bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental Toxicity in the Pregnant Rabbit by theClass III Antiarrhythmic Drug Sotalol
Authors: Sköld Anna‐Carin , Danielsson Bengt R. 
Published: July 2004

Abstract:The purpose of this study was to investigate the potential of sotalol to cause developmental toxicity in the pregnant rabbit. Sotalol is a β‐adrenoceptor blocking drug which also has class III antiarrhythmic properties via Ikr channel blockade. Experiment 1: Nine pregnant New Zealand White rabbits were given doses of either 300, 225, or 150 mg/kg of sotalol during gestational days, called Days, 13–16 which resulted in total litter loss. Experiment 2: A single dose of sotalol, 100 or 150 mg/kg was administered during Days 8–17 to 15 rabbits. Dosing on Day 8, 9, or 10 resulted in a slightly higher incidence of embryonic death compared to historical controls. There was marked increased embryonic death of 55–90% (four does with total litter loss), decreased number of live foetuses per litter, and elevated mean foetal weight after dosing during Days 12–16. Experiment 3: 16 pregnant rabbits were administered single doses of sotalol of either 100, 85, 75, 60 or 50 mg/kg on Day 14. The main finding was increased embryonic death, which ranged from total litter loss to ∼30% at 50 mg/kg. At 50 mg/kg, the maternal Cmax, AUC1–24 hr, and t1/2 were approximately 45 μM, 340 μmol×hr/l, and 6 hr, respectively. In conclusion, sotalol treatment resulted in embryonic death in the rabbit in early pregnancy in the same way as has been seen for other drugs with Ikr blocking properties (class III antiarrhythmics) in rodents. The observed developmental toxicity in the rabbit is most likely secondary to embryonic arrhythmia as has been shown in rodent studies. The results may indicate that Ikr blocking agents are developmental toxicants across species including man.
Altered Expression of Lung Cytochrome P450 3A1 in Rat after Exposure to Sulfur Mustard
Authors: Pons Françoise , Calvet Jean‐Henri , Haag Muriel , Raeppel Véronique , Keravis Thérèse , Frossard Nelly 
Published: July 2004

Abstract:Expression of cytochromes P450 (CYP) and glutathione S‐transferases in the lung may be affected by inhaled pollutants. We have investigated the effect of sulfur mustard on the expression of CYP 1A1, 2B1, 2E1 and 3A1, as well as of α‐, μ‐ and π‐glutathione S‐transferases in rat lung. Sulfur mustard (0.025, 0.05 or 0.1 mg/kg) or its vehicle was administered to anaesthetized animals by intratracheal injection. Expression of CYP and glutathione S‐transferases was analysed 24 hr after administration of the vesicant warfare using western blotting. Preservation of airway epithelium integrity after animal exposure to sulfur mustard was confirmed by histological examination of tracheal and lung tissues from control and treated animals. Constitutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from control rats, whereas CYP 1A1 and 2E1 proteins were not detected. Animal exposure to sulfur mustard enhanced CYP 3A1 protein levels by 80 to 103%. In contrast, exposure to sulfur mustard neither modified CYP 2B1 expression, nor led to detectable expression of CYP 1A1 or 2E1. Constitutive levels of α‐, μ‐ and π‐glutathione S‐transferase proteins were found in lung tissue from control rats. Exposure to sulfur mustard had no effect on expression of either of the glutathione S‐transferases. Our results show that intratracheal exposure to sulfur mustard selectively increases CYP 3A1 expression in rat lung. Taking into account the major role of CYP of the 3A family in the metabolism of drugs, up‐regulation of CYP 3A1 by sulfur mustard might have important therapeutic consequences.
Pharmacological Antagonism of the Slow‐Activating Delayed Rectifying Potassium Channel (IKs) Has No Effect on Cochlear Structure and Function in vivo
Authors: Whitworth Craig A. , Rybak Leonard P. , Kemp Ramon , Spence Stan 
Published: July 2004

