Genetic diversity of feline immunodeficiency virus: dual infection, recombination, and distinct evolutionary rates among envelope sequence clades

For the rapid genetic analysis of feline immunodeficiency virus (FIV), we developed a heteroduplex mobility assay (HMA) that utilizes a PCR-amplified fragment of the FIV envelope gene spanning the third and fourth variable regions of the envelope surface protein coding sequence. Viral sequences were successfully amplified from blood specimens from 98 naturally infected cats from Australia, Canada, Germany, Italy, South Africa, and the United States. Eighty were clearly assignable to the A or B envelope sequence subtypes. Three belonged to subtype C, one was dually infected with viruses harboring the A and B env subtypes, and several were categorized as outliers to any of the established subtypes or as probable intersubtype recombinants. Some geographic clustering was evident, with subtypes A and B found in greater frequency in the western and eastern regions of the United States, respectively. Subtypes A, B, and C were found on more than one continent, and countries with more than two samples analyzed contained at least two subtypes. The broadest representation of subtypes was found in Munich, Germany, where three subtypes and one virus that was not classifiable by HMA were found. Thirteen samples were selected for DNA sequence determination over the same region of env used for HMA. Analysis of all available FIV env sequences from this and previous studies revealed the existence of recombinant viruses generated from subtype A/B, B/D, and A/C envelope gene sequences. Subtype A env sequences were less diverse than subtype B sequences, although both groups had well-supported clusters. Furthermore, the mutational pattern giving rise to diversification in the two subtypes differed, with the subtype A viruses showing half as many synonymous site mutations compared to subtype B yet showing similar levels of nonsynonymous site changes. These results are consistent with the hypothesis that FIV-B is an older virus group and is possibly more host adapted than FIV-A.     

Akathisia in adults with mental retardation: development of the Akathisia Ratings of Movement Scale (ARMS)

We developed an akathisia rating scale for use with persons who have mental retardation and screened for the occurrence of akathisia in three samples: 66 adults receiving maintenance neuroleptic treatment, 20 adults not receiving neuroleptics, and 8 adults undergoing neuroleptic dose reduction. The scale had an acceptable level of interrater reliability and validly measured group differences related to neuroleptic treatment status. Using an empirically derived cut-off-score, we estimated the prevalence rate for akathisia to be 5% in neuroleptic-free subjects, 17% in neuroleptic-maintenance subjects, and 25% in neuroleptic-reduction subjects. Akathisia, dyskinesia, and stereotypy manifested as qualitatively different movement topograhies. The occurrence of dyskinesia stereotyped movement disorder was associated significantly with an increased occurrence of akathisia.     

Reduction of neuropeptide Y binding sites in the rat hippocampus after electroconvulsive stimulations

The role of vasoactive intestinal peptide (VIP) was investigated when mucosal stroking and 5-hydroxytryptamine (5-HT) were used to activate neural reflexes that stimulate chloride secretion in the guinea pig colon. Muscle-stripped segments of colon containing intact submucosal ganglia without myenteric ganglia were set up in modified flux chambers in order to record short-circuit current (Isc). Mucosal stroking with a brush for 1 s or a pulse of 5-HT (injection of 15 microliters of 100 microM 5-HT into 1.5 ml of mucosal solution) caused an increase in Isc that was reduced by the VIP antagonist, neurotensin6-11-VIP7-28, in a concentration-dependent manner. The Isc responses to mucosal stroking and a 5-HT pulse were reduced by 53% and 58%, respectively, by 2 microM neurotensin6-11-VIP7-28. The residual Isc response in the presence of neurotensin6-11-VIP7-28 was abolished by atropine. Blockade of 5-HT1P receptors on submucosal afferent neurons decreased Isc responses to stroking or a 5-HT pulse. The residual Isc response after 5-HT1P receptors were blocked was reduced by only 11-14% by neurotensin6-11-VIP7-28. In the presence of blockade of both 5-HT1P and VIP receptors, atropine abolished the Isc response to both stimuli. The observations suggest that the neural circuitry activated by stroking includes at least two independent pathways. One pathway contains VIP neurons which receive inputs directly or indirectly from 5-HT1P receptor-containing afferents. A second pathway involves muscarinic cholinergic transmission that is independent of 5-HT1P and VIP receptor activation.     

