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1.
Nervenarzt ; 88(12): 1358-1366, 2017 Dec.
Article in German | MEDLINE | ID: mdl-29101527

ABSTRACT

The most common neurodegenerative disease in childhood is spinal muscular atrophy (SMA). The severe infantile type 1 (Werdnig-Hoffman disease) makes 60% of SMA in total. These children usually die within 18 months without ventilation. New therapeutic approaches have led from the theoretical concept to randomized controlled clinical trials in patients. For the first time, a pharmacological treatment of SMA has been approved. The early detection of the disease is decisive for the success of therapy. All previous data suggest starting treatment early and when possible prior to the onset of symptoms considerably improves the outcome in comparison to a delayed start. The goal must be the presymptomatic diagnosis in order to initiate treatment before motor neuron degeneration. Technical and ethical prerequisites for a molecular genetic newborn screening are given.


Subject(s)
Neonatal Screening , Spinal Muscular Atrophies of Childhood/prevention & control , Child, Preschool , Early Diagnosis , Early Medical Intervention , Exons/genetics , Gene Deletion , Genetic Carrier Screening , Humans , Infant , Infant, Newborn , Phenotype , Prognosis , RNA, Messenger/genetics , Randomized Controlled Trials as Topic , Spinal Muscular Atrophies of Childhood/diagnosis , Spinal Muscular Atrophies of Childhood/drug therapy , Spinal Muscular Atrophies of Childhood/genetics , Survival of Motor Neuron 1 Protein/genetics , Survival of Motor Neuron 2 Protein/genetics
2.
Fetal Diagn Ther ; 25(2): 264-8, 2009.
Article in English | MEDLINE | ID: mdl-19521093

ABSTRACT

Prenatal diagnosis of generalized arterial calcification of infancy (GACI) (OMIM #208000) is difficult and rare. There are various known gene mutations in ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) locus 6q22-q23. We present a case of suspected intrauterine diagnosis at 29 weeks of gestation in a consanguineous couple. The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. An intrauterine therapy with bisphosphonates was considered, but delayed due to rapid deterioration in fetal Doppler flows with suspected fetal asphyxia. The couple was informed about the most unfavorable prognosis in fetal hydrops, however, they opted for elective delivery. A cesarean section was performed. Early neonatal death occurred due to primary intracranial hemorrhage. Postmortem and genetic testing confirmed a novel mutation in the ENPP1 gene.


Subject(s)
Atherosclerosis/diagnostic imaging , Calcinosis/diagnostic imaging , Hydrops Fetalis/diagnostic imaging , Phosphoric Diester Hydrolases/genetics , Pyrophosphatases/genetics , Ultrasonography, Prenatal , Adult , Aorta/diagnostic imaging , Aorta/pathology , Atherosclerosis/complications , Atherosclerosis/genetics , Calcinosis/complications , Calcinosis/genetics , Consanguinity , Female , Humans , Hydrops Fetalis/genetics , Hydrothorax/complications , Hydrothorax/diagnostic imaging , Hydrothorax/genetics , Infant, Newborn , Male , Mutation , Pregnancy , Umbilical Arteries/diagnostic imaging , Umbilical Arteries/pathology
3.
Curationis ; 29(2): 56-65, 2006 May.
Article in English | MEDLINE | ID: mdl-16910135

ABSTRACT

The aim of this contextual, exploratory, descriptive and qualitative study was to describe strategies to improve the performance of learners in a nursing college. The article seeks to deal with factors relating to nursing education that contribute to the poor performance of learners and to outline related strategies to improve the situation. Three focus group interviews were conducted. One group was formed by seven tutors, and the other two groups were formed by fourth-year learners following a four-year comprehensive diploma course. All participants voluntarily took part in the study. Data was analyzed using the descriptive method of open coding by Tesch (in Creswell, 1994:154-156). Trustworthiness was ensured in accordance with Lincoln and Guba's (1985:290-326) principles of credibility, conformability, transferability and dependability. The findings were categorized into issues pertaining to nursing education as follows: curriculum overload; lack of theory and practice integration; teaching and assessment methods that do not promote critical thinking; tutors' lack of skills and experience; inadequate preparation of tutors for lectures; insufficient knowledge of tutors regarding outcomes-based education approach to teaching and learning; inadequate process of remedial teaching; discrepancies between tutors' marking; lack of clinical role-models and high expectations from the affiliated university as regards standards of nursing development programme by the staff development committee of the nursing college under study for implementation. Future research should focus on the effectiveness of the described strategies to improve the learners' performance. It is also recommended that similar studies be conducted or replicated in other nursing colleges to address the problem of poor performance of learners engaged in a four-year comprehensive diploma course.


