A 10-year analysis of VTEC microbiological clearance times, in the under-six population of the Midlands, Ireland.

Verotoxin-producing Escherichia coli (VTEC) is a significant problem in the under-six population in the Midlands, Ireland. VTEC spreads by person-to-person transmission and children attending childcare facilities are excluded until they achieve two consecutive negative stool samples. This report analyses 10 years data on the number of days children under the age of six take to microbiologically clear VTEC. We identified from our data that the median clearance time for VTEC was 39 days, interquartile range (IQR) 27-56 days, maximum clearance time 283 days. At 70 days from onset of infection, 90% of children had cleared the infection. These findings were slightly more prolonged but consistent with international literature on VTEC clearance times for children. Asymptomatic children cleared VTEC infection significantly faster (median time 25 days IQR 13-43 days) than symptomatic children (median time 43 days IQR 31-58 days). Symptomatic children older than 1 year of age cleared VTEC infection significantly faster (median time 42 days IQR 31-57) than symptomatic children year under 1 year (median time 56 days IQR 35-74 days). This report identifies clear data which can be used to more accurately advise parents on time periods required to achieve microbiological clearance from VTEC.

Pulmonary fibrosis and exposure to steel welding fume.

BACKGROUND: Arc welders who have been exposed to high concentrations of steel welding fume for prolonged periods of time may develop pulmonary fibrosis but the nature of the fibrotic changes has been debated over the last 80 years without any clear international consensus. AIMS: To characterize the nature of the pulmonary fibrosis that develops in response to steel welding fume exposure and to provide a working hypothesis that would explain the findings of the existing research, to provide a platform for future research and to inform future occupational and clinical management of welders with pulmonary effects from welding fume. METHODS: Review of the world literature on pulmonary fibrosis and welding of steel in all languages using PubMed, with further secondary search of references in the articles found in the primary search. Google and Reference Manager were used as further confirmatory search tools. RESULTS: Only case series and case reports were found but these provided consistent evidence that the consequence of exposure to steel welding fume at high levels for a prolonged period of time is a type of pulmonary fibrosis similar to, and possibly the same as, respiratory bronchiolitis which eventually develops into desquamative interstitial pneumonia with ongoing exposure. CONCLUSIONS: Steel welding fume may cause an occupational respiratory bronchiolitis which may develop into de squamative interstitial pneumonia with ongoing exposure. This concept may explain the difficulties in interpreting the wider literature on welding fume and lung function at lower exposures and may also explain the increased risk of lung cancer in welders.

Vaccinating welders against pneumonia.

BACKGROUND: In 2011, the Department of Health in England recommended that welders should each receive a single dose of the 23-valent pneumococcal polysaccharide vaccine (PPV23). AIMS: To assess the evidence behind the advice and its practical implications. METHODS: The review was informed by a systematic search in Medline, which related pneumonia to welding and/or exposure to metal fume, and was supplemented using the personal libraries of the authors. RESULTS: There is consistent evidence that welders die more often of pneumonia, especially lobar pneumonia, are hospitalized more often for lobar and pneumococcal pneumonia, and more often develop invasive pneumococcal disease (IPD). It is estimated that one case of IPD may be prevented over a 10-year period by vaccinating 588 welders against pneumococcal infection. CONCLUSIONS: A good case exists that employers should offer PPV23 vaccination to welders and other employees exposed to metal fume. Additionally, reasonable measures must be taken to minimize exposure to welding fume, and welders should be encouraged not to smoke.

Work-related stress and Type 2 diabetes: systematic review and meta-analysis.

BACKGROUND: Work-related psychosocial stress has been hypothesized to increase the individual risk of Type 2 diabetes; however, observational epidemiological studies investigating the association between work-related psychosocial stress and Type 2 diabetes have provided an inconsistent picture. AIMS: To evaluate whether work-related psychosocial stress (defined by a work-related stress model or by long work hours) is associated with the risk of Type 2 diabetes. METHODS: A systematic review of the literature was conducted until March 2010. Studies eligible for inclusion were published observational epidemiological studies of adult participants in community or occupational settings if they had a measure of work-related stress on a validated scale or a measure of work hours or overtime assessed prior to, or at the same time as, assessment of Type 2 diabetes status. Where possible, meta-analysis was conducted to obtain summary odds ratios of the association. RESULTS: We located nine studies (four prospective, one case-control and four cross-sectional). The meta-analyses did not show any statistically significant associations between any individual aspect of work-related psychosocial stress or job strain and risk of Type 2 diabetes. CONCLUSIONS: The specific hypothesis that a working environment characterized by high psychosocial stress is directly associated with increased risk of Type 2 diabetes could not be supported from the meta-analysis.

