The Cancer, Lifestyle and Evaluation of Risk Study (CLEAR): Rationale and design of an unmatched "case-spouse control" study of over 10,000 participants in New South Wales, Australia.

INTRODUCTION: The New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) is an open epidemiological bioresource, using an all cancer unmatched case-spouse control design. Participant characteristics and selected confirmed associations are compared to published estimates: current smoking and lung cancer; country of birth and melanoma; body mass index (BMI) and bowel cancer; and paternal history of prostate cancer and prostate cancer, to illustrate the validity of this design. MATERIAL AND METHODS: Cases are NSW residents, ≥18 years, with an incident cancer of any type. Controls are cancer-free spouses of cases. Participants complete a consent form, a questionnaire, and provide an optional blood sample. For analyses, odds ratios for males and females are calculated for cancers and exposures of interest, by sex-matching controls to cases. RESULTS: 10,816 participants (8569 cases, 2247 controls, 54% female) recruited to-date, median age: 61.6 y cases, 61.3 y controls. The top five cancer types are female breast (n=1691), prostate (n=1102), bowel (n=888), melanoma (n=608), and lung (n=265). Adjusted odds ratios (OR) were: 20.65 (95% CI: 13.25-32.19) for lung cancer in current versus never smokers; 1.16 (1.05-1.28) for bowel cancer per 5 kg/m(2) increment in BMI; 1.41 (1.01-1.96) for melanoma in Australian-born compared to those born in UK/Ireland; and 2.47 (1.82-3.37) for prostate cancer in men with versus without a paternal history of prostate cancer. DISCUSSION: This study design, where controls are the spouses of cases diagnosed with a variety of cancers and which are analysed unmatched, avoids potential biases due to overmatching, considered problematic in standard case-spouse control studies, and illustrates that risk estimates analysed are consistent with the published literature. CLEAR methodology provides a practical design to advance local knowledge on the causes of various leading and emerging cancers.

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT.

The aim of this study was to assess the frequency of potential drug-drug interactions (pDDIs) and adverse drug events (ADEs) associated with antimycotics in hospitalized patients with hematopoietic SCT (HSCT). Of the 120 HSCT recipients evaluated, 36 received antimycotics. A total of 124 ADEs were recorded in 32 of the 36 patients treated, with 54 ADEs being possibly and 9 probably related to antimycotics. Of the treatments with amphotericin B, 93% were associated with one or more possible and 36% with probable ADEs. The corresponding figures for lipid-based amphotericin B were 100% and 7%, for voriconazole 68% and 11% and for caspofungin 70% and 0%. A total of 57 potentially severe DDIs associated with antimycotics were detected in 31 of the 36 patients. Of these, 14 DDIs were a possible cause of an ADE and 5 (4 times a combination of voriconazole with CYA and once a combination of CYA with conventional amphotericin B) were probably related. Although the prevalence of pDDIs and ADEs is high in HSCT patients, ADEs related with a high probability to treatment with antimycotics are rare. Regarding the high prevalence of pDDIs, our findings underscore the importance of close monitoring of laboratory and clinical parameters, as well as dose adjustment for critical drugs, in patients with HSCT.

[Automobile drivers with retinal diseases - a prospective analysis]. / Kraftfahrzeuglenker mit Netzhautleiden - eine prospektive Studie.