Abstract:The experimental class III antiarrhythmic drug, L‐768673, prolongs the refractory period of cardiac myocytes by selectively blocking the slow‐activating delayed rectifying potassium (IKs) channel. The IKs channel has also been identified in vestibular dark cells and in the marginal cells of the stria vascularis. In the stria vascularis, the IKs channel plays an important role in cochlear homeostasis. Genetic null deletion of the IKs channel in mice and man results in profound hearing loss and cochlear pathology. Therefore, the purpose of the present study was to investigate the effect of L‐768673 on the auditory function and cochlear morphology in rats using auditory brainstem‐evoked response and light microscopy. Auditory testing was performed one week prior to dosing, following 14 days of administration and 28 days after the completion of dosing. L‐768673 (50 or 250 mg/kg/day for 14 days), had no significant effects on auditory function or cochlear morphology. The results of this study suggest that high doses of L‐768673 are not toxic to the inner ear of adult rats treated for 14 consecutive days, and that the ototoxic potential of orally administered L‐768673 and similar IKs‐selective compounds is unlikely at doses within the therapeutic range.
Quality of life and self-rated health in relation to changes in fruit and vegetable intake and in plasma vitamins C and E in a randomised trial of behavioural and nutritional education counselling
Authors: Steptoe Andrew , Perkins-Porras Linda , Hilton Sean , Rink Elizabeth , Cappuccio Francesco P. 
Published: July 2004

AbstractWe have carried out a randomised trial comparing brief behavioural counselling with nutritional education counselling to increase fruit and vegetable consumption and associated biomarkers in adults from a low-income neighbourhood. The objective of the present analysis was to assess the impact of interventions on quality of life and health status, and associations between changes in fruit and vegetable consumption, plasma vitamins C and E, and quality of life. Behavioural counselling and nutritional education counselling were carried out in 271 adults in two 15 min sessions in a primary-care setting. Physical and mental health status (medical outcome study short form 36) and self-rated health were assessed at baseline, 8 weeks and 12 months, and analysed on an intention-to-treat basis. Both groups reported increased fruit and vegetable consumption; plasma vitamin E and β-carotene also increased, with significantly greater changes in consumption and plasma β-carotene in the behavioural counselling condition. Physical and mental health status, and the proportion of participants in good self-rated health, increased in both groups to a similar extent. Individual differences in improvements in physical health status and self-rated health were correlated with increases in fruit and vegetable intake and in plasma vitamins C and E, independently of age, gender, ethnicity, financial status, smoking, BMI and use of vitamin supplements. We conclude that participation in the present study was associated with improved health-related quality of life. Increases in fruit and vegetable intake and plasma vitamin levels may stimulate beneficial changes in physical health status in socio-economically deprived adults.
Spontaneous Intracranial Hypotension Mimicking Aneurysmal Subarachnoid Hemorrhage
Authors: Schievink Wouter I. , Wijdicks Eelco F.M. , Meyer Fredric B. , Sonntag Volker K.H. 
Published: July 2004

AbstractOBJECTIVEAn excruciating headache of instantaneous onset is known as a thunderclap headache. A subarachnoid hemorrhage is the prototypical cause, but other serious disorders may also present with a thunderclap headache, including cerebral venous sinus thrombosis, carotid artery dissection, and pituitary apoplexy. We report a group of patients with thunderclap headaches as the initial manifestation of spontaneous intracranial hypotension caused by a spinal cerebrospinal fluid leak.METHODSAmong 28 patients with spontaneous intracranial hypotension due to a documented spinal cerebrospinal fluid leak, four (14%) initially experienced an excruciating headaches of instantaneous onset.RESULTSThe mean age of the four patients (two men and two women) was 35 years (range, 24–45 yr). Nuchal rigidity was present in the three patients who sought early medical attention, and they underwent emergency computed tomographic scanning, lumbar puncture, and cerebral angiography to rule out an aneurysmal subarachnoid hemorrhage. The delay between the onset of headache and diagnosis of intracranial hypotension ranged from 4 days to 5 weeks. A fourth patient did not seek medical attention until 1 month after the ictus.CONCLUSIONSpontaneous intracranial hypotension should be included in the differential diagnosis of thunderclap headache, even when meningismus is present.
Spontaneous Intraparenchymal Hemorrhage in Full-term Neonates
Authors: Sandberg David I. , Lamberti-Pasculli Maria , Drake James M. , Humphreys Robin P. , Rutka James T. 
Published: July 2004

