[Outcome of selective mating in the Entlebucher Mountain Dog for reduction of ureteral ectopia]. / Ergebnis der selektiven Verpaarung beim Entlebucher Sennenhund zur Reduktion der ureteralen Ektopie.

INTRODUCTION: The Entlebucher Mountain Dog is predisposed to ureteral ectopia and associated diseases of the urinary tract as well as the kidneys, which can have severe to lethal consequences. Due to the clustered occurrence of clinical signs in 11 % of Entlebucher Mountain dogs in the absence of a genetic test for ureteral ectopia, screening was introduced in 2008 to allow phenotype-based breeding selection. The ureteral orifices of the dogs are visualized by ultrasound and existing urinary retention or urinary incontinence is documented. The diagnostic findings were evaluated centrally with assignment to one of five phenotypes depending on the localization of the ureteral orifices and the renal and ureteral shape. Breeding approval and mating restrictions are the responsibility of the respective breeding associations and predominantly Entlebucher Mountain Dogs with extravesical ectopic ureters and/or clinical signs were excluded from breeding. The effect of phenotype-based selective mating on the incidence of ureteral ectopia and its clinical signs, as well as possible factors influencing the expression of the phenotype, were determined in the birth cohorts after the introduction of screening. Analysis of the data set of 1456 phenotyped Entlebucher Mountain Dogs showed, that at 11 % versus 5 %, males were more frequently assigned to the extravesical phenotype than females. The effect of phenotype-based breeding selection was examined in a subpopulation consisting of phenotyped parents and their offspring (n = 876). The prevalence of the extravesical phenotype decreased from 24 % in the 2005 to 2007 birth cohorts to 1,4 % in the 2015 to 2017 birth cohorts. Since 2015 almost no Entlebucher Mountain Dogs with incontinence, hydroureter or hydronephrosis have been recorded. It was feared that the additional selection measures to control ureteral ectopia in the small Entlebucher Mountain Dog population would intensify the inbreeding increase. However, this has so far remained absent. Therefore, as long as no genetic test is available, it is recommended to continue phenotype-based breeding selection with exclusion of dogs with extravesical ureteral ectopia and/or hydroureter/hydronephrosis/urinary incontinence, while keeping an eye on the development of the inbreeding coefficient.

INTRODUCTION: Le Bouvier de l'Entlebuch est prédisposé à l'ectopie urétérale et aux maladies associées des voies urinaires ainsi que des reins, ce qui peut entraîner des conséquences fatales. En raison de l'apparition de signes cliniques chez 11 % des chiens et en l'absence d'un test génétique pour l'ectopie urétérale, un dépistage a été introduit en 2008 pour permettre une sélection d'élevage basée sur le phénotype. Les orifices urétraux des chiens ont été visualisés par échographie et la rétention ou l'incontinence urinaire existante documentée. Les résultats du diagnostic ont été évalués de manière centralisée avec attribution à l'un des cinq phénotypes en fonction de la localisation des orifices urétéraux ainsi que de la forme des reins et des uretères. L'approbation pour la reproduction et les restrictions d'accouplement relèvent de la responsabilité des associations d'élevage respectives et les bouviers de l'Entlebuch présentant des uretères ectopiques extravésicaux et/ou des signes cliniques ont majoritairement été exclus de la reproduction. L'effet de cet accouplement sélectif basé sur le phénotype sur l'incidence de l'ectopie urétérale et de ses signes cliniques ainsi que les facteurs possibles influençant l'expression du phénotype ont été déterminés dans les cohortes de naissance après l'introduction du dépistage. L'analyse de l'ensemble des données de 1456 Bouviers de l'Entlebuch phénotypés a montré que, à 11 % contre 5 %, les mâles étaient plus fréquemment affectés au phénotype extravésical que les femelles. L'effet de la sélection d'élevage basée sur le phénotype a été examiné dans une sous-population composée de parents phénotypés et de leur progéniture (n = 876). La prévalence du phénotype extravésical est passée de 24 % dans les cohortes de naissance de 2005 à 2007 à 1,4 % dans les cohortes de naissance de 2015 à 2017. Depuis 2015, presque aucun bouvier d'Entlebuch présentant une incontinence, un hydrouretère ou une hydronéphrose n'a été enregistré. Une possible augmentation de la consanguinité due aux mesures de sélection supplémentaires visant à contrôler l'ectopie urétérale ne s'est pas produite. Par conséquent, tant qu'aucun test génétique n'est disponible, il est recommandé de poursuivre la sélection d'élevage basée sur le phénotype avec exclusion des chiens présentant une ectopie urétérale extravésicale et/ou une hydrouretère/hydronéphrose/incontinence urinaire, tout en surveillant l'évolution du coefficient de consanguinité.

