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Late pathophysiologic sequelae after utilization of an intravenacaval oxygenator in experimental animals.

The intravenacaval hollow fiber oxygenator (IVOX) has been shown to be remarkably free from acute adverse effects on the venae cavae, right heart, and lungs when indwelling experimentally in sheep and in human clinical trial patients. However, all pathophysiologic assessments reported to date have been carried out during or immediately after IVOX utilization. It is recognized that IVOX indwelling in the venae cavae for up to 3 weeks could produce minor or unrecognized acute injury that could become more evident or more harmful after several weeks had elapsed following removal of the device. Therefore, this current study was designed and carried out to assess any pathophysiologic sequelae that could be recognized on follow-up examination 4 months after removal of an IVOX device that had been indwelling in the venae cavae for from 7 to 13 days. Extensive clinical and physiologic assessments of the blood, hemodynamics, and pulmonary functional status of 8 sheep were carried out 4 months after removal of IVOX devices that had been indwelling for 7 to 13 days. Each animal was then euthanized and complete necropsy examination was conducted looking especially for gross or histologic lesions in the venae cavae, access veins, right heart, and lungs. Findings indicated that all animals were normal, without clinically or pathologically significant pathophysiologic abnormalities or adverse effects from the IVOX utilization. Detailed hematologic, hemodynamic, blood chemistry, pulmonary function, and gross and histopathologic findings, presented in graphic, tabular, and photographic form, document the conclusion that utilization of an IVOX device in normal sheep for from 7 to 13 days produces no significant adverse late pathophysiologic sequelae.

Animals↗

Severe sequelae of acute dental trauma in the primary dentition--a case report.

The incidence of traumatic injuries to primary teeth is high. Previous studies report frequencies ranging from 4% to 33% of all children. The damage limitation and the prevention of sequelae are goals that shall direct the treatment for dental trauma. Inappropriate approaches to dental trauma can cause more damage than the trauma itself. This article describes the diagnosis, management and follow-up of a 5-year-old boy who presented with uncommon sequelae of an inappropriate approach following a severe luxation of the primary maxillary right central incisors 2 years ago.

Child, Preschool↗

Evaluation of mechanical ventilation in newborn infants. II. Pulmonary and neuro-developmental sequelae in relation to original diagnosis.

The incidence of bronchopulmonary dysplasia (BPD) and neuro-developmental sequelae in 135 infants surviving intermittent positive pressure ventilation (IPPV) in the newborn period were studied in relation to primary disorders requiring IPPV. The rate of BPD increased over the 6-year study period in hyaline membrane disease survivors from 14% to 28%, but decreased in infants with apnoea repetens from 38% to 13%. Immaturity seemed to be one important factor for development of BPD. The incidence of neuro-developmental sequelae in IPPV treated infants fell from 22% to 13% over the years. In infants with birth weight below 1501 g the rate of neurological handicaps was 11%.

Airway Resistance↗

Late sequelae of gonadal, mediastinal and oral teratomas in childhood.

Thirty-two patients with gonadal or non-sacrococcygeal extragonadal teratomas who underwent operation in childhood were evaluated for different late sequelae. Follow-up times ranged from 5.0 to 40 years. Physical abnormalities resulting from surgery were seen in eight patients who had had oral or mediastinal primary teratomas. Radiographs revealed multiple spina bifida occulta lesions in three patients. The males, but not the females, showed signs of gonadal dysfunction. Impaired semen quality or abnormal serum concentrations of testosterone or gonadotrophins were found in five of 10 adult men who had had testicular or mediastinal teratomas. Thus, some late sequelae may be predicted from the site of the primary teratoma, but gonadal dysfunction in males and vertebral anomalies may occur irrespective of where the teratoma is situated.

Adolescent↗

Magnetic resonance imaging in children with neonatal asphyxia: correlation with developmental sequelae.

Magnetic resonance (MR) findings and developmental sequelae were examined in 60 patients with neonatal asphyxia. Nine patients with marked destruction of the cerebrum had the severest motor and mental disability. Six had lesions of the periventricular white matter and thalamus. Seven had border zone infarction with lesions of the white matter and thalamus. Nine had lesions of the middle-lateral part of the thalamus, putamen and peri-Rolandic area. Five with lesions of the thalamus, putamen and cerebral white matter had the severest motor and mental disability. Twenty with lesions of the thalamus and/or putamen had athetosis or clumsiness. Four with lesions of the opercular region, white matter and thalamus had feeding difficulty. Some correlation between MR findings and developmental sequelae was recognized.