Subject(s)
Education, Nursing, Diploma Programs/standards , Faculty, Nursing/standards , Teaching/methods , Curriculum , Focus Groups , Health Knowledge, Attitudes, Practice , Humans , South Africa
4.
Curationis ; 29(2): 66-76, 2006 May.
Article in English | MEDLINE | ID: mdl-16910136

ABSTRACT

UNLABELLED: This article forms part two of a bigger study that was conducted in a nursing college to explore and describe the reasons for the poor performance of learners. Part one of the study dealt with the issues pertaining to education, while this article (part two) seeks to describe issues pertaining to management, attitudes and values that lead to the poor performance of learners in the nursing college under study. A qualitative, exploratory and descriptive design that was contextual in nature was employed, and three focus groups interviews were conducted. Seven tutors formed one group while other two groups were formed by fourth-year learners following a comprehensive diploma course. All participants voluntarily participated in the study. Data was analyzed using the descriptive method of open coding in accordance with Tesch's protocol (in Creswell, 1994:154-156). Trustworthiness was ensured using the following principles: credibility, conformability, transferability and dependability (Lincoln & Guba 1985:290-326). Findings were categorized into issues pertaining to management, attitudes and values that had an influence on the poor performance of learners as follows: MANAGEMENT: Inadequate resources and study facilities; policies that change frequently; tutors' dissatisfaction with regard to staff development, the lack of involvement by management and lack of management support, staff shortage and maldistribution of staff members; ineffective selection process of learners; inconsistent regulations, and too many of them; policies and procedures resulting in confusion and poor discipline. Attitudes and values: Tutors' lack of motivation and interest, lack of respect by learners and no team work among tutors. Through a conceptualization process and the recommendations by participants, strategies to improve the learners' performance were described. It is recommended that these strategies be submitted to the staff development committee for implementation and future follow-up research be undertaken to determine the effectiveness of the strategies. It is also recommended that other nursing colleges replicate the study within their context.


Subject(s)
Attitude , Education, Nursing, Diploma Programs , Schools, Nursing/organization & administration , Focus Groups , Humans , Organizational Culture , Organizational Policy , Personnel Management , School Admission Criteria , South Africa
7.
Z Geburtshilfe Neonatol ; 209(3): 100-7, 2005 Jun.
Article in German | MEDLINE | ID: mdl-15995942

ABSTRACT

BACKGROUND: The embryological development of the kidneys and the urinary tract follows a complex choreography. Disorders are quite common. The incidence of disorders amounts to 0.3 - 0.8 % of live-born infants. In addition, several chromosomal anomalies are combined with renal malformations. The poor prognosis of some of these diseases is reflected in a perinatal mortality of 6.3 %. PATIENTS AND METHODS: Retrospectively 124 cases with fetal nephro-/uropathy detected by prenatal ultrasonography between 1996 and 2002 were analyzed. Features of hypo-dysplastic kidneys (uni- or bilateral) were seen in 21 cases. Multicystic kidney disease (uni- or bilateral) existed in 40 fetuses. In some cases of multicystic or dysplastic kidney diseases, extrarenal malformations were combined. 21 fetuses suffered from autosomal recessive polycystic kidney disease. 18 male unborns showed the typical picture of intravesical obstruction due to posterior uretheral valves. The prune belly syndrome was seen 4 times. Hydronephrotic kidneys with more than 5 mm pelvic dilatation were detected in 13 cases. Renal agenesis led to a lethal outcome perinatally in 5 cases. One child died of bilateral thrombosis of renal artery and venous system. RESULTS: The high incidence of diseases with a poor prognosis accounts for the high mortality of 50.8 % (intrauterine or postnatal death, induced abortion). Such a fatal outcome was observed in autosomal recessive polycystic kidney disease, bilateral multicystic dysplastic kidney disease, bilateral renal dysplasia combined with severe extrarenal malformations, intravesical obstruction, renal agenesis and bilateral thrombosis of the renal vessels. Only 60 children survived. Of these 26 needed urological surgery. 15 suffered from progressive renal insufficiency. During a follow-up of 8 - 58 months only 44 exhibited a normal renal function. CONCLUSIONS: Such complex renal and urological diseases in the fetus require an interdisciplinary management of the pregnancy.