Association between public media and trends in new acute coronary syndrome presentations during the first COVID­19 wave in the Netherlands.

BACKGROUND: We aimed to evaluate the association between public media and trends in new presentations of acute coronary syndrome (ACS) during the first wave of the coronavirus disease 2019 (COVID­19) in the Netherlands. METHODS: New ACS presentations per week in 73 hospitals during the first half of 2019 and 2020 were retrieved from the national organisation Dutch Hospital Data and incidence rates were calculated. Stratified analyses were performed by region, type of ACS and patient characteristics. RESULTS: After the first confirmed COVID­19 case and during lockdown, numbers declined by up to 41% (95% confidence interval (CI): 36-47%) compared to 2019. This reduction was more pronounced for non-ST-segment elevation myocardial infarction (NSTEMI) (48%; 95% CI: 39-55%) and unstable angina (UA; 50%; 95% CI: 40-59%) than for STEMI (34%; 95% CI: 23-43%). There was no association between ACS and COVID­19 incidence rate per region. After the steep decline, a public campaign encouraged patients not to postpone hospital visits. Numbers then increased, without a rebound effect. Trends were similar irrespective of sex, age or socio-economic status. During the outbreak, compared to coronary artery bypass graft procedures, relatively more (acute) percutaneous coronary interventions for NSTEMI and UA were performed. CONCLUSION: New ACS presentations decreased by up to 41%. Lockdown measures and public campaigns, rather than COVID­19 incidence, were associated with significant changes in new ACS presentations. Even though causality cannot be established, this emphasises the role of the public media and healthcare organisations in informing patients to prevent underdiagnoses of ACS and associated health damage.

Visual prognosis in immunocompetent patients with herpes zoster ophthalmicus.

PURPOSE: To determine the normal spectrum of ocular complications and associated visual outcome in patients with herpes zoster ophthalmicus. METHODS: This prospective observational cohort study included 73 immunocompetent adults with herpes zoster ophthalmicus, referred by their general practitioners within 7 days of skin rash onset. The follow-up period was 6 months. All patients received a 7-14-day course of systemic aciclovir treatment combined with longterm application of a lubricating ophthalmic ointment as long as the corneal epithelium was affected. Topical corticosteroids were strictly avoided in the acute phase of ocular disease. Acquired visual loss scores at 1, 2 and 6 months were based on best corrected visual acuity (BCVA) level and evaluation of the ophthalmological history and findings. RESULTS: Ophthalmic herpes zoster led to a variety of transient inflammatory reactions within the anterior eye segment of the involved side in 46 patients (63%), but did not seriously compromise their ultimate visual outcome. Mild to moderate visual loss, with corrected VA between 0.3 and 0.8, was found in 17 patients at 1 month (23%), in 10 patients at 2 months (14%) and in seven patients at 6 months follow-up (10%). None of the patients developed visual loss with a corrected VA of less than 0.3. CONCLUSION: Functional vision was retained in all ophthalmic zoster patients referred to the ophthalmologist in the acute phase of the disease by vigorous antiviral treatment and adequate prevention of corneal exposure.

Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus.

