bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgery for localized prostate cancer after renal transplantation
Authors: Hafron Jason , Fogarty James D. , Wiesen Ari , Melman Arnold
Published: January 2005

OBJECTIVE

To investigate the feasibility of perineal radical prostatectomy (RP) in renal transplant recipients with localized prostate cancer.

PATIENTS AND METHODS

The study comprised seven consecutive renal transplant patients who had a perineal RP between May 1991 and February 2004. All available clinicopathological data were reviewed.

Results

All seven patients successfully tolerated RP with no major complications. The mean (sd, range) age at surgery was 62.3 (2.5, 55–74) years and the mean interval from renal transplant to RP 86.5 (25.25, 24–192) months. There was no evidence of increased blood loss, operative duration, transfusion requirement, hospital stay or deterioration of graft function. The presence of an allograft did not alter the surgical approach or management of the patients after RP. The mean follow‐up was 22 (2–130) months and all seven patients were followed. One patient had evidence of biochemical recurrence with no radiographic evidence of metastatic disease. Serum prostate‐specific antigen was undetectable in the remaining patients.

CONCLUSION

A perineal RP in renal transplant recipients for treating localized prostate cancer offers many advantages over other treatments.
A critical review of diagnostic criteria for evaluating patients with symptomatic stress urinary incontinence
Authors: Chapple Christopher R. , Wein Alan J. , Artibani Walter , Brubaker Linda , Haab Francois , Heesakkers John P. , Lightner Deborah
Published: January 2005

The first paper in this section is a review by several highly respected authors of diagnostic criteria for evaluating patients with symptomatic stress urinary incontinence, and is followed by a review of the role of urgency and its measurement in the overactive bladder symptom syndrome, with emphasis on current concepts and future prospects. These are two important papers, which point the reader in the direction of a greater understanding of these conditions.

The concept of α‐blockade before a trial without catheter after acute urinary retention is revisited by authors from the UK, who used tamsulosin in a randomized controlled trial. They found that it is appropriate to recommend tamsulosin for such use in this condition.
The role of urinary urgency and its measurement in the overactive bladder symptom syndrome: current concepts and future prospects
Authors: Chapple Christopher R. , Artibani Walter , Cardozo Linda D. , Castro‐Diaz David , Craggs Michael , Haab Francois , Khullar Vik , Versi Eboo
Published: January 2005

OBJECTIVE

To review the concept of urinary urgency and its practical measurement in clinical trials, and advance the hypothesis that while urge is experienced by normal people, urgency is always pathological.

METHODS

According to the International Continence Society (ICS) definition, urgency is the primary symptom of the overactive bladder (OAB) syndrome, but in clinical trials there are inconsistencies in both the definition and assessment of urgency. We searched the PubMed and BIOSIS databases for publications and abstracts related to the clinical assessment of urgency in patients with OAB.

RESULTS

The differentiation of urgency from the normal physiological desire to void is discussed. In clinical studies of OAB, urgency has been measured both qualitatively and quantitatively. Existing qualitative assessment scales for urgency are deficient in accuracy, validation or both, and are largely inconsistent with the currently accepted ICS definition of urgency. The quantitative assessment of urgency by diary entry has been validated and may be the most accurate, reproducible and clinically meaningful method available for measuring this variable.

CONCLUSION

Based on the existing ICS definition of urgency as ‘a compelling desire to pass urine that is difficult to defer’, the concept of qualitative assessment of urgency may be flawed.
Tubularized‐incised plate urethroplasty in adults
Authors: Sharma Gyanendra
Published: January 2005

OBJECTIVE

To evaluate the results of tubularized incised‐plate (TIP) urethroplasty for distal and midshaft hypospadias in adults, and to underline technical aspects to decrease complications.

PATIENT AND METHODS

From December 1999 to January 2004, 13 patients with hypospadias and aged 18–26 years had a TIP urethroplasty as a primary repair. Five had distal penile and eight had midshaft hypospadias. In all cases a TIP urethroplasty was used as described for children. Urinary drainage was by a urethral Nelaton catheter connected to a urine bag.

RESULTS

The catheter was removed after 10 days and the patients asked to attend a follow‐up at 1, 3 and 6 months and then 6‐monthly; the maximum follow‐up was 3 years and the minimum was 3 months. One patient developed a fistula after the repair of distal penile hypospadias, which closed spontaneously after a month. All patients with a successful repair voided with a single straight urinary stream in a forward direction. They had a normally situated slit‐like glanular meatus.

CONCLUSION

TIP repair in adults is associated good results. There is no difference in terms of wound healing, infection, complication rates and overall success between the TIP repair in children and adults. The cosmetic and functional outcome was comparable to that in children.
Managing varicoceles in children: results with microsurgical varicocelectomy
Authors: Schiff Jonathan , Kelly Cathy , Goldstein Marc , Schelgel Peter , Poppas Dix
Published: January 2005

Authors from New York present their experience of elective varicocelectomy, using microsurgical techniques, in a large series of children. They found the procedure to be safe and effective, and gave a much lower complication rate than the published rate in open varicocelectomy.

The results of urethroplasty in post‐traumatic paediatric urethral strictures are presented by authors from Mansoura. They found the overall success of one‐stage perineal anastomotic repair of such strictures to be excellent, with very little morbidity.

OBJECTIVE

To report our experience of microsurgical subinguinal varicocelectomy in boys aged ≤ 18 years.