BACKGROUND: The study was designed to prospectively evaluate the driving habits of patients with retinal diseases, who were referred to the specialised retinal ambulatory care center of the Landesaugenklinik Salzburg. The main purpose of this study was to compare the legal requirements for visual acuity, as currently valid in Austria and Germany for driving motor vehicles, with the results found in this patients cohort and to analyse driving patterns of the patients with valid licenses. With these data, it seems possible to suggest a suitable time for a legally mandatory eye examination as to identify subjects with a potentially rising higher accident risk when driving. MATERIALS AND METHODS: In this study, 100 patients - all holders of a valid driving licence - with diabetic retinopathy or age related macular degeneration were enrolled. From each patient, the visual acuity (corrected or uncorrected depending on the driving habit) was recorded and a detailed questionnaire regarding the actual driving habits was requested. The resulting data were analysed in view of the legal requirements of both countries, Austria and Germany. RESULTS: Of 100 patients holding a valid driving licence a total of 31 were driving their motor vehicles with a legally insufficient visual acuity, 26 of 50 still driving. Of 50 patients suffering from diabetic retinopathy, 26 drove their cars illegally. Only 4 out of the above mentioned 31 patients had received sufficient information from their referring ophthalmologists. The average age of "illegal" drivers was 66.2 years. CONCLUSIONS: Within the European Community common legal requirements for driving a motor vehicle (regarding mainly the visual acuity) be clearly defined and a mandatory eye exam performed by qualified ophthalmologists for older subjects should be postulated. An individual and age related time limit to be placed on the driving licences of persons suffering from systemic diseases associated with relevant visual loss should to be discussed. Furthermore, ophthalmologists should be obliged to give detailed information to the patient with adequate documentation.

[Overweight and obesity in the Zurich canton. A LuftiBus study]. / Ubergewicht und Adipositas im Kanton Zürich. Eine LuftiBus Studie.

In this study the data from 30,598 subjects participating in the LuftiBus project during 1993-1998 were analyzed for the prevalence rates of overweight and obesity. 36.6% of men and 23.6% of the women in the total population were overweight (BMI 25.0-29.9 kg/m2) and 6.6% of the men as well as 7.5% of the women were obese (BMI > 30.0 kg/m2). At a younger age the women were in general lighter, however, with advancing age women became heavier than men. The prevalence data from this study are in quite good agreement with data from other Swiss epidemiologic studies as well international studies. The rather high prevalence rates of obesity show clearly that the problem of obesity can only be solved by preventive means.

Retinal detachment after silicone oil removal.

PURPOSE: To evaluate the causes of retinal detachment after silicone oil removal, to define possible risk factors and the anatomical and functional prognosis of this complication. METHODS: 112 eyes that underwent silicone oil removal were included. The group of eyes with retinal detachment after oil removal (18/112 eyes, 16.1%) was compared with the group with no postoperative retinal detachment. RESULTS: The most common cause for retinal detachment after oil removal was anterior PVR (77.8%). Initial PVR detachment, advanced PVR stages, anterior PVR, more preceding operations, aphakia/pseudophakia, myopia and shorter duration of the oil tamponade were significantly more represented in the group of eyes with retinal detachment after oil removal. The prognosis of retinal detachment after oil removal is poor. CONCLUSION: Some criteria could be regarded as risk factors for retinal detachment after silicone oil removal. Improvement of the results should be possible by considering these factors and by control of reproliferations.

Retrobulbar hemodynamics in amaurosis fugax; investigation by color Doppler velocity.

PURPOSE: The aim of the study is to determine blood flow and resistance parameters (Resistance Index-RI, Pulsatility Index-PI) in the retrobulbar arteries of patients suffering from amaurosis fugax. METHODS: Color Doppler velocity was used to measure blood flow velocity and vascular resistance in the ophthalmic artery, central retinal artery and lateral short posterior ciliary artery of 32 involved eyes in their afflictless interval. The patients' mean age was 60.1 years (range 29-85). The age- and sexmatched control group comprised 32 healthy volunteers (32 eyes). RESULTS: There was no significant difference neither in RI nor in PI of amaurosis fugax patients compared to the control group. CONCLUSIONS: We conclude that in almost all cases of amaurosis fugax no local disturbance of blood flow in the afflictless interval is noted. However, increased vessel resistance is noticed in some cases of amaurosis fugax: Giant cell arteritis, intraorbital vascular anomalies, intraorbital tumors. In these cases color Doppler velocity is able to give information on the extent of blood flow disorder and, in particular by the B-mode, the etiology can be assumed.

In vitro effectiveness of silicone oil removal.

