Living Donor Kidney Transplantation in a Patient With Epidermolysis Bullosa: A Case Report.

Severe recessive dystrophic epidermolysis bullosa is a very rare inherited disease with excessive blisters forming starting at birth. Surgical intervention in this population creates a challenge: preventing formation of new lesions while managing previously scarred tissues. We present a case of a 27-year-old patient with end-stage renal disease caused by rapidly progressive IgA nephropathy. Living donor kidney transplantation was performed under local, spinal and epidural anesthesia. Living kidney transplantation in epidermolysis bullosa patients with end-stage renal disease should not be a contraindication for transplantation and should be considered as a viable and feasible option after careful preparation.

Refining the phenotypical and mutational spectrum of Taybi-Linder syndrome.

Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.

[Detection of respiratory viruses--how, when, where and why?]. / Nachweis von Atemwegsviren--Wie, warum, wann und wo?

Respiratory viruses trigger the majority of common colds, acute respiratory illnesses in children during the cold season as well as acute exacerbations of asthma and chronic obstructive pulmonary disease. They also play a role in community acquired pneumonia. Unfortunately their detection is still difficult. The aim of this review is therefore to introduce the methods of detection and to present the current knowledge of the clinical role of respiratory viruses in different diseases.

Inflammatory response in acute viral exacerbations of COPD.

BACKGROUND: Respiratory viruses are important triggers of acute exacerbations of COPD (AE-COPD). However, the inflammatory response in virus-positive exacerbations is still not fully understood. METHODS: We investigated CRP, IL-6, IL-8, IL-10, IFN-gamma, blood and sputum cells in patients with acute exacerbation (n = 36) and in stable disease (n = 20) and correlated these parameters to virus detection in respiratory secretions. RESULTS: Similar to other studies we found a significant increase in systemic CRP and absolute numbers of blood leukocytes in AE-COPD patients. Sputum IL-6 levels and sputum eosinophils tended to be higher during exacerbation. In patients with detection of respiratory viruses in nasal lavage, local IL-6 production in sputum was significantly increased; FEV(1) was significantly decreased and both parameters were inversely correlated to each other. CONCLUSION: This study supports previous findings of both, increased local and systemic inflammation in acute exacerbation of COPD. In virus-associated exacerbations, IL-6 is significantly increased and negatively correlated to FEV1 indicating a relation between virus-induced inflammation and airway obstruction. However, regarding our finding and previous data, it is becoming increasingly clear that the mediators investigated so far do not permit identifying the etiology of AE-COPD. Hence, further studies are needed to better define the inflammatory response in AE-COPD in general and in viral exacerbations in particular.

[Donor nephrectomy: less fatigue and better quality of life following laparoscopic kidney removal compared with an open procedure by mini-incision: blind randomised study]. / Donornefrectomie: minder vermoeidheid en meer kwaliteit van leven na een laparoscopische uitname dan na een open ingreep met een mini-incisie: geblindeerd, gerandomiseerd onderzoek.

OBJECTIVE: Determining possible differences in living donor nephrectomy procedures: laparoscopy against mini-incision concerning discomfort to the donor and the maintenance of good graft function. DESIGN: Blind randomized study. METHOD: In two university medical centres, one hundred living kidney donors were randomly assigned to either total laparoscopic donor nephrectomy or mini-incision muscle-splitting open donor nephrectomy. Primary outcome was physical fatigue measured with the 'Multidimensional Fatigue Inventory' (MFI-20) during one-year follow-up. Secondary outcomes were physical function measured with the 'Short form-36' questionnaire, postoperative hospital stay, amount of pain, operating times and graft and patient survival. RESULTS: Donors who underwent laparoscopy experienced less fatigue (difference: -1.3; 95% CI: -2.4 - (-0.1)) and physical function was better (difference: 6.2; 95% CI: 2.0-10.3) during one-year follow-up. Those donors who underwent laparoscopy required less morphine (16 mg versus 25 mg; p = 0.005) and the duration of hospital stay was shorter (3 versus 4 days; p = 0.003). The laparoscopic procedure resulted in a longer operation time (221 versus 164 min; p < 0.001) a longer first warm ischaemia time (6 versus 3 min; p < 0.001) and less blood loss (100 versus 240 ml; p < 0.001). Recipient renal function and one-year graft survival rates did not differ. The number of preoperative and postoperative complications did not differ significantly between both surgery techniques. Conversions did not occur. CONCLUSION: Donor nephrectomy through laparoscopy led to less fatigue and a better quality of life compared with the open procedure. The safety factors for donors and recipients were comparable for both techniques. Laparoscopic donor nephrectomy is therefore the better surgical choice for kidney donor programmes with living donors.

