The South Asian cataract management study: complications, vision outcomes, and corneal endothelial cell loss in a randomized multicenter clinical trial comparing intracapsular cataract extraction with and without anterior chamber intraocular lens implantation.

OBJECTIVE: To determine clinical outcomes of primary intracapsular cataract surgery with and without implantation of anterior chamber lenses. DESIGN: A multicenter randomized clinical trial. PARTICIPANTS: One thousand two hundred twenty-nine male and female patients 40-75 years of age with senile cataract. METHODS: Study patients were recruited from screening eye camps and outpatient clinics. Randomization to the two treatment groups was performed after screening for predetermined inclusion and exclusion criteria. Demographics, visual acuity, intraocular pressures, and corneal endothelial cell data were recorded before surgery and at 6 weeks, 12 months, and 24 months after surgery. Monitoring of the study was secured by a standardized image documentation procedure on all patients using the IMAGEnet digital imaging system. Analysis of corneal endothelial cell images was performed with the Cell Soft software (Topcon Corporation, Japan). MAIN OUTCOME MEASURES: Visual acuity and central corneal endothelial cell loss. RESULTS: The patients were randomized to intraocular lens (IOL; n = 616) and no IOL (n = 613) implantation. Surgical complications were reported in 177 (14.4%) patients (IOL = 14.8%; no IOL = 14.0%). The most frequent complication observed was vitreous loss which occurred in 10.3% of eyes (IOL = 11.2%; no IOL = 9.5%). At the final examination (2 years after surgery), 88% of the operated eyes had a best corrected vision of 6/18 or better (IOL = 88.8%; no IOL = 86.6%). Analysis of corneal endothelial cell data showed a small but significantly greater cell loss 6 weeks after surgery in eyes with IOL compared with those without IOL, but no overall difference was found between the treatment groups in the long term follow-up. CONCLUSIONS: The findings indicate that there is a rationale for the use of anterior chamber intraocular lenses in primary intracapsular cataract surgery.

Results of biventricular endomyocardial biopsy in survivors of cardiac arrest with apparently normal hearts.

Seventeen young patients (10 males and 7 females, aged 14 to 38 years, mean 26.4) without overt organic heart disease, who had been resuscitated from sudden cardiac arrest and referred to our institution during the period 1984 to 1993 for diagnostic evaluation and electrophysiologic study-guided antiarrhythmic therapy, were studied. Patients underwent noninvasive (electrocardiography, echocardiography [2-dimensional and Doppler], and magnetic resonance imaging) and invasive (left ventricular [LV], right ventricular [RV], and coronary angiography, ergonovine testing, electrophysiologic study, and biventricular endomyocardial biopsy) cardiac studies. Six to 8 biopsy fragments per patient were processed for histology and electron microscopy and read by a pathologist blinded to clinical data. Antiarrhythmic drug testing included amiodarone, propafenone, and metoprolol. A cardioverter-defibrillator was implanted in patients with persistently inducible sustained ventricular tachycardia or ventricular fibrillation. Sequential cardiac biopsy specimens were obtained in patients with active myocarditis undergoing immunosuppressive treatment. Periodic 3-month follow-ups included echocardiography and Holter monitoring. Two groups of patients were distinguished by invasive and noninvasive examinations: group I consisted of 9 patients with entirely normal parameters; group II consisted of 8 patients with structural, nonspecific cardiac abnormalities. In this latter group, mild to moderate dilatation and hypokinesia of the left ventricle were documented in 4 patients, concentric LV hypertrophy was seen in three patients, and RV dysfunction was noted in 1 patient. Histologic examination was abnormal in in all patients and revealed specific lesions in 65% of them; LV biopsy specimens allowed a diagnosis in 3 of 7 myocarditic patients with normal RV histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy.