PATIENTS AND METHODS

Boys aged ≤ 18 years treated with microsurgical varicocelectomy between 1996 and 2000 at one institution were retrospectively reviewed. Indications for surgery included ipsilateral testicular atrophy, large varicocele or pain. Microsurgery was assisted by an operating microscope (×10–25) allowing preservation of the lymphatics, and the testicular and cremasteric arteries. Patient age, varicocele grade, complications and follow‐up interval were recorded.

RESULTS

In all there were 97 microsurgical subinguinal varicocelectomies (23 bilateral) in 74 boys (mean age 14.7 years). Left‐sided varicoceles were significantly larger (mean grade 2.9) than right‐sided (mean grade 1.4) varicoceles. The mean follow‐up was 9.6 months. There were four complications: two hydroceles, of which one resolved spontaneously after 4 months; one patient had persistent orchialgia that resolved after 8 months; and one developed hypertrophic scarring at the inguinal incision site. There were no infections, haematomas or intraoperative injuries to the vas deferens or testicular arteries. All boys were discharged home on the day of surgery.

CONCLUSIONS

Microsurgical subinguinal varicocelectomy in boys is a safe, minimally invasive and effective means of treating varicoceles. Compared with published results of the retroperitoneal mass ligation technique, which has a 15% overall complication rate and a 7–9% hydrocele occurrence rate, the microsurgical subinguinal approach appears to offer less morbidity, with a 1% hydrocele rate. We consider that microsurgical subinguinal varicocelectomy offers the best results with lower morbidity than other techniques.
Ectopic adrenocortical tissue found at groin exploration in children: incidence in relation to diagnosis, age and sex
Authors: Sullivan Jonathan G. , Gohel Manj , Kinder Richard B.
Published: January 2005

OBJECTIVE

To assess the incidence of ectopic adrenocortical tissue (EACT) in the groin in children, and examine the relationship between the incidence and the underlying diagnosis, age and sex.

PATIENTS AND METHODS

From computer records, all groin explorations between 1988 and 2002 in patients ≤15 years old were identified. Cases of EACT were identified from computer histology records, and the incidence in different groups compared.

RESULTS

Of 935 groin explorations, EACT was identified in 25 (2.7%); there were no cases in girls. The incidence was 0.7% at inguinal herniotomy (IH), 4.1% at ligation of the patent processus vaginalis for communicating hydrocele (P = 0.03 vs IH), and 3.3% at exploration for undescended testes (P = 0.02 vs IH). In boys with undescended testes the incidence of EACT was similar in different age groups (0–7 years, 3.3%; 8–15 years 3.2%, P= 0.96).

CONCLUSIONS

The overall incidence of EACT at groin exploration was 2.7%, with none detected in girls. There was no evidence of involution of EACT with increasing age. The incidence of EACT varied with the underlying diagnosis, but the reason for this is unknown.
Cystitis glandularis in children
Authors: Capozza Nicola , Collura Giuseppe , Nappo Simona , De Dominicis Mauro , Francalanci Paola , Caione Paolo
Published: January 2005

OBJECTIVE

To assess the characteristics of cystitis glandularis in children.

PATIENTS AND METHODS

Three cases of cystitis glandularis in children are described, occurring in boys aged 9–13 years. The presenting symptoms were gross haematuria in the first patient and frequency and urgency in the second. The third patient was asymptomatic and the lesion appeared as a wide thickening of the bladder wall on follow‐up ultrasonography for previous surgery. In all patients, a polypoid bladder mass was found at cystoscopy and diagnosed at histology. The endoscopic resection, with long‐term antibiotic prophylaxis, was the treatment of choice, with no recurrence at 12–30 months of follow‐up.

CONCLUSION

Cystitis glandularis has been rarely described in children, and is probably related to chronic or recurrent infections or an inflammatory reaction. Its potential premalignant significance is still the subject of debate.
Inhibition of Ki‐67 in a renal cell carcinoma severe combined immunodeficiency disease mouse model is associated with induction of apoptosis and tumour growth inhibition
Authors: Kausch Ingo , Jiang Hai , Ewerdwalbesloh Nina , Doehn Christian , Krüger Stefan , Sczakiel Georg , Jocham Dieter
Published: January 2005

OBJECTIVE

To evaluate the effects of suppressing the expression of Ki‐67 (expressed in proliferating cells) by antisense oligonucleotides (asON) directed against Ki‐67 (which specifically inhibit the proliferation of tumour cells and tumour growth in cell culture and in subcutaneous murine tumour models) on the growth, cell viability and angiogenic activity of a preclinical renal cell carcinoma (RCC) severe combined immunodeficiency disease (SCID) mouse model.

MATERIALS AND METHODS

Human RCC cells (SK‐RC‐35) were incubated with asON and control ON in the presence of a cationic lipid in monolayer cell culture. To test Ki‐67 as a target for antitumour therapy in more complex models, asON were administered to three‐dimensional RCC (SK‐RC‐35) spheroid cultures and to SCID mice bearing subcutaneous SK‐RC‐35 xenografts. For animal studies, 1 × 106 SK‐RC‐35 cells were implanted subcutaneously. Subsequently, asON or ON were injected intraperitoneally daily for 14 days at 10 mg/kg/day. Tumour size, weight and status of metastasis were documented daily and after death, respectively. The number of apoptotic cells, Ki‐67‐positive cells and the microvessel density in tumour sections was determined immunohistochemically. Quantitative reverse transcription‐polymerase chain reaction of Ki‐67 mRNA was also assessed for the tumours.