Detection of c-K-ras mutations in fine needle aspirates from human pancreatic adenocarcinomas.

Formalin-fixed paraffin-embedded tissue specimens obtained by fine needle aspiration of pancreatic masses from 47 patients were examined retrospectively for cytology and the presence of mutant c-K-ras oncogenes. Point mutations of c-K-ras in codon 12 were detected by RNA-DNA RNAse A mismatch cleavage after in vitro DNA amplification of the cellular c-K-ras sequences by the polymerase chain reaction. Of the 36 patients with pancreatic adenocarcinoma, mutant c-K-ras oncogenes were detected in 18 of 25 (72%) with malignant cytologies, 2 of 8 (25%) with atypical cytologies, and 0 of 3 with benign aspiration cytologies. The remaining 11 patients without pancreatic adenocarcinomas did not have mutant c-K-ras genes detectable by the assay. The diagnosis of pancreatic adenocarcinoma was based upon clinical follow-up. The presence of mutant c-K-ras oncogenes did not significantly affect survival in the patients studied. Mutant c-K-ras genes were found at the time of initial clinical presentation in the majority of pancreatic adenocarcinomas, suggesting an important role of the mutation in oncogenesis. In conjunction with cytology, our approach represents an application for cancer diagnosis at the molecular genetic level.

Altered blood androgens in elderly men with prostate hyperplasia.

Plasma testosterone (T) and dihydrotestosterone (DHT) were measured in the plasma of otherwise healthy men ages 60-90 who had prostate hyperplasia. The androgens were measured by specific radioimmunoassays using paper and celite column chromatography. In the elderly subjects, plasma T was 466+/-35 (SE) ng per 100 ml which is reduced (p less than 0.05) as compared with values from younger men. In contrast, DHT levels were elevated when compared with values from men ages 20-39, 89 (53-152) versus 49 (33-74) 95% confidence ng per 100 ml. Analysis of data by the Mann Whitney U test demonstrates that the groups are different (p less than 0.001). These studies indicate that DHT levels and T/DHT ratios are altered in unstressed elderly men with BPH. Further study is necessary to delineate the source of DHT and whether these altered androgen levels are the cause of prostate hypertrophy or an unrelated effect of aging.

Granulomatous inflammation in pineal germinoma. A cause of diagnostic failure at stereotaxic brain biopsy.

We report four patients with pineal germinoma in whom the initial procedure for obtaining a tissue diagnosis was a stereotaxic biopsy. In all four cases, the biopsy showed granulomatous inflammation with epithelioid cells and lymphocytes. In one case, the granulomatous inflammation was accompanied by classical germinoma. Another case exhibited malignant cells considered nondiagnostic for a specific neoplasm. Two cases had no evidence of a malignant tumor; they were composed entirely of granulomatous inflammation. In two of the three cases where the diagnosis was not established by the first biopsy, a second stereotaxic biopsy showed pineal germinoma. Tissue obtained at resection in the third patient revealed large areas of granulomatous inflammation accompanying the germinoma. Immunoperoxidase stains for ferritin and placental alkaline phosphatase did not increase diagnostic yield. We conclude that a finding of granulomatous inflammation in a stereotaxic biopsy specimen of a pineal mass should suggest a diagnosis of germinoma, followed by sampling from several different target points within the lesion.

Intermediate filament expression in astrocytic neoplasms.

Immunohistochemical analysis of 30 paraffin-embedded astrocytic neoplasms was performed to correlate the expression of intermediate filament proteins with histologic subtype. Each tumor was studied with monoclonal antibodies to keratin, vimentin, desmin, 200-kd neurofilament protein, and glial fibrillary acidic protein (GFAP). Immunoreactivity with the anti-keratin monoclonal antibodies AE1 and AE3 was demonstrated in 24 cases (80%) including 4 of 6 (66%) well-differentiated astrocytomas (WDAs), 10 of 12 (83%) anaplastic astrocytomas (ANAs), and 10 of 12 (83%) glioblastomas multiforme (GBMs). These cases were further studied with the monoclonal antikeratin antibodies 34 beta E12 and 34 beta H11. Of the 24 AE1/AE3-positive cases, 14 (58%) reacted with 34 beta E12. None of the cases was reactive with 34 beta H11. Vimentin expression was demonstrated in 24 cases (80%), including 2 of 6 (33%) WDAs, 11 of 12 (92%) ANAs, and 11 of 12 (92%) GBMs. Coexpression of keratin and vimentin was observed in 20 cases (67%), including 2 of 6 WDAs, 9 of 12 (75%) ANAs, and 9 of 12 (75%) GBMs. Immunoreactivity with GFAP antibody was present in all 30 (100%) cases, but none of the tumors was reactive with antibodies to desmin or 200-kd neurofilament protein. These findings demonstrate that expression of both keratin and vimentin intermediate filaments is common in astrocytic neoplasms regardless of histologic grade.