PURPOSE: To evaluate the effectiveness of silicone oil removal from the human eye under in vitro conditions. METHODS: Six keratoplasty donor eyes were vitrectomized and filled with silicone oil (5000 centistokes). After oil removal, the amount of residual oil was determined by quantifying the silicon content of the eyes. Six control eyes were prepared without oil filling. RESULTS: The six control specimens showed a silicon content of 2.83-10.2 microg (mean 5.06 microg, SD 3.19), the six test specimens a silicon content of 70.54-297.10 microg (mean 163.91 microg, SD 86.89). The difference is significant (p<0.05). The amount of residual oil in the test eyes was 192.0-856.2 microg (0.0037-0.0179% of the applicated oil quantity). CONCLUSION: The low magnitude of residual intraocular oil after oil removal shows that silicone oil could be removed to almost 100% when emulsification and biological mechanisms of oil retention are excluded. This could favour early silicone oil removal.

Silicone oil tamponade in eyes with posterior staphyloma and retinal detachment caused by macular hole.

PURPOSE: A retinal detachment caused by a macular hole in an eye with a posterior staphyloma presents a therapeutical challenge. Vitrectomy and silicone oil tamponade might be a therapeutic strategy in such eyes. METHODS: We report on three eyes of three patients with retinal detachment caused by a macular hole in the presence of a posterior staphyloma, where a vitrectomy and a silicone oil filling was performed. RESULTS: In all three eyes the retina could be reattached. After oil removal, the retina remained attached in all three eyes until the end of the follow-up period (mean 18.7 months). In all three eyes, visual acuity improved, no major complications were noted. CONCLUSION: The use of silicone oil in eyes with retinal detachment caused by a macular hole in the presence of a posterior staphyloma presents a therapeutic option and we discuss this strategy as a primary treatment for these eyes.

Anterior chamber contamination during cataract surgery with intraocular lens implantation.

PURPOSE: To measure anterior chamber bacterial and fungal contamination at the beginning and end of cataract surgery with intraocular lens (IOL) implantation in a large series of patients and to determine the influence of preoperative treatment and operative technique on contamination. SETTING: Department of Ophthalmology, County Hospital of Salzburg, Austria. METHODS: This prospective study comprised 700 consecutive patients having planned cataract extraction (511 phacoemulsification, 189 extracapsular cataract extraction [ECCE]). Thirty-four patients required an anterior vitrectomy; 8 myopic patients did not receive an IOL. A preoperative smear and two intraoperative (at the beginning and end of surgery) anterior chamber aspirates were obtained from each patient. Postoperative smears were obtained at discharge. Three preoperative treatments were evaluated: no lacrimal system irrigation, no topical antibiotic (n = 282); lacrimal system irrigation with balanced saline solution, no topical antibiotic (n = 243); lacrimal system irrigation, antibiotic (neomycin) eyedrops (n = 175). All patients received topical indomethacin twice a day preoperatively. RESULTS: Preoperative conjunctival smears showed bacterial growth in 76.6% of eyes, with coagulase-negative staphylococci (75%) the most common bacteria. Anterior chamber aspirates were culture positive in 14.1% at the beginning and in 13.7% at the end of surgery, with coagulase-negative staphylococci and corynebacteria the most common. Contamination rates of conjunctival smears taken at discharge were significantly lower (35%) than those taken preoperatively. There was no statistically significantly higher risk of anterior chamber contamination in eyes having ECCE than in those having phacoemulsification. Preoperative treatment did not statistically significantly influence intraoperative aqueous humor contamination rates. There were no cases of acute postoperative endophthalmitis. CONCLUSION: Bacteria entered the anterior chamber during cataract extraction and remained there at the end of surgery in a significant percentage of patients. Surgical technique, preoperative antibiotics, and preoperative lacrimal system irrigation had no statistically significant effect on contamination.

Silicone oil removal: results, risks and complications.

