Newborn hearing screening and cochlear implantation: impact on spoken language development.

OBJECTIVES: This study retrospectively evaluates the effect of newborn hearing screening on age at diagnosis, age at cochlear implantation and spoken language development in severely hearing-impaired children. METHODS: Age at diagnosis, age at cochlear implantation and language development were evaluated in a group of early screened (n = 149) and a group of late screened (n = 139) severely hearing-impaired children. Language outcomes were quantified as language quotients (LQs) on the Reynell Developmental Language Scales and Schlichting Expressive Language Test at 1,2, and 3 years after cochlear implantation. RESULTS: Early screened children were significantly younger than late screened children at the time of hearing loss diagnosis and cochlear implantation. Furthermore, early screening was associated with better receptive and expressive spoken language skills after cochlear implantation. CONCLUSION: The results of this retrospective study indicate that the newborn hearing screening program in Flanders and The Netherlands resulted in earlier intervention in deaf children, which beneficially influenced spoken language development.

Acute kidney injury reduces the hepatic metabolism of midazolam in critically ill patients.

INTRODUCTION: Acute kidney injury (AKI) is a common and serious complication increasing morbidity and mortality from all causes of hospital admission. We have previously shown that AKI decreases midazolam metabolism, a substrate of the cytochrome P450 3A (CYP3A) enzymes and our primary aim was to determine if this effect is dependent on the severity of AKI. We also present preliminary data on the functional impact of different genotypes of CYP3A. METHODS: Critically ill patients at risk of AKI and admitted to a general intensive care unit were categorised after initial resuscitation according to the RIFLE criteria for AKI. Midazolam (1mg) was administered and the serum concentration of midazolam measured at 4 h. Samples were taken for CYP3A genotyping. RESULTS: Seventy-three patients were assigned to categories R, I and F of the RIFLE criteria or C (controls). Midazolam concentrations (ng mL(-1)) increased significantly (p = 0.002) as the severity of AKI worsened [control 3.1 (1.4-5.9), risk 4.7 (1.3-10.3), injury 3.9 (2.0-11.1) and failure 6.8 (2.2-113.6)] and were predicted by the duration of AKI (p = 0.000) and γ-glutamyl transferase (p = 0.005) concentrations. Increasing BMI negatively predicted the midazolam concentration (p = 0.001). Preliminary data suggest this effect is diminished if the patient expresses functional CYP3A5. CONCLUSION: Increasing severity and duration of AKI are associated with decreased midazolam elimination. We propose that this is caused by impaired CYP3A activity secondary to AKI. The exact mechanism remains to be elucidated. This may have important implications for our drug treatment of critically ill patients.

Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Hyperglycaemia is associated with poor outcomes from pneumonia, myocardial infarction and stroke, but the effect of blood glucose on outcomes from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been established. Recent UK guidelines do not comment on measurement or control of blood glucose in AECOPD. A study was therefore undertaken to determine the relationship between blood glucose concentrations, length of stay in hospital, and mortality in patients admitted with AECOPD. METHODS: Data were retrieved from electronic records for patients admitted with AECOPD with lower respiratory tract infection in 2001-2. The patients were grouped according to blood glucose quartile (group 1, <6 mmol/l (n = 69); group 2, 6.0-6.9 mmol/l (n = 69); group 3, 7.0-8.9 mmol/l (n = 75); and group 4, >9.0 mmol/l (n = 71)). RESULTS: The relative risk (RR) of death or long inpatient stay was significantly increased in group 3 (RR 1.46, 95% CI 1.05 to 2.02, p = 0.02) and group 4 (RR 1.97, 95% CI 1.33 to 2.92, p < 0.0001) compared with group 1. For each 1 mmol/l increase in blood glucose the absolute risk of adverse outcomes increased by 15% (95% CI 4 to 27), p = 0.006. The risk of adverse outcomes increased with increasing hyperglycaemia independent of age, sex, a previous diagnosis of diabetes, and COPD severity. Isolation of multiple pathogens and Staphylococcus aureus from sputum also increased with increasing blood glucose. CONCLUSION: Increasing blood glucose concentrations are associated with adverse clinical outcomes in patients with AECOPD. Tight control of blood glucose reduces mortality in patients in intensive care or following myocardial infarction. A prospective study is now required to determine whether control of blood glucose can also improve outcomes from AECOPD.

Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients.

