Analysis of brain and spinal MRI measures in a common domain to investigate directional neurodegeneration in motor neuron disease.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back. METHODS: In this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z-scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z-scores, with gradients hypothesised to represent directionality of neurodegeneration. RESULTS: At group-level, z-scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient - 0.24, [95% CI - 0.62, 0.14], p = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p < 0.001), and between C5 and C6 cord levels (0.98, [95% CI 0.58, 1.38], p < 0.001). DISCUSSION: Analysis of brain and cervical spinal MRI data in a common domain enabled investigation of pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, and requires further investigation in larger cohorts.

Factors associated with HIV seroconversion in gay men in England at the start of the 21st century.

OBJECTIVES: To detect and quantify current risk factors for HIV seroconversion among gay men seeking repeat tests at sexual health clinics. DESIGN: Unmatched case control study conducted in London, Brighton and Manchester, UK. METHODS: 75 cases (recent HIV positive test following a negative test within the past 2 years) and 157 controls (recent HIV negative test following a previous negative test within the past 2 years) completed a computer-assisted self interview focused on sexual behaviour and lifestyle between HIV tests. RESULTS: Cases and controls were similar in socio-demographics, years since commencing sex with men, lifetime number of HIV tests, reasons for seeking their previous HIV tests and the interval between last HIV tests (mean = 10.5 months). Risk factors between tests included unprotected receptive anal intercourse (URAI) with partners not believed to be HIV negative (adjusted odds ratio (AOR) and 95% confidence interval 4.1, 1.8 to 9.3), where increased risk was associated with concomitant use of nitrite inhalants, receiving ejaculate and increasing numbers of partners. Independent risk was also detected for unprotected insertive anal intercourse (UIAI) with more than one man (AOR 2.7, 1.3 to 5.5) and use of nitrite inhalants (AOR 2.4, 1.1 to 5.2). CONCLUSIONS: HIV serodiscordant unprotected anal intercourse remains the primary context for HIV transmission among gay men, with increased risk associated with being the receptive partner, receiving ejaculate and use of nitrite inhalants. Although the HIV transmission risk of URAI is widely acknowledged, this study highlights the risk of UIAI and that nitrite inhalants may be an important facilitator of transmission when HIV exposure occurs.

Modelling the effectiveness of chlamydia screening in England.

BACKGROUND: Several developed countries have initiated chlamydia screening programmes. Screening for a sexually transmitted infection has both direct individual and indirect population-wide effects. Mathematical models can incorporate these non-linear effects and estimate the likely impact of different screening programmes and identify areas where more data are needed. METHODS: A stochastic, individual based dynamic network model, parameterised from UK screening studies and data on sexual behaviour and chlamydia epidemiology, was used to investigate the likely impact of opportunistic screening on chlamydia prevalence. Three main strategies were considered for <25 year olds: (1) annual offer to women; (2) annual offer to women or if changed partner within last 6 months; (3) annual offer to men and women. Sensitivity analyses were performed for key screening parameters including uptake rate, targeted age range, percentage of partners notified, and screening interval. RESULTS: Under strategy 1, continuous opportunistic screening of women <25 years of age is expected to reduce the population prevalence by over 50% after 5 years. Prevalence is also expected to decrease in unscreened older women and in men. For all three strategies screening those aged over 25 results in small additional reductions in prevalence. Including men led to a faster and greater reduction in overall prevalence, but involved approximately twice as many tests as strategy 1 and 10% more than strategy 2. The frequency of attendance at healthcare sites limits the number of opportunities to screen and the effect of changing the screening interval. CONCLUSIONS: The model suggests that continuous opportunistic screening at high uptake rates could significantly reduced chlamydia prevalence within a few years. Opportunistic programmes depend on regular attendance at healthcare providers, but there is a lack of high quality data on patterns of attendance. Inequalities in coverage may result in a less efficient and less equitable outcome.

Recent trends in diagnoses of HIV and other sexually transmitted infections in England and Wales among men who have sex with men.