PURPOSE: We studied the results and complications of silicone oil removal applying basic criteria for the selection of eyes. METHODS: The criteria for oil removal: 1. Completely attached retina for at least 4 weeks, 2. Absence of tractions and active proliferations, 3. Preoperative vision > 0.01. The oil was removed from 90 of 261 oil filled eyes (removal rate: 34.5%). 83 eyes were included in the further study. FOLLOW-UP: 1.3-62.5 months (mean 15.7). RESULTS: Visual acuity improved (> or = 1 line) in 40 of the 83 eyes (48.2%), remained unchanged in 22 eyes (26.5%) and deteriorated (> or = 1 line) in 21 eyes (25.3%). COMPLICATIONS: reproliferations (42.2%), retinal detachment (20.5%), pressure rises (27.7%), lens opacification (36.7%), severe keratopathy (8.4%). CONCLUSION: Silicone oil removal has a distinct rate of complications, despite preoperative selection of eyes with a better prognosis. Reduction of reproliferations and weighing of risk and benefit could improve the results.

Hematopoietic augmentation by a beta-(1,4)-linked mannan.

CARN 750 (injectable acemannan) is a polydispersed beta-(1,4)-linked acetylated mannan isolated from the Aloe barbadensis plant. It has multiple therapeutic properties including activity in wound repair and as a biological agent for the treatment of neoplasia in animals as well as the ability to activate macrophages. We report herein that CARN 750 directly or indirectly has significant hematoaugmenting properties. We observed that the subcutaneous administration of CARN 750 significantly increases splenic and peripheral blood cellularity, as well as hematopoietic progenitors in the spleen and bone marrow as determined by the interleukin-3-responsive colony-forming unit culture assay and the high-proliferative-potential colony-forming-cell (HPP-CFC) assay (a measure of primitive hematopoietic precursors) in myelosuppressed (7 Gy) C57BL/6 mice. The greatest hematopoietic effect was observed following sublethal irradiation in mice receiving 1 mg CARN 750/ animal, with less activity observed at higher or lower doses. Further, CARN 750, following daily injection, has activity equal to or greater than the injection of an optimal dose of granulocyte-colony-stimulating factor (G-CSF) in myelosuppressed mice. In this comparison, significantly greater activity was observed in the splenic and peripheral blood cellularity, and in the frequency and absolute number of splenic HPP-CFC as compared to the mice receiving G-CSF at 3 micrograms/animal. CARN 750, when administered to myelosuppressed animals, decreased the frequency of lymphocytes with a concomitant significant increase in the frequency of polymorphonuclear leukocytes (PMN). However, owing to the increased cellularity, a significant increase in the absolute number of PMN, lymphocytes, monocytes and platelets was observed, suggesting activity on multiple cell lineages. The latter is the primary difference in activity as compared to G-CSF which has activity predominantly on PMN.

A system for obtaining undiluted intraoperative vitreous biopsy samples.

For many analyses of the vitreous, it is essential to obtain undiluted vitreous specimens under sterile conditions intraoperatively. In this new technique, a metal device is integrated into the aspiration system. The device fits on standard laboratory plastic containers with integrated caps. Undiluted vitreous accumulates in the container, which is then removed and sent to the laboratory. With a new container in place, vitrectomy can be continued as usual. This technique is simple, safe, effective, and inexpensive.

Color Doppler ultrasound investigation of the therapeutic effect of plasmapheresis on a lymphoplasmocytoid lymphoma (immunocytoma): a case of central retinal artery occlusion.

The lymphoplasmocytoid immunocytoma (Waldenström's disease) is a non-Hodgkin's lymphoma of low malignancy. The disease is defined by the production of monoclonal IgM-globulins in the bone marrow. These macroglobulins affect the aggregation of thrombocytes and bind the coagulation factors, which leads not only to hemorrhagical diathesis, but also to hyperviscosity syndrome. We present the rare case of a 79-year-old woman suffering from an immunocytoma with sudden painless loss of vision in her right eye. Ophthalmoscopic examination revealed an occlusion of the central retinal artery. The immediately performed blood examination showed the following results: IgM serum level was 6610 mg/dl (normal range: 60-370 mg/ dl), kappa-paraproteinemia showed values of 702 mg/dl (normal range: 200-440 mg/dl), and the plasma viscosity was 3.4 mPa/s (normal range: 1.5-1.72 mPa/s). Plasmapheresis was promptly initiated. Subsequently, the highly pathological serum levels were markedly lower and sight improved from complete amaurosis to qualitative vision. Blood-flow velocity and vascular resistance parameters (resistive index) in all nutritious vessels [ophthalmic artery (OA), posterior ciliar arteries (PCA) and central retinal artery (CRA)] were recorded before and after each of the six cycles of plasmapheresis, using color Doppler velocity (CDV). It was proven that even after the first plasmapheresis, circulation in the central retinal artery was restored. After each further cycle of plasmapheresis, an improvement in blood-flow velocity in OA, PCA, and CRA was recorded by CDV. CDV verifies variations in circulation of the eye vessels and gives an objective assessment of the influence of therapy.