AbstractOBJECTIVESpontaneous intraparenchymal hemorrhage is extremely rare in full-term newborns. Reports to date have been limited to descriptions of individual cases, small groups within larger studies of intracranial hemorrhage, and one series of four patients. Structural lesions are rarely identified, and the majority of patients described have been managed without surgical intervention.METHODSAnalysis of a computerized database of pediatric neurosurgical patients from January 1960 to February 2000 identified full-term newborns younger than 3 months of age with nontraumatic intraparenchymal hemorrhages. Prenatal histories, labor and delivery histories, clinical presentations, imaging studies, management, and outcomes were reviewed.RESULTSEleven full-term newborns with spontaneous intraparenchymal hemorrhages were identified. The majority had normal prenatal courses. Most presented within the first 2 days of life (6 of 11 patients), and the most common presenting sign was seizure (7 of 11 patients). No cause was identified in 6 of 11 patients; the remainder were attributed to coagulopathy (n = 3), ruptured intracranial aneurysm (n = 1), or hemorrhagic infarction (n = 1). Eight patients underwent surgical hematoma evacuation on the basis of radiographic evidence of significant mass effect, evidence of signs of elevated intracranial pressure, or both. Three patients did not receive surgical intervention. There were no subsequent hemorrhages or deaths during a mean follow-up period of 4.5 years (range, 1–16 yr). Four patients had normal neurological outcomes, four had motor deficits (one of whom additionally demonstrated cognitive delay), and three had delayed speech.CONCLUSIONNo cause is identified in most newborns with spontaneous intraparenchymal hemorrhage. Radiographic evidence of mass effect or signs of elevated intracranial pressure may necessitate surgical hematoma evacuation. Outcome varies widely and may be normal, even in patients with sizeable intraparenchymal hemorrhages.
Are Nonfunctioning Pituitary Adenomas Extending into the Cavernous Sinus Aggressive and/or Invasive?
Authors: Yokoyama Shunichi , Hirano Hirofumi , Moroki Koichi , Goto Masamichi , Imamura Shinichi , Kuratsu Jun-ichi 
Published: July 2004

Abstract

OBJECTIVE
We studied nonfunctioning pituitary adenomas extending to the cavernous sinus to gain insight into the discrepancy between their histologically benign nature and frequent extension into the cavernous sinus.

METHODS
We studied 10 patients with nonfunctioning pituitary adenomas that completely encircled the cavernous carotid artery (extension group). All 10 patients underwent surgery to remove intrasellar and/or suprasellar parts of the adenomas. Ten patients with nonfunctioning pituitary adenomas without cavernous sinus extension comprised the control group. Tumor size follow-up data were obtained by magnetic resonance imaging. Immunostaining was performed for Ki-67, cathepsin B, and matrix metalloprotainase-9. To assess the wall thickness, 10 cavernous sinuses were removed from the cranial base of adult cadavers, and the walls were examined histologically.

RESULTS
Magnetic resonance imaging demonstrated no remarkable growth in most of the patients during the follow-up period (mean, 65.8 mo). There was no statistical difference in Ki-67, cathepsin B, and matrix metalloprotainase-9 immunostaining between the extension group and the control group. The cadaver study demonstrated that the medial wall was significantly thinner than the superior and the lateral walls (P &lt; 0.0005). We found small defects in the capsule histologically in 3 of 30 sections.

CONCLUSION
Our results indicate that most of nonfunctioning pituitary adenomas extending into the cavernous sinus are neither aggressive nor invasive. The high incidence of cavernous sinus extension of benign adenomas may be caused by the weakness of the medial wall of the cavernous sinus.
Management Strategy for Adult Patients with Dorsal Midbrain Gliomas
Authors: Yeh David D. , Warnick Ronald E. , Ernst Robert J. 
Published: July 2004

Abstract

OBJECTIVE:
Dorsal midbrain gliomas (DMGs) involving the tectum occur more commonly in children than in adults. These lesions are often indolent in nature, and patients require treatment only for obstructive hydrocephalus. Because limited information is available concerning adults with this type of lesion, we describe our experience and management strategy in adults with DMGs.

METHODS:
We retrospectively reviewed the charts and magnetic resonance imaging scans of five adult patients (four men, one woman; mean age, 51.6 yr; range, 23–69 yr) who were treated from March 1992 to August 2001 for DMGs involving the tectum. The mean follow-up time for these patients was 71.4 months (range, 25–113 mo). We analyzed the data to determine the optimal treatment strategy and outcomes of patients with DMGs. Tumor volume was analyzed objectively with Scion Image software (Scion Corp., Frederick, MD) to document changes in volume and determine whether treatment strategy differed significantly with tumor size.