Adolescent↗

Thoracic sequelae after surgical closure of the patent ductus arteriosus in premature infants.

Thirty-six children (median chronological age 6 years 1 month) who had undergone surgical closure of a patent ductus arteriosus through a left posterolateral thoracotomy in the neonatal period (median gestational age 32 weeks) were investigated prospectively with respect to anatomical and functional changes of the chest. At follow-up examination, residual or recurrent patent ductus arteriosus was not observed. Three patients had chronic bronchial obstruction. Two patients showed pathological musculoskeletal thoracic sequelae that did not require any treatment at the time of follow-up; persistence of immediate postoperative left phrenic palsy (n = 1) and thoracic scoliosis (n = 1). Twenty of the 27 patients in whom chest X-ray was performed had minor radiological skeletal anomalies in the form of rib deformation or fusion related to the thoracotomy, lesions which have a potential to induce thoracic scoliosis. Left shoulder elevation at chest X-ray and isolated left arm dysfunction at clinical examination were not observed. Despite the low incidence of scoliosis and the absence of left arm dysfunction observed at mid-term follow-up in our series, the incidence of minor rib deformations with a potential to induce severe anomalies such as scoliosis should motivate late follow-up examination at adolescence to definitively assess the prevalence of thoracic sequelae after surgical closure of the patent ductus arteriosus in premature infants.

Bronchial Diseases↗

Sequelae of storage in Fabry disease--pathology and comparison with other lysosomal storage diseases.

AIM: To evaluate the sequelae of the lysosomal storage of globotriaosylceramide (Gb3) in a series of patients with Fabry disease. METHODS: Biopsy and post-mortem samples from 12 patients with Fabry disease were examined microscopically, including, in some cases, immunohistochemistry and electron microscopy. Where possible, comparisons were made with other lysosomal storage disorders. RESULTS: Storage of Gb3 in cardiocytes leads commonly to progressive hypertrophy, which is a non-specific phenomenon also observed in other lysosomal storage disorders. Capillary endothelial storage was associated with a tendency for capillary basement membrane multiplication. In the single angiokeratoma studied, the basement membrane was rudimentary. Sinusoids in the adrenal cortex and liver displayed either a slight degree of storage or were unaffected. The glomeruli of the kidney exhibited focal hyalinization starting in the mesangial region. Proximal tubular cells were essentially free of lysosomal accumulation, including protein absorption droplets, despite the presence of proteinuria. In only one case, an autopsied Fabry heterozygote, were the proximal tubular cells loaded with protein absorption droplets. The arterial wall in large muscular arteries (coronary, renal and intrarenal) displayed arteriopathy with pronounced involvement of the smooth muscle cells in the media. Arteriopathy started with storage, followed by cell degeneration and breakdown, extracellular matrix deposition and, often, calcification (confined to the muscular layer). Smooth muscle cells occasionally exhibited shrinkage-type necrosis, with dispersion of the stored lipid into the dense cytoplasmic mass. Intimal and mitral valve fibroblasts exhibited variable storage, which was associated with cell loss and necrosis. Intensive storage was found in Leydig cells and in the epididymal epithelium. CONCLUSION: These long-term sequelae of Gb3 storage are mostly irreversible. Some may interfere with enzyme replacement therapy. It is important, therefore, to consider starting enzyme replacement therapy as early as possible.

Adolescent↗

Acute encephalitis, a poliomyelitis-like syndrome and neurological sequelae in a hamster model for flavivirus infections.

Infection of hamsters with the murine flavivirus Modoc results in (meningo)encephalitis, which is, during the acute phase, frequently associated with flaccid paralysis, as also observed in patients with West Nile virus encephalitis. Twenty percent of the hamsters that recover from the acute encephalitis develop life-long neurological sequelae, reminiscent of those observed, for example, in survivors of Japanese encephalitis. Magnetic resonance imaging and histology revealed severe lesions predominantly located in the olfactory-limbic system, both in hamsters with acute encephalitis as in survivors. Prominent pathology was also detected in the spinal cord of hamsters with paralysis. Modoc virus infections in hamsters provide a unique model for the study of encephalitis, a poliomyelitis-like syndrome and neurological sequelae following flavivirus infection.

Animals↗

Mild head injury: neuropathology, sequelae, measurement and recovery.

