Familial cerebellar ataxia with cerebrovascular amyloid

We report a rare association of familial cerebellar ataxia (without dementia) and cerebrovascular amyloid. Postmortem neuropathological examination of one member of the family showed amyloid angiopathy of the central nervous system with heavy infiltration of capillaries in the hippocampus and cerebellum.     

Significance of urinary excretion of fibrin degradation products during treatment of glomerulonephritis.

189 patients with various types of glomerular disease were studied. Creatinine clearance, protein excretion and urinary excretion of fibrin degradation products (FDPs) were measured before and at various intervals (up to 42 months) after starting treatment with indomethacin, alone or in combination with other drugs. The following observations were made: a. Patients with a urinary FDP in excess of 2 mg/24 hours before treatment had a significantly lower creatinine clearance and a significantly higher protein excretion than patients excreting less than 2 mg FDP/24 hours, indicating that FDP excretion reflects the severity of the renal disease. b. During treatment, the incidence of high FDP excretion decreases progressively, but remains high in patients who ultimately develop renal insufficiency. c. There is no correlation between the initial value of FDP excretion and the subsequent changes in creatinine clearance and proteinuria during treatment. This implies either that the initial FDP excretion has no prognostic value or, perhaps more likely, that disease activity is modified by treatment. d. The best correlation between FDP excretion and evolution is found in proliferative glomerulonephritis. There are reason to suppose that, in this group at least, the treatment influenced the evolution of the disease.     

Alternating chemo-immunotherapy with temozolomide and low-dose interleukin-2 in patients with metastatic melanoma

Temozolomide is a rapidly absorbed chemotherapeutic agent, achieving significant central nervous system penetration. Previous clinical trials suggested that temozolomide in sequence with low-dose recombinant human interleukin-2 might be an efficacious and relatively non-toxic chemo-immunotherapeutic treatment, which may synergistically eliminate tumours. The primary objective was to determine the safety and tolerance of temozolomide administered orally 200 mg/m days 1-5, in sequential combination with subcutaneous injections of 4.5x10 IU recombinant human interleukin-2 on days 8-11, 15-18 and 22-25 in patients with measurable, progressive metastatic malignant melanoma without radiological signs of central nervous system metastases. The secondary objectives were to determine tumour response and time to progression. Twenty-seven patients were included, of which four were non-evaluable for response. Twenty-three patients tolerated the regimen with side effects below grade 3 according to the World Health Organization (WHO) scale. Three patients suspended the treatment because of WHO grade 3 side effects already during the first 3 days of the first course of temozolomide. Seven patients showed no tumour progression during the first four treatment cycles. Two patients had complete responses, three partial responses and two stable disease at the end of the four cycles defined by the protocol and they continued the treatment until signs of relapse or a maximum of 21 courses. Five of these patients are still alive. Thrombocytopenia was significantly more pronounced in patients with objective response and stable disease than in non-responders to therapy. The median time to progression for all patients was 3.1 months and for responding and stable disease patients was 15 months. Five of 23 treated patients (22%) developed brain metastases during follow-up. Temozolomide in combination with recombinant human interleukin-2 is a well-tolerated regimen for outpatient treatment and the bio-chemotherapy combination induced durable clinical responses. Thrombocytopenia might be a positive predictive factor for response to therapy.     

Human papilloma virus (HPV) is rarely detected in malignant melanomas of sun sheltered mucosal membranes

Human papillomavirus (HPV) has been associated with some types of human cancer. The aim of this study was to investigate if HPV could be associated with human primary malignant melanoma in non sun-exposed body areas like mucous membranes. Through the Swedish National Cancer Registry, in compliance with the rules of the Human Ethical Committee, histopathological specimens were collected from different pathological laboratories throughout Sweden. The histopathological diagnosis was reviewed, and from 45 primary melanomas, tumour tissue was micro-dissected and analysed further. A protocol for detection of HPV DNA using general HPV primers GP5 + /GP6+ or CPI/IIG, which together identify 36 different HPV subtypes, was developed. This protocol could detect presence of HPV DNA in less than 10 ng of DNA of a control cell that contained 1-2 copies of HPV type 16/cell. Before HPV testing the melanoma samples were examined for amplifiable DNA by a β-microglobulin PCR and 39 were positive. Thirty-five of these could be evaluated for HPV DNA and no samples were positive according to all five defined criteria for HPV positivity although two were positive according to 4/5 criteria. In conclusion, HPV is rarely detected in primary malignant melanomas of non-sun exposed body areas.     

Overweight and obesity in twenty-year-old Swedes in relation to birthweight and weight development during childhood

Aim: To describe the frequency of overweight and obesity from birth to 20 years of age and analyse weight at 20 years of age in relation to weight and weight development during early childhood and adolescence. Methods: A longitudinal, population‐based study, which followed 496 children from birth to 20 years of age. Information about weight and height was collected from health records at child health centres and school health care. At 20 years of age, weight and height measurements were taken by one of the authors. Results: At 20 years of age, 124 (25%) of the youth were obese or overweight. Of these youths, 60% had normal weight at 5.5 years. Of the teenagers who were overweight/obese at 15 years, 79% remained overweight/obese at 20 years of age. Out of the 124 overweight/obese at 20, 47% had normal weight at 15 years. [Corrections added after online publication on April 18, 2012: ‘Out of the 124 obese at 20’ has been changed to ‘Out of the 124 overweight/obese at 20’]. No relation was found between rapid weight gain during preschool age and overweight and obesity in 20‐year‐olds. Conclusions: The majority of those who were overweight/obese at 20 years of age were recruited after 5.5 years of age, and half of them in their late teens. Thus, during the preschool period, the entire population should be the target of primary prevention from overweight/obesity and, in the case of teenagers, prevention strategies should be developed for the whole population as well as treatment strategies for teenagers with established overweight/obesity.     