RESULTS:
Tumors in two of these patients were found incidentally, and three others presented with obstructive hydrocephalus. Magnetic resonance imaging scans demonstrated an isolated tectal glioma in one patient, tectal and tegmental (periaqueductal) gliomas in three patients, and a tectal glioma with right thalamic extension in one patient. Treatment consisted of routine follow-up for the two asymptomatic patients and cerebrospinal fluid diversion surgery for the three patients with hydrocephalus. Volumetric analysis demonstrated that all asymptomatic patients had tumors smaller than 9.3 cm3, and symptomatic patients had tumors larger than 28.5 cm3. All follow-up magnetic resonance imaging scans revealed stable dorsal midbrain lesions, and no patient required tumor-specific therapy.

CONCLUSION:
Although tumors of the dorsal midbrain occur primarily in the pediatric population, similar tumors may occur in adults. As has been learned from experience with children, these lesions are often clinically and radiographically stable and require only appropriate therapy for obstructive hydrocephalus. We advocate a similar conservative strategy of routine imaging follow-up and treatment for hydrocephalus in adult patients. Surgery and other therapy should be reserved for patients with progressive lesions.
Meningovenous Structures of the Petroclival Region: Clinical Importance for Surgery and Intravascular Surgery
Authors: Ozveren Mehmet Faik , Uchida Koichi , Aiso Sadakazu , Kawase Takeshi 
Published: July 2004

Abstract

OBJECTIVE:
The goals of this investigation were to perform a detailed analysis of petroclival microanatomic features, to investigate the course of the abducens nerve in the petroclival region, and to identify potential causes of injury to neurovascular structures when anterior transpetrosal or transvenous endovascular approaches are used to treat pathological lesions in the petroclival region.

METHODS:
Petroclival microanatomic features were studied bilaterally in seven cadaveric head specimens, which were injected with colored silicone before microdissection. Another cadaveric head was used for histological section analyses.

RESULTS:
A lateral or medial location of the abducens nerve dural entrance porus, relative to the midline, was correlated with the course and angulation of the abducens nerve in the petroclival region. The angulation of the abducens nerve was greater and the nerve was closer to the petrous ridge in the lateral type, compared with the medial type. The abducens nerve exhibited three changes in direction, which represented the angulations in the petroclival region, at the dural entrance porus, the petrous apex, and the lateral wall of the internal carotid artery. The abducens nerve was covered by the dural sleeve and the arachnoid membrane, which became attenuated between the second and third angulation points. The abducens nerve was anastomosed with the sympathetic plexus and fixed by connective tissue extensions to the lateral wall of the internal carotid artery and the medial wall of Meckel's cave at the third angulation point. There were two types of trabeculations inside the sinuses around the petroclival region (tough and delicate).

CONCLUSION:
The petroclival part of the abducens nerve was protected in a dural sleeve accompanied by the arachnoid membrane. Therefore, the risk of abducens nerve injury during petrous apex resection via the anterior transpetrosal approach, with the use of the transvenous route through the inferior petrosal sinus to the cavernous sinus, should be lower than expected. The presence of two anatomic variations in the course of the abducens nerve, in addition to findings regarding nerve angulation and tethering points, may explain the relationships between adjacent structures and the susceptibility to nerve injury with either surgical or endovascular approaches. Venous anatomic variations may account for previously reported cases of subarachnoid hemorrhage with the endovascular approach.
Magnetic Resonance Imaging-guided Stereotactic Limbic Leukotomy for Treatment of Intractable Psychiatric Disease
Authors: Montoya Alonso , Weiss Anthony P. , Price Bruce H. , Cassem Edwin H. , Dougherty Darin D. , Nierenberg Andrew A. , Rauch Scott L. , Cosgrove G. Rees 
Published: July 2004

Abstract

OBJECTIVE:
To assess the efficacy and complication rates of magnetic resonance imaging-guided stereotactic limbic leukotomy for the treatment of intractable major depressive disorder (MDD) and obsessive-compulsive disorder (OCD).

METHODS:
We conducted preoperative evaluations and postoperative follow-up assessments of efficacy and complications for 21 patients who underwent limbic leukotomy. Efficacy was based on physician- and patient-rated global assessments of functioning, as well as evaluations using disease-specific rating scales commonly used in studies of MDD and OCD.