Head injuries are common in industrialized countries and the majority of them are defined as 'minor' or 'mild' injuries (MHI). These terms, however, can be misleading because the sequelae that often follow such injuries can cause significant detriment to psychosocial and interpersonal functioning Clinical psychologists in most areas of specialism are likely to encounter MHI because of their high frequency and the types of problems they can cause. An overview of the body of knowledge on this subject is therefore of some importance. This paper reviews the literature concerning the neuropathology, measurement, sequelae and recovery of MHI. The following subjects are addressed: (i) the relationship between the neuropathology of severe head injury and the neuropathology of MHI; (ii) the limitations of traditional measures of head injury severity (e.g. post-traumatic amnesia) when applied to MHI; (iii) factors relevant to the recovery of post-concussion symptoms following MHI; and (iv) intervention and treatment following MHI.

Brain↗

Intellectual, educational, and behavioural sequelae after cranial irradiation and chemotherapy.

Cognitive and educational sequelae are inconsistently reported in children treated with cranial irradiation for acute lymphoblastic leukaemia. This study investigated differences in these skills after cranial irradiation, controlling the effects of chemotherapy and psychosocial factors. Three groups were evaluated: 100 children diagnosed with acute lymphoblastic leukaemia and treated with cranial irradiation and chemotherapy; 50 children diagnosed with acute lymphoblastic leukaemia or other cancers and treated with chemotherapy alone; and a healthy control group of 100 children. Children in the clinical groups stopped treatment at least two years before evaluation and had no history of relapse. Children were aged between 7 and 16 at the time of assessment. Evaluation included cognitive, educational, and behavioural measures. Analyses found that children receiving cranial irradiation and chemotherapy performed more poorly than non-irradiated groups on intellectual and educational tests, with verbal and attentional deficits most pronounced. Children receiving chemotherapy alone performed similarly to controls, suggesting such treatment is not associated with adverse neurobehavioural sequelae.

Adolescent↗

Regressed retinopathy of prematurity and its sequelae in children aged 5-10 years.

Regressed retinopathy of prematurity (ROP) and its sequelae were studied in children born prematurely (less than 1501 g birth weight and/or less than 33 weeks gestational age) in Stockholm county during 1976-81. Through various searches of the records at the different eye departments and other sources in Stockholm county we found that 134 out of a total of 528 premature babies (25.4%) had needed ophthalmic care for different reasons. They were re-examined and reliable information on the fundus could be obtained for 105 of them. The frequency of regressed ROP was 45.5%. Severe forms with vitreoretinal scarring and retinal traction were seen in 9.7% of cases and moderate forms with pigmentary changes and/or vitreoretinal interphase changes in 35.8%. The sequelae of regressed ROP were mainly reduction of visual acuity and myopia. Children with a birth weight below 1000 g and a gestational age less than 30 weeks presented the highest rate of regressed ROP (68.5% and 61.9%) and ocular abnormalities.

Blindness↗

Sequelae after modified Fontan operation: postoperative haemodynamic data and organ function.

OBJECTIVE: To investigate the specific sequelae of the Fontan operation, and particularly the potential sequelae of chronically elevated systemic venous pressure. DESIGN: A retrospective analysis of clinical and haemodynamic data and evaluation of organ function in 80 surviving patients undergoing modified Fontan operation for various forms of underlying functionally univentricular hearts. PATIENTS: 65 patients (81%) who had undergone a total cavopulmonary anastomosis and 15 an atriopulmonary anastomosis. Follow up ranged from 12 to 106 months (mean 54 (SD 23) months). RESULTS: 62 patients underwent postoperative cardiac catheterisation (mean systemic venous pressure 10.5 (2.5) mm Hg and cardiac index 3.1 (0.7) l/min/m2). Older age at operation was significantly correlated with both higher systemic venous pressure and lower cardiac index. Atrial arrhythmia was documented on Holter electrocardiogram in 17%. Protein losing enteropathy (with abnormal alpha 1-antitrypsin clearance) was found in 2/80 patients (2.5%). Ten patients had hypoproteinaemia, with a significantly higher incidence in patients after total cavopulmonary anastomosis and young age at operation. Liver function tests reflecting liver synthesis and metabolism were normal in all, whereas mild cholestasis was found in nearly 30%-predominantly in patients with a cardiac index of < 3 l/min/m2 (P = 0.045). Five patients (6.2%) developed atrial thrombosis. Coagulation factor analysis in 44 patients showed protein C deficiency in 11 (25%); laboratory signs of activation of the coagulation system were found in four of these (9%). None of the abnormal laboratory indices was significantly related to underlying cardiac malformation, postoperative systemic venous pressure, or follow up interval. CONCLUSIONS: A high proportion of clinically asymptomatic patients had abnormal laboratory findings on mid-term follow up. Detailed evaluation of organ function is necessary to detect the need for further diagnostic procedures before clinical symptoms develop.