Relevance of human metapneumovirus in exacerbations of COPD.

BACKGROUND AND METHODS: Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. RESULTS: We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 x 10(5) viral copies/ml in nasal lavage and 1.88 x 10(5) viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. CONCLUSION: HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.

Effect of intraabdominal pressure elevation and positioning on hemodynamic responses during carbon dioxide pneumoperitoneum for laparoscopic donor nephrectomy: a prospective controlled clinical study.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum (PP) increases mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) but decreases stroke volume (SV) and cardiac output (CO). This study evaluated the hemodynamic effects of elevated intraabdominal pressure (IAP) occurring during laparoscopic donor nephrectomy (LDN). METHODS: Twenty-two patients undergoing LDN were investigated and hemodynamic parameters, P(v)CO2) (carbon dioxide partial pressure), and VCO2 (carbon dioxide production) were monitored during the procedure. Before and after PP, IAP was raised from 12 to 20 mmHg and the hemodynamic effects were measured every 30 s. RESULTS: During IAP of 12 mmHg and stable serum CO2, there was no change in SV compared to preinsufflation levels. When IAP was elevated from 12 to 20 mmHg, SV initially decreased (p < 05), followed by an increase in MAP and SVR (p < 0.05). CONCLUSION: This study shows that with the fluid and ventilation protocol used, PP has no significant effect on SV at an IAP of 12 mmHg, whereas increasing IAP to 20 mmHg does. In this study, the hemodynamic effects induced by CO2 PP of 12 mmHg are not due to changes in serum CO2. Compression of the venous system during a PP of 20 mmHg reduces preload, with an subsequent increase in SVR.

Evaluation of a real-time polymerase-chain reaction for severe acute respiratory syndrome (SARS) associated coronavirus in patients with hospitalised exacerbation of COPD.

One year after the first outbreak infections with SARS associated coronavirus were again reported and the clinical picture varied. Because health care facilities will have to initiate immediate preventive action in cases of probable SARS we tested the potential of PCR to exclude SARS associated coronavirus in patients hospitalized with respiratory symptoms. Based on primers published recently a real time Taqman PCR was established and evaluated. Lower respiratory tract specimens of patients with acute exacerbation of COPD were investigated. 141 patients with mild to moderate COPD were included. The assay was specific, sensitive, precise and reproducible and allowed absolute quantification without cross-reactivity to other respiratory viruses. None of the samples were positive for SARS associated coronavirus. Our RT-PCR for SARS associated coronavirus is a valid and practicable method to further exclude SARS in X-ray negative patients with respiratory symptoms, even in the presence of other respiratory RNA viruses.

Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases.

Respiratory syncytial virus (RSV) is known to cause acute lower respiratory tract infections (ARI) in young children and is involved in exacerbation of chronic obstructive pulmonary disease (COPD) in adults. The role of RSV in stable COPD and the viral load in different respiratory diseases has not been investigated to date. The present authors established and evaluated a quantitative TaqMan real-time polymerase chain reaction assay specific for RSV subgroup A. Absolute quantification for the determination of viral load input was achieved using a control plasmid. The assay allowed for a quantification over a >6-log range and a detection limit of <10 RSV copies per reaction mixture. The assay was 30 times more sensitive than conventional nested polymerase chain reaction assays. Interassay SD was 1.3 and coefficient of variation 4.7% on average. Clinical specimens from infants with ARI (n=62) and elderly adults with COPD (n=125) were compared for viral loads. A total of 47% RSV-positive samples were found in the ARI study group and 28% in the COPD study group. The viral load of both study groups was found to differ significantly. In the ARI study group the viral load was increased almost 2000-fold, suggesting acute infection in this group and former or latent infection in the COPD group. Respiratory syncytial virus-A specific TaqMan real-time polymerase chain reaction assay is a sensitive and rapid method for the determination of viral load in clinical samples. It enables differential statements concerning the involvement of respiratory syncytial virus in acute lower respiratory tract infections and chronic obstructive pulmonary disease to be achieved.

Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined. METHODS: Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied. RESULTS: Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03). CONCLUSION: Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated.