Subject(s)
Fetal Diseases/epidemiology , Fetal Diseases/mortality , Kidney Diseases/diagnostic imaging , Kidney Diseases/mortality , Risk Assessment/methods , Urologic Diseases/diagnostic imaging , Urologic Diseases/mortality , Female , Fetal Diseases/embryology , Germany/epidemiology , Humans , Incidence , Kidney Diseases/embryology , Male , Retrospective Studies , Risk Factors , Ultrasonography , Urologic Diseases/embryology
8.
Neuropediatrics ; 36(2): 98-103, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15822022

ABSTRACT

The restless legs syndrome (RLS) occurs in adulthood with a prevalence of 5 to 10% and can be associated with diabetes mellitus. The prevalence in childhood, however, is unknown. We asked consecutive children with type 1 (insulin-dependent) diabetes mellitus as well as their parents and siblings about RLS according to a standardised questionnaire. Altogether, 46 patients (25 female, 12.0 +/- 3.7 years), 50 siblings (29 female, 12.3 +/- 5.5 years) and 75 parents (41 mothers, 40.4 +/- 5.1 years; 34 fathers, 42.5 +/- 5.3 years; 1.3 % with diabetes mellitus) were included. One patient (2.2%), one sibling (2.0%), and 14 parents (18.7%) were diagnosed as having RLS. Disturbances of sleep initiating, sleep maintenance and daytime tiredness were similar in patients and siblings. There was a significant association of higher HbA1c values (mean 7.7 +/- 2.2%) with sleep initiating problems. The mean dose of international units of insulin/kg body weight/day (0.79 +/- 0.26 IU) was not associated with the presence of RLS or sleep problems. To conclude, there seems to be no association of diabetes mellitus type 1 with RLS in children and adolescents. However, there is a relationship between diabetes and sleep disturbances and an optimally controlled diabetes mellitus might be an important factor for an improved sleep initiation.


Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Restless Legs Syndrome/complications , Restless Legs Syndrome/epidemiology , Sleep Wake Disorders/complications , Adolescent , Adult , Body Weight/physiology , Chi-Square Distribution , Child , Family Characteristics , Female , Humans , Insulin/administration & dosage , Male , Middle Aged , Parent-Child Relations , Retrospective Studies , Statistics, Nonparametric
9.
J Psychosom Res ; 57(5): 473-6, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15581651

ABSTRACT

OBJECTIVE: For parents, the premature birth of a child represents a traumatic event for which they are poorly prepared. To date, the focus of scientific interest has been on maternal psychological stress responses, such as anxiety and depression, or on appropriate coping mechanisms, whereas only scant attention has been paid to the traumatic aspect of the maternal experience after very low-birth-weight (VLBW) birth. The present study is the first to investigate the posttraumatic stress response of mothers after the birth of a VLBW infant in a prospective longitudinal study. METHODS: Fifty mothers of VLBW infants were examined at four measuring time points (1-3 days pp, 14 days pp and 6 and 14 months pp) with respect to posttraumatic symptoms [Impact of Event Scale (IES-R)], psychiatric diagnosis (SKID I for DSM-IV) and the extent of depression [Beck Depression Inventory (BDI) and Montgomery Asberg Depression Scale (MADRS)] and anxiety [State-Trait Anxiety Inventory (STAI) and Hamilton Anxiety Scale (HAMA)]. The control group comprised a group of 30 mothers after the uncomplicated spontaneous birth of a healthy child. RESULTS: At all four measuring timepoints (except 6 months pp), the mothers of the premature infants recorded significantly higher values for traumatic experience and depressive symptoms and anxiety compared with the controls. In contrast to the mothers in the control group, the mothers of the premature infants displayed no significant reduction in posttraumatic symptoms (IES-total), even 14 months after birth. CONCLUSION: The results indicate that the situation of a mother who has given birth to a VLBW infant is a complex, with long-term traumatic event necessitating ongoing emotional support extending beyond the period immediately after the birth.