RESULTS

Treatment of RCC cells with asON resulted in a specific inhibition of cell growth in monolayer and spheroid cell culture. Systemic administration of Ki‐67‐directed asON significantly decreased tumour growth (P = 0.009) in SCID mice. Immunohistochemical staining of tumour specimens showed stronger inhibition of Ki‐67‐positive cells in asON‐treated tumours (mean 27.8%) than in controls (mean 42.5–57%). Furthermore, there were about twice as many apoptotic cells after asON treatment. There was no significant difference among treatment groups for microvessel density.

CONCLUSION

These results indicate that Ki‐67 represents a suitable antiproliferative target, and that asON are a potent agent inhibiting tumour growth and apoptosis, but not tumour vascularization, in human RCC.
Evaluation of hypoxia‐inducible factor 1α overexpression as a predictor of tumour recurrence and progression in superficial urothelial bladder carcinoma
Authors: Theodoropoulos Vasilios. E. , Lazaris Andreas. C. , Kastriotis Ioannis , Spiliadi Chariclia , Theodoropoulos George E. , Tsoukala Vasiliki , Patsouris Efstratios , Sofras Frank
Published: January 2005

OBJECTIVES

To investigate the possible role of hypoxia‐inducible factor 1α (HIF‐1α, a transcription factor important in regulating O2 homeostasis and physiological responses to oxygen deprivation) in the recurrence and progression of superficial urothelial bladder cancer, and to examine its expression in relation to proliferation status, apoptotic activity and intratumoral angiogenesis.

PATIENTS AND METHODS

Paraffin wax‐embedded tissue from 140 patients with superficial primary urothelial bladder carcinoma was immunostained for HIF‐1α, Ki‐67, single‐stranded DNA antibody for apoptotic cells, p53, bcl‐2, vascular endothelial growth factor and CD31 antigen. We calculated the proliferative rate, the apoptotic index and the microvessel density (MVD). The mean (sem) follow‐up was 46 (3.5) months, within which 86 patients relapsed while 18 progressed to a higher tumour stage and/or grade.

RESULTS

HIF‐1α expression was more common in high‐grade superficial urothelial carcinomas. The positivity was related to increased proliferative activity (P = 0.012), apoptotic rate (P = 0.006) and MVD (P < 0.001). HIF‐1α overexpression had a marginal adverse influence on progression‐free survival (P = 0.058; univariate analysis), but when combined with p53 overexpression, the unfavourable impact was statistically important (P = 0.028). In multivariate analysis, only grade and the high Ki‐67 labelling index were significant predictors of recurrence‐free survival, while T‐stage and the HIF‐1α+/p53+ phenotype emerged as the only independent variables of adverse prognostic significance for time to progression.

CONCLUSIONS

HIF‐1α overexpression combined with aberrant mutant p53 nuclear protein accumulation seem to indicate an aggressive phenotype, suggesting a potential biological model predictive of future risk of disease progression in patients with superficial urothelial bladder carcinoma. These indicators may be helpful in clinical practice to discriminate superficial bladder cancer worth a more intensive follow‐up, or more aggressive treatment.
Interleukin‐4 gene intron‐3 polymorphism is associated with transitional cell carcinoma of the urinary bladder
Authors: Tsai Fuu‐Jen , Chang Chao‐Hsiang , Chen Chang‐Chung , Hsia Te‐Chun , Chen Huey‐Yi , Chen Wen‐Chi
Published: January 2005

OBJECTIVE

To evaluate whether polymorphism of the interleukin‐4 gene exon 3, and of the interleukin‐1β gene exon 5 and promoter region, are associated with transitional cell carcinoma (TCC) of the urinary bladder, as cytokines are hypothesized to be important in cancer formation.

PATIENTS, SUBJECTS AND METHODS

The study included 138 patients with TCC of urinary bladder and 105 healthy controls living in the same area. Each genetic polymorphism was typed using polymerase chain reaction‐based restriction analysis. Genotype distribution and allelic frequencies between patients and controls were compared.

RESULTS

There were significant differences in genotype and allelic distribution of intron 3 RP1/RP2 polymorphism (P < 0.001), but no significant difference in genotype distribution or allelic frequencies of the interleukin‐1β gene polymorphism between patients with bladder cancer and controls.

CONCLUSION

The interleukin‐4 gene intron 3 polymorphism is associated with bladder cancer and is a potential genetic marker in screening for the possible causes of bladder cancer.
In vivo accumulation of different hypericin ion pairs in the urothelium of the rat bladder
Authors: Huygens Ann , Kamuhabwa Appolinary R. , Van Cleynenbreugel Ben , Van Poppel Hendrik , Roskams Tania , De Witte Peter A.M.
Published: January 2005

OBJECTIVE

To optimise the diagnostic and phototherapeutic efficacy of hypericin in superficial bladder cancer, by developing a bladder instillation fluid that does not depend on the presence of plasma proteins for an appropriate and reliable urothelial uptake of hypericin.

MATERIALS AND METHODS

Sodium hypericinate (in distilled water, in sodium phosphate buffer, or in polyethylene glycol) and several other hypericinate salts (potassium, lysine, TRIS or hexylamine) were instilled with no plasma constituents into the rat bladder. The accumulation of hypericin was assessed with fluorescence microscopy.