PURPOSE: Longitudinal analysis of varicella-zoster virus DNA on the ocular surface of patients with herpes zoster ophthalmicus. METHODS: Clinical specimens were obtained from the bulbar conjunctival surface with a cotton-tipped swab at weekly intervals for 6 consecutive weeks from 21 patients with acute ophthalmic zoster with a skin rash duration of less than 7 days. All patients received oral valacyclovir 1000 mg three times daily for 10 days without additional corticosteroids. The swabs were analyzed by means of polymerase chain reaction for the presence of varicella-zoster virus and herpes simplex virus type 1 DNA. Conjunctival swabs were also obtained from a control group of 20 patients with cataract. RESULTS: On inclusion, varicella-zoster virus DNA was present on the ocular surface of 19 of the 21 patients. Six varicella-zoster virus DNA-positive patients had no signs of ocular inflammation. All control swabs were negative for both varicella-zoster virus and herpes simplex virus DNA. The duration of varicella-zoster virus DNA detection from rash onset varied from 2 to 34 days. The number of days between the onset of herpes zoster skin rash and the latest positive varicella-zoster virus DNA test was significantly longer in patients whose age was equal to or above the median age of 66 years than in the younger patients (Mann-Whitney test: P =.0004). At 6-week follow-up, all conjunctival swabs were negative for varicella-zoster virus DNA. However, at that time, the eyes of seven patients were still inflamed. CONCLUSION: The duration of varicella-zoster virus DNA shedding in herpes zoster ophthalmicus is highly variable and age dependent, and is probably related to the host immune response.

Risk and prognostic factors of postherpetic neuralgia and focal sensory denervation: a prospective evaluation in acute herpes zoster ophthalmicus.

OBJECTIVES: To determine the general risk and the prognostic factors of postherpetic neuralgia and focal sensory denervation in ophthalmic zoster disease. STUDY DESIGN: A prospective clinical study. SETTING: An ophthalmic practice participating in an eye-care network. PATIENTS: A cohort of 81 immunocompetent adult patients with herpes zoster ophthalmicus and referred by their general practitioner during the acute phase of the disease. METHODS: Various acute phase clinical parameters were determined via patient history and regular ophthalmic examinations. At a 2-month follow-up, the intensity of postherpetic neuralgia, rated on a 4-point verbal scale, and focal sensory denervation was determined. Skin tactile sensation within the ophthalmic dermatomes was tested with use of a cotton-wool tip, and corneal sensitivity was measured with use of a Cochet-Bonnet esthesiometer by comparing each eye. Statistical analysis was performed via chi2 analysis or Fisher exact test to identify prognostic factors of postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. RESULTS: At a 2-month follow-up, pain of varying intensity was reported by 38 participants (47%). Of these patients, 25 patients (31%) rated their pain as mild, 8 patients (10%) rated their pain as moderate pain, and 5 patients (6%) rated their pain as severe. At that time, focal loss of normal skin or corneal sensation was detected in 49 patients (60%). Patient age, acute neuralgia score, manifestation and extent of acute skin rash, signs of ocular inflammation, and nontrigeminal cranial nerve involvement were all associated with prolonged pain and tactile sensory loss. CONCLUSIONS: The severity of acute skin rash, based on a specific manifestation of cutaneous herpes zoster eruptions, and the extent of infection to other neural pathways were clearly associated with postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. These findings suggest that the inability of the immune system to control the spread of replicating varicella-zoster virus in the initial phase of the disease is an important factor in the pathogenesis of chronic zoster-related neuropathy.

[Enteral, nutritional support for critically ill patients]. / Enterale, nutritionele ondersteuning van kritieke patiënten.