Comparison of clinicians and an artificial neural network regarding accuracy and certainty in performance of visual field assessment for the diagnosis of glaucoma

Purpose: To compare clinicians and a trained artificial neural network (ANN) regarding accuracy and certainty of assessment of visual fields for the diagnosis of glaucoma. Methods: Thirty physicians with different levels of knowledge and experience in glaucoma management assessed 30‐2 SITA Standard visual field printouts that included full Statpac information from 99 patients with glaucomatous optic neuropathy and 66 healthy subjects. Glaucomatous eyes with perimetric mean deviation values worsethan ?10 dB were not eligible. The fields were graded on a scale of 1–10, where 1 indicated healthy with absolute certaintyand 10 signified glaucoma; 5.5 was the cut‐off between healthy and glaucoma. The same fields were classified by a previously trained ANN. The ANN output was transformed into a linear scale that matched the scale used in the subjective assessments. Classification certainty was assessed using a classification error score. Results: Among the physicians, sensitivity ranged from 61% to 96% (mean 83%) and specificity from 59% to 100% (mean 90%). Our ANN achieved 93% sensitivity and 91% specificity, and it was significantly more sensitive than the physicians (p < 0.001) at a similar level of specificity. The ANN classification error score was equivalent to the top third scores of all physicians, and the ANN never indicated a high degree of certainty for any of its misclassified visual field tests. Conclusion: Our results indicate that a trained ANN performs at least as well as physicians in assessments of visual fields for the diagnosis of glaucoma.     

Evaluation of the DiversiLab System for Detection of Hospital Outbreaks of Infections by Different Bacterial Species

Many bacterial typing methods are specific for one species only, time-consuming, or poorly reproducible. DiversiLab (DL; bioMérieux) potentially overcomes these limitations. In this study, we evaluated the DL system for the identification of hospital outbreaks of a number bacterial species. Appropriately typed clinical isolates were tested with DL. DL typing agreed with pulsed-field gel electrophoresis (PFGE) for Acinetobacter (n = 26) and Stenotrophomonas maltophilia (n = 13) isolates. With two exceptions, DL typing of Klebsiella isolates (n = 23) also correlated with PFGE, and in addition, PFGE-nontypeable (PFGE-NT) isolates could be typed. Enterobacter (n = 28) results also correlated with PFGE results; also, PFGE-NT isolates could be clustered. In a larger study (n = 270), a cluster of 30 isolates was observed that could be subdivided by PFGE. The results for Escherichia coli (n = 38) correlated less well with an experimental multilocus variable number of tandem repeats analysis (MLVA) scheme. Pseudomonas aeruginosa (n = 52) showed only a limited number of amplification products for most isolates. When multiple Pseudomonas isolates were assigned to a single type in DL, all except one showed multiple multilocus sequence types. Methicillin-resistant Staphylococcus aureus generally also showed a limited number of amplification products. Isolates that belonged to different outbreaks by other typing methods, including PFGE, spa typing, and MLVA, were grouped together in a number of cases. For Enterococcus faecium, the limited variability of the amplification products obtained made interpretation difficult and correlation with MLVA and esp gene typing was poor. All of the results are reflected in Simpson''s index of diversity and adjusted Rand''s and Wallace''s coefficients. DL is a useful tool to help identify hospital outbreaks of Acinetobacter spp., S. maltophilia, the Enterobacter cloacae complex, Klebsiella spp., and, to a somewhat lesser extent, E. coli. In our study, DL was inadequate for P. aeruginosa, E. faecium, and MRSA. However, it should be noted that for the identification of outbreaks, epidemiological data should be combined with typing results.Pulsed-field gel electrophoresis (PFGE) is generally considered the “gold standard” method for the typing of many bacterial species. Other commonly used typing procedures include multilocus sequence typing (MLST), Multiple-locus variable number of tandem repeats analysis (MLVA), and amplified fragment length polymorphism analysis (6, 8, 11, 14, 21). But all of these methods suffer from different drawbacks. They are specific for one species, time-consuming, or poorly reproducible. The recently introduced DiversiLab (DL) system (bioMérieux) potentially overcomes these limitations. This typing technique is based on the repetitive-sequence-based PCR (rep-PCR) for typing (3, 4, 23, 24). This method was developed in the 1990s and, though still used today, suffers from reproducibility problems. The DL system is a semiautomated rep-PCR with a high level of standardization, in particular for the electrophoresis step by using a Bioanalyzer (Agilent Technologies, Inc., Santa Clara, CA). This reduces reproducibility problems due to variation in assay conditions. The analysis software allows the comparison of individual amplification product patterns (peak patterns), which enables easier interpretation of the patterns, but a virtual gel image is also generated. The patterns can be stored in a database and used for comparison. An important advantage of DL is that a result can be obtained in 1 day starting from a pure culture. A number of studies investigating DL have been published (5, 7, 16, 18, 19), but these were limited to one species and sometimes used collections or made comparisons at the level of MLST, a method which is not discriminatory enough for hospital outbreak analysis.In this study, we evaluated the DL system for the identification of established hospital outbreaks of a number of bacterial species, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium, Escherichia coli, the Enterobacter cloacae complex, Acinetobacter species, Klebsiella species, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, using typed collections.