RESULTS

The diagnostic and phototherapeutic efficacy of hypericin depends on its ability to penetrate the tumour lesions sufficiently to show a fluorescent signal or elicit a photodynamic response. Several instillation fluids meet the purpose, as the urothelial accumulation of hypericin was similar to that obtained with the instillation fluid supplemented with plasma proteins, used in clinical practice. The highest concentrations of hypericin in the urothelium of the rat bladder were obtained with hypericin instillation solutions prepared with distilled water or 20% polyethylene glycol 400 in distilled water. Fluorescence microscopy showed that hypericin was selectively localized in the urothelium. Furthermore, all variables investigated (hydrophilic/lipophilic balance, pH, saline, presence of organic solvent) can dramatically influence the in vivo accumulation of hypericin.

CONCLUSION

An appropriate and reliable urothelial uptake of hypericin does not depend on the presence of plasma protein supplements in the bladder instillation fluid.
Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy
Authors: Røste L. S. , Taubøll E. , Mørkrid L. , Bjørnenak T. , Sætre E. R. , Mørland T. , Gjerstad L.
Published: January 2005

Disturbances of reproductive endocrine hormones are more often found in men with epilepsy than in the general population. There is an ongoing debate whether this can be attributed to chronic use of antiepileptic drugs or to the epilepsy itself. The aim of the present study was to evaluate the degree of endocrine disturbances in men with epilepsy compared with healthy controls, and to investigate whether there was a drug‐specific effect of valproate (VPA) or carbamazepine (CBZ). Men with epilepsy, 20–40 years old, having used either VPA (n = 16) or CBZ (n = 19) as monotherapy for >2 years were included and compared with age‐matched controls. Men with epilepsy (VPA + CBZ) had significantly lower FSH values and higher C‐peptide values compared with controls. Regarding possible drug‐specific effects, the VPA treated patients had significantly higher dehydroepiandrosterone (DHEAS) levels and lower FSH and LH concentrations compared with the controls, whereas there were no differences in testosterone, testosterone/sexhormone‐binding globulin (SHBG) ratio or androstenedione levels. Men on VPA also had significantly lower free carnitine/total carnitine, which may have implications for sperm motility, and also higher insulin and C‐peptide concentrations. The CBZ treated patients had significantly lower testosterone/SHBG ratio than the controls. Compared with the CBZ treated patients, men on VPA had significantly higher DHEAS concentrations and lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) as well as a lower free carnitine/total carnitine ratio. A marked age dependency was found in all three groups regarding several of the endocrine hormones. In conclusion, drug‐specific endocrine effects of VPA and CBZ were found in men with epilepsy. Long‐term VPA treatment leads to significant changes in DHEAS, FSH, LH, insulin, C‐peptide and carnitine ratio. Long‐term CBZ treatment leads to significant lower testosterone/SHBG ratio. A strict age matching were found to be of importance in the evaluation of endocrine function in men.
Postural stability of Parkinson's disease patients is improved by decreasing rigidity
Authors: Bartolić A. , Pirtošek Z. , Rozman J. , Ribarič S.
Published: January 2005

Postural instability has a big impact on the quality of life of patients with Parkinson's disease (PD) as it often leads to an insecure stance and fall. We investigated if postural stability in these patients improves by decreasing rigidity with a dopaminergic agonist. In our study, we tested eight PD patients with no concomitant diseases. Their age was 61 ± 2 years (mean ± SE) and their Hoehn‐Yahr score was 3 ± 0.1. The patients were evaluated according to the Unified Parkinson's Disease Rating Scale for motor function (mUPDRS) and with stabilometric measurements of forward–backward and side‐to‐side body oscillations during free stance with eyes open. Both evaluations were performed in an ‘off’ state and in an apomorphine‐induced ‘on’ state. As expected, the mUPDRS score was significantly decreased in the ‘on’ state with posture being improved in six patients, gait in eight patients and postural stability in seven of eight patients. In addition, apomorphine caused a significant reduction of the relative amplitude of lower frequencies and an increase of the relative amplitude of higher frequencies of forward–backward body oscillations. The results of stabilometry and mUPDRS evaluations are in agreement with the effect of apomorphine on rigidity, indicating that postural stability of PD patients is improved by decreasing rigidity.
Fall‐related brain injuries and the risk of dementia in elderly people: a population‐based study
Authors: Luukinen H. , Viramo P. , Herala M. , Kervinen K. , Kesäniemi Y. A. , Savola O. , Winqvist S. , Jokelainen J. , Hillbom M.
Published: January 2005

Severe head injury in early adulthood may increase the risk of dementia in older age, but it is not known whether head injury in later life also increases the risk of dementia. A representative sample (82%) of persons aged 70 years or older with a Mini‐Mental State Examination (MMSE) test score of ≥26 (n = 325) were followed‐up for 9 years to record all their fall‐related head injuries resulting in traumatic brain injury (TBI). At the end of the follow‐up period, 152 persons (81% of the surviving population) were examined for clinical dementia, according to DSM‐IV criteria. Eight persons sustained a TBI and 34 developed dementia. Brain injury was associated with younger age at detection of dementia even when adjusted for sex and educational status (low educational status significantly associated with dementia); age‐specific hazard ratio (95% confidence interval) 2.80 (1.35–5.81). In a population scoring ≥28 points in the baseline MMSE an apolipoprotein E (ApoE) ɛ4 phenotype was also associated with younger age at the time of detecting dementia; 3.56 (1.35–9.34), and the effect of brain injury and ApoE ɛ4 phenotype was synergistic; 7.68 (2.32–25.3). We conclude that fall‐related TBI predicts earlier onset of dementia and the effect is especially high amongst subjects who carry the ApoE ɛ4 allele.
Intracranial arterial and arteriovenous malformations presenting with infarction. Lausanne Stroke Registry study*
Authors: Herzig R. , Bogousslavsky J. , Maeder P. , Maeder‐Ingvar M. , Reichhart M. , Urbano L. A. , Leemann B.
Published: January 2005