Urogenital tract abnormalities in sons of women treated with diethylstilbestrol.

Since in utero exposure to diethylstilbestrol (DES) is known to cause abnormalities of the female genital tract later in life, exposed male offspring were located, surveyed by mail, and compared with unexposed male offspring from the same period and medical practices. The exposed and unexposed respondents appeared comparable and did not differ in their response to most medical questions. However, a larger proportion of exposed than of unexposed boys had experienced problems in passing urine (12.9% vs. 1.8%, P = .0003) and abnormalities of the penile urethra (4.4% vs. 0%; P = .017).

Shunt surgery for priapism: review of results.

In a review of the literature on shunt operations for priapism, 100 case reports were found. The over-all result in terms of potency is 61 per cent. In general there is little difference in outcome between the cavernosus-saphenous vein and cavernosus-spongiosum shunts. If the former surgical procedure is to be performed, a unilateral operation appears to yield better results than a bilateral one. Various causes of priapism are noted in relation to results of surgery, and the complications of shunt procedures are discussed. Equally good results are noted whether the operation is performed early or relatively late in the disease.

Renal angiomyolipoma: two varieties.

Two cases of symptomatic renal angiomyolipoma are presented, and their distinctive clinical, radiologic, and histologic features are discussed. In the first case the scout film demonstrated radiolucency of the tumor which helped to distinguish it from carcinoma. In the second case, which was associated with tuberous sclerosis, the renal lesion was large and unifocal, and the local lymph nodal involvement with tumor raised the possibility of malignant transformation.

Twenty-eight-day courses of antibiotics for urinary tract infection.

A prospective double-blind study was performed in which 30 adult patients with recurrent urinary tract infections due to Escherichia coli, and Proteus mirabilis organisms were treated by twenty-eight-day courses of either ampicillin, 500 mg. four times a day, or trimethoprim-sulphamethoxazole, 2 tablets twice a day. In terms of freedom from infection fifty-six days after the cessation of treatment in both complicated and uncomplicated infections, trimethoprim-sulphamethoxazole yielded results superior to those of ampicillin. In comparing the results of this study with those of a similar study in which the same agents were given for ten-day courses it appears that only in the complicated infection is there an advantage in giving a prolonged course of trimethoprim-sulphamethoxazole. This study did not generate any evidence to support the extension of ampicillin therapy for urinary tract infection beyond ten days.

Papillary adenocarcinoma of prostate.

Papillary adenocarcinomas of the prostate are rare tumors which may arise from the prostatic ducts and the utricle; 2 cases are described. The diagnosis of these tumors is best established by cystourethroscopy and transurethral resection. The more common prostatic acinar adenocarcinoma is frequently associated with these tumors. The histopathologic recognition of papillary adenocarcinoma of the prostate and its differentiation from acinar adenocarcinoma is important since the natural history and response to treatment may be different.

Prostate carcinoma: measures to improve therapeutic response and prevent complications.

Between 1965 and 1973, 80 patients with prostatic carcinoma were treated with definitive supervoltage irradiation; 35 patients received adjuvant estrogens. A favorable tumor response was uniformly observed in patients with less advanced tumors who received a minimum of 6,000 rads tumor dose and adjuvant estrogens. Radiation complications were frequent and severe in patients with locally advanced tumors who had antecedent lower urinary tract surgery and received a minimum of 7,000 rads tumor dose. Complications were less frequent in patients who received adjuvant estrogens, and complications were uncommon and mild in patients who received less than 7,000 rads.

Gastro-oesophageal reflux in children.

Disordered motility of the gastrointestinal tract in children is usually manifest as gastro-oesophageal reflux disease. Reflux is common in infants but usually resolves spontaneously with time. If severe enough to merit investigation, 24-hour ambulant oesophageal pH monitoring is the most widely used investigation, though it does have disadvantages. Upper gastrointestinal endoscopy and biopsy may be required to diagnose oesophagitis. Treatment follows a step-wise approach, progressing from positioning and feed-thickening in infants, through to pharmacological management with prokinetic agents and/or acid-suppression, and surgery for a very small proportion of children whose symptoms do not respond to optimal medical therapy.