Subject(s)
Infant, Very Low Birth Weight , Mother-Child Relations , Stress Disorders, Post-Traumatic/etiology , Stress Disorders, Post-Traumatic/psychology , Adult , Case-Control Studies , Emotions , Female , Humans , Infant, Newborn , Pregnancy , Prospective Studies , Psychiatric Status Rating Scales , Social Support
10.
Nuklearmedizin ; 43(4): 124-8, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15316579

ABSTRACT

AIM: The TCTUs (global (99m)Tc-pertechnetate thyroid uptake under suppression) can be used as an estimate of the iodine clearance of non-TSH regulated tissue. High TCTUs levels are characteristic for Graves' disease (GD). Decreased uptake has been described in autoimmune thyroiditis (AIT). However, systematically investigated data in a larger series of AIT-patients with subclinical or overt hyperthyroidism are not published so far. The purpose of this study is the evaluation of the TCTUs in the differentiation between AIT and GD in patients with hyperthyroidism. METHODS: We determined the TCTUs in 59 patients with untreated hyperthyroid GD and in 51 patients with AIT who had subclinical or manifest hyperthyroidism without medication. Patients with GD were characterized by the presence of hyperthyroidism, decreased echogenicity of the thyroid, elevation of TSH-receptor autoantibodies (TRAb). AIT was defined by a decreased echogenicity of the thyroid, absence of elevated TSH-receptor autoantibodies (TRAb), autoantibodies against the thyroid peroxidase (anti-TPO) and spontaneous remission or development of subclinical hypothyroidism within 3 months. RESULTS: Thyroid volumes of patients with AIT were significantly lower than those of patients with GD (p <0.05). TRAb levels were significantly higher in GD-patients (median: 19.5 U/ml; range: 15.3-35 U/ml) than in AIT-patients (median: 1.3 U/ml; range: 0-4.1 U/ml). 73% (38/59) of patients with GD had elevated anti-TPO levels. In these patients anti-TPO levels (median: 768 U/l; range: 83-6397 U/l) were not significantly different from anti-TPO levels of patients with AIT (median: 834 U/l; range: 107-8675 U/l; p = 0.17). TCTUs values of patients with AIT were significantly lower (p <0.05; median: 0.9%; range: 0.1-3.2%) than those of patients with GD (median: 5.7%; range: 1.9-28.3%). CONCLUSION: In our patients quantitative thyroid scintigraphy with (99m)TcO(4)(-) offered rapid and reliable differentiation between hyperthyroid GD and AIT.


Subject(s)
Graves Disease/diagnostic imaging , Thyroiditis, Autoimmune/diagnostic imaging , Diagnosis, Differential , Humans , Hyperthyroidism/etiology , Observer Variation , Radionuclide Imaging , Retrospective Studies
11.
BJU Int ; 93(3): 388-92, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14764144