Cerebral aneurysms and arteriovenous malformations (AVMs) are well‐known sources of intracranial hemorrhage, but can also manifest as other clinical symptoms or remain clinically asymptomatic. The aim was to document and analyze cases of aneurysm or AVM with brain infarction. Survey on 4804 stroke patients treated at the Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland between 1978 and 2000 using the Lausanne Stroke Registry. Twenty patients presented with cerebral aneurysm and 21 with cerebral AVM. Hemorrhage was present in 100% of the AVM and in 75% of the aneurysm patients; in one (5%) of the remaining aneurysm patients, aneurysm and infarction were located in different territories. Infarction associated with Sylvian artery aneurysm was found in three (15%), vertebrobasilar ischemia because of fusiform left vertebral artery aneurysm in one (5%), and dural fistula draining to the distal transversal and left sigmoid sinus associated with a stroke in the territory of the left anterior inferior cerebellar artery in one patient. Ischemic stroke is infrequent, but important, complication in unruptured intracranial aneurysms and AVMs. The early recognition and therapy of these vascular malformations in selected patients can avoid a major neurological deficit or death caused by their rupture.
Association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy
Authors: Kountouras J. , Deretzi G. , Zavos C. , Karatzoglou P. , Touloumis L. , Nicolaides T. , Chatzopoulos D. , Venizelos I.
Published: January 2005

The aim of this study was to investigate a possible association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Of 17 consecutive patients with Guillain–Barré syndrome (GBS), 13 patients (six females; mean age 50 ± 24 years) with AIDP were investigated. Clinical status was evaluated according to Hughes’ score, and electrophysiological tests were performed within 2 weeks from disease onset. Helicobacter pylori infection was detected histologically and serum H. pylori‐specific IgG antibodies were analysed by ELISA. Twenty asymptomatic patients (12 females; mean age 63 ± 8 years), undergoing upper gastrointestinal endoscopy for investigation of mild iron deficiency anaemia, served as controls. Helicobacter pylori was found in 12 of 13 AIDP patients (92%), and in 10 of 20 controls (50%), (P = 0.02). Electrophysiological studies showed demyelination in all AIDP patients. High levels of anti‐H. pylori IgG antibodies correlated with advanced clinical status. Five of seven AIDP patients with high levels of anti‐H. pylori IgG antibodies had delayed F‐wave latencies, indicating affection of proximal segments of peripheral nerves. Helicobacter pylori infection seems to be more frequent in AIDP patients. Anti‐H. pylori titre might reflect advanced clinical status. Anti‐H. pylori IgG antibodies are also associated with involvement of the proximal parts of peripheral nerves in AIDP.
Critical reappraisal of referrals to electromyography and nerve conduction studies*
Authors: Podnar S.
Published: January 2005

A large number of examinees referred to electromyographic (EMG) laboratories do not have symptoms or signs suggestive of a peripheral nervous system disorder, and the aim of the present study was to check this. All examinees evaluated by the author in a ‘general’ EMG laboratory in the first 4 months of 2002 were included. Data on examinees, referral physicians and diagnoses, clinical symptoms and signs, and electrodiagnostic findings were statistically evaluated. Three hundred examinees, 42% men, were included. A neurological diagnosis was provided in 55% of referrals. Electrodiagnostic abnormalities were found in 45% of examinees. Using multivariate statistics, a positive effect of neurological referral diagnosis, history of paraesthesias and of weakness and sensory loss on examination, and a negative effect of history of pain on pathological electrodiagnostic findings were found. Except 20 patients with carpal tunnel syndrome, no patient with normal clinical examination had abnormal electrodiagnostic findings. Our study confirmed the inappropriateness of referrals to electrodiagnostic examination to screen patients for peripheral nervous disorders. We propose electrodiagnostic examination mainly of patients with unequivocal clinical signs of a peripheral nervous system lesion and of patients with typical symptoms of the carpal tunnel syndrome.
Clinical features associated with medically unexplained stroke‐like symptoms presenting to an acute stroke unit
Authors: Nazir F. S. , Lees K. R. , Bone I.
Published: January 2005

In many areas of secondary care, symptoms unexplained by disease account for around one‐third of all patients seen. We sought to investigate patients presenting with medically unexplained stroke‐like symptoms to identify distinguishing features which may help to identify a non‐organic aetiology. Patients given a discharge diagnosis of medically unexplained stroke‐like symptoms over the preceding 11 years were identified retrospectively from a prospectively completed stroke unit database. Age‐ and sex‐matched controls with ischaemic or haemorrhagic stroke or transient ischaemic attack were also identified. Clinical features on presentation, ischaemic risk factors, alcohol history, marital status and history of depression or anxiety were examined. Previous or subsequent admissions with medically unexplained syndromes were also examined via record linkage with hospital discharge records. A medically unexplained syndrome was assumed to be present if an International Classification of Diseases 9 discharge code for one or more of the thirteen conditions forming recognized functional syndromes was given. Logistic regression was applied to determine predictors of non‐organicity. One hundred and five patients and controls, 1.6% of all stroke unit admissions were identified, 62% (65 patients) were females. Mean age was 50.3 ± 14.9. Compared with age‐ and sex‐matched controls patients with medically unexplained stroke‐like symptoms were significantly more probable to have a headache at presentation (47% vs. 26%, P = 0.0004), have a diagnosis of one or more additional medically unexplained syndromes (24% vs. 11%, P = 0.007) but significantly less probable to present with symptoms of vertebrobasilar dysfunction (32% vs. 61%, P < 0.0001). A history of anxiety or depression, as recorded in the notes, was not found to be associated with a medically unexplained presentation. Medically unexplained stroke‐like presentations are common (1.6% of all stroke presentations), they are most strongly predicted by the presence of other functional somatic syndromes, headache and the absence of symptoms of vertebrobasilar dysfunction.
Effects of power training on muscle structure and neuromuscular performance
Authors: Kyröläinen H. , Avela J. , McBride J. M. , Koskinen S. , Andersen J. L. , Sipilä S. , Takala T. E. S. , Komi P. V.
Published: January 2005

