[Tyrosine kinase inhibitor-associated choroidopathy]. / Tyrosinkinaseinhibitor-assoziierte Choroidopathie.

A 66-year-old male patient presented to the ophthalmology department with bilateral blurred vision, which had persisted for 1 week. Due to a pulmonary melanoma metastasis, the patient received a combination treatment with dabrafenib and trametinib. At the first presentation visual acuity was 1.2 on the right and 1.0 on the left. A normotensive intraocular pressure was measured in both eyes. Fundoscopy showed bilateral white, areolar alterations in the choroid and choroid folds and in the left eye a bullous choroidal detachment. Bilateral neurosensory detachment and subretinal fluid were found in optical coherence tomography (OCT). After reduction of the local treatment for pressure reduction and under local and systemic anti-inflammatory treatment, the choroidal swelling was progressive, the visual acuity dropped to 0.5 in the right and to 0.1 in the left eye. A significant regression of the findings occurred only after pausing the treatment with trametinib. Visual acuity rose to 1.0 (left) and 0.8 (right). The OCT showed a dry macula on the right and a small amount of residual subretinal fluid in the left eye.

Prevalence of macrolide resistance mechanisms in Streptococcus pneumoniae isolates from a multicenter antibiotic resistance surveillance study conducted in the United States in 1994-1995.

Two main mechanisms of macrolide resistance have been described in erythromycin-resistant Streptococcus pneumoniae (ERSP): a ribosomal methylase, ErmAM, and a macrolide efflux pump, MefE. In this study, we examined the prevalence of these mechanisms in 114 clinical isolates of ERSP from a 30-center study conducted in the United States between November 1994 and April 1995. The isolates were screened by polymerase chain reaction for the presence of known macrolide resistance genes. Seventy (61%) ERSP contained the macrolide efflux gene (mefE), whereas 36 isolates (32%) contained the biosomal methylase gene (ermAM). Isolates that were ermAM-positive had constitutive macrolide resistance. The minimum inhibitory concentrations (for which 90% of isolates were susceptible) of clarithromycin for the efflux-positive strains were much lower than those for the ermAM-positive strains (4 microg/mL vs. >128 microg/mL, respectively). The efflux mechanism is the predominant form of macrolide resistance in the United States.

Variability in susceptibilities of Haemophilus influenzae to clarithromycin and azithromycin due to medium pH.

The National Committee for Clinical Laboratory Standards (NCCLS) methods for susceptibility testing of Haemophilus influenzae in Haemophilus test medium allow a pH range of 7.2 to 7.4. However, it is known that bacteria may appear to be less susceptible to macrolides at lower pHs. Forty-four strains of H. influenzae were tested for their susceptibilities to clarithromycin and azithromycin by the disk diffusion and broth microdilution methods. The isolates appeared to be less susceptible at pH 7.2 than at pH 7.4 by both methods. Clarithromycin was less active at pH 7.2 against 43% of the isolates by the disk diffusion method and against 52% of the isolates by the broth microdilution method. Similarly, azithromycin was less active at pH 7.2 against 41 and 45% of the isolates by the disk diffusion and broth microdilution methods, respectively. Forty-two isolates were classified as clarithromycin susceptible and all isolates were classified as azithromycin susceptible by the disk diffusion method, regardless of the medium pH. However, only 21 isolates were clarithromycin susceptible at pH 7.2 and 34 isolates were susceptible at pH 7.4 by the broth microdilution method, even though quality control results indicated valid testing at both pHs. This study indicated that the results of tests of the susceptibility of H. influenzae with clarithromycin and azithromycin are highly dependent on the pH of the medium. Test results and their interpretations varied even when the medium pH was within the NCCLS-approved range and, coupled with the current NCCLS breakpoint of 8 microg/ml in the case of clarithromycin, may explain some of the observed discordances between the disk diffusion and broth microdilution methods.

In vitro granulocyte aggregation.

Granulocyte aggregation in EDTA-blood from a patient with rheumatoid arthritis is described. The phenomenon was observed three times within a 10-month period. The blood leukocyte count in a Coulter Counter decreased approximately 30% within 6 h, without resulting in overt leukopenia. Simultaneously, increasing numbers of granulocyte aggregates turned up in smears. There were no indications of thrombocytes being involved in the phenomenon.

Susceptibility of Campylobacter pylori to macrolides and fluoroquinolones.