BACKGROUND: Enteroviral RNA sequences have been demonstrated in the myocardium of patients with myocarditis or dilated cardiomyopathy from presentation to end-stage disease. The prognosis of heart muscle disease has not previously been evaluated in relation to the detection of enterovirus in myocardial biopsy tissue. METHODS AND RESULTS: We studied 123 consecutive patients with heart muscle disease prospectively. Multiple endomyocardial biopsy samples taken from all patients during diagnostic cardiac catheterization were classified histologically and were examined for enteroviral RNA by use of an enterovirus group-specific hybridization probe. Three enterovirus-negative patients with cardiac amyloidosis were excluded from subsequent analysis. Enteroviral RNA sequences were detectable in 41 (34%) of the remaining 120 patients (group A), while 79 (66%) had no virus detected (group B). The groups did not differ significantly in age, sex, symptomatic presentation, or hemodynamic characteristics; duration of symptoms was significantly shorter in group A (7.8 +/- 9.6 versus 14.9 +/- 19.0 months, P < .05). At follow-up (mean, 25 months; range, 11 to 50 months), patients from group A had an increased mortality compared with those in group B (25% versus 4%, respectively; P = .02). Mortality was also statistically greater in patients with symptomatic cardiac failure (P = .02), those with elevated left ventricular end-diastolic pressures (P = .03), and those in New York Heart Association functional classes III and IV (P = .05). Multivariate regression analysis, however, showed that only the presence of enterovirus RNA and symptomatic heart failure were of independent prognostic value. CONCLUSIONS: These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome.

The behaviour of tympanic membrane perforations in tissue culture: a scanning electron microscopic study.

The effects of keeping rat tympanic membranes with an artificially made pars tensa perforation in tissue culture were observed under a scanning electron microscope. After one day and onwards, spreading and thickening of the keratinizing, outer squamous epithelium (OE) was noted. In addition, ballooning of the innermost cells of the outer epithelium apposing the inner tympanic epithelium (IE) was seen. No appreciable reaction was noted in the connective tissue layer of the drum. The inner tympanic epithelium appeared to be swollen, containing spherical structures in the cytoplasm, especially close to the area of contact with the outer meatal epithelium. No complete cover of the drum defect was seen after 14 days of tissue culture. Hyperplasia and spreading of the keratinizing, outer squamous epithelium of the drum is not sufficient to achieve covering of a drum perforation and complete healing cannot take place unless supported by granulation tissue formation.

Influence of ethanol ingestion on the cornea.

The corneal thickness variations on both eyes of thirteen healthy volunteers were measured in absence and presence of ethanol with ultrasound pachymetry. During ethanol ingestion, to a serum ethanol concentration of 0.98 +/- 0.22 g/l, a small and transient, but statistically significant increase of the corneal thickness appeared (3.0 +/- 3.4% right eye - 4.3 +/- 2.9% left eye, p < 0.05). We suggest that ethanol causes a transient depression of the endothelial pump activity. The measured effect on the cornea is too small to cause reduced visual acuity on Snellen chart. However, a resulting loss of contrast sensitivity may have consequences for car driving and safety work.

Injury to the cornea due to fish bile.

A retrospective study of 207 patients with chemical eye injuries in northern Norway revealed that fish bile was the causal agent in 14%. Fish bile caused superficial corneal erosions in 28 of 29 cases. All but one of the patients were professional fishermen or fish industry workers. In one case delayed medical care led to serious corneal opacity. Provided that there was immediate and abundant rinsing of the affected eye and good medical care, the prognosis of fish bile injuries was fairly good. The mechanisms for corneal damage due to fish bile are not clear.

Dilated cardiomyopathy and myocarditis in Kenya: an endomyocardial biopsy study.

We have studied, by light and electron microscopy, left ventricular endomyocardial biopsy specimens from 18 African patients (14 men) with idiopathic dilated cardiomyopathy in Nairobi. Nine patients (50%) had evidence of healing myocarditis, that is the presence of a mild inflammatory cell infiltration within the myocardium. Interstitial fibrosis was prominent in five patients (28%) and in all 18 specimens there were hypertrophied muscle fibres. Therefore, half of the patients with idiopathic dilated cardiomyopathy had histological signs of a previous myocarditis. There was no serological evidence of a previous or recent coxsackie infection or any other common viral infections. It seems probable that the myocarditis was due to an inappropriate immunological reaction to myocardial muscle.

De novo expression of MHC class I and class II antigens on endomyocardial biopsies from patients with inflammatory heart disease and rejection following heart transplantation.