A cryptic deletion of 2q35 including part of the PAX3 gene detected by breakpoint mapping in a child with autism and a de novo 2;8 translocation.

We report a de novo, apparently balanced (2;8)(q35;q21.2) translocation in a boy with developmental delay and autism. Cross species (colour) paint (Rx) and SKY FISH, forward and reverse chromosome painting, and FISH with subtelomeric probes were used to examine the patient's karyotype, but further rearrangements were not detected. FISH with region specific clones mapping near 2q35 and 8q21.2 breakpoints and STS mapping performed on the isolated derivative chromosomes were used to refine the location of the breakpoints further. A cryptic deletion of between 4.23 and 4.41 Mb in extent and involving at least 13 complete genes or transcription units was found at the breakpoint on 2q35. The deletion includes the promoter and 5' untranslated region of the paired box 3 (PAX3) gene. The child has very mild dystopia canthorum which may be associated with the PAX3 haploinsufficiency. The 8q21.2 breakpoint is within MMP16 which encodes matrix metalloproteinase 16. We postulate that the cryptic deletion and rearrangement are responsible for the patient's phenotype and that a gene (or genes) responsible for autism lies at 2q35 or 8q21.2. The results present a step towards identifying genes predisposing to autism.

The childbirth experience: a study of 295 new mothers.

BACKGROUND: The childbirth experience is multidimensional, and therefore difficult to describe and explain. Studies of it have produced inconsistent findings, and the phenomenon is often confused with satisfaction with the care provided. This study aimed to clarify different aspects of the birth experience, and to identify factors that could explain the variation in women's overall assessment of it. METHODS: All Swedish-speaking women in a large city who gave birth during a two-week period in 1994 were given a questionnaire one day after the birth, and 295 (91%) of the questionnaires were returned. Information about the labor process and medical interventions was collected from hospital records. RESULTS: Women usually experienced severe pain and various degrees of anxiety, and most were seized with panic for a short time or some part of their labor. Despite these negative feelings, most women felt greatly involved in the birth process, were satisfied with their own achievement, and thought they had coped better than expected. The overall experience was assessed as positive by 77 percent of women and negative by 10 percent. No statistical difference was observed between primiparas and multiparas in total birth experience, and few differences in the specific aspects of the birth. Of the 38 variables tested in regression analysis, the six that contributed to explaining women's overall birth experience were support from the midwife (sensitivity to needs), duration of labor, pain, expectations of the birth, involvement and participation in the birth process, and surgical procedures (emergency cesarean section, vacuum extraction, forceps, episiotomy). CONCLUSIONS: The study showed that negative and positive feelings can coexist, thus confirming the multidimensional character of the birth experience. Women's assessment of their childbirth is influenced by both physical and psychosocial factors, highlighting the importance of a comprehensive approach to care in labor.

Detection of hemizygosity at the elastin locus by FISH analysis as a diagnostic test in both classical and atypical cases of Williams syndrome.

A small pilot study has been carried out in order to assess the reliability of the detection of hemizygosity at the elastin locus by fluorescence in situ hybridisation (FISH) analysis, as a diagnostic test in both classical and atypical cases of Williams syndrome (WS). Five subjects with WS and five others in whom a diagnosis could not be confirmed on clinical criteria alone were evaluated. Hemizygosity at the elastin locus by FISH analysis was detected in all classical Williams syndrome cases and in three of the five atypical subjects. Furthermore, a combination of a few specific facial features found to be present in all subjects with the elastin gene hemizygosity has been suggested to aid the index of clinical suspicion.

The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis.

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.

[An empirical comparison of 5 standard procedures for one-dimensional scaling]. / Ein empirischer Vergleich von fünf Standard-Verfahren zur eindimensionalen Skalierung.

Scales on the badness of 10 offenses/crimes are derived by using the five most common scaling methods: averaging of the badness-ratings of the stimuli on an 11-point scale; mean ranks of complete rankings of the 10 stimuli; Thurstone scales for complete forced-choice and constant-sum pair comparisons, resp.; and ratio scales derived from pairwise ratio judgments for all pairs. From older investigations, a logarithmic correspondence of ratio scales and Thurstone or average ratings, resp., can be predicted. The data corroborate this prediction. They show furthermore that the ratio scale has an exceedingly close, logarithmic relation to each of the other four scales. We therefore conclude that, once a universe has been shown to be scalable, a scale can be constructed very economicaly by simply averaging ratings.