BACKGROUND: The risk of nosocomial infection is increased in critically ill patients by stress hyperglycaemia. Glucose is not normally detectable in airway secretions but appears as blood glucose levels exceed 6.7-9.7 mmol/l. We hypothesise that the presence of glucose in airway secretions in these patients predisposes to respiratory infection. METHODS: An association between glucose in bronchial aspirates and nosocomial respiratory infection was examined in 98 critically ill patients. Patients were included if they were expected to require ventilation for more than 48 hours. Bronchial aspirates were analysed for glucose and sent twice weekly for microbiological analysis and whenever an infection was suspected. RESULTS: Glucose was detected in bronchial aspirates of 58 of the 98 patients. These patients were more likely to have pathogenic bacteria than patients without glucose detected in bronchial aspirates (relative risk 2.4 (95% CI 1.5 to 3.8)). Patients with glucose were much more likely to have methicillin resistant Staphylococcus aureus (MRSA) than those without glucose in bronchial aspirates (relative risk 2.1 (95% CI 1.2 to 3.8)). Patients who became colonised or infected with MRSA had more infiltrates on their chest radiograph (p<0.001), an increased C reactive protein level (p<0.05), and a longer stay in the intensive care unit (p<0.01). Length of stay did not determine which patients acquired MRSA. CONCLUSION: The results imply a relationship between the presence of glucose in the airway and a risk of colonisation or infection with pathogenic bacteria including MRSA.

New insights into the glucose oxidase stick test for cerebrospinal fluid rhinorrhoea.

Rhinorrhoea is a clinical sign of cerebrospinal fluid (CSF) leakage in patients with skull fracture, but can also be attributable to respiratory secretions or tears. Laboratory tests confirming the presence of CSF are not sufficiently rapid to support clinical decision making in the emergency department and may not be universally available. Detection of glucose in nasal discharge was traditionally used to diagnose CSF leak at the bedside, but has fallen into disuse as it has poor positive predictive value. We propose an algorithm to improve the diagnostic value of this test taking into consideration factors we have found to affect the glucose concentration of respiratory secretions. In patients at risk of CSF leak, nasal discharge is likely to contain CSF if glucose is present in the absence of visible blood, if blood glucose is <6 mmol x L(-1), and if there are no symptoms of upper respiratory tract infection.

In vitro and in vivo regulation of antioxidant response element-dependent gene expression by estrogens.

Understanding estrogen's regulation of phase II detoxification enzymes is important in explaining how estrogen exposure increases the risk of developing certain cancers. Phase II enzymes such as glutathione-S-transferases (GST) and quinone reductase protect against developing chemically induced cancers by metabolizing reactive oxygen species. Phase II enzyme expression is regulated by a cis-acting DNA sequence, the antioxidant response element (ARE). It has previously been reported that several antiestrogens, but not 17beta-estradiol, could regulate ARE-mediated gene transcription. Our goal was to determine whether additional estrogenic compounds could regulate ARE-mediated gene expression both in vitro and in vivo. We discovered that physiological concentrations (10 nm) of 17beta-estradiol repressed GST Ya ARE-dependent gene expression in vitro. Treatment with other endogenous and anti-, xeno-, and phytoestrogens showed that estrogen receptor/ARE signaling is ligand, receptor subtype, and cell type specific. Additionally, GST and quinone reductase activities were significantly lowered in a dose-dependent manner after 17beta-estradiol exposure in the uteri of mice. In conclusion, we have shown that 17beta-estradiol, and other estrogens, down-regulate phase II enzyme activities. We propose estrogen-mediated repression of phase II enzyme activities may increase cellular oxidative DNA damage that ultimately can result in the formation of cancer in some estrogen-responsive tissues.

Recurrent 'sterile' verrucous cyst abscesses and epidermodysplasia verruciformis-like eruption associated with idiopathic CD4 lymphopenia.

Rupture of follicular (epidermoid) cysts is believed to be the consequence of bacterial infection. We report a 24-year-old man with idiopathic CD4 lymphopenia and chronic Mycobacterium avium intracellulare infection who developed multiple, recurring painful abscesses over the distal extremities that increased in number and severity when systemic steroid and interferon-gamma treatment was instituted for interstitial lung disease. Cultures were consistently negative for microorganisms, but pathological examination revealed ruptured epidermoid cyst walls with human papillomavirus (HPV) viropathic changes (keratinocytes with perinuclear halos and abundant basophilic keratohyaline granules). Cutaneous examination showed numerous, widespread flat-topped papules and achromic macules over the extremities, head and neck. Nested polymerase chain reaction analysis for HPV DNA revealed that the abscess-related cyst walls harboured epidermodysplasia verruciformis (EV)-associated HPV types 20, 24, alb-7 (AY013872) and 80. His cutaneous lesions harboured HPV types 3, 8 and 80. Similar to past reports, our patient developed an EV-like eruption in the setting of immunodeficiency. In this instance, EV-associated HPV infection of the follicular infundibular epithelium or pre-existing cysts in the setting of immunodeficiency may have led to cystic growth, rupture and subsequent painful inflammation.