Inflammation of the heart muscle is caused either by infection (i.e. coxsackie virus) resulting in myocarditis or by rejection following heart transplantation. These processes induce activation of the immune system. We examined endomyocardial biopsies from patients with myocarditis, perimyocarditis and rejection following heart transplantation and compared these to biopsies from patients with coronary artery disease. The biopsies were examined immunohistologically with specific monoclonal antibodies against class I and class II molecules of the major histocompatibility complex (MHC). MHC class I antigens on the normally negative myocytes were evident in myocarditis (38%) and in rejection after heart transplantation (68%). In the interstitium there was an increase of both MHC class I and class II antigens. MHC class II antigens, however, were never seen on myocytes. MHC class I antigens are required for the action of CD 8 positive cytotoxic T cells. Therefore myocytes which express MHC class I antigens are susceptible to cytotoxic effects of the immune system. MHC class II antigens are essential to T helper cells. By cytokine release, activated T helper cells play a central role in the initiation, regulation and mediation of an immune response in myocarditis and rejection following heart transplantation.

Morphological recognition of viral heart disease.

A large number of endomyocardial biopsies have been analysed from 1.978 patients clinically diagnosed as suffering from dilated cardiomyopathy. In 1.125 patients non-specific changes of a dilated, hypertrophied myocardium were found consistent with a clinical diagnosis of dilated cardiomyopathy. The most interesting group consisted of 676 patients among which 549 cases showed clear evidence of myocarditis. The so-called "Dallas Criteria" have been described in detail and categorised into acute, active, on-going, resolving (healing) and resolved (healed) phases. Categorization is important for therapeutic reasons. Morphological analysis performs the bases upon which other investigations can be undertaken.

Facial palsy and partial accommodative insufficiency associated with sulphasalazine treatment in a patient with ankylosing spondylitis.

We report on a patient with peripheral facial nerve palsy and blurred near vision in association with sulphasalazine treatment. The possibility of this being an adverse reaction to sulphasalazine is discussed.

McLeod syndrome: a distinct form of neuroacanthocytosis. Report of two cases and literature review with emphasis on neuromuscular manifestations.

McLeod syndrome was originally described on the basis of a specific blood group phenotype with weak expression of Kell antigens. This erythrocyte abnormality also causes acanthocytosis. The haematological findings are associated with abnormalities in other organ systems, including neuromuscular manifestations. A 51-year-old patient was followed up for 11 years. He presented with persistent muscle creatine kinase elevation and progressive heart disease and later developed a slowly progressive neuropathy and choreic movements. His younger brother presented with grand mal seizures, involuntary movements and high muscle creatine kinase when aged 43 years. Clinical myopathy was absent in both, yet muscle biopsy showed mild myopathic changes. The presence of a motor axonopathy was supported by electrophysiological findings. One brother also showed sensory axonopathy. The movement disorder suggested accompanying basal ganglia dysfunction. Earlier reports of McLeod syndrome are reviewed with respect to neuromuscular involvement. Absence of the Kx membrane protein seems to be the cause of this multi-system disorder.

The pathogenesis of dilated cardiomyopathy.

Using the WHO/ISFC definition and recommendations of nomenclature for cardiomyopathies, the aetiology is unknown. Over many years research has concentrated on defining pathogenetic mechanisms and owing to the widespread use of the bioptome-permitting recovery of fresh endomyocardial tissue-myocarditis has emerged as being intimately involved in the pathogenesis of dilated cardiomyopathy. In approximately 2,000 patients with a presumed diagnosis of dilated cardiomyopathy, myocarditis was found in 28% of these cases. The morphological diagnosis of myocarditis has been fraught with difficulties and, in attempt to establish criteria for its recognition, a group of cardiovascular pathologists (the author among them) met in Dallas in 1984. These criteria are detailed and categorization into acute, resolving (healing) and resolved (healed) has been emphasized because of important therapeutic implications. The cause of myocarditis has been established as being due to coxsackie B viruses. Up to recent times such findings could only be surmised by investigations such as micro-neutralization tests. It was not until the hydridization probe was employed that direct proof was provided. These studies together with immunological consequences continue to be investigated in the hope of providing a rational approach to therapy.

Myocardial bridges: morphological and functional aspects.

OBJECTIVE: To assess the arrangement of myocardial bridges. DESIGN: A necropsy study of 90 consecutive hearts (56 male, 34 female). RESULTS: Myocardial bridges, either single or multiple, were seen in 50 (55.6%) of the 90 hearts. The left anterior descending artery was the most commonly affected artery. Thirty five of the 50 hearts which contained in total 41 muscle bridges were dissected further with a magnifying glass. Two different types of muscle bridges could be identified. Thirty one of these 41 myocardial bridges were superficial, crossing the artery transversely towards the apex of the heart at an acute angle or perpendicularly. The remaining 10 myocardial bridges crossed the left anterior descending coronary artery and surrounded it by a muscle bundle that arose from the right ventricular apical trabeculae and crossed the artery transversely, obliquely, or helically before terminating in the interventricular septum. CONCLUSIONS: The superficial type of myocardial bridge does not seem to constrict the artery during systole but the deep muscle bridges, by virtue of their relation with the left anterior descending coronary artery, could twist the vessel and thus compromise its diastolic flow. This may result in ischaemia.