Critically ill patients are characterized by acute changes in their metabolism, which are described by the term 'hypermetabolism'. In combination with anorexia, hypermetabolism leads to a negative energy and nitrogen balance. Consequently, wound healing can be inhibited, resistance is reduced, and (multiple) organ failure can occur. With the aid of nutritional support these consequences can be counteracted. During hypermetabolism protein breakdown is increased, and it is necessary to supply extra protein in the diet of critically ill patients. The amino acid glutamine is an important source of energy for enterocytes, and extra glutamine can improve the protective function of the intestinal mucosa. Branched amino acids serve as energy source during the acute phase. Arginine can reduce symptoms of encephalopathy by improving the conversion of ammonia to urea. Extra arginine in the diet also improves resistance. Because of the increased energy demand, diets for critically ill patients should be rich in fat. Moreover, extra n-3 fatty acids can improve immune function. A diet supplemented with extra zinc seems warranted because of its beneficial effect on wound healing and its inhibitory effect on protein breakdown. The enteral route is preferred because it protects the mucosal barrier of the gut, and it is less expensive and easier than the parenteral route. An enteral diet for critically ill patients is presented. Various factors that determine the choice of technique for enteral feeding are discussed.

Soluble ICAM-1 serum levels in patients with intermediate uveitis.

AIM: To investigate whether serum levels of soluble intercellular adhesion molecule 1 (sICAM-1) can serve as a marker of the presence of systemic disease in intermediate uveitis. METHODS: In a multicentre study sICAM-1 serum levels were measured in 61 patients with idiopathic intermediate uveitis, controls included 56 uveitis patients with a systemic disease (26 sarcoid associated uveitis and 30 HLA-B27 positive acute anterior uveitis), 58 uveitis patients without systemic disease (30 toxoplasma chorioretinitis and 28 Fuchs' hetrochromic cyclitis), and 21 normal controls. The clinical records of the patients with intermediate uveitis were analysed for disease characteristics at the time of blood sampling and for a relation with the development of a systemic disease after a mean follow up of 4.5 years. RESULTS: Increased serum levels of sICAM-1 were found in 34 out of 61 patients with intermediate uveitis and were significantly different when compared with toxoplasmosis, Fuchs' cyclitis, and healthy controls (p<0.001). Elevated sICAM-1 levels were also found in 18 out of 26 patients with sarcoid uveitis and in 11 out of 30 patients with HLA-B27 associated anterior uveitis. Raised sICAM-1 levels in the intermediate uveitis group were significantly associated with active ocular disease (p<0.01) and the presence of vitreous exudates (p<0.05). Increased levels of sICAM-1 correlated with interleukin 8 levels (IL-8) (tested in a previous study in the same group of intermediate uveitis patients) in patients with active systemic involvement. Follow up of the patients showed that an established or suspected systemic disease was found more often in the 21 intermediate uveitis patients with increased sICAM-1 and IL-8 levels compared with the other 40 patients with intermediate uveitis (p<0.01). CONCLUSIONS: The measurement of both sICAM-1 and IL-8 can be used as a marker for ocular disease activity and for a predisposition of developing an associated systemic disease in intermediate uveitis patients.

Elevated serum IL-8 levels are associated with disease activity in idiopathic intermediate uveitis.

AIM: To find a laboratory indicator for systemic involvement in intermediate uveitis. METHODS: Interleukin 8 (IL-8) and C reactive protein (CRP) serum levels were measured in patients with idiopathic intermediate uveitis (n = 61), uveitis controls (n = 143), and normal controls (n = 29). The records of those with intermediate uveitis were reviewed with the emphasis on disease activity and severity as characterised by the presence of cystoid macular oedema, vitreous exudates or snowbank formation, papillitis, and periphlebitis. RESULTS: Increased serum IL-8 (> or = 20 pg/ml) was found in 27 out of 61 patients with intermediate uveitis (p < 0.01), 12 of 27 patients with sarcoid uveitis (p < 0.05), in 19 of 30 patients with HLA-B27 associated acute anterior uveitis (p < 0.05), and in five of 29 healthy controls. Raised IL-8 levels in intermediate uveitis were significantly associated with active disease (p < 0.001) and the presence of vitreous exudates (p < 0.001), papillitis, and periphlebitis (p < 0.01). Elevated CRP levels were found in 12 of the 143 uveitis controls but in none of the intermediate uveitis patients or normal controls. During follow up an associated systemic disease was more frequently noticed in patients with an elevated serum IL-8 at entry into the study. CONCLUSIONS: Elevated IL-8 serum levels were found in patients with active intermediate uveitis of unknown origin. An elevated IL-8 level seems to predispose the patient to a later development of associated systemic disease.

