[A stochastic test for validity control of visual acuity statements]. / Ein stochastischer Test zur Validitätskontrolle von Visusangaben.

BACKGROUND: When a patient's statement of reduced visual acuity (VA) does not correspond to the ophthalmologic findings, the validity of the statement should be checked before intensive diagnostics are initiated, because the statement may be untrue or may overstate a factual reduction in VA. A primary question is whether the patient's statement differs from his or her true VA, and if so, by how much. Especially in examinations for medical opinion, individuals may be well informed on how to check the validity of VA statements. Thus, modifications of standard test strategies are required. We examined a new test that was designed to allow probabilistic evaluation. PATIENTS AND METHODS: The optotype board has the form of a poster measuring 150 cm in height and 125 cm in width. It contains 16 lines corresponding to the logarithmic VA levels from 0.12 up to 4.0 at a distance of 5 m. Each line consists of nine Landolt-Cs with four alternative orientations. VA was determined by a 1/1 criterion for each single measurement at each of the nine optotype columns. In cases of low vision (VA <0.25), the test distance was reduced accordingly. The test was given to 100 patients (VA 0.012-2.75), 20 healthy subjects (VA >1.0) who were requested to simulate a VA of 0.1, and 13 individuals who were examined for medical opinion, nine of whom were suspected (by results of other testing) of stating nonorganic visual deterioration. The mean and the individual distribution of the nine single values were analyzed and compared with the distribution within a typical psychometric function as determined by a Monte Carlo simulation on 100,000 single measurements. RESULTS: None of the 100 normally cooperative patients yielded more than seven idential single values, and only one yielded seven. The single values scattered by one to three lines. Of the 20 pseudomalingerers (examined at a distance of 2.5 m), in seven subjects (35%) we found an atypical pattern of single values (seven or nine identical values). VA results of those 10 subjects who could read the calibration column on the board (reference distance 5 m) scattered around 0.06. Results of those 10 subjects who were examined after the calibration column had been replaced with lower values (reduced by a factor of 4) scattered around 0.13. Of the nine individuals examined for medical opinion who were suspect of stating too low a VA, six (67%) showed an atypical distribution of single values. CONCLUSION: This convenient test is a practical tool both for regular determination of visual acuity and for detection of false statements by means of an atypical psychometric function. It also allows for application of further validity checks. Intentionally false statements can be influenced by misleading calibration values.

A method for the production of cryopreserved aliquots of antigen-preloaded, mature dendritic cells ready for clinical use.

Dendritic cells (DC) are increasingly used as a vaccine. Unfortunately, a satisfactory cryopreservation of DC in the absence of FCS is not yet available, so that laborious repeated generation of DC from fresh blood or frozen peripheral blood mononuclear cells for each vaccination has been required to date. We now aimed at developing an effective cryopreservation method, and by testing several variables found that it was crucial to combine the most advantageous maturation stimulus with an improved freezing procedure. We generated monocyte-derived DC from leukapheresis products by using GM-CSF and IL-4 and showed that amongst several known maturation stimuli the cocktail consisting of TNF-alpha+IL-1 beta+IL-6+PGE(2) achieved the highest survival of mature DC. We then systematically explored cryopreservation conditions, and found that freezing matured DC at 1 degrees C/min in pure autologous serum+10% DMSO+5% glucose at a cell density of 10x10(6) DC/ml gave the best results. Using this approach 85-100% of the frozen DC could be recovered in a viable state after thawing (Table 1). The morphology, phenotype, survival as well as functional properties (allogeneic mixed leukocyte reaction, induction of influenza matrix or melan A peptide-specific cytotoxic T cells) of these thawed DC were equivalent to freshly prepared ones. The addition of CD40L or TRANCE/RANKL further improved DC survival. Importantly, we demonstrate that DC can effectively be loaded with antigens (such as Tetanus Toxoid, influenza matrix and melan A peptides) before cryopreservation so that it is now possible to generate antigen-preloaded, frozen DC aliquots that after thawing can be used right away. This is an important advance as both the generation of a standardized DC vaccine under GMP conditions and the carrying out of clinical trials are greatly facilitated.

Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion.