ABSTRACT

OBJECTIVES: To report a retrospective study of unilateral multicystic dysplastic kidneys (MCDK) in children, assessing the contralateral kidneys and urinary tract, the functional consequences, and the urological and nephrological management and outcome, as unilateral MCDK is the most common cause of renal cystic disease in children, and malformations of the contralateral urinary tract and kidney (pelvi-ureteric obstruction, megaureter, reflux, renal dysplasia) have been reported. PATIENTS AND METHODS: The study included 97 patients (60 boys, 37 girls) with MCDK seen between 1985 and 1998; 82 were diagnosed in utero by ultrasonography (US). After birth, the diagnosis was verified by US, renal scanning (in 93) or intravenous urography (in four), and 89 (92%) had voiding cysto-urethrography (VCUG). Of the 97 children, 87 (90% had a mean (range) follow-up of 44.3 (15-115) months. RESULTS: The MCDK was removed in 17 children; the follow-up of 75 children (five lost to follow-up) showed total involution of the MCDK in 25%, shrinkage in 60% and a stable size in 15%. None had any sign of malignancy. The contralateral kidney showed anomalies in 19 of 97 children (20%); 12 had a dilated renal pelvis (two with megaureter), six had a high echogenicity of the contralateral kidney (one had reflux, and two also pelvic dilatation). In only four of the 89 children was reflux found by VCUG; 16 of the 19 anomalies were detected by US. Five children needed surgery on the contralateral urinary tract (three a pyeloplasty, and one each a pyeloplasty plus ureteroneocystostomy, and an antireflux procedure). Of the contralateral kidneys 43% showed compensatory hypertrophy. There was mild renal insufficiency in three children; renal function seemed to be slightly impaired in many. Five infants had hypertension (four with spontaneous resolution) caused by renal scarring after pyelonephritis or inborn dysplasia of the contralateral kidney. There were symptomatic urinary tract infections in seven children. CONCLUSION: US can be used safely to diagnose unilateral MCDKs and malformations of the contralateral urinary tract and kidney. In cases where US of the dysplastic kidney remains uncertain renal scintigraphy is necessary to detect the lack of renal function. The low rate of reflux makes routine VCUG unnecessary if the contralateral upper urinary tract and kidney appear to be normal on US. Nephrectomy of the dysplastic kidney in typical cases is also unnecessary. A long-term nephro-urological follow-up of children with MCDK is recommended.


Subject(s)
Multicystic Dysplastic Kidney/therapy , Child , Child, Preschool , Female , Glomerular Filtration Rate/physiology , Humans , Hypertrophy , Infant , Kidney/pathology , Male , Multicystic Dysplastic Kidney/diagnostic imaging , Multicystic Dysplastic Kidney/physiopathology , Nephrectomy/methods , Pregnancy , Retrospective Studies , Ultrasonography, Prenatal , Urinary Tract Infections/etiology
12.
Thorax ; 58(7): 613-7, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12832680

ABSTRACT

BACKGROUND: Chronic airway inflammation and recurrent infections are a core phenomenon in cystic fibrosis (CF). Diagnosing acute infectious exacerbations is difficult in the presence of chronic inflammatory processes. S100A12 exhibits proinflammatory functions via interaction with the multiligand receptor for advanced glycation end products. Blocking this interaction inhibits inflammatory processes in mice. METHODS: The expression of S100A12 in lung specimens of patients with end stage lung disease of CF was investigated, and S100A12 levels in the serum of patients with acute infectious exacerbations of CF were measured. RESULTS: Immunohistochemical studies of CF lung biopsy specimens revealed a significant expression of S100A12 by infiltrating neutrophils. High S100A12 levels were found in the sputum of patients with CF, and serum levels of S100A12 during acute infectious exacerbations were significantly increased compared with healthy controls (median 225 ng/ml v 46 ng/ml). After treatment with intravenous antibiotics the mean S100A12 level decreased significantly. There was also a significant difference between S100A12 levels in patients with acute infectious exacerbations and 18 outpatients without exacerbations (median 225 ng/ml v 105 ng/ml). CONCLUSIONS: S100A12 is extensively expressed at local sites of inflammation in CF. It is a serum marker for acute infectious exacerbations. High local expression of S100A12 suggests that this protein has a proinflammatory role during airway inflammation and may serve as a novel target for anti-inflammatory treatments.


Subject(s)
Bacterial Infections/complications , Cystic Fibrosis/metabolism , S100 Proteins/metabolism , Adolescent , Adult , Bronchitis/metabolism , C-Reactive Protein/metabolism , Child , Child, Preschool , Cystic Fibrosis/complications , Enzyme-Linked Immunosorbent Assay , Humans , Immunohistochemistry/methods , Infant , S100A12 Protein , Sputum/metabolism , Statistics, Nonparametric
13.
Klin Padiatr ; 215(2): 86-9, 2003.
Article in German | MEDLINE | ID: mdl-12677549

ABSTRACT

We report of a prematurely born infant, who was admitted to hospital at the age of 6 months due to seizures. The seizures continued despite of an improved electroencephalogram due to varying medications. The boy had episodes of hypokaliaemia, diarrhea, and tachycardia which were treated in critical care unit. Not before 3 months of continued treatment and diagnostic work up in three different hospitals had passed the underlying poisoning with theophylline by the mother was proved. The toxicity of theophylline is well known. Adverse reactions occur frequently during theophylline therapy. There are numerous reports of suicidal intoxications with theophylline. Non-accidental poisoning with theophylline has not yet been reported in the context of Munchausen syndrome by proxy.