Detection of congenital müllerian duct anomalies using three-dimensional ultrasound

PURPOSE: The purpose of this study was to assess the value of 3-dimensional sonography in the diagnosis of congenital müllerian duct anomalies, which cause infertility, preterm labor, and first trimester abortion. METHODS: A prospective study was undertaken in which 40 patients with histories of repeated spontaneous abortions or infertility were first examined using conventional 2-dimensional sonography or hysterosalpingography. Three-dimensional transvaginal sonography was then performed. RESULTS: Twenty-eight women had müllerian duct abnormalities, and 12 women had normal uterine anatomy. Müllerian duct defects detected in this study were unicornuate uterus (3), bicornuate uterus (3), complete or partial septate uterus (12), arcuate uterus (9), and didelphic uterus (1). The diagnosis of müllerian duct anomalies in these patients was confirmed by laparoscopic and/or hysteroscopic examinations. Three-dimensional sonography demonstrated all congenital uterine abnormalities with a sensitivity and specificity of 100%. Separate uterus and bicornuate uterus could be correctly diagnosed using 3-dimensional sonography in 11 (92%) of 12 cases and 3 (100%) of 3 cases, respectively. These 2 abnormalities were commonly confused with each other using hysterosalpingography and conventional sonography. CONCLUSIONS: Three-dimensional sonography with image reconstruction is less expensive and less invasive than hysterosalpingography for the assessment of uterine anatomy and diagnosis of müllerian duct abnormalities. The ability to visualize both the uterine cavity and the myometrium on a 3-dimensional scan facilitates the diagnosis of uterine anomalies and enables the differentiation of septate from bicornuate uteri for preoperative surgical planning.     

Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and enhances the effects of herpes simplex virus thymidine kinase gene therapy

Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increasing the BBTB delivery of GCV. In vitro, a significant bystander cytocidal effect of GCV was shown in mixed HSV-tk-transduced (HSV-tk+) and control vector-transduced (HSV-tk-) C6 glioma cultures. A dose-dependent cytotoxic effect of GCV on untransformed C6 cells was also shown. In vivo, rats with 100% HSV-tk+ or 100% HSV-tk- intracerebral C6 gliomas were treated for 7 days with intravenous infusions of GCV alone or with GCV and RMP-7 (2.5 microg/kg/day). The growth of HSV-tk+ and HSV-tk- gliomas decreased with increasing doses of GCV. A high dosage (100 mg of GCV/kg/day) eradicated all HSV-tk- and HSV-tk+ tumors. An intermediate dosage (5 mg of GCV/kg/day) reduced the growth of HSV-tk- gliomas by 42% if given alone, and by 88% in combination with RMP-7. A low dosage (0.5 mg of GCV/kg/day) in combination with RMP-7 enhanced the regression of HSV-tk+ gliomas by 87% compared with GCV alone. Low-dose GCV was ineffective in HSV-tk- tumors. RMP-7 increased [3H] GCV tumoral uptake by 2.6- and 1.7-fold in the tumor center and periphery, respectively. We conclude that RMP-7 could be an important adjunctive treatment for suicide gene therapy of brain tumors, while an RMP-7/GCV combination may also have a significant antitumor effect in untransfected gliomas.     

Teledermatology and in-person examinations: a comparison of patient and physician perceptions and diagnostic agreement

PURPOSE: The aim of this study was to assess the outcome of reoperation following photorefractive keratectomy related to different techniques. MATERIAL AND METHODS: 265 retreated eyes were divided into 5 groups; low to moderate myopia, high myopia, enlargement, abrasion, and non-compliance. The low to moderate group was further subdivided into 5 categories based on the surgical approach of the reoperation. Outcomes were compared at 12 months after reoperation. RESULTS: There was no statistically significant difference in the median refraction prior to initial PRK, before reoperation, and after reoperation between the 5 categories 66%, of all reoperated patients achieved an uncorrected visual acuity of 0.5 or better after 12 months. 72% had a postoperative refraction between +/- 1 diopter. The other 4 groups were not statistically analyzed due to the wide variety of patients included and non-compliance. CONCLUSION: In low to moderate myopes, approximately 97% achieve uncorrected visual acuity of 0.5 or better following PRK, including one reoperation.     

Ruthenium-106 brachytherapy for peripheral retinal capillary hemangioma

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ruthenium-106 brachytherapy of large peripheral retinal capillary hemangiomas. DESIGN: A retrospective case series. PARTICIPANTS: In 25 eyes of 24 patients, peripheral capillary retinal hemangiomas were treated. INTERVENTION: Brachytherapy using 106-ruthenium/106-rhodium plaques was performed. MAIN OUTCOME MEASURES: Eyes were reviewed for hemangioma regression after brachytherapy, occurrence of retinal detachment, requirement of additional vitreoretinal surgery, final visual outcome, and final retinal status. RESULTS: Preoperative mean visual acuity of all eyes treated was 20/60, mean hemangioma diameter was 3.8 mm, corresponding to approximately 2 disc diameters. In 14 eyes, the retina was attached before surgery, 8 eyes showed an exudative detachment, and 3 eyes showed a traction detachment. Fifteen patients had definite von Hippel-Lindau syndrome. Twenty-three of 25 hemangiomas could be destroyed by single brachytherapy. In 16 eyes, a favorable outcome could be achieved. In nine eyes, outcome was unfavorable, characterized by a severe drop in visual acuity, a persisting exudative retinal detachment, or a recurrent traction detachment. In one eye requiring repeated brachytherapy, irradiation retinopathy occurred. Hemangiomas up to a size of approximately 5.0 mm without preoperative exudative detachment could be treated safely by brachytherapy, whereas a larger hemangioma size or a pre-existing exudative retinal detachment predisposed to an unfavorable outcome. CONCLUSION: Solitary peripheral retinal hemangioma can be ablated effectively by ruthenium-106 brachytherapy. A favorable outcome can be expected if the hemangioma diameter is 5.0 mm or smaller and if there is no preoperative exudative retinal detachment.     