OBJECTIVE: Most patients with fibromyalgic syndrome (FMS) complain of sleep disturbances, fatigue, and pain. These symptoms might be a consequence of changed melatonin (MT) secretion, since MT is known to have sleep promoting properties. Moreover, serum concentrations of two MT precursors (tryptophan and serotonin)--affecting both sleep and pain perception--appear to be low in patients with FMS. Therefore, the objective of this investigation was to study whether serum MT (s-MT) level is also low in these patients. DESIGN: Eight patients with FMS and 8 healthy sex-, BMI-, and age-matched controls were included in the study. s-MT concentrations were determined every second hour between 1800 and 0800 h. Urine was collected between 2200 and 0700 h for determination of urinary MT excretion. To evaluate total MT secretion between 1800 and 0800 h and MT secretion during the hours of darkness (between 23 and 07 h) individual MT areas under the curve (AUC) were calculated and expressed as group means. RESULTS: The FMS patients had a 31% lower MT secretion than healthy subjects during the hours of darkness (MT AUC 2300-0700 h (mean +/- SEM): 1.70 +/- 0.17 vs 2.48 +/- 0.38 nmol/l; P < 0.05). Also the s-MT peak value was significantly lower in the patient group: 0.28 +/- 0.03 vs 0.44 +/- 0.06 nmol/l; P < 0.05). CONCLUSION: Patients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.

Studies on the chronic oral toxicity of an analgesic drug combination consisting of acetylsalicylic acid, paracetamol and caffeine in rats including an electron microscopical evaluation of kidneys.

The analgesic drug combination Thomapyrin consisting of acetylsalicylic acid (CAS 50-78-2, ASA), paracetamol (CAS 103-90-2, NAPAP) and caffeine (CAS 58-08-2) in the ratio 5:4:1 was investigated for its chronic toxicity in rats. For comparison the individual drugs ASA and NAPAP as well as the double combination ASA+NAPAP were tested in equipotent doses. 20 male and 20 female rats per group (Chbb:THOM/SPF) received doses of 50, 100 and 200 mg/kg of the combination ASA+NAPAP+caffeine, 45 and 180 mg/kg of the combination ASA+NAPAP, and 50 and 200 mg/kg of the individual drugs ASA or NAPAP over a period of 6 months. The daily dose was splitted into two parts and administered 3 h apart. The rats were single housed under standardized conditions with free access to food and drinking water. Plasma concentrations were measured in four additional animals of all high dose groups after the last dosing at seven time points. Besides the usual routine toxicological investigations the kidneys of five females per group were investigated by transmission electron microscopy. All investigations were performed according to GLP regulations. All animals behaved unobtrusively throughout the study with only minor impairment of general conditions in some animals of all ASA, ASA+NAPAP+caffeine and the high dose NAPAP groups. Dose related mortality was observed in the groups receiving ASA alone or in combination, partly with rales and tonic convulsions immediately prior to death. Body weight gain was decreased in males but not in females of the ASA+NAPAP+ caffeine and ASA groups. No consistent drug- and dose-dependent changes in hematological, clinico-chemical or urinanalytical parameters were observed, except for a slight increase in excretion of epithelial cells in both genders of the ASA groups. Plasma drug level monitoring demonstrated that the pharmacokinetics of ASA were not altered by co-administration of caffeine or NAPAP or vice versa. In males, maximum plasma concentrations (Cmax) and areas under the curve (AUC) for ASA and NAPAP tended to be slightly lower than in females. The plasma concentrations reached in the study represent a low multiple (2.2-7.9) of therapeutic plasma levels. Therefore, the results reported in the study can be considered representative for normal therapeutic use of the analgesic combination ASA+NAPAP+caffeine. Gastric erosions in the ASA and ASA+NAPAP+caffeine groups, increased kidney weights in females given 200 mg/kg ASA+NAPAP+caffeine, and dose-dependently increased liver weights in females given 200 mg/kg ASA and decreased liver weights in males at 100 and 200 mg/kg ASA-NAPAP+caffeine were the only consistent drug-induced changes observed at necropsy. Except for the above mentioned ulcer, all histopathological findings were iatrogenic or spontaneous lesions. The kidneys demonstrated initial stages of age-associated nephropathy at comparable incidence and severity in all groups including controls. Semi-thin section evaluation and transmission electron microscopy showed only minor changes. Taking all tubular and vascular changes together (total mean), the animals of the NAPAP group were slightly more affected than those of the other groups. Summing up it can be concluded that the nephrotoxic potential of the combination ASA+NAPAP+caffeine, if existing at all, was marginal even after prolonged administration, and that it does not exceed that of the monosubstances when given at pharmacologically equipotent doses and clinically relevant exposures.

