Paul G.H. Mulder

Incidence of contact-lens-associated microbial keratitis and its related morbidity

BACKGROUND The incidence of contact-lens-associated microbial keratitis is uncertain and its related morbidity in the general population of contact-lens wearers is not known. We examined these issues in a prospective epidemiological study. METHODS We surveyed all practising ophthalmologists in the Netherlands to identify all new cases of microbial keratitis reported during a 3-month period in 1996. Follow-up telephone calls were made to examine ocular morbidity. We undertook annual nationwide telephone surveys between 1994 and 1997 to estimate the prevalence of contact-lens wear. FINDINGS Of 440 ophthalmologists contacted, 379 provided information. There were 92 cases of microbial keratitis; 17 used daily-wear rigid gas-permeable lenses, 63 daily-wear soft lenses, and 12 extended-wear soft lenses. The estimated annualised incidence of microbial keratitis was 1.1 per 10,000 (95% CI 0.6-1.7) users of daily-wear rigid gas-permeable lenses, 3.5 per 10,000 (2.7-4.5) users of daily-wear soft lenses, and 20.0 per 10,000 (10.3-35.0) users of extended-wear soft lenses (p<0.00001 for comparison between all groups), Five of the 92 patients achieved a final visual acuity of 20/70 or less. Pseudomonas and Serratia spp were the organisms most commonly isolated. Pseudomonas keratitis accounted for the largest mean diameter of corneal ulcers, the highest mean number of days in hospital, the greatest number of mean outpatients visits, and the poorest visual acuity outcome. INTERPRETATION The incidence of microbial keratitis among users of extended-wear soft contact lenses in the Netherlands is similar to that reported in the USA during 1989. Awareness of risk factors and improvement in contact-lens materials have not led to a decrease in incidence. Overnight wear should be strongly discouraged.

Proteinuria after renal transplantation affects not only graft survival but also patient survival

Background. Proteinuria is associated with an increased risk of renal failure. Moreover, proteinuria is associated with an increased death risk in patients with diabetes mellitus or hypertension and even in the general population. Methods. One year after renal transplantation, we studied the influence of the presence of proteinuria on the risk of either graft failure or death in all 722 recipients of a kidney graft in our center who survived at least 1 year with a functioning graft. Proteinuria was analyzed both as a categorical variable (presence versus absence) and as a continuous variable (quantification of 24 hr urine). Other variables included in this analysis were: donor/recipient age and gender, original disease, race, number of HLA-A and HLA-B mismatches, previous transplants, postmortal or living related transplantation, and transplantation year. At 1 year after transplantation, we included: proteinuria, serum cholesterol, serum creatinine, blood pressure, and the use of antihypertensive medication. Results. In the Cox proportional hazards analysis, proteinuria at 1 year after transplantation (both as a categorical and continuous variable) was an important and independent variable influencing all endpoints. The influence of proteinuria as a categorical variable on graft failure censored for death showed no interaction with any of the other variables. There was an adverse effect of the presence of proteinuria on the graft failure rate (RR=2.03). The influence of proteinuria as a continuous variable showed interaction with original disease. The presence of glomerulonephritis, hypertension, and systemic diseases as the original disease significantly increased the risk of graft failure with an increasing amount of proteinuria at 1 year. The influence of proteinuria as a categorical variable on the rate ratio for patient failure was significant, and there was no interaction with any of the other significant variables (RR=1.98). The death risk was almost twice as high for patients with proteinuria at 1 year compared with patients without proteinuria. The influence of proteinuria as a continuous variable was also significant and also without interaction with other variables. The death risk increased with increasing amounts of proteinuria at 1 year. Both the risks for cardiovascular and for noncardiovascular death were increased. Conclusion. Proteinuria after renal transplantation increases both the risk for graft failure and the risk for death.

The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital setting: a pilot study.

