Long-Term Follow-Up of Choroidal Neovascularization in Pathological Myopia Treated with Intravitreal Ranibizumab.

Background: The purpose of this contribution is to report our functional results on the efficacy of intravitreal ranibizumab for submacular choroidal neovessels (CNV) in high myopia, and to compare the roles of optical coherence tomography (OCT), fluorescein angiography and visual acuity changes in the treatment decision prior to each injection. Patients and Methods: This is a retrospective study performed in Jules Gonin Eye Hospital. It included all patients with myopic CNV treated with intravitreal ranibizumab injections with a minimum follow-up of 24 months. After an induction dosing from 1 to 3 injections, the follow-up was based on a pro re nata regimen. Ophthalmic evaluation, best corrected visual acuity, and OCT were done at each visit, and fluorescein angiography at baseline and if neovascular activity was suspected. Retreatment criteria included metamorphopsia, visual loss of ≥ 5 ETDRS letters, any fluid on OCT and/or leakage on fluorescein angiography. Results: 24 eyes were included in the study. Mean follow-up was 49 months. Mean visual acuity improved significantly from 62.8 ± 13.8 letters at baseline to 72.8 ± 12.9 letters at last follow-up visit (p = 0.001). The mean number of injections was 2.2 in the first year and below 1 for the following years. The sensitivities of fluorescein angiography, SD OCT, and visual acuity loss ≥ 5 letters were 62.6 %, 51.4 %, and 40 %, respectively. The fluorescein angiography showed a significantly higher sensitivity in treatment decision than OCT (p = 0.007). Conclusion: Our study has shown that ranibizumab injections provide a significant long-term visual benefit in myopic CNV with a small number of injections. Fluorescein angiography has a preponderant role in the treatment decision of active myopic CNV.

Low penetrance in facioscapulohumeral muscular dystrophy type 1 with large pathological D4Z4 alleles: a cross-sectional multicenter study.

BackgroundFacioscapulohumeral muscular dystrophy type 1(FSHD1) is an autosomal dominant disorder associated with the contraction of D4Z4 less than 11 repeat units (RUs) on chromosome 4q35. Penetrance in the range of the largest alleles is poorly known. Our objective was to study the penetrance of FSHD1 in patients carrying alleles ranging between 6 to10 RUs and to evaluate the influence of sex, age, and several environmental factors on clinical expression of the disease. Methods A cross-sectional multicenter study was conducted in six French and one Swiss neuromuscular centers. 65 FSHD1 affected patients carrying a 4qA allele of 6¿10 RUs were identified as index cases (IC) and their 119 at-risk relatives were included. The age of onset was recorded for IC only. Medical history, neurological examination and manual muscle testing were performed for each subject. Genetic testing determined the allele size (number of RUs) and the 4qA/4qB allelic variant. The clinical status of relatives was established blindly to their genetic testing results. The main outcome was the penetrance defined as the ratio between the number of clinically affected carriers and the total number of carriers. Results Among the relatives, 59 carried the D4Z4 contraction. At the clinical level, 34 relatives carriers were clinically affected and 25 unaffected. Therefore, the calculated penetrance was 57% in the range of 6¿10 RUs. Penetrance was estimated at 62% in the range of 6¿8 RUs, and at 47% in the range of 9¿10 RUs. Moreover, penetrance was lower in women than men. There was no effect of drugs, anesthesia, surgery or traumatisms on the penetrance. Conclusions Penetrance of FSHD1 is low for largest alleles in the range of 9¿10 RUs, and lower in women than men. This is of crucial importance for genetic counseling and clinical management of patients and families.

Pathological changes in anabolic androgenic steroid users.

Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users. The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated. 98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases. Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

Pathological video game use among young Swiss men: the use of monothetic and polythetic formats to distinguish between pathological, excessive and normal gaming

There is no agreement about the distinction between pathological, excessive and normal gaming. The present study compared two classifications for defining pathological gaming: the polythetic format (gamers who met at least half of the criteria) and monothetic format (gamers who met all criteria). Associations with mental, health and social issues were examined to assess differences between subgroups of gamers. A representative sample of 5,663 young Swiss men filled in a questionnaire as part of the ongoing Cohort Study on Substance Use Risk Factors (C-SURF). Game use was assessed with the Game Addiction Scale. Mental, social and physical factors (depression, anxiety, aggressiveness, physical and mental health, social and health consequences), gambling and substance use (illicit drug use, alcohol dependence and problematic cannabis use) were also assessed. The results indicated that monothetic gamers shared problems with polythetic gamers, but were even more inclined to mental health issues (depression, anxiety, and aggressiveness) and were more vulnerable to other dependencies like substance use, alcohol dependence or gambling. A second analysis using Latent Class Analysis confirmed the distinction between monothetic and polythetic gamers. These findings support the use of a monothetic format to diagnose pathological gaming and to differentiate it from excessive gaming.

Neurobiology of pathological gambling. Brain imaging and epidemiological studies

Pathological gambling, a form of behavioral addiction, refers to maladaptive, compulsive gambling behavior severely interfering with an individual’s normal life. The prevalence of pathological gambling has been estimated to be 1–2% in western societies. The reward deficiency hypothesis of addiction assumes that individuals that have, or are prone, to addictions have blunted mesolimbic dopamine reward signaling, which leads to compulsive reward seeking in an attempt to compensate for the malfunctioning brain reward network. In this research project, the effects of gambling were measured using brain [11C] raclopride PET during slot machine gambling and possible brain structural changes associated with pathological gambling using MRI. The subjects included pathological gamblers and healthy volunteers. In addition, impulse control disorders associated with Parkinson’s disease were investigated by using brain [18F]fluorodopa PET and conducting an epidemiological survey. The results demonstrate mesolimbic dopamine release during gambling in both pathological gamblers and healthy volunteers. Striatal dopamine was released irrespective of the gambling outcome, whether the subjects won or not. There was no difference in gambling induced dopamine release between pathological gamblers and control subjects, although the magnitude of the dopamine release correlated with gambling related symptom severity in pathological gamblers. The results also show that pathological gambling is associated with extensive abnormality of brain white matter integrity, as measured with diffusion tensor imaging, similar to substance-addictions. In Parkinson’s disease patients with impulse control disorders, enhanced brain [18F] fluorodopa uptake in the medial orbitofrontal cortex was observed, indicating increased presynaptic monoamine function in this region, which is known to influence signaling in the mesolimbic system and reward processing. Finally, a large epidemiological survey in Finnish Parkinson’s disease patients showed that compulsive behaviors are very common in Parkinson disease and they are strongly associated with depression. These findings demonstrate the role of dopamine in pathological gambling, without support for the concept of reward deficiency syndrome.

Hofbauer cells morphology and density in placentas from normal and pathological gestations

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

Clinical and pathological study of an outbreak of obstructive urolithiasis in feedlot cattle in southern Brazil

The epidemiology, clinical picture and pathology of an outbreak of urolithiasis in cattle in southern Brazil are described. The disease occurred in August 1999 in a feedlot beef cattle herd. Five out of 1,100 castrated steers were affected. Clinical signs included colic and ventral abdominal distension. White, sand-grain-like mineral deposits precipitated on the preputial hairs. Affected cattle died spontaneously 24-48 hrs after the onset of the clinical signs. Only one animal recovered after perineal urethrostomy. Necropsy findings included calculi blocking the urethral lumen of the distal portion of the penile sigmoid flexure, urinary bladder rupture with leakage of urine into the abdominal cavity and secondary fibrinous peritonitis. Daily water intake was low since water sources were scarce and not readily available. The animals were fed rations high in grains and received limited amounts of roughage. Biochemical analysis revealed that the calculi were composed of ammonium phosphate. A calcium-phosphorus imbalance (0.4:0.6) was detected in the feedlot ration. For the outbreak, it is suggested that contributing factors to urolith formation include insufficient fiber ingestion, low water intake and high dietary levels of phosphorus. No additional cases were observed in that feedlot after preventive measures were established. Similar dietary mismanagement in fattening steers has been associated with obstructive urolithiasis in feedlot beef cattle in other countries.