Subject(s)
Infant, Premature, Diseases/diagnosis , Munchausen Syndrome by Proxy/diagnosis , Poisoning/diagnosis , Theophylline/poisoning , Diagnosis, Differential , Electroencephalography/drug effects , Humans , Hypokalemia/chemically induced , Hypokalemia/diagnosis , Infant , Infant, Newborn , Male , Munchausen Syndrome by Proxy/psychology , Spasms, Infantile/chemically induced , Spasms, Infantile/diagnosis , Tachycardia/chemically induced , Tachycardia/diagnosis
14.
Dtsch Med Wochenschr ; 128(13): 667-70, 2003 Mar 28.
Article in German | MEDLINE | ID: mdl-12660899

ABSTRACT

HISTORY AND CLINICAL FINDINGS: A 46-year-old woman was referred to the neurosurgery department for treatment of a macroadenoma of the pituitary. She had complained of recurrent galactorrhoea for 7 years; a hysterectomy was performed 4 years ago. The clinical investigation was unremarkable, except for a slight galactorrheoa on both sides. INVESTIGATIONS: The endocrinological work-up revealed a moderately elevated prolactin level of 3133 mU/l (147 ng/ml) with intact pituitary functions. She had no visual impairment and the MRI depicted a pituitary tumor with a maximal diameter of 1.9 cm and both intra- and suprasellar extension. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: The diagnosis of a nonfunctioning macrodenoma with functional hyperprolactinemia was made and a selective transsphenoidal adenomectomy was performed. The primary histology showed a chromophobe adenoma. However, additional immunohistological investigations revealed distinct staining for prolactin. In the meantime, because of persistent galactorrhea and elevated prolactin levels, treatment with cabergolin 0.5 mg/week was started. This stopped galactorrhea and normalized the prolactin levels. A follow-up MRI after 3 months of treatment showed a significant shrinkage of the residual tumor. CONCLUSION: This case demonstrates that the differential diagnosis of macroprolactinoma with low secretory activity and functional hyperprolactinemia is very difficult preoperatively in individual cases. This is relevant because macroprolactinomas with low secretory activity can also be treated successfully with dopamine agonists. We therefore suggest a drug treatment trial with dopamine agonists in all macroadenoms with hyperprolactinemia, particularly in those with prolactin levels above 2000 mU/l (100 ng/ml).


Subject(s)
Hyperprolactinemia/surgery , Pituitary Neoplasms/surgery , Prolactinoma/surgery , Cabergoline , Diagnosis, Differential , Ergolines/therapeutic use , Female , Follow-Up Studies , Humans , Hyperprolactinemia/drug therapy , Hyperprolactinemia/etiology , Hyperprolactinemia/pathology , Magnetic Resonance Imaging , Middle Aged , Neoplasm, Residual/drug therapy , Pituitary Gland/pathology , Pituitary Gland/surgery , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/drug therapy , Pituitary Neoplasms/pathology , Postoperative Complications/drug therapy , Prolactinoma/diagnosis , Prolactinoma/drug therapy , Prolactinoma/pathology
15.
Intensive Care Med ; 28(5): 622-8, 2002 May.
Article in English | MEDLINE | ID: mdl-12029412