Adolescent↗

Sleep disorders are long-term sequelae of both bacterial and viral meningitis.

BACKGROUND: Many bacterial meningitis patients experience neurological or neuropsychological sequelae, predominantly deficits in short-term memory, learning, and attention. Neuropsychological symptoms after viral meningitis are observed less frequently. Sleep disturbance has been reported after both viral and bacterial meningitis. OBJECTIVES: To examine systematically the frequency and extent of sleep disturbance in meningitis patients. METHODS: Eighty six viral or bacterial meningitis (onset of acute disease at least 1 year previously) patients were examined using two standardised questionnaires (Schlaffragebogen B and the Pittsburgh Sleep Quality Index, PSQI) in conjunction with a standardised neurological examination, and compared to a control group of 42 healthy age-matched volunteers. RESULTS: Patients after both viral and bacterial meningitis described their sleep as reduced in quality and less restful than that of healthy control subjects; both patient groups had a pathological mean PSQI total score. Impaired sleep scores after meningitis were not correlated to either the Glasgow Coma Scale or the Glasgow Outcome Scale. Moreover, no relationship between residual neurological dysfunction or depressivity and sleep quality was observed. CONCLUSIONS: Impaired sleep is a long-term consequence of meningitis. Additional, so far undetermined, factors other than the severity of concomitant neurological deficits are responsible for the development of this sequela.

Acute Disease↗

Neuropsychiatric sequelae one year after a minor head injury.

OBJECTIVE: To assess neuropsychiatric sequelae 1 year after minor head injury in a cross sectional study using home interviews with patients and their relatives at 1 year after head injury. METHODS: The study cohort included 148 adults who were admitted to hospital after a minor head injury between 1 July 1994 and 30 June 1995 and showed clinical or radiological evidence of brain injury. Main outcome measures used in the study were the Glasgow outcome scale, Edinburgh rehabilitation status scale, Barthel index, clinical interview schedule-revised, mini mental state examination, and assessment of symptoms of postconcussional syndrome. RESULTS: At one year follow up, four (2.9%) patients had a severe disability, 35 (25.5%) had a moderate disability, and 95 (69.3%) had no disability according to the Glasgow outcome scale. A slightly higher proportion (33.3%, n=45) showed disability according to the Edinburgh rehabilitation status scale. Thirty one patients (23.1%) scored <24 in the mini mental state examination. These were mostly patients over the age of 65. Twenty three patients (17.2%) were diagnosed as psychiatric cases according to the clinical interview schedule-revised scale. Seventy four (55.2%) patients showed one of the symptoms of postconcussional syndrome. The most commonly shown neurobehavioural problems were irritability (30%), sleep disturbance (29%), and impatience (27%). CONCLUSION: One year after a minor head injury, a substantial proportion of patients showed neuropsychiatric sequelae.

Adolescent↗

Evidence for the role of demyelination, HLA-DR alleles, and cytokines in the pathogenesis of parvovirus B19 meningoencephalitis and its sequelae.

OBJECTIVE: To review the clinical and pathological features of parvovirus B19 meningoencephalitis and its sequelae in 12 previously published cases, and to perform additional tests to determine the pathogenesis of the disease. METHODS: Cases were reviewed and available serum and cerebrospinal fluid (CSF) tested for antiganglioside antibodies and a range of cytokines. In situ hybridisation for parvovirus B19 DNA was performed on postmortem brain tissue in two cases. HLA-DRB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: Cerebellar involvement was suggested either clinically or pathologically in four cases. In the two cases with postmortem histology, there was marked atrophy of the molecular and granular layers of the cerebellum with focal loss of Purkinje cells. Brain scanning by MRI or CT was done in six cases during the acute phase. Three were abnormal with evidence of demyelination. Three had markedly enlarged ventricles, in two of which there was high signal intensity from the white matter on both T1 and T2 weighted images. The three cases with abnormal brain scans had long term neurological sequelae (mental retardation, personality change, altered affect). In situ hybridisation on available postmortem brain tissue was negative in the two cases tested. All cases in which HLA-DR alleles were determined carried at least one of the following alleles: HLA-DRB1*01, *04, *07, *09, *15, *16. Available serum and CSF was tested for antiganglioside antibodies (all negative) and for a panel of cytokines, which had a similar profile in both serum (n = 5) and CSF (n = 1) during the acute phase. Cytokines that were consistently detectable were IL-6 (mean 726.20 pg/ml), TNFalpha (50.64 pg/ml), IFNgamma (39.64 pg/ml), GM-CSF (216.12 pg/ml), and MCP-1 (154.43 pg/ml); IL-1beta, IL-5, and IL-13 were undetectable. CONCLUSIONS: HLA-DR associations, an increased cytokine response, and benefit from immunomodulatory treatment (in one case) support a role for the immune response in the pathogenesis of parvovirus B19 meningoencephalitis.