Treatment of isolated tibial fractures in cats and dogs.

We report here a review of 33 cases of isolated tibial fractures (i.e., with the fibula intact) in 10 cats and 23 dogs, presented to four orthopaedic referral clinics. The purpose of this study was to identify factors to be considered when selecting the therapy for an isolated tibial fracture in cats and dogs. The animal species, the size of the dog breed, the age of the patient, the type of tibial fracture, the presence of an additional fracture, the treating clinic, the therapy applied, and the results after treatment were taken into account. A step-backward logistic regression analysis was applied to the series of cases to examine possible relations among the covariates. Treatment outcome was found by logistic regression analysis to depend significantly (P < or = 0.05) on age, the presence of an additional fracture, and the therapy applied. No other relations were present between the covariates. In the immature cat or dog with an isolated tibial fracture, treatment by external splinting has a good prognosis. In the mature cat or dog with an isolated tibial fracture, rigid fixation by external fixator or internal fixation is the method of choice.

Progressive neuronopathy in two Cairn terrier litter mates.

Clinical, histopathological, and EM findings are described for two Cairn terrier litter mates, an 18-months-old male and an 11-month-old female with progressive neuronopathy. The initial clinical signs were characterized by hind limb weakness and ataxia, which deteriorated with exercise. These signs progressed over several months to tetraparesis. Pathological examination revealed extensive chromatolytic degeneration of neurons and moderate secondary Wallerian-type degeneration in the spinal cord and brain stem. Progressive neuronopathy can be differentiated clinically from globoid cell leukodystrophy, another progressive neurological disorder in Cairn terriers, by the exercise-induced deterioration of the neurological signs. Progressive neuronopathy occurs only in Cairn terriers and because of the similarity in age of onset and the occurrence in one litter, an inherited disease is suspected.

Two families with dyshidrotic ectodermal dysplasia associated with ingrowth of corneal vessels, limbal hair growth, and Bitôt-like conjunctival anomalies.

Five cases from two unrelated families with a hitherto unknown combination of dyshidrotic ectodermal dysplasia with corneal vessel ingrowth, limbal hair follicles with hairs, and Bitôt-like spots in the conjunctiva are described. The corneal lesions were slowly progressive. In one pedigree, autosomal recessive inheritance is most likely, in the other there is uncertainty about the mode of inheritance. According to the criteria of Pinheiro and Freire-Maya, the mentioned cases can be classified into subgroup 1-2-4. The cases under investigation showed no palisades of Vogt like those seen in aniridia and after radiation therapy. We also found an absence of goblet cells in the affected individuals. We suggest therefore that the corneal and conjunctival anomalies are possibly caused by a stem cell disorder.

[Classifications of 202 tibial fractures in dogs and cats]. / Classificatie van 202 tibiafracturen bij hond en kat.

202 Tibial fractures, in 138 dogs and 64 cats, were classified according to the system of Unger. The animals were presented between 1989 and 1994 to four Dutch veterinary orthopaedic referral clinics. In addition to the type of fracture, demographic information was taken into account including the species, the age of the patient, the size of the breed, the treatment, whether it was a open or closed fracture and the orthopaedic clinic. Possible correlation between the type of fracture and the variables, as well as correlations among the latter, were examined statistically. In this study 73% of the tibial fractures in dogs and cats were in the diaphysis, oblique fracture being the most frequent (24%). Proximal tibial fractures in dogs were usually extra-articular and 87% of these involved avulsion of the tibial tubercle. Malleolar fractures accounted for 57% of the distal fractures. A significant correlation was found between the localization of the fracture (proximal, diaphyseal or distal) and the species (cat or dog), between an avulsion fracture of the tibial tubercle and the age in dogs, between an incomplete tibial fracture and the age, between a malleolar fracture and a complicated (i.e., open) fracture, between a butterfly fracture and a complicated fracture, and between the applied therapy and the orthopaedic clinic. The classification system of Unger is very useful for inventory and documentation, but because of the lack of data about physeal fractures, the degree of injury to the surrounding soft tissues, and the influence of differences between surgeons, it cannot be used to determine therapy.

