Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.     

Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.     

Paediatric dacryocystorhinostomy

Of 258 cases of dacryocystorhinostomy performed on children in the period September 1981 to September 1991, 130 were for simple, unresolved congenital nasolacrimal duct obstruction. Other indications for surgery included punctal agenesis, lacrimal fistula, post-traumatic and post-inflammatory canalicular obstruction. Of 177 children without canalicular pathology, 171 (96%) were relieved of symptoms with one operation, without canalicular intubation. Of 81 cases with canalicular disease, 55 of 70 (79%) who underwent DCR plus canalicular intubation, and 10 of 11 who underwent DCR plus Lester-Jones tube, were substantially improved with one operation. No child required peroperative or postoperative blood transfusion. Dacryocystorhinostomy in childhood, in experienced surgical hands, is a safe procedure, achieving relief of symptoms in most cases, particularly in the absence of canalicular disease.     

The Dk project: an interlaboratory comparison of Dk/L measurements

The oxygen transmissibilities (Dk/L) of a set of 48 contact lenses made from 8 different materials were measured by 4 laboratories. The L/Dk measurements from each laboratory were compared and correlated. Samples which were not masked with a fixed front surface aperture during measurement were corrected for edge effects. This paper shows that provided L/Dk is calculated for each lens using the same technique and Dk is derived using a graphical method of calculation, similar results can be obtained by all laboratories. However, the agreement was less good for materials of Dk greater than 70 x 10(-11) (cm2/s) (ml O2/ml x mm Hg).     

Inpatient management of asthma in the Chicago suburbs: the Suburban Asthma Management Initiative (SAMI).

BACKGROUND: Assessment of inpatient asthma management has generally been limited to urban settings, including Chicago, which is known for its high asthma morbidity and mortality. Previously published data have been based on survey methodology. The Suburban Asthma Consortium (SAC) sought to obtain patient-based data unique to the Chicago suburbs to improve asthma care in those areas. OBJECTIVE: To evaluate current inpatient asthma management based on the 1997 National Asthma Education and Prevention Program (NAEPP). DESIGN: Retrospective chart review of all hospitalized patients 3-65 years bearing asthma-related ICD-9 codes for fiscal year 2002 in community, nonteaching hospitals in Chicago suburbs. RESULTS: Nine hundred two cases were submitted from seven hospitals. The majority ( > or = 75%) received inhaled bronchodilators, systemic steroids, oxygen and pulse oximetry. Antibiotic use (67%), chest radiography (85%), complete blood count (77%), and electrolytes (59%) appeared excessive in view of NAEPP recommendations. Peak flow monitoring (PFM) was recorded on admission in 45% of patients 5 years old and older; 52% had PFM during hospitalization. Thirty-eight percent of patients were taking ICS prior to admission; of those not on ICS, only 12% were newly diagnosed asthmatics. Overall, 51% of patients were discharged with ICS. Patients were more likely to receive ICS at discharge if they had required intensive care (ICU), had been on ICS prior to admission, were referred to an asthma specialist while hospitalized, or were insured. Patients with Medicare/Medicaid (MC/MA) had more repeat emergency visits and hospitalizations, longer lengths of stay, and received less ICS at discharge. Depending on the parameter, 41% or less patients received discharge planning education and were not more likely to have received education if in the ICU. Results ranged significantly between hospitals for most parameters (p < 0.05 or less). CONCLUSION: Study subjects received appropriate acute therapy and oxygen monitoring, but there was a divergence from NAEPP recommendations regarding PFM, ICS use, antibiotics, and laboratory evaluation. Patients receiving MC/MA experienced higher morbidity and received less ICS. Discharge asthma education was suboptimal for most hospitals. Most parameters demonstrated significantly wide practice variations between hospitals. Peak flow monitoring and patient education findings differed significantly from those in survey-conducted studies.     

A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia.