The value of endomyocardial biopsies in myocarditis and dilated cardiomyopathy.

Since the introduction of the bioptome in 1962, examination of fresh endomyocardial tissue has been undertaken progressively in many centres despite the misgivings of some investigators. In my own experience, I have examined biopsies from 3225 patients, of whom 1978 were suspected to have dilated cardiomyopathy. Of these patients, 549 showed evidence of myocarditis. Categorization into active (acute), resolving (healing) and resolved (healed) stages is important because of therapeutic implications. It is concluded that endomyocardial biopsies are of immense value in dilated cardiomyopathy where the relationship with myocarditis has become established. Even though in many cases only non-specific features are found, biopsy excludes those conditions that can result in a hypertrophied, dilated heart. Biopsy also forms the baseline for further investigations, such as virological, immunological, morphometric analyses and distinction from alcohol effects, all of which have thrown light on the pathogenetic mechanism of dilated cardiomyopathy.

Immune response to the endothelium in myocarditis, dilated cardiomyopathy and rejection after heart transplantation.

The role of endothelial cells in inflammatory heart disease and rejection after heart transplantation is only partly understood. To determine whether an immune reaction against endothelial cells occurs we examined endomyocardial biopsies from patients with myocarditis (n = 13), dilated cardiomyopathy (n = 23), no clinical rejection (n = 10) and moderate to severe rejection after heart transplantation (n = 10). These were compared to 'normal' donor hearts with monoclonal endothelial-specific antibodies EN4, Pal-E and F VIII-related antigen. Nearly all endothelial cells were stained positively with EN4. There were no significant changes in the binding of the antibodies except in rejection when Pal-E and F VIII-related antigen were significantly increased. It is concluded that apart from their possible role as antigen-presenting cells, endothelial cells are important targets in rejection after heart transplantation. Damage or cytolysis of endothelial cells may cause both altered transendothelial permeability and functional decrease in antigen presentation.

Molecular probes for detection of persisting enterovirus infection of human heart and their prognostic value.

Enteroviruses are well recognized in the aetiology of myocarditis. Molecular hybridization using enterovirus group-specific probes shows that virus can be detected in endomyocardial biopsies and persists in myocardium after the inflammation heals. Virus persistence is associated with the subsequent development of dilated cardiomyopathy, progressing to end-stage disease requiring cardiac transplantation. Infectious virus cannot usually be isolated from myocardium nor can virus-specific antigens be detected after the initial inflammatory stage. Patients with healed myocarditis or dilated cardiomyopathy may have no histological evidence of inflammation despite detection of virus-specific RNA sequences by molecular hybridization. Persisting enterovirus RNA in dilated cardiomyopathy is the strongest known predictor of poor prognosis. The molecular mechanism of virus persistence is the selection of defective virus mutants during the initial phase of disease.

Marfan's disease and Erdheim's cystic medionecrosis. A study of their pathology.

Differentiation between Marfan's disease, or its forme fruste counterpart and Erdheim's cystic medionecrosis can be made in cases of aortic dilatation or dissection. This study examined the morphological features at light microscopy of aortic tissue, removed at surgery in 10 patients with Marfan's disease. A separate group consisted of 24 patients who did not express the complete Marfan phenotype but had family members who displayed the full and typical features of the disease. This group represented the so-called 'forme fruste' variant. These two groups were compared with 12 patients in whom a histopathological diagnosis of Erdheim's cystic medionecrosis had been made. Finally normal aortic tissue from post-mortem subjects were made available representing controls. In each case the degree of elastic fragmentation and cystic change of the aortic media was assessed and tabulated. The results indicate that severe fragmentation of elastic is similarly identifiable in both Marfan and Marfan forme fruste groups and that differentiation is easy pathologically from subjects with the comparatively modest fragmentation seen in Erdheim's cystic medionecrosis. Although cystic change was encountered in all groups, its severity tended to parallel the age of the subject, and we consider from our study that Erdheim's cystic medionecrosis represents no more than an exaggerated age-related change.