Ethical issues in community-based cancer control: considerations in designing interventions.

Intervention studies are essential in the drive to reduce the burden of cancer in the United States. The means to accomplish primary and secondary cancer prevention is possible through health education focused on smoking, dietary changes, and the judicious application of screening technologies. The goal is to demonstrate these can work in the "real world" of the community workplace. The challenge of designing and conducting effective studies must include practical solutions to ethical as well as methodological issues.

Effect of irradiation, packaging, and postirradiation cooking on the thiamin content of chicken meat.

The effect of irradiation with X rays or electrons, irradiation and storage temperature, and postirradiation cooking on the thiamin content of vacuum- or air-packaged minced chicken meat was examined. Samples irradiated with 3-kGy X rays (50 Gy/min) or electrons (5 kGy/min) contained less thiamin than the control specimens, but no differences between both irradiation methods were detected. The thiamin content in samples stored and/or irradiated at 5 degrees C was between 13 and 24 microg per 100-g product lower than in samples stored and/or ionized at -18 degrees C. The same difference in thiamin content was found for specimens packaged in a vacuum or air package, respectively. Vacuum packaging lead to a greater loss of drip than air-packaged samples. The biggest loss of thiamin, 31.1 and 28.0% for X rays and electron beams, respectively, was measured for vacuum-packaged specimens stored and irradiated at 5 degrees C. Compared with the cooked minced chicken breast meat, a higher thiamin content (6 to 17 microg of thiamin per 100-g product) was obtained for the raw samples. When irradiation and vacuum packaging were compared as two separate preservation techniques, the two methods had approximately the same effect on the thiamin content of the minced chicken meat. The mean temperature of the samples after cooking was 87.2 +/- 4.9 degrees C. However, significant differences in internal temperature after cooking of the samples were measured between air- and vacuum-packaged samples.

The effect of N-acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure.

We have investigated the effect of N-acetylcysteine on hemodynamic variables, oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction in patients with fulminant hepatic failure using independent methods of determining DO2 and VO2, thereby eliminating the effect of mathematical coupling, which may have biased previous studies. In 11 patients with severe fulminant hepatic failure, we documented the hemodynamic effects of N-acetylcysteine during the first 5 hours of a standard infusion regime and simultaneously measured VO2 using a method based on respiratory gas analysis. We related physiological changes to plasma N-acetylcysteine concentrations, and compared this group with 7 patients who received placebo infusions. A variable hemodynamic response to N-acetylcysteine was observed that did not differ significantly in comparison with the placebo group, and did not correlate with plasma drug concentrations. The most significant relationship observed between DO2 and VO2 in any patient predicted a 13-mL x min(-1) x m(-2) increase in VO2 when DO2 increased by 100 mL x min(-1) x m(-2); in 8 patients, VO2 was independent of DO2 over the range observed. In the group that received N-acetylcysteine, a small (mean 6 [SD 6] mL x min(-1) x m[-2]) increase in VO2 occurred in comparison with baseline after 1 hour of infusion (P < .01), but changes were not significantly different from the placebo group and were not sustained. N-Acetylcysteine infusion did not increase oxygen extraction or result in an improvement in whole-blood lactate levels or base excess during the study period. We conclude that N-acetylcysteine infusion does not result in clinically relevant improvements in global VO2, or in clinical markers of tissue hypoxia in patients with severe fulminant hepatic failure.

Cerebral blood flow and metabolism in patients with chronic liver disease undergoing orthotopic liver transplantation.

