Topically applied treatments for external genital warts in nonimmunocompromised patients: a systematic review and network meta-analysis.

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02-3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12-0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.

Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Mini-Mental Status Examination as predictors of mortality in the elderly.

OBJECTIVE: Because the number of elderly is increasing worldwide, cognitive dysfunction becomes important health care issue. This study investigated the association between cognitive dysfunction and mortality in the elderly. METHOD: Data were analyzed from a longitudinal mortality follow-up study of 2712 Korean elderly aged 60 and over, examined in 2002 with complete data followed an average 6.03 years. Measurements included socio-demographic and clinical factors and Mini-Mental State Examination (MMSE). MMSE was categorized into groups with no, mild, or moderate cognitive dysfunction, and the subscores of MMSE domains were categorized into no dysfunction or dysfunction. The Cox proportional hazards models were conducted to examine the association between MMSE score and mortality, after adjusting for age, gender, education and other socio-demographic factors. RESULTS: Death during follow-up occurred in 318 subjects. The mortality risk was significantly associated with the elderly with mild cognitive dysfunction [hazard ratio (HR) = 1.93] and with moderate cognitive dysfunction (HR = 2.66). 'Orientation-to-time' (HR = 1.39) and 'Attention' (HR = 1.48) domains of MMSE were independently associated with mortality. CONCLUSION: This study showed that cognitive dysfunction independently predicted mortality in the elderly. Cognitive dysfunction should be considered part of identifying the elderly at high risk for mortality.

Increased levels of p21WAF1/Cip1 in human brain tumors.

The cdk inhibitor p21WAF1/Cip1 (p21), which can be transcriptionally activated by p53, functions to block cell cycle progression. In this study, we analysed the expression of p21 in normal and reactive brain and in gliomas of various malignancy grades. Southern blotting showed no p21 gene deletion. Western blotting and immunohistochemical assay showed that the levels of p21 protein in normal and reactive brain tissue were very low; however, p21 was elevated in a majority of gliomas tested, regardless of their malignancy grades. In glioblastoma multiforme, marked elevation of p21 was observed in samples harboring either wild-type or mutant p53. But, in anaplastic astrocytomas, the level of p21 was not elevated in samples harboring mutant-type p53. Immunohistochemical staining of paraffin-embedded astrocytomas and glioblastomas showed that tumor cells and not contaminating normal cells were positive for p21. Therefore, overexpression of p21 appears to be an early event in the development of glial neoplasms and p53-dependent p21 expression appears to be tumor grade specific.

Rapid analysis of the short tandem repeat HUMTH01 by capillary electrophoresis.

Using capillary electrophoresis, we demonstrate separation and analysis of the short tandem repeat HUMTH01 in under 10 min with 3 bp resolution. Separation of the PCR products, which range in size from 179 to 203 bp, is achieved using hydroxyethyl cellulose as the separation medium and a novel single-step voltage gradient. Internal standards on either side of the alleles are used to size the PCR products with an average standard deviation of 0.5 bp. DNA typing patterns obtained with this system are compared to samples separated by polyacrylamide slab gel electrophoresis.

Malignant intraventricular schwannoma. Case report.

The authors present the clinical, radiological, and pathological features of a malignant schwannoma occurring in the right lateral ventricle of a 40-year-old man. Metastasis to both cerebellopontine angles and to the cerebellum was found 7 months after subtotal removal of the tumor.

Bacterial expression, purification of full length and carboxyl terminal fragment of Alzheimer amyloid precursor protein and their proteolytic processing by thrombin.

Human amyloid protein precursor(APP770) and its carboxyl terminal portion (CT105) including beta/A4 domain were highly expressed using strong expression systems in E. coli. These recombinant APP peptides were purified with a combination of urea solubilization and ion-exchange chromatography and used for proteolytic processing by thrombin. Three thrombin cleavage sites were predicted by the decrease of APP770 and the appearance of M(r) 56, 27 and 18 kDa fragments containing beta/A4 domain on SDS-PAGE gel and on the immunoblot. A similar but limited proteolysis of platelet APPs exposed to thrombin resulted in the stimulated production of 60 and 27 KDa carboxyl terminal peptides containing the intact beta/A4. This thrombin mediated proteolysis was completely blocked by hirudin, the specific thrombin inhibitor. These results suggest that thrombin may play a role in altered processing of APP to generate potentially amyloidogenic intermediates in vivo leading to amyloid deposition.

Impact response of the intervertebral disc in a finite-element model.