Batch-by-batch analysis of topographic changes induced by sutured and sutureless clear corneal incisions.

PURPOSE: To evaluate the effect of a suture on surgically induced corneal topographic changes in 5.0 mm clear corneal incisions. SETTING: University Eye Hospital, Vienna, Austria. METHODS: Thirty-seven eyes that had cataract surgery were included in the prospective study. A 5.0 mm long and 0.3 mm deep precut was followed by preparation of a corneal tunnel. After phacoemulsification and intraocular lens implantation, the self-sealing wound was left unsutured in 19 eyes; one radial 11-0 nylon suture was applied in 18 eyes. Using a TMS-1 videokeratoscope, corneal topography was measured preoperatively and at 1 week and 1 and 3 months postoperatively. The topographic data were evaluated by statistical batch-by-batch analysis. Each topographic image was cut into 178 fields in eight concentric rings. The refractive values of these fields were stored in a database. Differences between the four readings of each patient were calculated and the mean differences of the 178 fields in each group were transformed into color-coded maps. The significance of topographical changes and group comparisons of induced changes were computed by Wilcoxon tests. RESULTS: Both groups exhibited significant temporal flattening and vertical steepening. The unsutured eyes also displayed significant nasal flattening. Sutureless 5.0 mm clear corneal incisions induced significantly more vertical steepening and nasal flattening than sutured incisions. CONCLUSION: Application of one radial 11-0 nylon suture in 5.0 mm temporal clear corneal incisions significantly reduced shape changes in the nasal corneal region.

Comparison of results and complications following combined ECCE-trabeculectomy versus small-incision-trabeculectomy and posterior chamber lens implantation.

PURPOSE: To compare the efficacy and complication rate of two standard cataract extraction techniques with different incision lengths when combined with trabeculectomy. METHODS: 54 eyes after combined ECCE, posterior chamber lens implantation and trabeculectomy (ECCE-group) are compared with 49 eyes following phacoemulsification, trabeculectomy and implantation of a folded flexible posterior chamber lens (small-incision group). Minimum follow-up was 24 months. RESULTS: Glaucoma control was achieved in all eyes of both groups. There was a tendency towards a higher number of patients without therapy in the small-incision group (82% versus 65%, p = 0.07). Final mean IOP (14.2 +/- 3.0 mmHg versus 15.5 +/- 2.7 mmHg, p = 0.02) and mean therapy index (0.2 +/- 0.5 versus 0.4 +/- 0.6, p = 0.03) were significantly lower in the small-incision group. Postoperative complications such as severe fibrin effusion (41% versus 18%, p = 0.018), early postoperative IOP rises > 25 mmHg (18% versus 2%, p = 0.009), filtering bleb scarring (63% versus 8%, p < 0.0001) and the total number of complications (87% versus 63%, p = 0.006) were significantly higher in the ECCE-group. CONCLUSION: With the decrease of the incision size necessary for the cataract extraction a reduction of postoperative complications and better functional results are achieved in combined cataract/glaucoma surgery.

Comparison of recalled and validated oral contraceptive histories.

From a case-control study of the relation between oral contraceptives and breast cancer carried out in East Germany during 1982-1986, the authors obtained information on oral contraceptive use through interviews of study subjects and from the records of prescribing gynecologists. The degree of agreement regarding information from these two sources was assessed for 234 breast cancer cases and 524 controls who had ever used oral contraceptives. Agreement between information obtained from medical records and that from interviews on total duration of use, number of episodes of use, and time since first and last use was reasonably good, and levels of agreement did not differ appreciably between cases and controls. Lower levels of agreement were observed for individual brand names and the duration of use of specific brands. Attempts should be made to obtain information on specific brands from medical records when investigating the effects of individual preparations.