Changes in cerebral hemodynamics and metabolism associated with anesthesia and liver transplantation may present particular hazards for patients with cirrhosis. Fifteen patients undergoing liver transplantation were studied, 7 of whom had encephalopathy. Cerebral blood flow (CBF) was measured at the start of surgery, during veno-venous bypass and post reperfusion, using a method based on the Kety-Schmidt method. Cerebral metabolism was assessed by measuring the cerebral metabolic rate for oxygen (CMRO2) and the lactate oxygen index (LOI). The cerebral vascular reactivity to carbon dioxide (CO2) was studied during the preanhepatic and post reperfusion phases. During the preanhepatic period, the median CBF was 44 mL/100 g/min at an arterial carbon dioxide tension (PaCO2) of 3.8 kPa. After reperfusion the CBF increased (P < .02) to 102 mL/100 g/min, the arterial hydrogen ion concentration increased from 39 nmol/L to 53 nmol/L (P < .02) and the jugular venous oxygen saturation from 74% to 89% (P < .02). CBF was similar in patients with and without encephalopathy. The cerebral vascular reactivity to CO2 remained intact, although after reperfusion, the CBF for a given PaCO2 was greater, and the slope of the CBF/CO2 response curve diminished. The CMRO2 was normal in patients without encephalopathy. In the encephalopathic patients, the CMRO2 was low during all stages of transplantation (0.54, 0.86, 1.24 mL/100 g/min, respectively). Patients with encephalopathy may be at increased risk of hypoxemic brain injury during transplantation. To minimize this possibility, more detailed neurological monitoring may be useful.

Non-arteritic anterior ischemic optic neuropathy and refraction.

A small cup-disk ratio has been reported as a risk factor in non-arteritic anterior ischemic optic neuropathy. Hyperopia is possibly related with a small cup-disk ratio. The purpose of the present study is to compare the refraction of 37 eyes with non-arteritic anterior ischemic optic neuropathy with a sex and age matched control group of 74 eyes. In our study, mild hyperopia was more frequently observed in the anterior ischemic optic neuropathy group than in the control group.

Improving residents' knowledge of cancer prevention: are physicians prepared for prevention?

BACKGROUND: Primary care physicians recognize the goal of integrating cancer-prevention strategies into clinical practice. However, there is little formal training in cancer prevention and early detection. This study describes the effectiveness of a cancer-prevention curriculum called "Recommendations for Cancer Prevention (ReCaP) for Residents" for primary care residency programs. METHODS: The ReCaP for Residents curriculum was organized into eight instructional modules by organ site-specific areas for which there are established primary and secondary cancer-prevention recommendations. The modules include content outlines, learning objectives, slides, and case studies. In-house faculty and 21 residents of two family practice programs participated in an intervention comprising seven one-hour modular presentations during their regular summer teaching program. An established cancer-prevention knowledge test with 100 test items was used to test the residents' knowledge before and after the intervention; the data were analyzed by factor analysis with principal-component extraction and varimax rotation. RESULTS: The residents knew significantly more about cancer prevention after the ReCaP for Residents program. The mean overall prevention knowledge increased significantly (p < .05), and the scores of six of eight specific organ-site areas also increased. CONCLUSION: This study provided evidence that ReCaP for Residents was an effective curriculum for increasing residents' knowledge of cancer prevention. The authors recommend that more extensive programs of this type be implemented.

[Short-term ciprofloxacin treatment of bacillary dysentery due to Shigella dysenteriae type 1 in Rwandan refugees]. / Traitement court par la ciprofloxacine de la dysenterie bacillaire à Shigella dysenteriae type 1 chez des réfugiés Ruandais.

In 1994, an outbreak of dysentery caused by Shigella dysenteriae type I resistant to all public health antibiotics in vitro occurred among rwandan refugees in Zaïre. The only active antimicrobial agent available was ciprofloxacin. It was administered to hospitalized patients in a conventional 5-day schedule. To ration the supply for the benefit of the greatest number, a randomized blinded study was performed to compare the effectiveness of short-term treatment (1 g of ciprofloxacin in a single daily doses for 2 days) with that of the standard treatment (1 g of ciprofloxacin in two daily doses for 5 days). The study included 57 refugees over the age of 15 years with dysentery. Shigella dysenteriae type I was identified in 26 patients. Except for sex distribution, there was no significant difference in clinical and bacteriologic features of the two populations. Treatment failed in 12 cases, i.e., 7 of 29 patients who received the short-term treatment and 5 of 28 patients who received the standard treatment. Efficacy of ciprofloxacin was not dependent on the mode of treatment, taking into account clinical or bacteriologic criteria. These results indicated that the duration of ciprofloxacin treatment for dysentery caused by Shigella dysenteriae type 1 could be shortened to two days. Short-term treatment has several advantages. One is cost-effectiveness since fluoroquinolones are costly and scarce. Another is to allow treatment of a greater number of patients by improving compliance.