ABSTRACT

OBJECTIVE: As bolus instillation of surfactant can lead to acute pulmonary, hemodynamic and cerebral side effects, we tested whether pulmonary mechanics and gas exchange differ between slow surfactant infusion and bolus administration. DESIGN AND SETTING: Prospective, randomized pilot study in a tertiary care university hospital. PATIENTS AND METHODS: Of 20 consecutive preterm infants (27-35 weeks' gestation) with severe respiratory distress syndrome) who were enrolled 14 with bovine surfactant finally were analyzed. INTERVENTIONS: Six treatments were administered by slow endotracheal surfactant infusion and eight as a bolus. Static compliance (C(stat)) and resistance (R(rs)) were measured every 3 min. RESULTS: C(stat) first decreased and then increased in both groups. In the infusion group C(stat) after 90 min was significantly higher than after bolus treatment but not after 15 or 45 min. R(rs) increased about threefold, with large fluctuations in the bolus group. After 90 min PaO(2)/FIO(2) had increased from 111+/-44 to 254+/-69 in the bolus group and from 86+/-40 to 238+/-102 in the infusion group, but early FIO(2) reduction and increase in PaO(2)/FIO(2) seemed delayed in the infusion group. CONCLUSIONS: Very slow infusion of natural surfactant is at least as effective as bolus instillation in terms of improvement in C(stat) and oxygenation after 90 min. However, until 90 min the course of C(stat) and indices of gas exchange seem superior after bolus therapy. Because R(rs) is substantially increased, long expiratory times are required to yield complete exhalation.


Subject(s)
Pulmonary Surfactants/administration & dosage , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/physiopathology , Airway Resistance/drug effects , Humans , Infant, Newborn , Infant, Premature , Instillation, Drug , Lung Compliance/drug effects , Pilot Projects , Prospective Studies , Pulmonary Gas Exchange/drug effects , Respiratory Function Tests , Respiratory Mechanics/drug effects , Statistics, Nonparametric
16.
Hum Genet ; 110(4): 327-33, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11941481

ABSTRACT

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia, an autosomal recessive inherited defect of the urea cycle. Most patients described so far have presented with the classical form of the disease. There are also patients with a mild form of citrullinemia in whom the exact molecular basis and clinical relevance are uncertain. Mutations in the human ASS gene have not yet been described in mildly affected or asymptomatic patients with citrullinemia. The genomic sequence of the human ASS gene is not precisely known making mutation analysis difficult. Here, the entire genomic DNA sequence and mutations in the ASS gene of patients with the classical and mild form of the disease are described. The mutations c.1168G-->A (G390R) and IVS13+5 G-->A and the novel mutation c.323G-->T (R108L) have been found to be associated with classical citrullinemia, whereas the novel mutations c.535T-->G (W179R), and c.1085G-->T (G362V) have been detected on alleles of the mildly affected patients. Thus, mutations found in the human ASS gene of asymptomatic children with biochemical abnormalities and in some cases enzymatically proven citrullinemia have allowed us to classify these cases as ASS-deficient patients. The elucidation of the structure of the human ASS gene has made possible the use of intronic primers for molecular analysis of patients with mild disease and the classical form, and provides another option for prenatal diagnostics in affected families with the severe type.


Subject(s)
Argininosuccinate Synthase/genetics , Citrullinemia/diagnosis , Amino Acid Sequence , Argininosuccinate Synthase/chemistry , Base Sequence , Citrullinemia/genetics , DNA Primers , DNA, Complementary , Humans , Molecular Sequence Data , Sequence Homology, Amino Acid
17.
Br J Radiol ; 75(890): 180-4, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11893644

ABSTRACT

We describe the successful treatment of a neonate with Kasabach-Merritt syndrome who received local irradiation and interferon alpha therapy after failure of corticosteroid treatment. A male neonate, born after an uneventful pregnancy, had a huge haemangioma involving the upper right cervical region as well as severe thrombocytopenia. He was treated with corticosteroids, interferon alpha and radiotherapy. Prednisolone therapy (5 mg kg(-1) day(-1)) was started at 41 days of age. No therapeutic effect was observed after 2 weeks. At this time the tumour size had increased dramatically, platelet counts had decreased progressively and coagulation abnormalities had developed. Because corticosteroid therapy had been ineffective and the child was in a life-threatening condition, irradiation was delivered up to a total dose of 9.5 Gy in five fractions. Simultaneously, prednisolone therapy was slowly decreased and interferon alpha therapy (3 million U m(-2) day(-1)) was started and continued for 6 weeks. After irradiation with 9.5 Gy and beginning interferon alpha therapy, the tumour decreased in size and coagulation parameters normalized within 4 weeks. 6 months later, platelet counts and coagulation parameters were still normal. The tumour had further decreased in size. No acute severe side effects were observed. Radiation therapy combined with interferon alpha treatment is an alternative treatment modality when high dose corticoid steroid therapy has been ineffective in patients with Kasabach-Merritt syndrome, despite the risks of growth delay and secondary malignancy. In children showing no response to corticosteroids, radiotherapy and/or interferon alpha should be considered in Kasabach-Merritt syndrome.