[Contamination of intraocular fluid in pars plana vitrectomy]. / Kontamination intraokularer Flüssigkeiten bei Pars-plana-Vitrektomien.

UNLABELLED: Endophthalmitis after pars plana vitrectomy is rare, with an incidence of 0.05-0.14%. The aim of this study was to evaluate the microbiological situation during pars plana vitrectomy and to ascertain what organisms and how many enter the eye during the operation. PATIENTS AND METHODS: Twenty-five consecutive subjects undergoing primary pars plana vitrectomy were included in the study. Patients were excluded if they had evidence of local or systemic infections or had undergone antibiotic therapy within 3 weeks before surgery. A standard three-port pars plana vitrectomy was performed on each patient. Preoperative smears of the conjunctiva and intraoperative aspirates of the vitreous were taken immediately after sclerotomy, and aspirates of the intraocular fluid at the conclusion of operation. RESULTS: We obtained preoperative smears from the conjunctival sac of all patients, and found that 19 patients (76%) had positive cultures, with coagulase-negative staphylococci as the most commonly isolated organisms, (n = 14; 56%). Vitreous--aspirated immediately after sclerotomy--was sterile in 68% (n = 17). In 32% (n = 8) contamination occurred, the microorganisms isolated being coagulase-negative staphylococci (20%) and Staphylococcus aureus (12%). Five of the samples (20%) of intraocular fluid from the vitreous cavity--aspirated before wound closure--were contaminated, coagulase-negative staphylococci (8%) and Staphylococcus aureus (12%) again being found in culture. In no case did postoperative endophthalmitis develop. CONCLUSIONS: This study demonstrates that bacteria enter the eye during pars plana vitrectomy and that there is a change in the contaminating bacterial species during operation. Even if bacteria remain in the eye after pars plana vitrectomy, postoperative endopthalamitis does not necessarily develop.

Studies on optimal dose and administration schedule of a hematopoietic stimulatory beta-(1,4)-linked mannan.

Several complex carbohydrates have been found to significantly stimulate hematopoiesis. CARN 750, a polydispersed beta-(1,4)-linked acetylated mannan isolated from the Aloe vera plant, has been shown to have activity in wound repair, to function as a antineoplastic, and to activate macrophages. We report, herein, the hematoaugmenting properties of CARN 750 and its optimal dose and timing of administration in an animal model of irradiation-induced myelosuppression. We observed that subcutaneous injections of 1 mg/animal of CARN 750 had equal or greater stimulatory activity for white blood cell (WBC) counts and spleen cellularity as well as on the absolute numbers of neutrophils, lymphocytes, monocytes and platelets than did higher or lower doses of CARN 750 or an optimal dose of granulocyte-colony stimulating factor (G-CSF). Hematopoietic progenitors, measured as interleukin-3-supported colony forming units-culture (CFU-C) and high proliferative potential colony-forming cells (HPP-CFC) assays, were similarly increased by CARN 750 in the spleen but not in the bone marrow. The frequency of splenic HPP-CFCs and absolute number of splenic HPP-CFCs and CFU-Cs were optimally increased by 1 mg/animal of CARN 750. In contrast, bone marrow cellularity, frequency and absolute number of HPP-CFCs and CFU-Cs had as a dosage optimum 2 mg/animal of CARN 750. These parameters were similarly increased by G-CSF. In studies to determine the optimal protocol for the administration of CARN 750 we found that the hematopoietic activity of CARN 750 increased with the frequency of administration. The greatest activity in myelosuppressed mice was observed for all hematopoietic parameters except the platelet number in mice receiving daily administration of 1 mg/animal of CARN 750 with activity equal to or greater than G-CSF.

