Trends in the incidence of basal cell carcinoma by histopathological subtype

Background As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem. Objective In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades. Methods We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007. Results An annual increase of the number of BCCs of 7% for both genders was shown. The age‐standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100 000 men and from 61.7 to 189.8 per 100 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%. Conclusion The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non‐surgically, might reduce the workload in the busy dermatologists practice.     

Retinal Laser Damage Thresholds as a Function of Image Diameter

The eyes of rhesus monkeys were exposed to argon (514.5 nm) and ruby (694.3 nm) laser irradiation using various retinal image diameters which were estimated by microphotometric techniques. The experimental design for both wavelengths produced image diameters of 40μ to 50μ for the “minimal” case and approximately 500μ to 1,000μ for the larger irradiance series employed. Extramacular retinal exposure sites were examined by ophthalmoscopic and histopathological techniques. Flat preparations of the pigmented epithelium and sensory layers of the retina were utilized in the confirmation of damage at low power levels. All data were statistically analyzed to establish trends, and results were compared for the wavelengths employed. Results indicate that retinal damage is primarily dependent on energy distribution as a function of image diameter and exposure duration.     

The reproducibility of a food frequency questionnaire among controls participating in a case‐control study on cancer

This study was designed to test the reproducibility of a food frequency questionnaire used in a population‐based case‐control study on diet and pancreatic cancer. Repeat questionnaires covering the same time period were obtained using 63 male and female population controls, 35–79 years of age. For selected food items included in the case‐control study, the attenuation of the odds ratios due to random error was estimated. Using 54 male and female population controls, 35–79 years of age, we conducted a second study to examine the agreement between original and repeat interviews when the time interval between interview and the period of interest was constant.

In the first study, the median correlation coefficient was 0.72 for foods (ranging from 0.36 and 0.59 for subgroups of vegetables to 0.96 for alcoholic beverages) and 0.77 for nutrients (ranging from 0.62 for β‐carotene to 0.85 for energy and 0.91 for ethanol). In the second study, the median correlation coefficient was 0.68 for foods (ranging from 0.28 for eggs to 0.87 for alcoholic beverages) and 0.75 for nutrients (ranging from 0.48 for β‐carotene to 0.76 for energy).

We conclude that for most items the agreement between original and repeat estimates was moderate (r> 0.50) to high (r > 0.70). Moderate agreement was found for 28 of 33 food items (85%) and for all 21 nutrient items (100%) and high agreement for 19 of 33 of food items (56%) and 15 of 21 nutrient items (71 %). In the second study, agreement was somewhat lower but closely paralleled the results of the first study. On average, random error presumably attenuated most of the observed diet‐cancer relationships only moderately; i.e., an observed odds ratio of 1.5 and a correlation coefficient of 0. 70 yield an unattenuated odds ratio of 2.1.     

Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane

Two new murine monoclonal antibodies, AK 1 and SZ 1, reactive with the human platelet glycoprotein (GP) Ib-IX complex have been produced by the hybridoma technique. Both AK 1 and SZ 1 immunoprecipitated the GP Ib-IX complex from Triton X-100-solubilized, periodate-labeled platelets. With trypsinized, labeled platelets, AK 1, SZ 1, and FMC 25 (epitope on GP IX) immunoprecipitated a membrane-bound proteolytic fragment of the GP Ib-IX complex consisting of GP IX and an congruent to 25,000 mol wt remnant of the alpha-chain of GP lb disulfide-linked to the beta-subunit. Unexpectedly, although AK 1 and SZ 1 immunoprecipitated purified GP Ib-IX complex, neither antibody immunoprecipitated the individual components of this complex, GP Ib or GP IX. When GP Ib and GP IX were recombined, however, AK 1 and SZ 1 again immunoprecipitated the reformed complex, strongly suggesting that both antibodies were recognizing an epitope present only on the intact complex. Cross-blocking studies indicated that AK 1 and SZ 1 recognized a very similar or identical epitope that was proximal to the epitope for FMC 25. Both AK 1 and SZ 1 bound to a similar number of binding sites (congruent to 25,000) on intact platelets as monoclonal antibodies directed against either GP lb or GP IX. The combined data suggests that GP lb and GP IX are fully complexed in the intact platelet membrane.     