STUDY DESIGN: A three-dimensional nonlinear poroelastic finite-element model of a vertebra disc was used to analyze the biomechanical effects of impact loading on the spinal segment. OBJECTIVES: To predict changes in biomechanical parameters such as intradiscal pressure, dynamic stiffness, stresses in the endplate region, and the shock-absorbing mechanism of the spine under different impact duration/loading rates, and to investigate the relation between the rate of loading and the fracture potential of the vertebral body. SUMMARY OF BACKGROUND DATA: It is not practical to discern the role of impact duration using experimental protocols. Analytical studies are better suited to this purpose. However, previous poroelastic finite-element models of the motion segments have dealt mostly with creep phenomena. METHODS: A three-dimensional, L3-L4 motion-segment, finite-element model was modified to incorporate the poroelastic properties of the disc, endplate, and cancellous core, and thus simulate the shock-absorbing phenomena. The results were analyzed under variable impact durations for a constant maximum compressive impact load of 3 kN. RESULTS: For a shorter impact duration and a given F(max), relatively high cancellous core pressure was generated as compared with a case of long impact duration, although the amount of impulse was increased. In contrast, relatively constant pore pressures were generated in the nucleus regardless of the impact duration. The changes in spinal segment stiffness as a function of impact duration indicated that for a shorter duration of impact, high dynamic stiffness increases the stability of the spinal segment against the impact load. However, the corresponding increase in stresses within the vertebral body and endplate may produce fractures. CONCLUSIONS: The finite-element technique was used to address the role of impact duration in producing trauma to the spinal motion segment. Within the limitations of the model, the results suggest that fractures are likely to occur under shorter impact duration conditions. Depending on the strength of the region, a fracture may be initiated in the endplate region or the posterior wall of the cortical shell. The nucleus pressure is independent of the impact duration and depends only on the magnitude of the impact force.

Changes in ulnar variance in relation to forearm rotation and grip.

We studied radiographs of the wrists of 120 healthy volunteers in order to determine the normal range of ulnar variance. They had been taken in various positions under both unloaded (static) and loaded (dynamic) conditions. Pronation posteroanterior, supination anteroposterior and neutral posteroanterior views were taken of each wrist before and during a maximum grip under identical conditions. The mean normal ulnar variance in neutral rotation was +0.74+/-1.46 mm, a value which was significantly lower in males than in females. We found negative variance in 26% of cases. We measured maximum ulnar variance (UVmax +1.52+/-1.56 mm) when gripping in pronation and minimum ulnar variance (UVmin +0.19+/-1.43 mm) when relaxed in supination. We subtracted UVmin from UVmax to calculate a mean maximum dynamic change in ulnar variance of 1.34+/-0.53 mm. We consider this database of normal values to be useful for both the diagnosis and treatment of conditions related to discrepancy in radio-ulnar length and for clinical research.

Perfusion MR imaging in gliomas: comparison with histologic tumor grade.

OBJECTIVE: To determine the usefulness of perfusion MR imaging in assessing the histologic grade of cerebral gliomas. MATERIALS AND METHODS: In order to determine relative cerebral blood volume (rCBV), 22 patients with pathologically proven gliomas (9 glioblastomas, 9 anaplastic gliomas and 4 low-grade gliomas) underwent dynamic contrast-enhanced T2*-weighted and conventional T1- and T2-weighted imaging. rCBV maps were obtained by fitting a gamma-variate function to the contrast material concentration versus time curve. rCBV ratios between tumor and normal white matter (maximum rCBV of tumor / rCBV of contralateral white matter) were calculated and compared between glioblastomas, anaplastic gliomas and low-grade gliomas. RESULTS: Mean rCBV ratios were 4.90 degrees +/- 1.01 for glioblastomas, 3.97 degrees +/- 0.56 for anaplastic gliomas and 1.75 degrees +/-1.51 for low-grade gliomas, and were thus significantly different; p <.05 between glioblastomas and anaplastic gliomas, p <.05 between anaplastic gliomas and low-grade gliomas, p <.01 between glioblastomas and low-grade gliomas. The rCBV ratio cutoff value which permitted discrimination between high-grade (glioblastomas and anaplastic gliomas) and low-grade gliomas was 2.60, and the sensitivity and specificity of this value were 100% and 75%, respectively. CONCLUSION: Perfusion MR imaging is a useful and reliable technique for estimating the histologic grade of gliomas.

Verification by polymerase chain reaction of vertical transmission of Theileria sergenti in cows.

To evaluate the transplacental transfer of Theileria sergenti infection in cattle, we used DNA probes to detect T. sergenti in 6 pregnant cows and their calves. All the animals were monitored by parasitologic, serologic, and polymerase chain reaction (PCR) assays for a predicted 875-base-pair (bp) DNA product and a 684-bp amplicon detected by nested PCR in the blood and spleens of aborted fetuses. An open reading frame (ORF) starting at nucleotide 170 and terminating at position 1021 was shown to code for a polypeptide of 283 amino acid residues. All 6 dams and 5 calves were positive for T. sergenti in all tests. One calf was positive only with nested PCR. We conclude that transplacental transmission of T. sergenti is a significant problem. The relevance of the data in the programmed introduction of new (especially pregnant) animals into established clean herds needs serious consideration with regard to control of theileriosis and other tickborne diseases.

High dose melphalan and ABMT with or without abdominal radiotherapy as consolidation treatment for ovarian carcinoma in complete remission or with microscopic residual disease.