OBJECTIVES: To examine trends in rates of diagnoses of HIV and other sexually transmitted infections (STIs) in men who have sex with men (MSM) in England and Wales between 1997 and 2002. METHODS: Estimates of the MSM population living in England and Wales, London and the rest of England and Wales were applied to surveillance data, providing rates of diagnoses of HIV and STIs and age group specific rates for HIV and uncomplicated gonorrhoea. RESULTS: Between 1997 and 2002, rates of diagnoses of HIV and acute STIs in MSM increased substantially. Rates in London were higher than elsewhere. Rises in acute STIs were similar throughout England and Wales, except for uncomplicated gonorrhoea and infectious syphilis, with greater increases outside London. Rates of gonorrhoea diagnoses doubled between 1999 and 2001 (661/100,000, 1271/100,000, p<0.001) in England and Wales followed by a slight decline to 1210/100,000 (p=0.03) in 2002-primarily the result of a decline in diagnoses among men aged 25-34 (1340/100,000, 1128/100,000, p<0.001) and 35-44 (924/100,000, 863/100,000, p=0.03) in London. HIV was the third most common STI diagnosed in MSM in England and Wales and the second in London, with the highest rate (1286/100,000) found among men aged 35-44 in London in 2002. CONCLUSIONS: Rates of diagnosis of HIV and other STIs have increased substantially among MSM in England and Wales. Increases show heterogeneity by infection, geography, and age over time. Rates in London were twice those seen elsewhere, with greatest changes over time. The observed changes reflect concomitant increases in high risk behaviour documented in behavioural surveillance survey programmes.

[Coexistence of unilateral retinoblastoma and Leber-Coats's disease in contralateral eye-case report]. / Przypadek wspólistnienia jednostronnego siatkówczaka z choroba Lebera-Coatsa w drugim oku.

PURPOSE: A case report of retinoblastoma and Leber-Coats' disease coexistence--two diseases which are very dangerous to the organ of vision. MATERIAL AND METHODS: The paper presents a young patient who was sent to our Clinic at the age of 6 with very advanced unilateral retinoblastoma. He underwent enucleation of the eyeball as the initial treatment. Histopathological examination confirmed clinical diagnosis without infiltration of optic nerve or sclera. After 9 years of oncological observation there were characteristic changes for Leber's angiomatosis (temporo-inferior part of the retina) in another eye. Laserocoagulation of changes was performed twice. RESULTS: During 14 years of observation there was no retinoblastoma recurrence. In the peripheral part of the retina in the only eye there is constant progression of vessel changes which are the sources of periodical preretinal bleeding. In the macular region there were extensive exudative changes which lifted the retina and caused the total secondary retinal detachment. Laser photocoagulation, cryopexy and steroid therapy were ineffective. Ultimately the patient's visual acuity at distance deteriorated to light perception.

[Immunologic tests in patients with idiopathic uveitis--preliminary reports]. / Badania immunologiczne u chorych z samoistnym zapaleniem tylnego odcinka blony naczyniowej--doniesienie wstepne.

AIM: This study aimed to evaluate the immune system function in patients with uveitis of unknown aetiology. METHODS: The clinical material comprised 19 patients with endogenous uveitis. In all cases the following immunological tests were performed: serum immunoglobulins A, G, M, total IgE, circulating immune complexes, complement components C3c and C4-all determined by laser nephelometry; antinuclear antibodies assessed with indirect immunofluorescence method using HEp-2 cell lines; and antineutrophil cytoplasmic antibodies using indirect immunofluorescence test. In 4 cases lupus anticoagulant was measured with APTT and dRVVT assays. RESULTS: Among our 19 examined patients immunological abnormalities were found in 12 cases. Changes in immunoglobulin concentrations were found in 8 cases. In 4 patients abnormalities of the complement system were observed. Antinuclear antibodies with speckled pattern in indirect immunofluorescence were present in 7 cases. CONCLUSION: In a proportion of patients with endogenous uveitis mild immunological abnormalities were present, suggesting an autoimmune background of the disease. Studies of the immunological profile can therefore help in better evaluation of the patients. It remains to be determined whether the observed immunological alterations are of any importance in the pathogenesis of the studied disease.