The in-vitro activities of several 14-, 15- and 16-membered macrolides and fluoroquinolones against Campylobacter pylori were determined. In general, 14-membered macrolides, such as clarithromycin and flurithromycin, were more active than the 15-membered macrolide, azithromycin, which was more active than 16-membered macrolides, such as miocamycin and rokitamycin. Fluoroquinolones, except ciprofloxacin and A-61827, were less active than macrolides. Clarithromycin was the most active of the new compounds against C. pylori and was as active as ampicillin. MICs of all compounds at pH 5.5 were increased when compared to MICs determined at pH 7.3. All compounds had MBCs which were the same as or within one two-fold dilution of their MICs. Frequencies of spontaneous resistance development by C. pylori NCTC 11637 at four and eight times the MIC of the compounds were low and ranged from less than 1 x 10(-9) to 1 x 10(-7).

Comparative in vitro activities of new 14-, 15-, and 16-membered macrolides.

The in vitro activities of several 14-, 15- and 16-membered macrolides were compared with that of erythromycin. In general, 14-membered macrolides such as erythromycin, clarithromycin, and flurithromycin were more active against streptococci and Bordetella pertussis than was the 15-membered macrolide azithromycin, which was more active than 16-membered macrolides such as miocamycin and rokitamycin. Clarithromycin was the most active compound against Streptococcus pyogenes, pneumococci, Listeria monocytogenes, and Corynebacterium species. Legionella pneumophila was most susceptible to miocamycin, clarithromycin, and rokitamycin. Branhamella catarrhalis, Neisseria gonorrhoeae, and Haemophilus influenzae were most susceptible to azithromycin. Azithromycin and dirithromycin were the most active compounds against Campylobacter jejuni. MICs of 16-membered macrolides for strains expressing inducible-type resistance to erythromycin were less than or equal to 1 microgram/ml, whereas none of the compounds had activity against strains expressing constitutive-type resistance. The MICs of roxithromycin, miocamycin, rokitamycin, and josamycin increased in the presence of human serum, whereas MICs of the other compounds either were unchanged or decreased.

A longitudinal study of the influence of azathioprine on natural killer cell activity.

Natural killer (NK) cell activity against K562 target cells was studied in six patients with definite or classical rheumatoid arthritis before and during treatment with azathioprine. Azathioprine induced suppression of NK cell activity, but treatment with azathioprine for 5-8 months was necessary before NK cell activity was completely suppressed. In vitro incubation of mononuclear cells from a healthy donor with azathioprine or 6-mercaptopurine in concentrations not reducing cell viability did not inhibit NK cell activity, nor did sera from patients treated with azathioprine for more than 6 months.

Characterization of the in vitro effects of glucocorticosteroids on NK cell activity.

The NK cell activity of mononuclear cells as well as monocyte-depleted, Percoll-fractionated, NK cell-enriched effector cells against K 562 target cells was inhibited by methylprednisolone (MP) and hydrocortisone (HC) in a dose-dependent manner. The effector/target cell conjugate formation was studied in a single cell agarose assay, and it was shown that MP and HC partly inhibited the NK cell activity by inhibition of the adhesion of effector cells to target.

Ambulatory 24-hour continuous electrocardiographic monitoring in 54 patients with ankylosing spondylitis.

Of 54 patients with ankylosing spondylitis 48 were found to be HLA B27 positive. Ambulatory 24-hour Holter monitoring revealed electrocardiographic 'abnormalities' in 12 of the 48 HLA B27 positive patients. To our knowledge this is the first ambulatory Holter monitoring of a group of patients with ankylosing spondylitis, and the outcome seems to suggest a relationship between the tissue type HLA B27 and the occurrence of electrocardiographic 'abnormalities'. The frequency of atrioventricular block (types I and III) and atrial tachycardia was significantly higher in this group of patients than that found in similar studies of healthy adults. The frequency of psoriasis and cardiac murmurs was increased among the patients with electrocardiographic 'abnormalities'.

Baseline and interferon-enhanced natural killer cell activity in rheumatoid arthritis.

Natural killer (NK) cell activity against the leukemia cell line K-562 was tested in 45 patients with rheumatoid arthritis (RA) who either had not received any remission-inducing drugs for more than 6 months or had received penicillamine for at least 6 months. Baseline NK cell activity and interferon (IF)-enhanced NK cell activity did not differ from that observed in 45 controls matched for age and sex, and neither NSAID (non steroidal anti-inflammatory drugs) nor penicillamine influenced NK cell activity. There was no correlation between NK cell activity and acute-phase reactants.

Shuttle case records: link between general practice and the specialist unit.