PIP: Researchers used the results of interview data on oral contraceptive (OC) use in both breast cancer cases and hospital controls to compare the accuracy of their recall with data from gynecologic records. The 234 breast cancer cases were patients at the Central Institute of Cancer Research in Berlin, the German Democratic Republic. The 524 age=matched controls were patients in the ear, nose, and throat; eye; orthopedic; and skin wards at Klinikum Berlin-Buch, the district hospital. All the data were collected between November 1982 and June 1986. Interviewers used a calendar and samples of OC brands to help the women recall periods of use and brand names used. The availability of gynecologists' records was significantly associated with use of medical care, including cervical smears, duration of OC use, and the time since last OC use (p .01). When the interval since first and last OC use within 12 months, the agreement between patients and gynecologists was essentially the same for both cases and controls (first OC use, 72.4% vs. 67.8%; weighted kappa = .81 vs. .79; p .001) (last OC use, 80.4% vs. 68.7%, weighted kappa = .86 vs. .89; p .001). The highest percentages of agreement on ever use of OCs occurred with the most recently introduced brand name (Minisiston, 98.7% for cases and 99% for controls) and phasic OCs (Deposiston, 97.9% and 96.4%, respectively; Sequenz-Ovosiston, 92.7% and 89.9%, respectively). These findings showed that use of a calendar and brand samples results in rather accurate recall of overall OC use. They also indicated that having breast cancer does not affect recall of OC use. This study's investigators suggested that in studies examining the effects of individual substances or doses, researchers should try to obtain data from medical records.

Local immunoglobulin production in synovial tissue in patients with Lyme borreliosis.

A study was made to find out whether immunoglobulins are produced locally in synovial tissue in patients with Lyme borreliosis. Synovial fluid specimens from six patients with Lyme borreliosis were compared with those from 25 patients with rheumatoid arthritis, psoriatic arthritis, unspecified oligoarthritis or arthrosis (control group). Agarose electrophoresis revealed local oligoclonal IgG and IgM bands in the synovial fluid of two patients with Lyme borreliosis, but no local bands were observed in the control group. An index for local synthesis of immunoglobulins in synovial fluid was calculated in analogy with the IgG index for cerebrospinal fluid. The two patients with Lyme borreliosis in whom oligoclonal bands were seen in the synovial fluid showed the highest synovial fluid IgG indices and the highest concentrations of specific IgG antibodies against Borrelia spirochetes in synovial fluid. The presence of local oligoclonal immunoglobulin bands and a high synovial fluid IgG index suggest that immunoglobulins are produced locally within the synovial tissue in some patients with Lyme borreliosis. The increase in immunoglobulins may be a response to a local invasion of Borrelia spirochetes or may represent an immune reaction which continues after the spirochetes no longer are viable.

[Use of oral contraceptives in East Germany by middle-aged females]. / Zur Anwendung oraler Kontrazeptiva in der DDR bei Frauen mittleren Alters.

This study was based on the data from 1214 women included in the controlled group within a hospital-based case-control study on the association between breast cancer and the use of oral contraceptives. This is a sample of middle-aged women. Women with a reason for referral, presumably associated with infertility, were excluded. Oral contraceptives are (apart from coitus interruptus) in 76% of the cases the method of contraception most frequently used, followed by the rhythm method and condoms. The use depends strongly on the age. Only 40% of the women, now 55-60 years of age, ever used oral contraceptives, whereas 91% of those now under 40 have been using them. Other connections can be seen with level of education, marital status, and reproduction and sex life. With the use of special preparations, there are differences between women of younger and older generations, partially based on the different times these preparations were introduced to the market. The exclusive use of sequential oral contraceptives decreases in the older cases.

Formation of lipoxin A by granulocytes from eosinophilic donors.

The formation of arachidonic acid-derived lipoxygenase products was examined with human granulocytes obtained from eosinophilic donors. These eosinophil-enriched leukocyte populations, challenged in vitro with the ionophore of divalent cations A23187, transformed both exogenous and endogenous sources of arachidonic acid to several lipoxygenase-derived products, including 5(S), 6(R),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid (lipoxin A). Lipoxin A was detected and characterized by high-pressure liquid chromatography (HPLC), ultraviolet absorbance, and gas-liquid chromatography-mass spectroscopy. Neither lipoxin B nor 6(S)-LXA was consistently detected in extracts from these incubations. The amounts of lipoxin A formed were proportional to the percentage of eosinophils present in the suspension. The results indicate that granulocytes from eosinophilic donors can generate lipoxin A.