[Long-term observations of ocular toxocariasis in children and youth]. / Odlegle obserwacje toksokarozy ocznej u dzieci i mlodziezy.

PURPOSE: To evaluate the clinical status and ELISA test changes in a group of children with ocular toxocariasis. METHODS: We enrolled 37 patients in the studies. The follow-up period lasted at least 3 years (3-15 years) after the diagnosis had been established. In all cases a complete ophthalmological examination and actual ELISA test were performed. We compared the clinical status in two groups of patients: one with positive and the other with negative ELISA test at the time of control examination. RESULTS: In a majority of initially positive serological patients the control ELISA test for Toxocara canis antigen was negative. In these cases various post-inflammatory lesions in the anterior and posterior pole of the eye were present. In 8 cases the ELISA test was positive, despite the absence of active inflammatory process. In 5 serologically positive patients the active inflammation was observed. In more than 50% of cases the visual acuity was decreased. CONCLUSION: Ocular toxocariasis is a long-lasting, severe type of uveitis that requires long treatment and causes dramatic visual impairment. ELISA test is a sensitive method indicating the intensity of inflammation in ocular toxocariasis.

[Use of cryopexy in treatment of retinoblastoma]. / Zastosowanie kriopeksji w leczeniu siatkówczaka.

UNLABELLED: The aim of this work is to present our own experience in the treatment of retinoblastoma with cryopexy. MATERIAL AND METHODS: 24 children were observed, among whom 23 had bilateral and 1 unilateral retinoblastoma. We applied transconjunctival cryopexy to small neoplasmatic foci in retina located anterior to the equator. In 21 eyes this treatment was supplementary to brachytherapy and photocoagulation. We used probes of temperature -65C. Each freezing lasted about 20 seconds. The treatment was repeated every 6-8 weeks. In some cases different degree of post-surgical hemorrhages occurred. RESULTS: In 1/4 of cases already after a single freezing the tumour was destroyed and cicatrized. Only in 2 out of 24 treated eyes the desired effect was not reached. CONCLUSION: Cryopexy is an effective method of treatment of small foci of retinoblastoma located in the periphery of the eye fundus. This method is usually supplementary to brachytherapy.

[Twenty year observation of a severe case of bilateral retinoblastoma]. / Dwudziestoletnia obserwacja ciezkiego przypadku obustronnego siatkówczaka.

PURPOSE: To present a case of a girl with bilateral retinoblastoma, who, despite of the continuing development of the disease, survived for twenty years. METHODS: Neoplasmatic lesions, diagnosed in the child's left eye at age of 2, were so advanced that it was necessary to enucleate the eyeball. Relatively late, i.e. after 7 years, the tumour appeared in the second eye. This eye was treated with xenon-arc photocoagulation and 60Co irradiation. RESULTS: In spite of many years of treatment the lesions were progressing. Enucleation of the second eye was much delayed due to the lack of consent of the parents. 15 months after enucleation a recurrence appeared in the eye socket. Surgical treatment was supplemented by irradiation of the eye socket and by chemotherapy. After 20 years of intensive treatment the patient died because of generalized neoplasmatic disease. CONCLUSION: This case confirms the necessity of prolonged, careful observation of patients with retinoblastoma.

[The fate of children after bilateral enucleation of the eyeball because of retinoblastoma]. / Losy dzieci po obustronnym usunieciu galek ocznych z powodu siatkówczaka.

The authors present the fate of children with particularly severe form of retinoblastoma, in whom despite of treatment both eye balls had to be enucleated. In Ophthalmological Clinic in Kraków there were 70 such cases in the last 30 years, but information was obtained only about 52 children observed for at least 5 years. From among those children 23 (45%) died because of metastases of the tumour. Among the surviving 29, 3 are deeply mentally retarded and remain in nursing homes. The further 22 children maintain average or normal level of mental development, despite the loss of both eyes, they attend schools for the blind and find their place in the society. The remaining four children are talented above average, surprisingly independent, and two among them are university graduate. Owing to the enucleation of the second eye with an advanced tumour the children survived and found their places in the society.