Final height and its predictive factors after renal transplantation in childhood.

A retrospective study is reported assessing final height (FH) and its predictive factors in 52 patients (31 male, 21 female) who underwent renal transplantation (RTx) before the age of 15 y. They received prednisone daily or on alternate days as well as azathioprine. The study period covered 20 y. FH remained below the third height percentile [height standard deviation score for chronologic age (hSDSCA) < -1.88] for most of these patients (77% males, 71% females). Median (range) FH was 165.0 (143.0-176.8) cm in males and 153.0 (135.0-168.4) cm in females. Median difference between FH and target height was 15.0 and 15.4 cm for males and females, respectively. For both sexes, the median hSDSCA was already below -1.88 at the start of the first hemodialysis, after which it decreased significantly until the first RTx. After RTx, there was no significant improvement of hSDSCA. The predictive factors for FH were determined by evaluating various factors simultaneous in a multiple regression analysis. This analysis provided a regression equation for predicting FH. A higher hSDSCA at the time of the first RTx and alternate-day versus daily prednisone therapy both had a significantly positive influence on FH, whereas a longer duration of reduced GFR (< 50 mL/min/1.73 m2) had a significantly negative effect on FH. Other factors such as age or bone age at first RTx, primary renal disease, duration of initial dialysis, repeat RTx, and the cumulative dose of prednisone did not influence FH significantly. In conclusion, 71-77% of patients that received their first renal transplant before the age of 15 ended up with severely short adult stature. Optimization of the hSDSCA at first RTx appears very important. Long-term administration of prednisone on alternate days would then result in optimal FH, particularly if the GFR remains above 50 mL/min/1.73 m2.

Growth after renal transplantation in prepubertal children: impact of various treatment modalities.

A retrospective study evaluated posttransplant growth of 70 prepubertal children during the first 2 y after renal transplantation (RTx). Immunosuppressive treatment consisted of prednisone administered either daily or on alternate days in combination with either azathioprine or cyclosporin A. The increment in height standard deviation score for chronologic age during the first 2 y after RTx was less than 0.5 SD for 70% of the study population. The predictive factors for posttransplant growth were determined by evaluating several factors and treatment modalities singly and simultaneously in a multiple regression analysis. Patients with the most severe growth retardation at RTx appeared to have the most pronounced growth spurt after RTx, but even they never had complete catch-up growth, and 2 y after RTx they were still shorter than those with less severe growth retardation at RTx. Alternate-day instead of daily prednisone administration had a significantly positive influence, whereas a high cumulative dose of prednisone, azathioprine instead of cyclosporin A therapy, and a persistently reduced GFR (GFR < 50 mL/min/1.73 m2) had a significantly negative influence on catch-up growth during the 2 y after RTx. Other factors, such as gender, chronologic and bone age at RTx, primary renal disease, duration of initial dialysis, repeat RTx, and target height SD score for chronologic age, whether evaluated singly or simultaneously with other significant factors, appeared to have no significant influence on post-RTx growth. Thus, 70% of the prepubertal children do not experience appreciable catch-up growth during the first 2 y after RTx. Optimization of pretransplant height appears very important. Immunosuppressive treatment with cyclosporin therapy in combination with a minimal dose of alternate-day prednisone would then result in optimal post-transplant growth, particularly if the GFR remains above 50 mL/min/1.73 m2).

