The occurrence of antimicrobial substances in toilet, sink and shower drainpipes of clinical units: A neglected source of antibiotic residues.

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference. To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02 µg·L-1 to a maximum of 79 mg·L-1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.

[Skin disorders in malignant hematologic diseases]. / Hautveränderungen bei malignen hämatologischen Erkrankungen.

Numerous cutaneous manifestations have been reported in patients with hematologic malignancies. This review provides an overview on this subject by dividing skin lesions into three main groups: (1) skin disorders due to vascular changes (dilatation, occlusion and inflammation), (2) unspecific (e.g. paleness, opportunistic infections) and specific skin lesions (e.g. leukemia cutis), and (3) the large group of paraneoplastic skin disorders. Emphasis is placed on clinical findings and therapeutic options of those paraneoplastic syndromes that are most frequently found in hematologic malignancies.

Efficacy of low-dose methotrexate in the treatment of dermatomyositis skin lesions.

A limited number of case series has indicated that methotrexate (MTX) might be a useful drug in the treatment of dermatomyositis (DM), a rare autoimmune disease involving the skin and muscles. However, these earlier studies mainly focused on the efficacy of MTX on DM muscular symptoms. To analyse the efficacy of MTX on skin lesions in DM, the records of 34 patients with DM seen between 2004 and 2009 were retrospectively analysed, and the DM skin disease activity at different time points was determined, with specific focus on cutaneous features using the validated Cutaneous Dermatomyositis Activity Index (CDASI) score. The lesional inflammation was scored in primary skin biopsies. Additionally, we performed a systematic review of the available literature. In our series, 11 patients with DM received MTX, and in 8 of them, MTX led to a significant reduction of the DM skin lesions. CDASI scores decreased from 15.7 to 6.4 (P < 0.01) within 2-3 months, supporting the effectiveness of MTX in skin disease in DM. The lymphocytic infiltrate in primary skin lesions of MTX responders was significantly more pronounced than that in nonresponders. These results indicate that MTX might be an effective drug to treat the cutaneous symptoms of DM, as measured by the validated CDASI. Interestingly, MTX responders histologically presented a significantly stronger lesional lymphocytic inflammatory infiltrate than did nonresponders. These findings suggest that the functional inhibition of lymphocyte migration in the skin might be an important mechanism of MTX in the treatment of DM.

Recent developments of bio-molecular motors as on-chip devices using single molecule techniques.

The integration of microfluidic devices with single molecule motor detection techniques allows chip based devices to reach sensitivity levels previously unattainable.

Coherently controlled ultrafast four-wave mixing spectroscopy.

A novel approach to coherent nonlinear optical spectroscopy based on two-dimensional femtosecond pulse shaping is introduced. Multiple phase-stable output beams are created and overlapped at the sample in a phase-matched boxcars geometry via two-dimensional femtosecond pulse shaping. The pulse timing, shape, phase, and spectral content within all beams may be specified, yielding an unprecedented level of control over the interacting fields in nonlinear spectroscopic experiments. Heterodyne detection and phase cycling of the nonlinear signal are easily implemented due to the excellent phase stability among all output beams. This approach combines the waveform generation capabilities of magnetic resonance spectroscopy with the wavevector specification and phase matching of nonlinear optical spectroscopy, yielding the control capabilities and signal selectivity of both. Results on four prototype systems are used to illustrate some of the novel possibilities of this method.

Percutaneous closure of patent foramen ovale.

AIM: To review the safety and efficacy of percutaneous closure of patent foramen ovale (PFO) in symptomatic patients without the use of general anaesthesia or echocardiographic guidance. METHOD: All patients accepted for percutaneous PFO closure by our service from August 2002 to August 2004 were included. Patient demographics and clinical information were obtained from clinical records and by telephone interview. Follow-up outcomes recorded were recurrence of systemic thromboembolism, residual shunt, and change in pattern of migraines. RESULTS: Forty consecutive adult patients, of whom 19 (48%) had an atrial septal aneurysm (ASA), underwent PFO closure using the Amplatzer occluder device with fluoroscopic guidance alone. Their mean age was 45 +/- 10 years (range 23-63 years) and 24 (60%) were male. The indications for closure were ischaemic stroke (n = 26), transient ischaemic attack (TIA) (n = 8), both stroke and TIA (n = 2), refractory hypoxia (n = 2), platypnoea-orthodeoxia (n = 1) and severe migraine with seizures (n = 1). Twenty patients suffered a single neurological event and 16 suffered >1 event, including six with only radiographic evidence of >1 event. Mean procedure time was 17.7 +/- 9.6 min and fluoroscopy time was 6.7 +/- 7.3 min. Implanted device sizes were 18 mm (n = 1), 25 mm (n = 37) and 35 mm (n = 2). In 33 patients, the procedure was performed as a day-case. No complications were encountered. No further neurological events occurred in 39 patients at a mean follow-up time of 11 +/- 7 months (3-25 months) nor was a significant shunt detected in the 34 who underwent follow-up echocardiography. CONCLUSIONS: Percutaneous closure of PFO with or without ASA, under local anaesthesia and without echocardiographic guidance, is a safe and effective procedure which can be performed as a day-case. This has now become our standard clinical practice.