General practitioners have participated in the long term follow up of 367 patients who have undergone treatment with potent antirheumatic drugs at this hospital. Over the past two and a half years we have used the "shuttle case record" system, whereby patients' records are mailed back and forth between our department and general practitioners. This seems to work well. It is safe for the patients, and they save time and money in travel. The general practitioners like it, it improves communication between them and the specialist unit, and it enables the specialist unit to use its resources and manpower more effectively. The system may also be used to monitor patients with other chronic disorders, and it may be a valuable tool for doing research in general practice.

Methylprednisolone pulse therapy induced fall in natural killer cell activity in rheumatoid arthritis.

Natural killer (NK) cell activity was studied in 8 patients with classic or definite rheumatoid arthritis (RA) by investigating the killing of K 562 cells by peripheral blood lymphocytes before, during, and after intravenous methylprednisolone pulse therapy (MPPT). MPPT produced a considerable fall in NK activity and after 3 months NK activity was less than half that before MPPT.

Work-related outcomes of the constructive-confrontation strategy in a job-based alcoholism program.

Most job-based alcoholism policies and programs incorporate a strategy of constructive confrontation. Data from two national samples of over 600 managers in a large corporation were collected to assess the effectiveness of this strategy with both problem drinkers and other problem employees. Results showed that supervisors of problem drinkers took more actions than did supervisors of employees with other problems. Work performance of problem-drinking employees improved more than that of other problem employees. Oral discussions containing both constructive and confrontational topics were positively associated with employees accepting help and with better work performance following intervention for both samples of employees. However, more severe forms of discipline--written warnings, suspensions or discharges--were negatively associated with work performance following intervention in both samples. The results suggest that (1) the strategy is most effective when repeated discussions balance both constructive and confrontational elements, and (2) the presence of the alcoholism policy encouraged supervisors to take more actions with problem drinkers, legitimated those actions and made the threat of discipline more credible.

Azathioprine as single drug in the treatment of rheumatoid arthritis induces complete suppression of natural killer cell activity.

Natural killer (NK) activity against K 562 target cells was studied in 60 patients with definite or classic rheumatoid arthritis (RA), grouped by medication into 1) Controls not in remission-inducing therapy, 2) Patients treated with penicillamine, and 3) Patients treated with azathioprine. NK activity was found to be completely suppressed in the azathioprine group as compared with the controls (3.2 +/- 4.2% versus 35.9 +/- 14.8% specific lysis; p less than 0.01) except for one patient who received incomplete azathioprine treatment. The NK activity was not suppressed in the penicillamine group.

Intermittent cyclophosphamide in refractory rheumatoid arthritis.

Three patients with refractory rheumatoid arthritis were treated with oral cyclophosphamide; in two cases this was supplemented with pulse treatment with methylprednisolone. Long term remission was induced in all three patients and was sustained until follow up at least nine months after the methylprednisolone was stopped. Leucopenia occurred but resolved when cyclophosphamide was reduced from daily to intermittent dosing. Intermittent treatment with cyclophosphamide, possibly in conjunction with pulses of methylprednisolone, may induce remission in patients with rheumatoid arthritis refractory to other forms of treatment.

A data-based examination of selection-bias in the evaluation of a job-based alcoholism program.

We describe the strategy of constructive confrontation present in most job-based alcoholism programs, and conclude that it is compatible with the major concepts and practices of discipline in the workplace. We review past evaluation studies of these programs, noting the rather remarkable positive outcomes often reported. We then review reasons for both accepting and rejecting these unusual findings. One of the major biases that could produce the favorable findings-selectivity bias-is then examined, using both field data and record data from a large national corporation. Samples from records in the review period 1964 through 1977 generated 377 case histories. The study also used field interviews in the same corporation in a national sample of 19 locations. We interviewed supervisors who had experienced an employee in the alcoholism program (A sample = 154) and a sample of all other supervisors (B sample = 351) who described a nonalcoholic problem employee and how he/she had been managed. The remainder of the report focuses upon two possible sources of selection bias: suspected but not referred cases in the field data, and incomplete, "lost," cases in the record data. In both instances, the selectivity seemed to be quite minimal, insufficient to damage the conclusion that the program intervention had produced significant positive changes in job performance.

Assessing personal, role, and organizational predictors of managerial commitment.

Using a role and exchange theory framework, this study examines the commitment to their organization and to the federal service of 634 managers in 71 federal government organizations. Results indicate that certain role factors such as tenure and work overload and personal factors such as attitude toward change and job involvement are strong influences on commitment. Implications of the findings and the need for further theoretical and methodological refinements are discussed.