Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability

The colorectum and uterine endometrium are the two most commonly affected organs in hereditary nonpolyposis colon cancer (HNPCC), but the genetic basis of organ selection is poorly understood. As tumorigenesis in HNPCC is driven by deficient DNA mismatch repair (MMR), we compared its typical consequence, instability at microsatellite sequences, in colorectal and endometrial cancers from patients with identical predisposing mutations in the MMR genes MLH1 or MSH2. Analysis of non-coding (BAT25, BAT26, and BAT40) and coding mononucleotide repeats (MSH6, MSH3, MLH3, BAX, IGF2R, TGF beta RII, and PTEN), as well as MLH1- and MSH2-linked dinucleotide repeats (D3S1611 and CA7) revealed significant differences, both quantitative and qualitative, between the two tumor types. Whereas colorectal cancers displayed a predominant pattern consisting of instability at the BAT loci (in 89% of tumors), TGF beta RII (73%), dinucleotide repeats (70%), MSH3 (43%), and BAX (30%), no such single pattern was discernible in endometrial cancers. Instead, the pattern was more heterogeneous and involved a lower proportion of unstable markers per tumor (mean 0.27 for endometrial cancers versus 0.45 for colorectal cancers, P < 0.001) and shorter allelic shifts for BAT markers (average 5.1 bp for unstable endometrial cancers versus 9.3 bp for colorectal cancers, P < 0.001). Among the individual putative "target" loci, PTEN instability was associated with endometrial cancers and TGF beta RII instability with colon cancers. The different instability profiles in endometrial and colorectal cancers despite identical genetic predisposition underlines organ-specific differences that may be important determinants of the HNPCC tumor spectrum.     

Provider–patient interaction in rural Cameroon—How it relates to the patient's understanding of diagnosis and prescribed drugs,the patient's concept of illness,and access to therapy

Objective

This cross-sectional survey examines the relation between provider–patient interaction and several patient-outcomes in a rural health district in Cameroon.

Methods

We used structured patient interviews and the Roter Interaction Analysis System (RIAS) for analysis of audio-recorded consultations.

Results

Data from 130 primary care consultations with 13 health-care providers were analysed. 51% of patients correctly named their diagnoses after the consultation; in 47% of prescribed drugs patients explained correctly the purpose. Patients’ ability to recall diagnoses was related to the extent of clarity a provider used in mentioning it during consultation (recall rates: 87.5% if mentioned explicitly, 56.7% if mentioned indirectly and 19.2% if not mentioned at all; p < 0.001). Two thirds of patients were able to describe their concept of illness before the consultation, but only 47% of them mentioned it during consultations. On average patients who mentioned their disease concept were faced with more remarks of disapproval from providers (1.73 vs 0.63 per consultation; p < 0.01). Although 41% of patients admitted problems with financial resources to buy prescribed drugs, discussion about financial issues was very rare during consultations. Providers issued financial questions in 32%, patients in 21% of consultations.

Conclusion

This study shows that provider–patient interaction in primary health care in a rural Cameroon district deserves more attention. It might improve the patients’ knowledge about their health condition and support them in beneficial health behaviour.

Practice implications

Our findings should encourage providers to give more medical explanation, to discuss patients’ health beliefs in a non-judgemental manner, and to consider financial issues more carefully.     

Concurrent infections with vector-borne pathogens associated with fatal anaemia in cattle: haematology and blood chemistry

An outbreak of a fatal haemolytic anaemia in a dairy herd of cattle in Switzerland was shown to be associated with infections with five vector-borne pathogens, namely Anaplasma marginale, A. phagocytophilum, Babesia bigemina, a Theileria spp belonging to the buffeli/sergenti/orientalis complex and haemotrophic Mycoplasma spp. The latter three had not been documented before this outbreak in Switzerland. To characterise the haematological and blood chemical changes in these unique cows, packed cell volume was determined in all 286 blood samples, blood smears, and complete haematology were performed from 285 and 173 blood samples, respectively, and biochemical parameters were assayed in 105 serum samples. Regenerative anaemia was the key sign of illness. Red blood cells of anaemic cattle were hypochromic and macrocytic. Anaemic animals had reduced platelet cell counts and increased total white cell counts. In addition, increased serum bilirubin, blood aspartate aminotransferase, gamma glutamyltransferase, glutamic dehydrogenase and blood urea nitrogen and decreased magnesium, calcium and albumin levels were found in anaemic cattle when compared to animals with normal packed cell volume. Most changes could not be attributed to a single infection. A. marginale seemed to be important in causing the outbreak, but co-infections may have aggravated the disease development and clinical signs. Thus, when encountering cattle with haemolytic anaemia, all of the mentioned pathogens should be included as differential diagnosis.     

Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy

Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.Subject terms: Cardiovascular diseases, Development, Medical genetics, Medical genomics     

Directed evolution of adeno-associated virus to an infectious respiratory virus

Respiratory viruses evolve to maintain infectivity levels that permit spread yet prevent host and virus extinction, resulting in surprisingly low infection rates. Respiratory viruses harnessed as gene therapy vectors have illustrated this limitation. We used directed evolution in an organotypic human airway model to generate a highly infectious adeno-associated virus. This virus mediated gene transfer more than 100-fold better than parental strains and corrected the cystic fibrosis epithelial Cl⁻ transport defect. Thus, under appropriate selective pressures, viruses can evolve to be more infectious than observed in nature, a finding that holds significant implications for designing vectors for gene therapy and for understanding emerging pathogens.     

眼前节内眼手术应用5％吡咯烷酮碘两种不同用法的前瞻性随机化比较研究

目的：确定5％吡咯烷酮碘采用两种不同的方法（结膜囊滴两滴和10ml溶液穹窿结膜冲洗）对降低结膜囊菌群的功效。方法：在这项前瞻性对照实验中。将行眼前节手术的200只眼随机分为对照组和研究组。两组病例术前均给予氧氟沙星滴眼液局部点眼和5％吡咯烷酮碘眶周区域皮肤擦洗消毒。术前对照组眼结膜囊内给予2滴5％吡咯烷酮碘溶液，研究组眼用5％吡咯烷酮碘溶液冲洗穹窿结膜。分别于术前和术后4个时间点行结膜细菌培养。结果：研究组78只眼中20只眼（26％）术前结膜细菌培养阳性：对照组94只眼中40只眼（43％）为阳性（P=0．02）。手术结束时。研究组78只眼中14只眼（18％）、对照组94只眼中30只眼（32％）结膜细菌培养阳性（PP=0．05）。结论：手术时应用5％吡咯烷酮碘溶液冲洗穹窿结膜与结膜囊仅点入两滴相比。前者显著降低了结膜细菌培养阳性率。     

Rapid, Simple Bioassay for 5-Fluorocytosine in the Presence of Amphotericin B

It is important that serum levels of 5-fluorocytosine (5FC) be measured to insure therapeutic levels while avoiding toxicity. This is particularly true in patients with renal insufficiency. The concurrent use of amphotericin B and 5FC complicates the measurement of 5FC in the serum, since fungi used in conventional bioassay systems are uniformly susceptible to amphotericin B. This paper describes the development of a simple, reliable, 6-h bioassay for 5FC in the presence of amphotericin B. The assay is based upon the fact that 5FC diffuses readily through yeast nitrogen base agar, whereas amphotericin B apparently does not. This assay allows rapid adjustments in therapy of patients receiving both 5FC and amphotericin B and has permitted us to maintain 5FC serum levels between limits of 25 and 120 μg/ml in patients with altered renal function.