Typesetting of terahertz waveforms.

We demonstrate programmable generation of temporally shaped terahertz waveforms in LiNbO3 by spatially shaping the beam profile of femtosecond excitation laser pulses with a spatial light modulator. The generated terahertz waveforms have amplitudes that are approximately proportional to the first spatial derivative of the excitation beam profile.

Pediatric cardiac transplant: results using a steroid-free maintenance regimen.

We report on survival, rejection, lymphoma and renal function following cardiac transplant using a steroid-free maintenance immunosuppressive regimen. We have performed 73 cardiac transplants in 71 children under 16 yr of age in the last 12 yr. There were eight perioperative and four late deaths giving actuarial survival of 88, 88, 85 and 70% at 1, 2, 5 and 10 yr, respectively. A total of 11 (15.3%) children had one episode of rejection (grade 3) in the first 6 months; one died and one was re-transplanted because of rejection. There was only one episode of late rejection (8 yr post-transplant) because of low drug levels in a patient with lymphoma and sepsis. This patient did not survive. Three other children (5.6%) also developed lymphoma and recovered but one died subsequently of graft failure. Four children have developed severe renal failure (glomerular filtration rate GFR <30 mL/min/m2). Two have not survived and one is expected to commence dialysis soon. The remainder have mild to moderate renal impairment. We report excellent survival and low rejection rates without use of long-term steroids. However the doses of cyclosporin used have had a significant effect on renal function in many cases.

Interventions for aortic coarctation.

The standard treatment of coarctation of the aorta is surgical. In the last 2 decades, however, treatment by catheter intervention has become more widespread, using either balloon angioplasty or primary stent implantation. Balloon angioplasty was originally used for recurrent coarctation after surgical repair but has now been shown equally effective for unoperated coarctation. The procedure produces a satisfactory gradient reduction in approximately 80% of patients, with transverse arch hypoplasia the main predictor of poorer outcome. Rates of restenosis and aneurysm formation are less than 10%. Primary stent implantation has been suggested as an option potentially superior to angioplasty alone. Stent implantation limits elastic recoil and potentially reduces aneurysm formation by reducing the amount of balloon stretch required. The incidence of suboptimal gradient reduction is low, probably 5% or less, as is the rate of restenosis. Aneurysm formation, vascular complications, and stent migration also occur in less than 5%. Catheter interventions are now an established treatment strategy for coarctation, with a good success rate and safety profile. The outcome for native and recurrent coarctation appears similar. The authors believe that for most adult patients with coarctation of the aorta, catheter intervention should be offered as initial therapy.

Renal function after pediatric cardiac transplantation: the effect of early cyclosporin dosage.

BACKGROUND: There is little data on renal function in pediatric heart transplant recipients. Early rejection is a major concern and most units run high cyclosporin A (CyA) levels during the 2 to 3 months after transplantation. We sought to document long-term renal function after transplantation and to assess influence of early CyA levels. METHODS: We reviewed all of our pediatric transplants between June 1985 and August 1998 who survived longer than 6 months (n = 54). Glomerular filtration rate (GFR) was estimated at 1, 2, 4, and 8 years posttransplantation using the Schwartz formula: GFR (mL/min/1.73m(2)) = [Ht(cm)/creatinine(micromol/L)] x X We also analyzed whether change in renal function correlated with trough CyA levels. RESULTS: Median age at transplant was 4 years and median follow-up was 5 years. Survival rates were 87% at 1 year and 80% at 5 years. Mean GFR pretransplant was 79 +/- 19 mL/min/1.73 m(2), reflecting prerenal impairment. One year later, mean GFR was 72 mL/min/1.73 m(2); after 2 years it was 65 mL/min/1.73 m(2), after 4 years (n = 35) it was 60 mL/min/1.73 m(2), and after 8 years (n = 14) it was 57 mL/min/1.73 m(2). CyA levels during the first 2 months correlated with the change in GFR during the first year (r(2) = 0.21). CONCLUSIONS: This study demonstrates for the first time that decline in renal function after heart transplantation correlates with early CyA exposure; this dysfunction persists even when CyA doses are subsequently reduced.