BACKGROUND: Neuroanatomic sexual dimorphisms have been correlated with behavioral differences between healthy men and women. We have reported higher orbitofrontal cortex to amygdala ratio (OAR) in women than men. Although gender differences in schizophrenia are evident clinically and correlate with neuroanatomic measures, their relationship to OAR has not been examined. METHODS: Magnetic resonance imaging was performed in 31 neuroleptic-na?ve schizophrenic patients (16 men) and 80 healthy volunteers (34 men), aged less than 50 years. An automated tissue segmentation procedure was combined with expert-guided parcellation of orbitofrontal and amygdala volumes. RESULTS: Men with schizophrenia had increased OAR relative to healthy men, whereas women had decreased OAR. Increased OAR in men with schizophrenia reflected abnormally low amygdala volumes, whereas decreased OAR in women reflected abnormally low orbitofrontal volumes. Less severe negative symptoms were associated with increased OAR in men but with decreased OAR in women. In men, increased amygdala volume was associated with greater symptom severity, whereas in women higher volumes of both amygdala and orbitofrontal regions were associated with lesser severity of negative symptoms. CONCLUSIONS: These opposite OAR abnormalities, whereby men show feminization and women masculinization, suggest gender-mediated effects of the underlying neuropathologic processes. The correlations with symptom severity suggest that neuroanatomic abnormalities in OAR reflect compensatory brain changes.     

The effect of spinal manipulation on pain and prostaglandin levels in women with primary dysmenorrhea.

OBJECTIVE: The primary objectives of this study were to compare the effect of spinal manipulation vs. sham manipulation on a) circulating plasma levels of the prostaglandin F2a metabolite, 15-keto-13,14-dihydroprostaglandin (KDPGF2a), b) perceived abdominal and back pain and c) perceived menstrual distress in women with primary dysmenorrhea. DESIGN: This randomized clinical pilot study investigated the outcome measures before and after either a spinal manipulation treatment (SMT) or a sham manipulation. SETTING: All subjects were treated at the National College Chiropractic clinic, a private chiropractic clinic in the suburban Chicago area. PARTICIPANTS: Forty-five women with a history of primary dysmenorrhea were recruited from the local community. The volunteers ranged in age from 20-49 (mean age = 30.3 yr), and were entered into the study between April 1990 and January 1991. Twenty-four were randomly assigned to the spinal manipulation group and 21 were assigned to the sham group. INTERVENTIONS: Subjects treated with spinal manipulation were placed in a side-lying position with the bottom leg straight and the top leg flexed at the knee and hip. They received a high-velocity, short lever, low-amplitude thrust to all clinically relevant vertebral levels within T10 and L5-S1 and the sacroiliac joints. In the sham manipulation, subjects were placed in a side-lying position with both hips and knees flexed. Their manipulation consisted of a similar thrust administered to the midline base of the sacrum. OUTCOME MEASURES: Perceived abdominal and back pain were measured with a visual analog scale, and menstrual distress was measured with the Menstrual Distress Questionnaire. Both were administered 15 min before and 60 min after treatment. Blood samples were collected by venipuncture for the determination of plasma levels of KDPGF2a at the same times. The plasma was then assayed for KDPGF2a by radioimmunoassay. RESULTS: Analysis of covariance and paired Student's t tests were used for the statistical evaluation. Immediately after treatment, the perception of pain and the level of menstrual distress were significantly reduced by SMT. This reduction was associated with a significant reduction in plasma levels of KDGPF2a in the SMT group. A significant and similar reduction in plasma KDPGF2a also occurred in the sham group, indicating that a placebo effect was associated with a single sham intervention. CONCLUSIONS: This randomized pilot study suggests that SMT may be an effective and safe nonpharmacological alternative for relieving the pain and distress of primary dysmenorrhea. However, the large change in KDPGF2a observed in both treatment groups clearly indicates that further studies with more subjects, studied over a longer time frame, are needed to resolve the question of a placebo effect.