RESULTS:
The mean time from limbic leukotomy to follow-up assessment was 26 months. On the basis of standard outcome measures, 36 to 50% of patients were considered to be treatment responders. Although permanent surgical morbidity was rare, there were reports of postoperative sequelae, including apathy, urinary incontinence, and memory complaints, which occurred in a substantial minority of cases.

CONCLUSION:
For this cohort of 21 patients with chronic severe MDD or OCD, who had experienced failure with an exhaustive array of previous treatments, limbic leukotomy was associated with substantial benefit for 36 to 50%. This rate is comparable to those of previous studies of limbic system surgery and indicates that limbic leukotomy is a feasible treatment option for severe, treatment-refractory MDD or OCD. Adverse consequences associated with the procedure included affective, cognitive, and visceromotor sequelae, which were generally transient.
Trans-supraorbital Approach to Supratentorial Aneurysms
Authors: Ramos-Zúñiga Rodrigo , Velázquez Héctor , Barajas Marco A. , López Ramiro , Sánchez Enrique , Trejo Sandra 
Published: July 2004

AbstractOBJECTIVEThe trans-supraorbital approach has the advantage of combining the keyhole principle with cranial base surgery. The anatomic fields that can be visualized with the use of this procedure have been demonstrated in cadavers, and the advantages and potential surgical applications of this procedure are described in this report. This article is the first to describe a group of intracranial supratentorial aneurysms.METHODSWe used the trans-supraorbital approach in 22 cases of supratentorial aneurysms. In this technique, an incision is made through the eyebrow, then a 3.5-cm craniotomy is performed with en bloc extension to the orbital arch, complemented by different drilling extensions of the orbital roof according to the surgical objective. We describe the anatomic details of the experimental work as well as the clinical results.RESULTSThe trans-supraorbital technique offers an unlimited wide exposure of neurovascular structures in this microsurgical corridor. The craniotomy extension allows greater exposure than the conventional keyhole supraorbital approach, which makes the technique safe for the patient and comfortable for the surgeon. All patient outcomes were successful; no serious complications from the surgical technique occurred. Our success was achieved through better microscopic illumination in the deep field and by gaining access to the complete supratentorial vascular territory with minimal cerebral retraction and an acceptable cosmetic result.CONCLUSIONThe trans-supraorbital approach is effective for gaining access to and treating supratentorial aneurysms. Also, the microsurgical field is more convenient in microscope-assisted surgery because total reliance on the endoscope is not required, and minimal brain retraction is needed. This modification of the keyhole procedure also provides multiple surgical options in this microsurgical corridor, using the principles of minimal invasiveness in cranial base surgery.
Both chaperone and isomerase functions of protein disulfide isomerase are essential for acceleration of the oxidative refolding and reactivation of dimeric alkaline protease inhibitor
Authors: Pandhare Jui , Deshpande Vasanti 
Published: August 2004

AbstractOxidative refolding of the dimeric alkaline protease inhibitor (API) from Streptomyces sp. NCIM 5127 has been investigated. We demonstrate here that both isomerase and chaperone functions of the protein folding catalyst, protein disulfide isomerase (PDI), are essential for efficient refolding of denatured‐reduced API (dr‐API). Although the role of PDI as an isomerase and a chaperone has been reported for a few monomeric proteins, its role as a foldase in refolding of oligomeric proteins has not been demonstrated hitherto. Spontaneous refolding and reactivation of dr‐API in redox buffer resulted in 45% to 50% reactivation. At concentrations <0.25 μM, reactivation rates and yields of dr‐API are accelerated by catalytic amounts of PDI through its isomerase activity, which promotes disulfide bond formation and rearrangement. dr‐API is susceptible to aggregation at concentrations >25 μM, and a large molar excess of PDI is required to enhance reactivation yields. PDI functions as a chaperone by suppressing aggregation and maintains the partially unfolded monomers in a folding‐competent state, thereby assisting dimerization. Simultaneously, isomerase function of PDI brings about regeneration of native disulfides. 5‐Iodoacetamidofluorescein–labeled PDI devoid of isomerase activity failed to enhance the reactivation of dr‐API despite its intact chaperone activity. Our results on the requirement of a stoichiometric excess of PDI and of presence of PDI in redox buffer right from the initiation of refolding corroborate that both the functions of PDI are essential for efficient reassociation, refolding, and reactivation of dr‐API.