Right ventricular dilatation in the fetus: a study of associated features and outcome.

Right ventricular dilatation is an infrequent finding at fetal echocardiography. Previous studies have documented an association with aortic coarctation. However, there are associations with other congenital abnormalities. We reviewed our experience of fetal right heart dilatation in order to recognize concurrent anomalies and to assess the outcome of the affected fetuses. We studied all fetuses with right ventricular dilatation over a 5-year period. We documented associated cardiac and noncardiac lesions, and outcome data were assessed in terms of the number of fetuses that were born live and the number surviving to 2 months of age. Forty-three fetuses with right heart dilatation were seen. Fifteen had associated cardiac abnormalities: most commonly coarctation (n = 4) and VSD (n = 4). Seven had associated noncardiac abnormalities. There were seven fetuses who also had chromosomal abnormalities. In total, there were three terminations of pregnancy, four intrauterine deaths, one stillbirth and 35 live-births. Twenty-eight were alive at 2 months of age (70% of the nonterminated pregnancies). Fetal right heart dilatation is frequently associated with both cardiac and noncardiac congenital abnormalities. Our outcome figures suggest a guarded prognosis be given during counseling of parents of fetuses with right heart dilatation.

Fetal diagnosis of lethal dysfunction of the right heart in three siblings.

A woman, having already delivered one child, underwent fetal echocardiography during three subsequent pregnancies. All three showed enlargement and poor function of the right-sided chambers. The first was still-born, the second died as a neonate, while the third pregnancy was terminated. Pathological examination revealed the same findings in each fetus, possibly representing a variation of Uhl's anomaly, or alternatively a hitherto unrecognised cardiomyopathic process.

Should we standardise the pre-operative management of babies with complete transposition?

BACKGROUND: Complete transposition is the most common form of neonatal cyanotic heart disease. The management of this condition has changed markedly in the last decade and there appears to be a significant variation between centres in terms of pre-operative management. OBJECTIVES/METHODS: We surveyed all paediatric cardiac surgical centres in the United Kingdom regarding pre-operative management, particularly performance and timing of balloon atrial septostomy and aortogram, imaging techniques used and discharge prior to surgery. RESULTS: There is significant variation in pre-operative management: 10 centres now perform septostomy outside the catheter lab and 11 without general anaesthesia. Eight centres use echo control only and only 3 perform routine aortograms. Three centres do not perform routine septostomy. The most common age for arterial switch was at 1-2 weeks, but some routinely performed this procedure up to 1 month of age and others aim for arterial switch before one week of age. Only 3 centres routinely discharge patients between septostomy and switch. CONCLUSIONS: Despite a trend towards echo guided septostomy and earlier arterial switch there is still considerable variation in early management of patients with transposition of the great arteries. Debate within the profession leading to a more standardised pre-operative management strategy would protect both the patient and the doctor involved in the care of children with complete transposition.

Right ventricular dysfunction in congenitally corrected transposition of the great arteries.

Although right ventricular (RV) dysfunction is an important complication in subjects with congenitally corrected transposition of the great arteries, its pathogenesis is poorly understood. We assessed the role of RV myocardial perfusion and found perfusion defects at rest in all 20 patients, involving 4.6 +/- 2.3 of a total of 12 segments; the extent of the resting perfusion defects correlated inversely with the RV ejection fraction.

Supraventricular electrical interaction in conjoined twins with common coronary sinus.

Conjoined twins with echocardiographic evidence of continuity of the coronary sinuses had identical heart rates on ECG. Both had broad, polyphasic QRS complexes, and various imaging modalities were unable to determine whether there was ventricular myocardial continuity. Administration of adenosine demonstrated that the broad polyphasic complexes were a "fusion" of the twins' individual QRS complexes, which could be clearly distinguished after administration of the drug. Ventricular pacing resulted in dissociation of the individual QRS complexes, thus demonstrating an absence of ventricular myocardial continuity. This was confirmed when the twins were successfully separated at the age of 10 months.

Myocardial infarction complicating neonatal enterovirus myocarditis.

A 10-week-old, 31-week gestation preterm boy re-presented with heart failure after an initial episode of neonatal aseptic meningitis with positive CSF enterovirus polymerase chain reaction. Investigation demonstrated global myocardial dysfunction with left ventricle posterolateral myocardial infarction. The boy's heart failure was controlled with medical treatment but his myocardial dysfunction persisted 9 months after presentation.

Neonatal ductus arteriosus aneurysm causing nerve palsies and airway compression: surgical treatment by decompression without excision.