The present study examines changes in muscle structure and neuromuscular performance induced by 15 weeks of power training with explosive muscle actions. Twenty‐three subjects, including 10 controls, volunteered for the study. Muscle biopsies were obtained from the gastrocnemius muscle before and after the training period, while maximal voluntary isometric contractions (MVC) and drop jump tests were performed once every fifth week. No statistically significant improvements in MVC of the knee extensor (KE) and plantarflexor muscles were observed during the training period. However, the maximal rate of force development (RFD) of KE increased from 18 836±4282 to 25 443±8897 N (P<0.05) during the first 10 weeks of training. In addition, vertical jump height (vertical rise of the center of body mass) in the drop jump test increased significantly (P<0.01). Simultaneously, explosive force production of KE muscles measured as knee moment and power increased significantly; however, there was no significant change (P>0.05) in muscle activity (electromyography) of KE. The mean percentage for myosin heavy chain and titin isoforms, muscle fiber‐type distributions and areas were unchanged. The enhanced performance in jumping as a result of power training can be explained, in part, by some modification in the joint control strategy and/or increased RFD capabilities of the KE.
Sonographic evaluations in elite college baseball athletes
Authors: Wang Hsing‐Kuo , Lin Jau‐Jia , Pan Shin‐Liang , Wang Tyng‐Guey
Published: January 2005

This study compared the thickness of the biceps and supraspinatus tendons, the widths of the subacromial space in the frontal and scapular planes, and abnormal sonographic findings in the shoulders of injured, and uninjured elite college baseball athletes and healthy controls. This study recruited two groups of 42 and 12 athletes, with and without histories of shoulder injuries, respectively, as well as one control group of 16 college students who were matched for physical characteristics but not involved in sports. The results showed that the thickness of the biceps and supraspinatus tendons and the subacromial space widths at 0° and 90° shoulder abduction in the frontal plane were significantly greater in the athletes than in the controls (P‐values <0.004). The occurrences of the acromioclavicular joint bulging, bicep tendon degeneration, infraspinatus tendon degeneration and infraspinatus cortical irregularity differ significantly between the injured athlete and the group of uninjured athletes and controls (P‐values <0.05). However, only infraspinatus tendon degeneration corresponded to the injury histories. There was a high similarity of sonographic spectrum of abnormal findings among the groups. Longitudinal follow‐ups are required to determine the clinical importance of the sonographic spectrums and the occurrences of abnormal finding in asymptomatic athletes' shoulders.
Skeletal muscle adaptation: training twice every second day versus training once daily
Authors: Hansen A. K. , Fischer C. , Plomgaard P. , Andersen J. L. , Saltin B. , Pedersen B. K.
Published: January 2005

Low muscle glycogen content has been demonstrated to enhance transcription of a number of genes involved in training adaptation. These results made us speculate that training at a low muscle glycogen content would enhance training adaptation. We therefore performed a study in which seven healthy untrained males performed one‐knee legged exercise training at a low glycogen (Low) protocol, whereas the other leg was trained at a high glycogen (High) protocol. Both legs were trained equally regarding workload and training amount. Day one: Both legs (Low+High) were trained for 1 h followed by 2 h of rest at a fasting state, where after one leg (Low) was trained for one more hour. Day 2: Only one leg (High) trained for 1 h. Days 1 and 2 were repeated for 10 weeks. As an effect of training, the increase in maximal workload was identical for the two legs. However, time till exhaustion at 90% was markedly more increased in the Low leg compared with the High leg. Resting muscle glycogen and the activity of the mitochondrial enzyme hydroxyacyl CoA dehydrogenase (HAD) increased with training, but only significantly so in LOW, whereas citrate synthase (CS) activity increased in both low and high. There was a more pronounced increase in CS activity when Low was compared with High. In conclusion, the present study suggests that training twice every second day may be superior to daily training.
Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly
Authors: Wiethoff Christopher M. , Wodrich Harald , Gerace Larry , Nemerow Glen R.
Published: January 2005

In contrast to enveloped viruses, the mechanisms involved in membrane penetration by nonenveloped viruses are not as well understood. In these studies, we determined the relationship between adenovirus (Ad) capsid disassembly and the development of membrane lytic activity. Exposure to low pH or heating induced conformational changes in wild-type Ad but not in temperature-sensitive Ad (
ts
1) particles that fail to escape the early endosome. Wild-type Ad but not
ts
1 particles permeabilized model membranes (liposomes) and facilitated the cytosolic delivery of a ribotoxin. Alterations in wild-type Ad capsids were associated with the exposure of a pH-independent membrane lytic factor. Unexpectedly, this factor was identified as protein VI, a 22-kDa cement protein located beneath the peripentonal hexons in the viral capsid. Recombinant protein VI and preprotein VI, but not a deletion mutant lacking an N-terminal amphipathic α-helix, possessed membrane lytic activity similar to partially disassembled virions. A new model of Ad entry is proposed based on our present observations of capsid disassembly and membrane penetration.
Interactions between Natural Killer Cells and Antibody Fc Result in Enhanced Antibody Neutralization of Human Immunodeficiency Virus Type 1
Authors: Forthal Donald N. , Landucci Gary , Phan Tran B. , Becerra Juan
Published: January 2005

