel Syndrome––Analysis of the Impact of Patient Personality in Altering Functional Outcome Following a Vascularised Hypothenar Fat Pad Flap Surgery

We retrospectively analysed 25 patients (27 hands) who had both clinical and electrophysiological confirmation of true recurrent carpal tunnel syndrome from January 2004 to December 2009. In all the patients, after releasing the nerve a vascularised fat pad flap was mobilised from the hypothenar region and sutured to the lateral cut end of flexor retinaculum. The patient characteristics, co-morbidities, duration of symptom, interval between first release and revision surgery and intra-operative findings were assessed against post-operative relief of pain, recovery of sensory and motor dysfunction. The average age of the patients was 58?years (43?C81) and the dominant hand was involved in 22 patients. Intra-operatively the nerve was compressed by scar tissue connecting the previously divided ends of the retinaculum in 18 and nine had scar tissue and fibrosis around the nerve. Following surgery 16 patients had complete recovery (asymptomatic at the first follow-up), eight had delayed recovery (partial recovery of symptoms at final follow-up) and three had a poorer outcome (persistence of preoperative symptoms at the final follow-up). The patients with delayed recovery/poorer outcome had a) Early recurrence; b) Diabetes mellitus; c) Obesity; d) Cervical spine problems; e) Involvement of non-dominant hand; and f) Intraoperative scar tissue and fibrosis. The hypothenar fat pad transposition flap provides a reliable source of vascularised local tissue that can be used in patients with recurrent carpal tunnel syndrome. The factors that were associated with poorer/delayed recovery were involvement of non-dominant hand, recurrence within a year from the previous surgery, intra-operatively scar tissue in the carpal tunnel and associated co-morbidities, like obesity diabetes mellitus and cervical spine problems.