A 4-kg male child, born at 34 weeks to a gestational diabetic mother, had a large ductus arteriosus aneurysm causing phrenic and recurrent laryngeal nerve palsies and large airway compression. The right and left atrial appendages and distal descending aorta were cannulated, allowing left heart partial or complete cardiopulmonary bypass as necessary. On bypass the ductus was ligated, decompressed, and oversewn but not excised. Examination 1 month later suggested resolution of the recurrent laryngeal palsy and echocardiography showed regression of the aneurysm. Ductus ligation and decompression was an effective surgical treatment, which is less likely to cause complications than resection.

The Ross procedure in children under ten years of age.

BACKGROUND AND AIMS OF THE STUDY: The potential advantages of the Ross procedure in children under 10 years of age have yet to be validated. Concerns remain regarding progressive dilatation of the pulmonary autograft and potential homograft stenosis. We present our experience in this age population. METHODS: A retrospective analysis of aortic root replacement using the Ross procedure in 11 young children (nine males, two females; median age 84 months; range 3 months to 10 years) between January 1996 and January 1999 was performed jointly in two pediatric surgical centers. RESULTS: There were no operative deaths. Mean hospital stay was 12 +/- 4 days, and mean follow up 14.5 +/- 8 months. The event-free survival (death, reoperation, endocarditis, arrhythmia) was 100%. Currently, nine children are in NYHA functional class I, and two in class II. The autograft and homograft were evaluated by serial echocardiography. There was no sign of progressive dilatation of the autograft. Aortic regurgitation was trivial in four children and mild in seven. No growth of the autograft was noted; this was consistent with minimal somatic growth. Homograft peak gradients remained low during the follow up. CONCLUSIONS: Although the pulmonary autograft procedure is more complex than other types of aortic valve replacement, it can be safely applied in children. Early follow up indicates satisfactory performance of the autograft. If dilatation will not occur, pulmonary root autograft may be an attractive substitute for diseased aortic valves in children.

Stimulation of mitochondrial gene expression and proliferation of mitochondria following impairment of cellular energy transfer by inhibition of the phosphocreatine circuit in rat hearts.

Mitochondria proliferate when cellular energy demand increases. However, the pathways leading to enhanced expression of mitochondrial genes are largely unknown. We tested the hypothesis that an altered flux through energy metabolism is the key regulatory event by decreasing mitochondrial energy supply to rat heart cells by creatine depletion. Electron microscopy showed that the density of mitochondria increased by 75% in such hearts (p < 0.01). Levels of representative mRNAs encoded on mitochondrial DNA (mtDNA) or on nuclear chromosomes were elevated 1.5 to 2-fold (p < 0.05), while the mtDNA content was unchanged. The mRNA for the nuclear encoded mitochondrial transcription factor A (mtTFA) was increased after GPA feeding (p < 0.05). Thus, we have shown that an impairment of mitochondrial energy supply causes stimulation of gene expression resulting in mitochondrial proliferation, probably as a compensatory mechanism. The observed activation of the mtTFA gene corroborates the important function of this protein in nuclear-mitochondrial communication.

Myocardial perfusion defects and associated systemic ventricular dysfunction in congenitally corrected transposition of the great arteries.

BACKGROUND: Patients with systemic ventricles of right ventricular morphology are at high risk of contractile dysfunction, the cause of which has not been fully elucidated. OBJECTIVE: To assess whether ischaemia or infarction contributes to ventricular impairment in unoperated patients with uncomplicated congenitally corrected transposition of the great arteries (TGA) by studying myocardial perfusion and function. SETTING: Paediatric and adult congenital cardiac clinics of a tertiary referral centre. PATIENTS: Five patients with congenitally corrected TGA but without associated structural cardiac defects (aged 3.5 to 34 years). INTERVENTIONS: Maximal exercise stress testing using standard or modified Bruce protocols. Sestamibi (technetium-99m methoxy isobutyl isonitrile) scanning after isotope injection at maximal exercise and rest. MAIN OUTCOME MEASURES: Maximum exercise capacity; right ventricular myocardial perfusion, regional wall motion, and thickening; right ventricular ejection fraction. RESULTS: The two youngest patients (3.5 and 11 years) had normal exercise capacity for age, while the others had reduced exercise performance. Sestamibi scanning showed reversible myocardial ischaemia in four patients and fixed defects indicating infarction in five. Irreversible defects were mostly associated with impaired wall motion and thickening. The ejection fraction was normal (65%) in the youngest patient but < 55% in the others (mean (SD) 47(11)%). CONCLUSIONS: Patients with unoperated congenitally corrected TGA have a high prevalence of myocardial perfusion defects, with consequent abnormalities of regional wall motion and thickening, and impaired ventricular contractility. These data suggest that ischaemia and infarction are important in the pathogenesis of ventricular failure in this condition.