Antibodies can prevent lentivirus infections in animals and may play a role in controlling viral burden in established infection. In preventing and particularly in controlling infection, antibodies likely function in the presence of large quantities of virus. In this study, we explored the mechanisms by which antibodies neutralize large inocula of human immunodeficiency virus type 1 (HIV-1) on different target cells. Immunoglobulin G (IgG) from HIV-infected patients was tested for neutralizing activity against primary R5 strains of HIV-1 at inocula ranging from 100 to 20,000 50% tissue culture infective doses. At all virus inocula, inhibition by antibody was enhanced when target cells for virus growth were monocyte-depleted, peripheral blood mononuclear cells (PBMCs) rather than CD4+lymphocytes. However, enhanced inhibition on PBMCs was greatest with larger amounts of virus. Depleting PBMCs of natural killer (NK) cells, which express Fc receptors for IgG (FcγRs), abrogated the enhanced antibody inhibition, whereas adding NK cells to CD4+lymphocytes restored inhibition. There was no enhanced inhibition on PBMCs when F(ab′)2was used. Further experiments demonstrated that the release of β-chemokines, most likely through FcγR triggering of NK cells, contributed modestly to the antiviral activity of antibody on PBMCs and that antibody-coated virus adsorbed to uninfected cells provided a target for NK cell-mediated inhibition of HIV-1. These results indicate that Fc-FcγR interactions enhance the ability of antibody to neutralize HIV-1. Since FcγR-bearing cells are always present in vivo, FcγR-mediated antibody function may play a role in the ability of antibody to control lentivirus infection.
Leucine-Specific, Functional Interactions between Human Immunodeficiency Virus Type 1 Nef and Adaptor Protein Complexes
Authors: Coleman Scott H. , Van Damme Nanette , Day John R. , Noviello Colleen M. , Hitchin Douglas , Madrid Ricardo , Benichou Serge , Guatelli John C.
Published: January 2005

The human immunodeficiency virus type 1 virulence protein Nef interacts with the endosomal sorting machinery via a leucine-based motif. Similar sequences within the cytoplasmic domains of cellular transmembrane proteins bind to the adaptor protein (AP) complexes of coated vesicles to modulate protein traffic, but the molecular basis of the interactions between these motifs and the heterotetrameric complexes is controversial. To identify the target of the Nef leucine motif, the native sequence was replaced with either leucine- or tyrosine-based AP-binding sequences from cellular proteins, and the interactions with AP subunits were correlated with function. Tyrosine motifs predictably modulated the interactions between Nef and the μ subunits of AP-1, AP-2, and AP-3; heterologous leucine motifs caused little change in these interactions. Conversely, leucine motifs mediated a ternary interaction between Nef and hemicomplexes containing the σ1 plus γ subunits of AP-1 or the σ3 plus δ subunits of AP-3, whereas tyrosine motifs did not. Similarly, only leucine motifs supported the Nef-mediated association of AP-1 and AP-3 with endosomal membranes in cells treated with brefeldin A. Functionally, Nef proteins containing leucine motifs down-regulated CD4 from the cell surface and enhanced viral replication, whereas those containing tyrosine motifs were inactive. Apparently, the interaction of Nef with the μ subunits of AP complexes is insufficient for function. A leucine-specific mode of interaction that likely involves AP hemicomplexes is further required for Nef activity. The μ and hemicomplex interactions may cooperate to yield high avidity binding of AP complexes to Nef. This binding likely underlies the unusual ability of Nef to induce the stabilization of these complexes on endosomal membranes, an activity that correlates with enhancement of viral replication.
Inhibition of Beta Interferon Induction by Severe Acute Respiratory Syndrome Coronavirus Suggests a Two-Step Model for Activation of Interferon Regulatory Factor 3
Authors: Spiegel Martin , Pichlmair Andreas , Martínez-Sobrido Luis , Cros Jerome , García-Sastre Adolfo , Haller Otto , Weber Friedemann
Published: January 2005

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus termed SARS-CoV. We and others have previously shown that the replication of SARS-CoV can be suppressed by exogenously added interferon (IFN), a cytokine which is normally synthesized by cells as a reaction to virus infection. Here, we demonstrate that SARS-CoV escapes IFN-mediated growth inhibition by preventing the induction of IFN-β. In SARS-CoV-infected cells, no endogenous IFN-β transcripts and no IFN-β promoter activity were detected. Nevertheless, the transcription factor interferon regulatory factor 3 (IRF-3), which is essential for IFN-β promoter activity, was transported from the cytoplasm to the nucleus early after infection with SARS-CoV. However, at a later time point in infection, IRF-3 was again localized in the cytoplasm. By contrast, IRF-3 remained in the nucleus of cells infected with the IFN-inducing control virus Bunyamwera delNSs. Other signs of IRF-3 activation such as hyperphosphorylation, homodimer formation, and recruitment of the coactivator CREB-binding protein (CBP) were found late after infection with the control virus but not with SARS-CoV. Our data suggest that nuclear transport of IRF-3 is an immediate-early reaction to virus infection and may precede its hyperphosphorylation, homodimer formation, and binding to CBP. In order to escape activation of the IFN system, SARS-CoV appears to block a step after the early nuclear transport of IRF-3.
Human Cytomegalovirus Genes in the 15-Kilobase Region Are Required for Viral Replication in Implanted Human Tissues in SCID Mice
Authors: Wang Weijia , Taylor Shannon L. , Leisenfelder Stacey A. , Morton Robert , Moffat Jennifer F. , Smirnov Sergey , Zhu Hua
Published: January 2005