Detection of intraocular antibody production to herpesviruses in acute retinal necrosis syndrome.

In order to improve the determination of the causative agent in acute retinal necrosis syndrome, we evaluated the detection of intraocular antibody production to herpesviruses in 28 patients with this disease. Intraocular antibody production was determined by calculation of the Goldmann-Witmer coefficient whereby specific antibody titers in the inflamed eye and circulation are related to the total IgG content in ocular fluid and serum. Specific antibody titers to herpesviruses and Toxoplasma were determined by the indirect immunofluorescence technique. Thirty-five patients with ocular toxoplasmosis, cataract, or proliferative vitreoretinal disorders were tested as controls. By this technique, intraocular antibody production to varicella zoster virus or herpes simplex virus could be established in 16 (57%) of the patients with the typical clinical features of acute retinal necrosis, compared to none of the controls. Of the 33 affected eyes, 21 (64%) had a visual outcome of less than 20/200. We concluded that detection of intraocular antibody production to herpesviruses may be a useful diagnostic tool in establishing the causative agents in acute retinal necrosis.

Chronic ocular zoster.

In a prospective open trial 40 patients suffering from acute herpes zoster ophthalmicus were treated with systemic acyclovir. An additional 10 patients were treated by topical acyclovir alone and dexamethasone eye-drops were administered to 5 of them to suppress ocular inflammation. In the topical treatment group the period of new skin lesion formation and progression of ocular inflammatory signs were significantly prolonged. Therapy with systemic acyclovir however resulted in a quick and complete resolution of ocular inflammation in all patients. Chronic ocular inflammation developed in 4 out of 10 patients treated with topical acyclovir. We consider chronic ocular zoster as a distinct clinical entity, possibly expressing a failing local immune response against VZV.

Laboratory tests in uveitis. New developments in the analysis of local antibody production.

Analysis of local intraocular antibody production is a valuable tool with which to confirm a suspected clinical diagnosis in uveitis. We have analysed paired serum and aqueous samples for the presence of specific antibodies against toxoplasma, cytomegalovirus, herpes simplex virus and varicella zoster virus. Of the patients retrospectively diagnosed as having toxoplasma chorioretinitis 75% had a positive antibody coefficient indicating specific antibody production in the eye. Local antibody production in the eye directed against CMV confirmed the suspected diagnosis of CMV retinitis in 50% of the AIDS patients investigated. So far we have not been able to demonstrate local antibody production against herpes simplex virus (26 samples tested). Two of three patients with acute retinal necrosis had a positive antibody coefficient against varicella zoster virus. Both of these patients had an even higher titer in the aqueous than in serum. Since the choice of therapy, in infectious uveitis, depends on the causative organisms, it is very important to confirm a suspected clinical diagnosis by means of aqueous humor analysis.

Cyclosporin in the treatment of severe chronic idiopathic uveitis.

In a randomised double-masked study of 27 patients with a severe chronic idiopathic uveitis we evaluated the efficacy, safety, and tolerability of cyclosporin. All received prednisone in a low dose (0.3 mg/kg/day). In 14 patients this was combined with cyclosporin in a single daily dose of 10 mg/kg/day, while 13 patients received a placebo. The dosages were tapered off in accordance with a protocol, and we compared the number of months of successful therapy before the uveitis relapsed. The efficacy results, as expressed in a Kaplan-Meier curve, were in favour of cyclosporin. Owing to the small sample size, however, this difference did not reach statistical significance. The immunosuppressive effect of cyclosporin was not permanent, and in all but one patient the intraocular inflammation relapsed on reduction of dosage. Rather small cumulative doses of cyclosporin proved to be nephrotoxic, but subjective tolerability for cyclosporin was good.

Therapy of ocular toxoplasmosis.

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n = 29); group 2. clindamycin, sulphadiazine and corticosteroids (n = 37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n = 8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n = 32). Patients from group 1 received leucovorin 5 mg twice a week. No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P less than 0.05). We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.