We initiated in February 1982 a pilot study of high dose melphalan (HDM) and ABMT as consolidation treatment for ovarian carcinoma. Eleven patients entered into this study; 6 patients received HDM and ABMT (group 1), 5 patients received HDM in combination with flash abdominal radiotherapy followed by ABMT (group 2). Two of 6 group 1 patients and 3 of 5 group 2 patients are still alive with NED more than 3 years after ABMT (58+, 72+, 37+, 39+, 43+) and are hopefully cured. Main toxicity was haematological, we have not observed any death related to therapy. HDM and ABMT compared favorably with other consolidation treatments (abdominopelvic radiotherapy or IP chemotherapy) and merits a larger evaluation.

Transfer of extensor carpi radialis longus or brevis for opponensplasty.

For the restoration of thumb opposition many types of tendon transfer techniques have been described. The flexor digitorum superficialis (FDS) of the ring finger is commonly selected as a motor. On occasion, however, the quality of the flexor muscles of the fingers or wrist is not good enough for tendon transfer and another available muscle must be selected. In this situation, we have preferred to use an extensor carpi radialis longus (ECRL) or brevis (ECRB) transfer to restore opposition of the thumb. Follow-up examination, at an average 5 years and 10 months after operation, showed that the results of ten of 11 transfers were excellent and the other was good.

Reference intervals for whole blood viscosity using the analytical performance-evaluated scanning capillary tube viscometer.

OBJECTIVES: This study was performed to establish the reference intervals for whole blood viscosity (WBV) using the analytical performance-evaluated scanning capillary tube viscometer (SCTV). DESIGN AND METHODS: The analytical performance of the SCTV was evaluated using three different levels of QC materials and sixty human EDTA-blood samples. To establish the reference intervals for WBV, 297 healthy individuals (123 men and 174 women) were selected from 1083 subjects. RESULTS: Within-day precisions with QC materials and human whole blood and between-day precisions with QC materials were below 5.0%, 6.6% and 8.0% in CVs at all shear rates, respectively. Comparison tests between the SCTV and the Brookfield viscometer showed a significant correlation (R(2)=0.972, p<0.001). The reference intervals for WBV in healthy men were 3.66-5.41cP at 300s(-1) and 23.15-36.45cP at 1s(-1) while those in women were 3.27-4.32cP at 300s(-1) and 18.20-27.36cP at 1s(-1), respectively. CONCLUSIONS: Using the analytical performance-evaluated SCTV, the reference intervals for WBV were established in healthy adults, which could be beneficial to the clinical utility of WBV in the aspect of appropriate modalities for the improvement of blood viscosity.

Epidemiological characteristics of the 2002 outbreak of foot-and-mouth disease in the Republic of Korea.

The Republic of Korea experienced a foot-and-mouth disease (FMD) outbreak during May-June 2002. The present study describes epidemiological characteristics of the 2002 FMD outbreak in Korea, including the pattern of the outbreak in both time and space, transmission routes among infected farms, and control measures. One of the notable features of the 2002 FMD epidemic in Korea was that the virus infected mostly pigs [15 of 16 infected premises (IPs)], despite the presence of other susceptible animals on infected and neighbouring farms. The epidemic showed temporal clustering at 8-9 day intervals, suggesting five generations of infection during the outbreak, and 13 of 16 (81.3%) IPs were located within a 10 km-radius of the index case. The clinical signs that prompted notification of infection included vesicles around hooves and snouts. The age of lesions was significantly less among cases reported by farmers compared with veterinarians. The high awareness of farmers from an earlier FMD outbreak greatly helped the animal hygiene authority in efforts associated with disease control and eradication. The outbreak was eradicated within <2 months as a result of the intensive control efforts of the animal hygiene authorities and the cooperation of the Korean people. Although the outbreak was a costly lesson for the Korean people, the experience gained will contribute to future efforts in the prevention and control of animal infectious diseases.

Swiss population data on three tetrameric short tandem repeat loci--VWA, HUMTHO1, and F13A1--derived using multiplex PCR and laser fluorescence detection.

Allele and genotype frequencies for 3 tetrameric short tandem repeat loci VWA, HUMTHO1, and F13A1 were determined in a Swiss population sample using multiplex PCR and subsequent electrophoresis in DNA sequencing gels processed by automated laser fluorescence detection. The technique allows single base pair resolution and rapid typing, with a concomitant reduction in the potential for human transcriptional typing errors. All loci meet Hardy-Weinberg expectations. In addition, there is little evidence for association of alleles among the 3 loci. The allelic frequency data can be used in forensic analyses and paternity tests to estimate the frequency of a multiple STR locus DNA profile in the Swiss population.

Extraction strategy for obtaining DNA from bloodstains for PCR amplification and typing of the HLA-DQ alpha gene.

A simple, practical approach for the extraction of PCR-amplifiable DNA for the HLA-DQ alpha gene from bloodstains deposited on various substrates is described. DNA from bloodstains is purified using Chelex 100 ion-exchange resin and then amplified. If amplification is not achieved, the extract is washed through a Centricon 100 dialysis/concentration tube. If the second amplification of this extract produces a negative result, the extract is processed with Chelex 100 again. This approach has been found to be reliable, safe, efficient and economical.