[Genetic markers and congenital cataract]. / Markery genetyczne a zacma wrodzona.

In this work an attempt has been made to analyze the relationship between genetic markers and the occurrence of congenital cataract in children. The study included 32 families with 66 children in whom various clinical forms of congenital cataract had been diagnosed. In all examined patients, genetic markers such as ABO, MN, Rh systems, Gm1 factor, acid phosphatase (ACP1), esterase D and haptoglobin group were determined. The results were compared with the control population. It was found that the frequency of occurrence of heterozygote phenotype Hp 2-1 is higher in families with congenital cataract with simultaneous decrease of the frequency of occurrence of homozygote Hp 2-2. The obtained data were compared with those of other authors.

[Preliminary results of observing 18 cases of retinoblastoma carried within the international research program RICS]. / Wstepne wyniki obserwacji 18 przypadków siatkówczaka prowadzonych w ramach miedzynarodowego programu badawczego RICS.

In the years 1988-1989, the Ophthalmological Clinic in Cracow took part in the International Research Programme on Retinoblastoma as one of 28 clinical centres in 14 countries. The study included 18 children with retinoblastoma, in most cases in the advanced stadium of the disease. As a rule, the eyes filled with tumours were enucleated, and the less advanced cases were treated with combined methods applying radiation with 60Co plaques with xenon arc photocoagulation, cryopexy, and chemotherapy. In 18 treated children 23 eyes were enucleated (in 5 children both eyes, in 6 children with bilateral retinoblastoma 1 eye, and 7 eyes in all unilateral cases). Six eyes with less advanced lesions were treated with combined methods. One child died because of metastases to the brain. The obtained data reveal that retinoblastoma is diagnosed too late, which decreases the chance of cure and causes great danger for the life of the child.

[Trabeculotomy and goniotomy in congenital glaucoma]. / Trabekulotomia i goniotomia w jaskrze wrodzonej.

The authors evaluated efficiency of antiglaucomatous surgery in 73 eyes of 50 children, staying under clinical control in the years 1969-1991. It was showed that after trabeculectomy, as the primary procedure, intraocular pressure was normalized much more often (40.9%) than after goniotomy (20.2%). In cases operated many times using different technics, more effective was goniotomy. Better visual acuity was found in cases with intraocular pressure well controlled after one surgical procedure. The most common complications connected with surgery were discussed.

Ocular toxocariasis in children and youth.

The number of infections with larvae of the Toxocara canis worm has been continuously increasing in the Polish population, and the diagnosis and treatment of this disease is difficult. The authors describe 81 cases of eye infection in children and youth at the age of 3 to 18 years. The lesions in 94 eyes were observed for 0.5 to 11 years. In all patients the diagnosis was confirmed by ELISA test. In the clinical picture various forms of uveitis and granuloma of the eye fundus were found. The treatment consisted in general and topical application of antihelmintics, antibiotics and corticosteroids. In 23 eyes photocoagulation, in 11 cryopexy, and in 3 vitrectomy was performed. Clinical improvement was observed in 50 eyes, stabilization of the lesions in 41 eyes, and deterioration in the remaining 3 eyes. The authors conclude that the best results are obtained through conservative treatment combined with photocoagulation and cryopexy.

[Value of studying the intraocular pressure in patients operated on for retinal detachment]. / Znaczenie badania cisnienia wewnatrzgalkowego u chorych operowanych z powodu odwarstwienia siatkówki.

The IOP was checked in 263 eyes operated for retinal detachment--before, during and after surgery. Statistically lower values of the IOP were observed in eyes with retinal detachment in comparison with the healthy fellow-eye and in cases with an extensive and prominent detachment. There was no interdependence between the values of the IOP--even showing considerable oscillations--and the occurrence of complications, the normalization of the postoperative IOP and the results of the treatment. The measurements of the IOP in the course of retinal detachment operation may have a significance in determining the indications for a drainage of the subretinal fluid and in evaluation of the degree of the retinal invagination.