Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany

The lack of epidemiological data on the frequency and/or burden of organic acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten potentially treatable OA and mtFATOD was assessed by active nation-wide surveillance on cases presenting with clinical symptoms using the German Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented by a second independent source: 3-monthly inquiries in the metabolic laboratories performing secondary selected screening for OA and mtFATOD. Frequency estimates for clinically symptomatic cases older than 7 days in a birth cohort of 844,575 conventionally screened children was compared to the frequency found in a cohort of 382,247 screened by MS-MS in Bavaria and Baden-Württemberg. The overall frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000–1:6,000) by MS-MS as compared to 1:23,000 (95% CI 1:36,000–1:17,000) in symptomatic cases presenting mainly with metabolic crisis. The contributions of medium-chain acyl-CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13 among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in four patients, was reported for 22/33 clinically symptomatic cases. No clinically symptomatic cases were reported from cohorts with screened by MS-MS. Conclusion: ten potentially treatable organic acidurias and mitochondrial fatty acid transport and oxidations disorders were more common than phenylketonuria with organic acidurias accounting for 28% of the cases detected by newborn screening and 39% of the cases identified on high risk screening. These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted.Abbreviations ESPED Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) - MCADD medium-chain acyl-CoA dehydrogenase deficiency - MS-MS tandem mass spectrometry - mtFATOD mitochondrial fatty acid transport and oxidation disorders - NBS newborn screening - OA organic acidurias     

Liposomal amphotericin B treatment for rhinocerebral mucormycosis: how much is enough?

Rhinocerebral Mucormycosis is a potentially life-threatening disease, which affects mainly immunocompromised patients. Treatment options include reversing immunosuppression, surgery and systemic and local administration of anti-fungal medication. Amphotericin B is the primary agent employed, but its use is often limited by frequent side effects. Complexing Amphotericin B with lipid structures avoids most of the negative side effects, most importantly the dose-limiting nephrotoxicity. No consensus has been reached regarding the appropriate duration, rate of administration or total dose of treatment. We present a case of a patient suffering from Rhinocerebral Mucormycosis treated by extensive surgery and Liposomal Amphotericin B. He was treated for 29 days at a rate of 3 mg/kg/d and a total dose of 5.6 gram. The dose of Liposomal Aphotericin B used in previously published articles ranged from 1.5 mg/kg/d to 5 mg/kg/d. The response to treatment may be evaluated by physical examination, microbiological cultures, radiological and pathological studies. Taking into account the considerable cost of liposomal Amphotericin B and other lipid complexed formulations, it is imperative to find out what is the appropriate treatment regime for Rhinocerebral and other mucormycosis infections.     

Laser-assisted uvulopalatoplasty for snoring: medium- to long-term subjective and objective analysis

OBJECTIVE: To assess the subjective and objective medium- to long-term results of laser-assisted uvulopalatoplasty for snoring. DESIGN: A nonrandomized, prospective, before-after trial. SUBJECTS AND INTERVENTIONS: Fourteen patients underwent laser-assisted uvulopalatoplasty surgery; 2 surgical techniques, which differ with respect to the mode of midline palatal vaporization, were used. MAIN OUTCOME MEASURES: Subjective analysis included a preoperative and 2 postoperative evaluations of the state of snoring: 4 weeks and 10.1 +/- 7.9 months (mean +/- SD) after completion of last laser treatment. In addition, a score on 5 other sleep-related symptoms was recorded before treatment and after 10.1 +/- 7.9 months; at that time, patients also estimated their overall satisfaction with the procedure. Objective analysis included preoperative nocturnal polysomnographic studies that were repeated postoperatively. RESULTS: A decline in snoring improvement from 79% (11/14) to 57% (8/14) was recorded; furthermore, state of snoring worsened from 7% (1/14) to 21% (3/14). Likewise, reevaluation of the 5 other sleep-related symptoms at the final follow-up visit uncovered a 57% improvement rate. Overall satisfaction with the procedure was 43%. The results of the postoperative objective studies corresponded to those of the subjective ones and demonstrated significant worsening of respiratory disturbance index in 3 (21%) of the 14 patients, who became mildly apneic. These findings were encountered with both laser techniques. CONCLUSIONS: The favorable subjective short-term results of laser-assisted uvulopalatoplasty deteriorated with time. In addition, postoperative nocturnal polysomnography showed that the procedure caused mild obstructive sleep apnea in a considerable number of patients who formerly were nonapneic snorers. These findings may be related to velopharyngeal narrowing and progressive palatal fibrosis, caused by the thermal damage inflicted by the laser beam.     