IntroductionA limitation of pre-hospital monitoring is that vital signs often do not change until a patient is in a critical stage. Blood lactate levels are suggested as a more sensitive parameter to evaluate a patients condition. The aim of this pilot study was to find presumptive evidence for a relation between pre-hospital lactate levels and in-hospital mortality, corrected for vital sign abnormalities.MethodsIn this prospective observational study (n = 124), patients who required urgent ambulance dispatching and had a systolic blood pressure below 100 mmHg, a respiratory rate less than 10 or more than 29 breaths/minute, or a Glasgow Coma Scale (GCS) below 14 were enrolled. Nurses from Emergency Medical Services measured capillary or venous lactate levels using a hand-held device on arrival at the scene (T1) and just before or on arrival at the emergency department (T2). The primary outcome measured was in-hospital mortality.ResultsThe average (standard deviation) time from T1 to T2 was 27 (10) minutes. Non-survivors (n = 32, 26%) had significantly higher lactate levels than survivors at T1 (5.3 vs 3.7 mmol/L) and at T2 (5.4 vs 3.2 mmol/L). Mortality was significantly higher in patients with lactate levels of 3.5 mmol/L or higher compared with those with lactate levels below 3.5 mmol/L (T1: 41 vs 12% and T2: 47 vs 15%). Also in the absence of hypotension, mortality was higher in those with higher lactate levels. In a multivariable Cox proportional hazard analysis including systolic blood pressure, heart rate, GCS (all at T1) and delta lactate level (from T1 to T2), only delta lactate level (hazard ratio (HR) = 0.20, 95% confidence interval (CI) = 0.05 to 0.76, p = 0.018) and GCS (HR = 0.93, 95% CI = 0.88 to 0.99, p = 0.022) were significant independent predictors of in-hospital mortality.ConclusionsIn a cohort of patients that required urgent ambulance dispatching, pre-hospital blood lactate levels were associated with in-hospital mortality and provided prognostic information superior to that provided by the patients vital signs. There is potential for early detection of occult shock and pre-hospital resuscitation guided by lactate measurement. However, external validation is required before widespread implementation of lactate measurement in the out-of-hospital setting.

Reproducibility of carotid vessel wall thickness measurements. the rotterdam study

We studied the reproducibility of measurement of ultrasonographically assessed common carotid intima-media thickness and assessed whether measurement error of intima-media thickness occurred randomly or was associated with potential determinants of atherosclerosis. Eighty participants of the Rotterdam Study underwent a second ultrasound scan of both carotid arteries within 3 months of the first scan. The replicate measurements involved the posterior intima-media thickness of the distal common carotid artery. Mean differences (SD) in intima-media thickness of the right common carotid artery between paired measurements of sonographers, readers and visits were -0.004 mm (0.10), 0.066 mm (0.07), and -0.013 mm (0.13), respectively. Similar results were obtained for the left common carotid artery. Measurement error of intima-media thickness, i.e. the absolute difference in measurements between two subsequent visits, increased significantly with increasing common carotid intima-media thickness. This association disappeared after logarithmical transformation of the intima-media thickness data. Age, sex, smoking, body mass index, serum lipids, fibrinogen, and systolic and diastolic blood pressure were not significantly associated with the measurement error of intima-media thickness. Our findings indicate that measurements of common carotid intima-media thickness are highly reproducible. Measurement error of intima-media thickness is small and appears to be proportional with the level of intima-media thickness and is not significantly associated with most risk factors for atherosclerotic vessel wall disease.

Histologic Features of the Early Stages of Age-related Macular Degeneration: A Statistical Analysis

The age distribution, frequency, and correlation among histologic macular changes, including formation of a basal laminar deposit, drusen, and thickening and calcification of Bruchs membrane, were studied by light microscopy. The authors studied 182 unpaired postmortem human maculae from patients between 8 and 100 years of age. In addition, 45 maculae of contralateral eyes and the peripheral retina of 50 eyes were studied. In 92%, Bruchs membrane was thickened starting at age 19, and calcifications in this membrane were found in 59% starting at age 33. In 37% of the maculae, hard drusen were found starting at age 34. Soft drusen were found in 10% beginning at age 54. Basal laminar deposit was found in 39% of the maculae starting at age 40. All changes correlated strongly with age (P less than 0.0001). No sex differences were found. Fellow eyes showed similar aging changes (P less than 0.001). The presence of basal laminar deposit in the macula correlated with basal laminar deposit-like material in the peripheral retina (correlation coefficient, 0.39; P less than 0.003), whereas drusen in the macula correlated with drusen in the peripheral retina (correlation coefficient, 0.42; P = 0.001). Geographic atrophy was found in 6.6% of the eyes from subjects older than 70 years and subretinal neovascularization in 3.8%, especially in the maculae with basal laminar deposit.

Prevention and treatment of thrombotic complications in essential thrombocythaemia : efficacy and safety of aspirin

The efficacy and safety of aspirin in the prevention and treatment of thrombosis in essential thrombocythaemia (ET) was retrospectively analysed in a cohort of 68 ET patients. 41 patients presented with thrombosis, five patients with bleeding; two patients had a paradoxical combination of bleeding and thrombosis at presentation. At presentation, patients with bleeding had significantly higher platelet and leucocyte counts than patients with thrombosis. During long‐term follow‐up the incidence of thrombosis was significantly reduced in patients receiving aspirin, either as monotherapy or in combination with cytoreduction. However, treatment with aspirin (500 mg/d) was associated with an increase in (minor) bleeding complications. In patients receiving aspirin, bleeding occurred particularly at platelet counts exceeding 1000×109/l. The overall 5‐ and 10‐years survival probability was 93% and 84% respectively, indicating that life expectancy in ET is close to normal. Although our data need confirmation in prospective clinical trials, they suggest that aspirin, particularly in lower doses (100 mg/d), may be a safe antithrombotic agent in ET with an acceptable risk for bleeding, if applied to patients with a platelet count <1000×109/l and/or absence of a bleeding history.

Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas

ObjectiveThis study was set up to identify patient-related factors favoring the application of either surgery or endoprostheses in the palliation of obstructive jaundice in subsets of patients with cancer of the head of the pancreas or periampullary region. Summary Background DataIn the palliation of obstructive jaundice, surgical biliodigestive anastomosis has traditionally been performed. Surgical biliary bypass is associated with high mortality (15% to 30%) and morbidity rates (20% to 60%) but little recurrent obstructive jaundice (0% to 15%). Biliary drainage with endoscopically placed endoprostheses has a lower complication rate, but recurrent obstructive jaundice is seen in up to 20% to 50% of patients. MethodsPatients with advanced cancer of the head of the pancreas or periampullary region treated at the University Hospital Dijkzigt, Rotterdam, The Netherlands, between 1980 and 1990 were reviewed. In 148 patients, data were compared concerning the morbidity and hospital stay after the palliation of obstructive jaundice with endoscopic endoprostheses or surgical biliary bypasses. These patients were stratified for long (> 6 months) and short (< 6 months) survival times. ResultsIn short-term survivors, the higher late morbidity rates after endoprostheses were offset by higher early morbidity rates and longer hospital stays after the surgical bypass. In long-term survivors, there was no difference in the hospital stay between the two groups, but the late morbidity rate was significantly higher in the endoprosthesis group. ConclusionsThese data suggest that endoscopic endoprosthesis is the optimal palliation for patients surviving less than 6 months and surgical biliary bypass for those surviving more than 6 months. This policy necessitates the development of prognostic criteria, which were obtained by Cox proportional-hazards survival analysis. Advanced age, male sex, liver metastases, and large diameters of tumors were unfavorable prognostic factors. With these factors, the risk of short- or long-term survival can be predicted. It is hoped that the application of these data may allow a rational approach toward optimal palliative treatment of this form of malignant obstructive jaundice.

Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma

When treating bronchial hyperresponsiveness to so‐called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time‐ and dose‐dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 μg bid.) in improving exercise‐ (EIB) and methacholine‐induced bronchoconstriction during 6 months of treatment, using a placebo‐controlled parallel group study design. Thirty‐seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV1) ≥70% predicted; EIB ≥20% fall in FEV1 from baseline; no inhaled steroids during the past 4 months) participated in a double‐blind, placebo‐controlled, 3‐arm parallel study. Children receiving placebo were re‐randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV1 from baseline) and methacholine challenge using a dosimetric technique (expressed as PD20) were performed repeatedly during the study.

Topographic anatomy of the eyelids, and the effects of sex and age

AIMS To describe the effects of sex and age on eyeball, eyelid, and eyebrow position. METHODS A cross sectional cohort study was performed in which both eyes of 320 normal subjects aged between 10 and 89 years were included. Of each 10 year age cohort, there were 20 men and 20 women. Frontal, as well as lateral, slides were taken of both eyes. On projected slides, a reference line through the medial canthi and vertical lines through the pupil centre and the lateral canthus were constructed. Using these lines, we measured the size of the horizontal eyelid fissure, the distance from the reference line to the pupil centre and to the lateral canthus, the distance between the pupil centre and the upper and lower eyelid margin, and the distance between the upper eyelid margin and the skin fold and eyebrow. On lateral slides, the distance between the lateral canthus and the anterior corneal surface was measured. RESULTS Between the ages of approximately 12 and 25 years, the horizontal eyelid fissure lengthened 3 mm, while the position of other eyelid structures remained virtually unchanged. Between the average ages of 35 and 85 years, the horizontal eyelid fissure gradually shortened again by about 2.5 mm. Meanwhile, the distance between the lateral canthal angle and the anterior corneal surface decreased almost 1.5 mm. Aging caused an increase of the distance between the pupil centre and the lower eyelid of about 1 mm in men, and 0.5 mm in women. Aging also caused a higher skin crease and raised eyebrows in men and women, but it did not affect the position of the pupil centre and the lateral canthus. Men showed an 0.7 mm larger horizontal eyelid fissure than women. In women, however, the eyebrows were situated about 2.5 mm higher than in men. CONCLUSION Aging mainly affects the size of the horizontal eyelid fissure, which lengthens by about 10% between the ages of 12 and 25, and shortens by almost the same amount between middle age and old age. Aging causes sagging of the lower eyelid, especially in men, and a higher skin fold and eyebrow position in both sexes. Aging does not affect the position of the eyeball proper, or of the lateral canthus.

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO–DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.