Myeloproliferative syndrome induced by MPSV in DBA/2 mice: presence of a mixed-colonies promoting activity (MPA) in the spleen

The myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) in DBA/2 mice stimulates the proliferation of pluripotent hemopoietic stem cells (HSC) and of progenitors committed toward granulomacrophagic and erythroid cell lines. This stimulation may result from a direct effect of the MPSV on HSC or from an indirect effect via locally secreted factors. Normal isogenic bone marrow cells were incubated in the mixed colony-forming unit system in semisolid medium supplemented with conditioned media obtained after incubating neoplastic spleen cells for 3 days at 37 degrees C. These spleen conditioned media contain an activity that is physically separable from MPSV by ultracentrifugation and which, in the presence of a very low quantity of erythropoietin, can induce in vitro the proliferation and differentiation of pluripotent HSC, detected by this Mix-CFU technique. We termed this activity mixed-colonies promoting activity (MPA). These results suggest that the hyperplasia of the nonlymphoid hematopoietic system in the neoplastic spleen results from an indirect effect of the MPSV on pluripotent HSC via locally secreted factors.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

Induction of ventricular fibrillation predicts sudden death in patients treated with amiodarone because of ventricular tachyarrhythmias after a myocardial infarction.

OBJECTIVE--To examine the value of programmed electrical stimulation of the heart in predicting sudden death in patients receiving amiodarone to treat ventricular tachyarrhythmias after myocardial infarction. DESIGN--Consecutive patients; retrospective study. SETTING--Referral centre for cardiology, academic hospital. PATIENTS--106 patients with ventricular tachycardia (n = 77) or ventricular fibrillation (n = 29) late after myocardial infarction. INTERVENTIONS--Programmed electrical stimulation was performed while on amiodarone treatment for at least one month. MEASUREMENTS AND MAIN RESULTS--In 80/106 patients either ventricular fibrillation (n = 15) or sustained monomorphic ventricular tachycardia (n = 65) was induced. After a mean follow up of 50 (SD 40) months (1-144), 11 patients died suddenly and two used their implantable cardioverter debfibrillator. By multivariate analysis two predictors for sudden death were found: (1) inducibility of ventricular fibrillation under amiodarone treatment (P << 0.001), and (2) a left ventricular ejection fraction of < 40% (P < 0.05). The survival rate at one, two, three, and five years was 70%, 62%, 62%, and 40% respectively for patients in whom ventricular fibrillation was induced, and 98%, 96%, 94%, 94% for patients with induced sustained monomorphic ventricular tachycardia. Where there was no sustained arrhythmia, five year survival was 100%. CONCLUSIONS--In patients receiving amiodarone because of life threatening ventricular arrhythmias after myocardial infarction, inducibility of ventricular fibrillation, but not of sustained monomorphic ventricular tachycardia, indicates a high risk of sudden death.     

Analysis of the cell infiltrate and expression of proinflammatory cytokines and matrix metalloproteinases in arthroscopic synovial biopsies: comparison with synovial samples from patients with end stage,destructive rheumatoid arthritis

BACKGROUND: Synovial tissue (ST) from end stage destructive rheumatoid arthritis (RA) and arthroscopic biopsies obtained during active inflammation might exhibit different characteristics. OBJECTIVE: To define the cell infiltrate and the expression of proinflammatory cytokines, angiogenic factors, and matrix metalloproteinases (MMPs) in ST selected at arthroscopy compared with that from end stage RA. METHODS: Synovial biopsy specimens were obtained from the actively inflamed knee joints of 13 patients with chronic RA by arthroscopy and compared with ST from 10 patients with end stage, destructive RA. Immunohistological analysis was performed to detect T cells, plasma cells, macrophages, fibroblast-like synoviocytes (FLS), and the expression of interleukin (IL)1beta, IL6, tumour necrosis factor alpha (TNFalpha), MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF. RESULTS: The expression of CD68+ macrophages was significantly higher in ST selected at arthroscopy than in samples obtained at surgery, both in the intimal lining layer and in the synovial sublining. The expression of CD3+ T cells also tended to be higher in arthroscopic samples. The expression of TNFalpha, IL6, MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF was on average higher in ST obtained at arthroscopy. In contrast, the expression of IL1beta was on average higher in surgical samples. CONCLUSION: Active arthritis activity is associated with increased cell infiltration, expression of proinflammatory cytokines, MMPs, and angiogenic growth factors in synovial biopsy samples selected at arthroscopy. Increased expression of IL1beta in the synovium of patients with destructive RA requiring joint replacement may well reflect the important role of IL1beta in cartilage and bone destruction.