Anatomical basis of sleep-related breathing abnormalities in children with nasal obstruction

OBJECTIVE: To define, in a group of children with nasal obstruction, the anatomical differences that differentiate those with quiet, unobstructed nocturnal respiration from those with obstructive sleep-related breathing abnormalities (snoring and obstructive sleep apnea). DESIGN: Case series. PATIENTS: Fifty-nine children aged 3 to 13 years (35 boys and 24 girls) with nasal obstruction and without tonsillar hypertrophy, known craniofacial syndromes, or neuromuscular diseases were included in the study. MAIN OUTCOME MEASURES: Each patient was categorized as to severity of nocturnal obstructive breathing symptoms. Angular and linear cephalometric measurements were used for assessment of craniofacial features. Clinical symptom scores were correlated with the cephalometric measurements. RESULTS: Significant craniofacial abnormalities were identified in patients prone to obstructive breathing patterns: increased flexure of the cranial base and bony nasopharynx, opening of the gonial angle, shortened mandibular length, dorsocaudal location of the hyoid, reduced posterior airway space, and increased velar thickness. CONCLUSIONS: A number of anatomical abnormalities may contribute to sleep-related abnormal breathing in otherwise normal children with nasal obstruction. Our results suggest that symptomatic children show some of the same skeletal and soft-tissue configurations that are found in adults with obstructive sleep apnea. While adenoidectomy is generally an effective treatment in children with obstructive sleep-related breathing abnormalities, the underlying craniofacial variances that remain after adenoidectomy may predispose these patients to redevelopment of obstructive breathing abnormalities in adulthood.     

Pet sensitivities in asthmatic children

A history of pet contact and/or apparent clinical sensitivity was obtained in 65 (55%) of 118 unselected asthmatic children. These 65 children were skin tested and their sera examined for specific IgE using the radioallergosorbent test. Those children who had apparent clinical sensitivities had larger skin test reactions and were more likely to have positive specific IgE results than those without apparent sensitivities. Positive skin tests were very common (80%), but the larger the skin test reaction (weal diameter greater than 4 mm diameter) the more likely was there to be a positive history or a positive specific IgE result. Hence a large skin test reaction can provide a helpful pointer to animal allergy of clinical importance. Commercially available animal extracts have limitations for diagnostic tests. A questionnaire survey of 150 day schools emphasized the potential opportunities for contact with animal allergens at school.     

Elastography: Imaging the elastic properties of soft tissues with ultrasound

Elastography is a method that can ultimately generate several new kinds of images, called elastograms. As such, all the properties of elastograms are different from the familiar properties of sonograms. While sonograms convey information related to the local acoustic backscatter energy from tissue components, elastograms relate to its local strains, Young's moduli or Poisson's ratios. In general, these elasticity parameters are not directly correlated with sonographic parameters, i.e. elastography conveys new information about internal tissue structure and behavior under load that is not otherwise obtainable. In this paper we summarize our work in the field of elastography over the past decade. We present some relevant background material from the field of biomechanics. We then discuss the basic principles and limitations that are involved in the production of elastograms of biological tissues. Results from biological tissues in vitro and in vivo are shown to demonstrate this point. We conclude with some observations regarding the potential of elastography for medical diagnosis.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

Detachment of subfoveal choroidal neovascularization in age-related macular degeneration

PURPOSE: To report the entity of partial detachment and folding of subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). DESIGN: Interventional case reports. METHODS: Review of the features of CNV detachment in two patients with CNV due to ARMD by contact lens slit-lamp biomicroscopy, fluorescein angiography, optical coherence tomography, and three-dimensional confocal scanning laser indocyanine green (ICG) angiography. RESULTS: One patient out of approximately 300 (0.5%) ARMD patients treated by photodynamic therapy (PDT) developed partial CNV detachment and folding 6 weeks after the second PDT treatment. Another patient out of approximately 100 (1.0%) ARMD patients treated by transpupillary thermotherapy (TTT) developed partial CNV detachment and folding 6 weeks after the second TTT treatment. The CNVs were large (2,500 microm to 4,500 microm) and located between the retina and the retinal pigment epithelium. In each, these findings were clearly visualized by slit-lamp biomicroscopy. Fluorescein angiography demonstrated an associated retinal pigment epithelium tear in one patient. Optical coherence tomography showed distinctive features and confocal scanning laser ICG further delineated the detached folded CNV. The best-corrected visual acuity improved in one patient from 20/80 to 20/40 and in the other from counting fingers at 6 feet to 20/200 after the CNV detachment. CONCLUSIONS: Partial CNV detachment and folding represent a unique, not previously reported, and possibly favorable outcome of PDT and TTT. The low energy and selectivity of these treatments may explain this phenomenon.     

Pulse-echo ultrasound speed measurements: progress and prospects

The data on the relationship of sound speed to tissue condition, and the development of methods for measurement of sound speed in vivo, are outlined. The methods developed by the authors are discussed. These include methods which use the spatial shift in images of targets viewed from different directions, time-of-flight measurements along incrementally tracked beams and echo tracking during transaxial compression of tissue. The reported sound-speed values are discussed, discrepancies noted and suggestions made on the potential clinical applications of in vivo sound-speed estimation.