Plasma thyroid hormone kinetics are altered in iron-deficient rats

Iron deficiency anemia is associated with lower plasma thyroid hormone concentrations in rodents and, in some studies, in humans. The objective of this project was to determine if plasma triiodothyronine (T3) and thyroxine (T4) kinetics were affected by iron deficiency. Studies were done at a near-thermoneutral temperature (30 degrees C), and a cool environmental temperature (15 degrees C), to determine plasma T3 and T4 kinetics as a function of dietary iron intake and environmental need for the hormones. Weanling male Sprague-Dawley rats were fed either a low Fe diet [iron-deficient group (ID), <5 microg/g Fe] or a control diet [control group (CN), 35 microg/g Fe] at each temperature for 7 wk before the tracer kinetic studies. An additional ID group receiving exogenous thyroid hormone replacement was also used at the cooler temperature. For T4, the disposal rate was >60% lower (89 +/- 6 vs. 256 +/- 53 pmol/h, P < 0.001) in ID rats than in controls at 30 degrees C, and approximately 40% lower (192 +/- 27 vs. 372 +/- 26 pmol/h, P < 0.01) in ID rats at 15 degrees C. Exogenous T4 replacement in a cohort of ID rats at 15 degrees C normalized the T4 concentration and the disposal rate. For T3, the disposal rate was significantly lower in ID rats in a cool environment (92 +/- 11 vs. 129 +/- 11 pmol/h, P < 0.01); thyroxine replacement again normalized the T3 disposal rate (126 +/- 12 pmol/h). Neither liver nor brown fat thyroxine 5'-deiodinase activities were sufficiently different to explain the lower T3 disposal rates in iron deficiency. Thus, plasma thyroid hormone kinetics in iron deficiency anemia are corrected by simply providing more thyroxine. This suggests a central regulatory defect as the primary lesion and not peripheral alterations.     

Long-term experience with clonazepam in patients with a primary diagnosis of panic disorder

OBJECTIVE: To assess the effect of the relief of obstruction on the ultimate function of the affected renal unit in urinary tuberculosis, and to identify predictors of functional recoverability. PATIENTS AND METHODS: Of a total of 82 patients with urinary tuberculosis presenting over 7 years, 38 with evidence of upper tract obstruction were analysed. All patients were assessed with pre-operative excretory urography, urinary mycobacterial cultures and serum chemistry. Patients with subnormally functioning kidneys were assessed with baseline renal scans. Preliminary intervention in the form of JJ stenting or percutaneous nephrostomy (PCN) was carried out in patients with reasonable renal function. Function was reassessed after 4 weeks to detect evidence of improvement and factors which could affect the outcome were determined. RESULTS: Thirty-eight patients had documented upper tract obstruction, of whom six had bilateral obstruction (total of 44 renal units). Ten renal units were not functioning at presentation, with a mean (SD) glomerular filtration rate (GFR) of 3.0 (5.73) mL/min, and no preliminary intervention was performed. In the remaining 34, preliminary intervention was carried out before definitive surgery (JJ stenting in 14, PCN in 15 and PCN followed by antegrade JJ stenting in five); 21 of these renal units were salvaged but 13 were lost despite overcoming the obstruction. Three of the 13 units deteriorated from having acceptable pre-treatment GFRs to becoming non-functional. Good renal cortical thickness, a low grade of renal involvement (Semb 1 or 2), the presence of more distal disease in the form of ureteric stricture and a GFR of > 15 mL/min were good predictors of renal recovery after diversion. CONCLUSIONS: The loss of some renal units seems inevitable in patients with urinary tuberculosis, despite advances in chemotherapy. Having pre-operative predictors of renal recovery may ensure optimal patient selection, thereby reducing the number of procedures and economic burden on the patient who does not require intervention.     

Arnold-Chiari malformation in a captive African lion cub

PURPOSE: Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS: The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS: The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS: Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.