Adolescent↗

Late pulmonary sequelae after childhood bone marrow transplantation.

BACKGROUND: Respiratory function in transplanted children is important because of the long life expectancy of bone marrow transplant recipients, particularly children. Attention is now being focused on the late sequelae of treatment on organ system function. A few papers have been published but available data are somewhat conflicting. METHODS: A cross sectional study aimed at evaluating the late effects of transplantation on lung function was performed in a group of 52 young patients who were given autologous or allogeneic bone marrow transplants during childhood for haematological malignancies. RESULTS: No patients reported chronic respiratory symptoms. The distribution of respiratory function patterns showed that only 62% of patients had respiratory function within the normal limits; 23% had a restrictive pattern and 15% had isolated transfer factor impairment. The percentage of patients with lung function abnormalities was higher in those who (1) received a bone marrow transplant after two or three complete remissions compared with those who were transplanted immediately after the first remission (54% vs 21%; p < 0.02), (2) underwent allogeneic bone marrow transplantation rather than an autologous transplantation (45% vs 26%; p = 0.06), and (3) had a pulmonary infection compared with those without (56% vs 26%; p = 0.07). CONCLUSIONS: In spite of the absence of chronic respiratory symptoms there is a high prevalence of children with late pulmonary sequelae after bone marrow transplantation. Regular testing is recommended after transplantation, in particular in subjects at higher risk of lung injuries, such as those receiving transplants after more than one remission, those receiving allogeneic transplants, and those having suffered from pulmonary infections. When lung function abnormalities become apparent, long term follow up is necessary to see whether they become clinically relevant. All patients should remain non-smokers after transplantation and should have active early and aggressive treatment for respiratory illnesses.

Adolescent↗

External Qi therapy to treat symptoms of Agent Orange Sequelae in Korean combat veterans of the Vietnam War.

We investigated the efficacy of Qi therapy as a non-pharmacological treatment for various symptoms presented by Korean combat veterans of the Vietnam War with Agent Orange Sequelae. Nine subjects volunteered to receive 30 minutes of Qi therapy, twice per day for 7 days. There was marked improvement in 89% of the patients with impaired physical activity, 86% of those with psychological disorder, 78% of those with heavy drug use, and 67% of those with fatigue, indigestion and high blood glucose levels. This data suggests that Qi therapy combined with conventional treatment has positive effects in reducing and managing the pain, psychosomatic disorders, and substance abuse in patients with Agent Orange Sequelae. We cannot completely discount the possible influence of the placebo effect, and more objective, clinical measures are needed to study the long-term effects of Qi therapy.

2,4,5-Trichlorophenoxyacetic Acid↗

Thoracic sequelae and complications of tuberculosis.

Pulmonary tuberculosis is caused by Mycobacterium tuberculosis when droplet nuclei laden with bacilli are inhaled. In accordance with the virulence of the organism and the defenses of the host, tuberculosis can occur in the lungs and in extrapulmonary organs. A variety of sequelae and complications can occur in the pulmonary and extrapulmonary portions of the thorax in treated or untreated patients. These can be categorized as follows: (a) parenchymal lesions, which include tuberculoma, thin-walled cavity, cicatrization, end-stage lung destruction, aspergilloma, and bronchogenic carcinoma; (b) airway lesions, which include bronchiectasis, tracheobronchial stenosis, and broncholithiasis; (c) vascular lesions, which include pulmonary or bronchial arteritis and thrombosis, bronchial artery dilatation, and Rasmussen aneurysm; (d) mediastinal lesions, which include lymph node calcification and extranodal extension, esophagomediastinal or esophagobronchial fistula, constrictive pericarditis, and fibrosing mediastinitis; (e) pleural lesions, which include chronic empyema, fibrothorax, bronchopleural fistula, and pneumothorax; and (f) chest wall lesions, which include rib tuberculosis, tuberculous spondylitis, and malignancy associated with chronic empyema. These varieties of radiologic manifestations can mimic other disease entities. Therefore, recognition and understanding of the radiologic manifestations of the thoracic sequelae and complications of tuberculosis are important to facilitate diagnosis.

Diagnosis, Differential↗