Different techniques of extracapsular cataract extraction: bacterial contamination during surgery. Prospective study on 230 consecutive patients.

This study was performed to investigate the correlation between the contamination of the anterior chamber and the technique of extracapsular cataract extraction (ECCE). Three different methods were used: uncomplicated planned ECCE, phacoemulsification involving suturing method, and sutureless technique. All patients had posterior chamber intraocular lenses implanted. Two hundred and thirty consecutive patients were included in this prospective study, and preoperative smears of the conjunctiva and intraoperative aspirates of the anterior chamber were investigated. Samples of the aqueous humor were taken at the beginning and at the end of the operation. Cultures were incubated and held for 14 days. More than 71% of the preoperative smears were contaminated by coagulase-negative staphylococci, the most commonly isolated bacteria. However, 27% of the patients had culture-positive anterior chamber aspirates intraoperatively, also with coagulase-negative staphylococci as the most frequent organisms. In no case did postoperative endophthalmitis develop. Preliminary results in a small population show that the contamination of the aqueous humor is statistically significantly less frequent if the cataract extraction is performed by phacoemulsification than if it is done without phacoemulsification. Another interesting finding is that anterior chamber contamination is not significantly more frequent, if a sutureless technique is used for cataract surgery.

[Postoperative leakage of silicone oil into the anterior chamber]. / Der postoperative Eintritt von Silikonöl in die Vorderkammer.

BACKGROUND: One reason for complications after silicone oil application is the postoperative entrance of silicone oil into the anterior chamber. In a retrospective study, we tried to define risk factors for oil entrance into the anterior chamber. METHODS: 159 Eyes of 148 patients, vitrectomized and filled with silicone oil between 1988 and 1992 were analysed. In 22 eyes (13.8%) silicone oil entered the anterior chamber postoperatively. Eyes with emulsified oil in the anterior chamber and eyes, where the oil entered the anterior chamber during cataract extraction were not included in this group. Diagnoses, postoperative fundus findings and lens status, intraocular pressure, depth of the anterior chamber and time of the oil entrance were analysed. RESULTS: Risk factors in the first 10 postoperative days (14 eyes = 63.6%) seem to be aphakia and choroidal effusions, especially if combined with buckling procedures (encircling bands). In the late postoperative period, i.e. up to 6.5 months (8 eyes = 36.4%), proliferative vitreoretinopathy was responsible for the entrance of silicone oil into the anterior chamber in all cases. The decreased production of aqueous humour combined with hypotony seems also to play an important role in this process. CONCLUSIONS: It seems that in the early postoperative period the frequency of oil entrance into the anterior chamber can only be lowered by a subtotal oil filling in aphakic eyes with accompanying encircling procedures. It remains open if radical amputation of the vitreous base can avoid peripheral reproliferations.

Bacterial contamination during extracapsular cataract extraction. Prospective study on 200 consecutive patients.

Postoperative endophthalmitis remains one of the most devastating complications of eye surgery. In recent years infections with so called 'nonpathogenic' organisms like Propionibacterium acnes or coagulase-negative staphylococci have gained in importance. 200 patients were included in this study, from whom preoperative smears of the conjunctiva and intraoperative aspirates of the anterior chamber (at the start and at the end of the operation) had been taken. All samples were investigated for aerobe and anaerobe microorganisms and fungi. 75% of the preoperative smears had been contaminated, with coagulase-negative staphylococci the most commonly isolated bacteria. But, in addition, 28% of the patients had culture-positive anterior chamber aspirates, also with coagulase-negative staphylococci as the most frequent organisms. In all cases inoculum sizes were extremely small (10-20 c.f.u./ml). Probably because of this small inoculum, but also due to the bacteriocidal qualities of the aqueous humor and the integrity of the posterior capsule sac, in no case had postoperative endophthalmitis developed. For the first time, our study tried to correlate the contamination of the anterior chamber aspirate to the used operation technique: first results show that the contamination of the aqueous humor is significantly lower (p < 0.03) if the cataract extraction is performed by phacoemulsification than if done without.