Subject(s)
Antineoplastic Agents/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Hemangioma/drug therapy , Hemangioma/radiotherapy , Interferon-alpha/therapeutic use , Combined Modality Therapy , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/radiotherapy , Humans , Infant, Newborn , Male , Syndrome , Thrombocytopenia/drug therapy , Thrombocytopenia/radiotherapy
18.
Am J Med Genet ; 104(1): 47-52, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11746027

ABSTRACT

We report two female patients, 11 and eight years old, with clinical findings consistent with the Floating-Harbor syndrome (FHS). The first patient presented with characteristic facial features, brachydactyly, broad thumbs, and delay of speech development, but less pronounced short stature (-2 standard deviation (SD) below mean) than previously reported. The second patient presented with short stature, characteristic facial features, brachydactyly, and delay of speech as well as mental development; she was successfully treated with growth hormone. Metacarpophalangeal pattern profiles (MCPP) were performed in both patients and compared to those of previously published patients.


Subject(s)
Abnormalities, Multiple/diagnosis , Craniofacial Abnormalities/diagnosis , Growth Disorders/drug therapy , Growth Hormone/therapeutic use , Child , Female , Growth/drug effects , Growth Disorders/diagnosis , Growth Hormone/deficiency , Humans , Speech Disorders/diagnosis , Syndrome , Treatment Outcome
19.
J Clin Invest ; 108(11): 1613-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11733556

ABSTRACT

We describe a new congenital disorder of glycosylation, CDG-If. The patient has severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, and impaired vision. CDG-If is caused by a defect in the gene MPDU1, the human homologue of hamster Lec35, and is the first disorder to affect the use, rather than the biosynthesis, of donor substrates for lipid-linked oligosaccharides. This leads to the synthesis of incomplete and poorly transferred precursor oligosaccharides lacking both mannose and glucose residues. The patient has a homozygous point mutation (221T-->C, L74S) in a semiconserved amino acid of MPDU1. Chinese hamster ovary Lec35 cells lack a functional Lec35 gene and synthesize truncated lipid-linked oligosaccharides similar to the patient's. They lack glucose and mannose residues donated by Glc-P-Dol and Man-P-Dol. Transfection with the normal human MPDU1 allele nearly completely restores normal glycosylation, whereas transfection with the patient's MPDU1 allele only weakly restores normal glycosylation. This work provides a new clinical picture for another CDG that may involve synthesis of multiple types of glycoconjugates.


Subject(s)
Congenital Disorders of Glycosylation/genetics , Mutation , Repressor Proteins/genetics , Adolescent , Amino Acid Sequence , Animals , Blood Protein Electrophoresis , CHO Cells , Cricetinae , Glycosylation , Humans , Male , Molecular Sequence Data , Oligosaccharides/analysis , Repressor Proteins/chemistry
20.
Eur J Ultrasound ; 14(2-3): 171-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11704435

ABSTRACT

We report on a preterm infant born at 30+5/7 gestational weeks who developed severe cystic cerebral lesions after exposure to a car accident one day before delivery. The literature on car accidents during pregnancy is reviewed with specific focus on neonatal neurological outcome.


Subject(s)
Accidents, Traffic , Cerebral Ventricles/injuries , Cysts/congenital , Infant, Premature, Diseases/etiology , Adult , Cerebral Ventricles/diagnostic imaging , Cysts/diagnostic imaging , Female , Humans , Infant, Newborn , Infant, Premature, Diseases/diagnostic imaging , Male , Pregnancy , Ultrasonography
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