Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age

The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.     

Validation and reproducibility of computerised cell-viability analysis of tissue slices

Background

The identification of live cells using membrane integrity dyes has become a frequently used technique, especially with articular cartilage and chondrocytes in situ where tissue slices are used to assess cell recovery as a function of location. The development of a reproducible computerised method of cell evaluation would eliminate many variables associated with manual counting and significantly reduce the amount of time required to evaluate experimental results.

Methods

To validate a custom computerised counting program, intra-person and inter-person cell counts of nine human evaluators (three groups – unskilled, novice, and experienced) were compared with repeated pixel counts of the custom program on 15 digitised images (in triplicate) of chondrocytes in situ stained with fluorescent dyes.

Results

Results indicated increased reproducibility with increased experience within evaluators [Intraclass Correlation Coefficient (ICC) range = 0.67 (unskilled) to 0.99 (experienced)] and between evaluators [ICC = 0.47 (unskilled), 0.85 (novice), 0.93 (experienced)]. The computer program had perfect reproducibility (ICC = 1.0). There was a significant relationship between the average of the experienced evaluators results and the custom program results (ICC = 0.77).

Conclusions

This study demonstrated that increased experience in cell counting resulted in increased reproducibility both within and between human evaluators but confirmed that the computer program was the most reproducible. There was a good correlation between the intact cell recovery determined by the computer program and the experienced human evaluators. The results of this study showed that the computer counting program was a reproducible tool to evaluate intact cell recovery after use of membrane integrity dyes on chondrocytes in situ. This and the significant decrease in the time used to count the cells by the computer program advocate its use in future studies because it has significant advantages.

     

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer.

In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9-1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer.     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

Does the publication of NICE guidelines for venous thromboembolism chemical prophylaxis influence the prescribing patterns of UK hip and knee surgeons?

IntroductionWe assessed the practice of surgeons regarding venous thromboembolism (VTE) chemical prophylaxis for total hip replacement (THR) and total knee replacement (TKR), before and after issuing of updated National Institute for Health and Care Excellence (NICE) guidance in 2018.MethodsA survey, circulated through the British Hip Society and regional trainee networks/collaboratives, was completed by 306 UK surgeons at 187 units. VTE chemical prophylaxis prescribing patterns for surgeons carrying out primary THR (n=258) and TKR (n=253) in low-risk patients was assessed after publication of 2018 NICE recommendations. Prescribing patterns before and after the NICE publication were subsequently explored.ResultsFollowing the new guidance, 34% (n=87) used low-molecular-weight heparin (LMWH) alone, 33% (n=85) aspirin (commonly preceded by LMWH) and 31% (n=81) direct oral anticoagulants (DOACs: with/without preceding LMWH) for THR. For TKR, 42% (n=105) used aspirin (usually monotherapy), 31% (n=78) LMWH alone and 27% (n=68) DOAC (with/without preceding LMWH). NICE guidance changed the practice of 34% of hip surgeons and 41% of knee surgeons, with significantly increased use of aspirin preceded by LMWH for THR (before=25% vs after=73%; p<0.001), and aspirin for TKR (before=18% vs after=84%; p<0.001). Significantly more regimens were NICE guidance compliant after the 2018 update for THR (before=85.7% vs after=92.6%; p=0.011) and TKR (before=87.0% vs after=98.8%; p<0.001).ConclusionOver one-third of surveyed surgeons changed their VTE chemical prophylaxis in response to 2018 NICE recommendations, with more THR and TKR surgeons now compliant with latest NICE guidance. The major change in practice was an increased use of aspirin for VTE chemical prophylaxis.     

Macrolide-Resistant Mycoplasma pneumoniae Infections in Children,Ohio, USA

Emergence of macrolide-resistant Mycoplasma pneumoniae (MRMp) challenges empiric macrolide therapy. Our goal was to determine MRMp rates and define characteristics of children infected with macrolide-sensitive M. pneumoniae (MSMp) versus MRMp in Ohio, USA. We cultured PCR-positive M. pneumoniae specimens and sequenced M. pneumoniae–positive cultures to detect macrolide resistance mutations. We reviewed medical records to compare characteristics of both groups. We identified 14 (2.8%) MRMp and 485 (97.2%) MSMp samples. Patients in these groups had similar demographics and clinical characteristics, but patients with MRMp had longer hospitalizations, were more likely to have received previous macrolides, and were more likely to have switched to alternative antimicrobial drugs. MRMp-infected patients also had ≈5-fold greater odds of pediatric intensive care unit admission. Rates of MRMp infections in children in central Ohio are low, but clinicians should remain aware of the risk for severe illness caused by these pathogens.     

Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2)

Background  

We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more) and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat), natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide) and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely.     

Y染色体或将在进化中消失

美国宾夕法尼亚州立大学的2位科学家在性染色体进化变异机制的研究上取得进展。研究发现,Y染色体比X染色体的演化速率快得多,这将导致Y染色体上的基因急剧丢失,如此,Y染色体将会完全消失,人类的传宗接代将受威胁。     

The prevalence of self-reported peptic ulcer in the United States.

OBJECTIVES. The purpose of this study was to draw a current picture of the sociodemographic characteristics of peptic ulcer in the United States. METHODS. During the National Health Interview Survey of 1989, a special questionnaire on digestive diseases was administered to 41,457 randomly selected individuals. Data were retrieved from public use tapes provided by the National Center for Health Statistics. Odds ratios were calculated by logistic regression after adjustment for sample weights in the survey. RESULTS. Of adult US residents, 10% reported having physician-diagnosed ulcer disease, and one third of these individuals reported having an ulcer in the past year. Old age, short education, low family income, being a veteran, and smoking acted as significant and independent risk factors. Gastric and duodenal ulcer occurred in both sexes equally often. Duodenal ulcer was more common in Whites than non-Whites, while gastric ulcer was more common in non-Whites. CONCLUSIONS. The age-related rise and socioeconomic gradients of peptic ulcer represent the historic scars of previous infection rates with Helicobacter pylori. The racial variations reflect different ages at the time of first infection; younger and older age at the acquisition of H. pylori appear to be associated with gastric and duodenal ulcer, respectively.