Nucleotide supplementation and the growth of term small for gestational age infants.

A double blind randomised controlled trial in small for gestational age (SGA) infants, whose intestinal mucosa was shown to be functionally impaired as a result of intrauterine undernutrition, was carried out to investigate the hypothesis that nucleotide supplementation of a milk formula could improve catchup growth. Anthropometric data were collected on 74 infants, 39 randomly allocated to the nucleotide supplemented group (group N) and 35 to a standard formula group (group S). From study entry to 2 months of age, infants in group N had significantly higher mean rates of weight gain (106.3 compared with 94.7 g/kg baseline weight/week) and length gain (21.8 v 19.7 mm/m baseline length/week). Over the whole six months for which the trial formula was provided group N had significantly higher mean rates of gain of weight (80.1 compared with 71.8 g/kg baseline weight/week), length (16.2 compared with 15.0 mm/m baseline length/week), and head circumference (11.8 compared with 10.8 mm/m baseline head circumference/week). Catchup growth in SGA infants is therefore improved by nucleotide supplementation of infant formula.

Faecal chymotrypsin in small for gestational age infants: effects of nucleotides and breast feeding.

The effect of diet on pancreatic exocrine function, measured by faecal chymotrypsin activity (FCA), was studied longitudinally in three groups of small for gestational age (SGA) infants in the first six months of life. The three groups comprised breastfed infants (group B), those randomly allocated to receive a standard infant formula (group S), or the same formula supplemented with nucleotides (group N). The three groups did not differ in their birthweight or gestational age. Nucleotide supplementation of infant formula improves catchup growth in SGA infants but whether this is due to effects on the gastrointestinal mucosa or the exocrine pancreas is not known. There were no differences in FCA at study entry but by one month group B had significantly lower values than the other groups, and this was maintained at 2, 4, and 6 months. Groups N and S did not differ significantly at any time point. Nucleotide supplementation of infant formula does not influence pancreatic exocrine function and its effect on growth is unlikely, therefore, to be mediated through the pancreas. This study shows that breast feeding is associated with lower FCA which may be related to the lower protein content of human milk. Reliable interpretation of FCA in young infants requires information about their diet.

Perinatal and infant nutrition. Nucleotides.

Nucleotides (NT) are ubiquitous intracellular compounds of crucial importance to cellular function and metabolism. Much recent interest has focused on NT as components of the non-protein nitrogen fraction of human milk. NT supplementation of infant formula has now been introduced in several countries. Biological effects of NT have been reported in several fields. Dietary NT have been shown to have important effects on several components of the immune system: they may enhance intestinal absorption of iron; they affect lipoprotein and long-chain polyunsaturated fatty acid metabolism; they may alter intestinal flora; and they have been demonstrated to have trophic effects on the intestinal mucosa and liver in several experimental situations. Clinical studies have shown NT supplementation of infant formula reduces the incidence of diarrheal episodes among socioeconomically deprived infants, and enhances catch-up growth in infants born small for gestational age. Further work will continue to try to identify other clinical situations in which NT may have a beneficial role.

Defaulters in general practice: reasons for default and patterns of attendance.

A series of 40 patients in general practice who failed to attend for their appointments were studied to look at their patterns of attendance over the previous five years, together with their reasons for default. The group not only defaulted more often than a group of age and sex matched controls but made significantly more visits to the surgery. Seventeen of the patients increased their default rate as their attendance rate increased over the five year period. The main reasons patients gave for defaulting on the occasion studied were: feeling too ill to attend (eight patients), resolution of symptoms (six) or forgotten/confused appointment time (seven). Four patients were thought by the general practitioner to need a home visit, two of whom were suffering from depression. Further research is needed to define those who would be expected to need a visit.

Rapid diagnosis of disseminated histoplasmosis in tissues.

Disseminated histoplasmosis may resemble other disseminated infections, including mycobacterial, fungal, and parasitic diseases, and may be difficult to diagnose and treat in a timely fashion. Diagnosis may depend on microbiologic cultures that may take several weeks for definitive identification, with consequent prolonged hospitalization of the patient. An immunoperoxidase method is described for rapid diagnosis in tissues of Histoplasma capsulatum that can be applied to cytologic smears, frozen sections, and paraffin-embedded tissues processed by routine procedures. The stain can accurately distinguish histoplasma organisms from several other morphologically similar fungi or parasites, and can yield a definitive diagnosis in much less time than microbiologic culture.