Since animal models for studying human cytomegalovirus (HCMV) replication in vivo and pathogenesis are not available, severe combined immunodeficiency mice into which human tissues were implanted (SCID-hu mice) provide an alternative and valuable model for such studies. The HCMV clinical isolates, including those of the Toledo strain, replicate to high titers in human tissue implanted into SCID mice; however, the attenuated AD169 strain has completely lost this ability. The major difference between Toledo and AD169 is a 15-kb segment, encoding 19 open reading frames, which is present in all virulent strains but deleted from attenuated strains. This fact suggests that crucial genes required for HCMV replication in vivo are localized to this region. In this study, the importance of this 15-kb segment for HCMV replication in vivo was determined. First, Toledo
BAC
virus (produced from a Toledo bacterial artificial chromosome) and AD169 virus were tested for growth in SCID-hu mice. Toledo
BAC
, like Toledo, grew to high titers in implanted human thymus and liver tissues, while AD169 did not. This outcome showed that the Toledo genome propagated in bacteria (Toledo
BAC
) retained its virulence. The 15-kb segment was then deleted from Toledo
BAC
, and the resulting virus, Toledo
Δ15kb
, was tested for growth in both human foreskin fibroblast (HFF) cells and SCID-hu mice. Toledo
Δ15kb
had a minor growth defect in HFF but completely failed to replicate in human thymus and liver implants. This failure to grow was rescued when the 15-kb region was inserted back into the Toledo
Δ15kb
genome. These results directly demonstrated that the genes located in the 15-kb segment are crucial for HCMV replication in vivo.
Human Dendritic Cells Transduced with Herpes Simplex Virus Amplicons Encoding Human Immunodeficiency Virus Type 1 (HIV-1) gp120 Elicit Adaptive Immune Responses from Human Cells Engrafted into NOD/SCID Mice and Confer Partial Protection against HIV-1 Challenge
Authors: Gorantla Santhi , Santos Kathlyn , Meyer VaKara , Dewhurst Stephen , Bowers William J. , Federoff Howard J. , Gendelman Howard E. , Poluektova Larisa
Published: January 2005

Small-animal models are needed to test human immunodeficiency virus (HIV) vaccine efficacy following viral challenge. To this end, we examined HIV-1-specific immune responses following immunization of nonobese diabetic-severe combined immunodeficient mice that were repopulated with human peripheral blood lymphocytes (hu-PBL-NOD/SCID mice). Autologous dendritic cells (DC) were transduced ex vivo with replication-defective, helper virus-free, herpes simplex virus type 1 (HSV-1) amplicons that expressed HIV-1 gp120 and were then injected into the hu-PBL-NOD/SCID mice. This resulted in primary HIV-1-specific humoral and cellular immune responses. Serum samples from vaccinated animals contained human immunoglobulin G that reacted with HIV-1 Env proteins by enzyme-linked immunosorbent assay and neutralized the infectivity of HIV-1 LAI and ADA strains. T cells isolated from the mice responded to viral antigens by producing gamma interferon when analyzed by enzyme-linked immunospot assay. Importantly, exposure of the vaccinated animals to infectious HIV-1 demonstrated partial protection against infectious HIV-1 challenge. This was reflected by a reduction in HIV-1ADAand by protection of the engrafted human CD4+T lymphocytes against HIV-1LAI-induced cytotoxicity. These data demonstrate that transduction of DC by HSV amplicon vectors expressing HIV-1 gp120 induce virus-specific immune responses in hu-PBL-NOD/SCID mice. This mouse model may be a useful tool to evaluate human immune responses and protection against viral infection following vaccination.
The Second Open Reading Frame of the Avian Reovirus S1 Gene Encodes a Transcription-Dependent and CRM1-Independent Nucleocytoplasmic Shuttling Protein
Authors: Costas Celina , Martínez-Costas José , Bodelón Gustavo , Benavente Javier
Published: January 2005

It was previously shown that the second open reading frame of the avian reovirus S1 gene encodes a 146-amino-acid nonstructural protein, designated p17, which has no known function and no sequence similarity to other known proteins. The results presented in this report demonstrate that p17 accumulates in the nucleoplasm of infected and transfected cells. An examination of the deduced amino acid sequence of p17 revealed the presence of a putative monopartite nuclear localization signal (NLS) between residues 119 and 128. Mutagenesis analysis revealed both that this sequence is indeed a functional NLS and that two of its basic residues are critical for the normal nuclear distribution of p17. An interspecies heterokaryon assay further showed that p17 shuttles continuously between the nucleus and the cytoplasm and that this activity is restricted to its NLS-containing C-terminal tail. Finally, an analysis of the intracellular distribution of p17 in the presence of inhibitors of both RNA polymerase II and CRM1 further revealed that the nucleocytoplasmic distribution of p17 is coupled to transcriptional activity and that the viral protein exits the nucleus via a CRM1-independent pathway.