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Fluorescence of blood-stained cornea.

Corneal blood staining represents deposition of hemoglobin and its breakdown products within the cornea. Pathologic examination of these corneas typically reveals degenerating endothelial cells and keratocytes. These degenerative changes have typically been attributed to the blunt trauma itself or to toxicity of the erythrocytic debris (a "localized hemosiderosis"). Another possible mechanism for this injury, however, is porphyrin-induced photosensitivity. Examination of frozen sections of an acutely blood-stained human cornea demonstrated fluorescence within all layers of the cornea, similar to that seen with hematoporphyrin derivative. The production of cytotoxic oxygen species within the blood-stained cornea exposed to light may contribute to endothelial and keratocyte degeneration. Limiting light exposure of blood-stained corneas or eyes with hyphemas might theoretically reduce light-induced and porphyrin-mediated toxicity.

Adult↗

A paramagnetic agent causing ochronotic arthropathy.

Magnetic resonance imaging (MRI) identified a paramagnetic substance in the hyaline cartilage of the hips and knees in a patient with ochronosis. Chemical studies characterized the paramagnetic agent as melanin. The free radicals contained in melanin were shown to initiate cytotoxicity. The loss of cartilage in ochronotic arthropathy now can be explained at the electron level using the superoxide theory of oxygen toxicity. Inappropriate metabolism of oxygen also may explain early cartilage degeneration in hemochromatosis, hemosiderosis, and Wilson's disease.

Cartilage, Articular↗

Diamond-Blackfan anemia. Natural history and sequelae of treatment.

To define further the natural history of treated Diamond-Blackfan anemia (DBA), a congenital anemia characterized by a paucity of erythroid precursors, we analyzed 76 patients diagnosed or followed at Children's Hospital, Boston, between 1931 and 1992. Although DBA is generally defined as macrocytic, we found that mean corpuscular volume in infants aged <5 months rarely exceeded the normal range and is of little diagnostic value. Macrocytosis in patients aged > or = 5 months was more striking. Nine of 16 patients who never received steroids experienced remissions, sometimes after years of transfusions. Thirty-one of 56 patients receiving corticosteroids responded. Of these 31, 13 experienced remissions, 11 remained steroid dependent and 7 later required transfusions. Most nonresponders maintained transfusion dependence. Patients frequently (64%) experienced treatment-related morbidity, most commonly hemosiderosis. The relative risk of leukemia was profoundly elevated (RR, 200; 95% CI, 54.5-512.1) and hematologic parameters at long-term follow-up were often abnormal. While potential responsiveness to steroids and relative ease of red cell transfusion make DBA one of the most treatable congenital marrow failure syndromes, both disease-related and treatment-related factors contributed to a limited prognosis (median survival, 38 years). Patients should be carefully monitored longitudinally for evidence of leukemia and adverse effects of therapy, and alternative treatment strategies should be considered on an individual basis.

Adolescent↗

Transvenous right ventricular pacing during cardiopulmonary resuscitation of pediatric patients with acute cardiomyopathy.

We describe the cardiopulmonary resuscitation efforts on five patients who presented in acute circulatory failure from myocardial dysfunction. Three patients had acute viral myocarditis, one had a carbamazepine-induced acute eosinophilic myocarditis, and one had cardiac hemosiderosis resulting in acute cardiogenic shock. All patients were continuously monitored with central venous and arterial catheters in addition to routine noninvasive monitoring. An introducer sheath, a pacemaker, and sterile pacing wires were made readily available for the patients, should the need arise to terminate resistant cardiac dysrhythmias. All patients developed cardiocirculatory arrest associated with extreme hypotension and dysrhythmias within the first 48 hours of their admission to the pediatric intensive care unit (PICU). Right ventricular pacemaker wires were inserted in all of them during cardiopulmonary resuscitation (CPR). In four patients, cardiac pacing was used, resulting in a temporary captured rhythm and restoration of their cardiac output. These patients had a second event of cardiac arrest, resulting in death, within 10 to 60 minutes. In one patient, cardiac pacing was not used, because he converted to normal sinus rhythm by electrical defibrillation within three minutes of initiating CPR. We conclude that cardiac pacing during resuscitative efforts in pediatric patients suffering from acute myocardial dysfunction may not have long-term value in and of itself; however, if temporary hemodynamic stability is achieved by this procedure, it may provide additional time needed to institute other therapeutic modalities.

Acute Disease↗

Variant of congenital dyserythropoietic anemia.

Nonspherocytic hemolytic anemia was diagnosed in a 34-year-old man with jaundice since childhood. Splenectomy at the age of 8 had no influence on the anemia. Bronze diabetes was diagnosed at age 31, presumably due to hemosiderosis and secondary hemochromatosis. Iron chelation was unsuccessful in controlling iron overload, but phlebotomies proved effective without aggravating the anemia. We believe the anemia represents a variant of congenital dyserythropoietic anemia, type I.

Adult↗

Reproductive health in patients with beta-thalassemia.

Homozygous transfusion-dependent beta-thalassemia patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Short stature, delayed sexual maturation, diabetes mellitus, hypothyroidism, hypoparathyroidism, and metabolic bone disease can and should be diagnosed as early as possible so that the intervention can be fruitful. Primary or secondary amenorrhea is due primarily to pituitary gonadotrope hemosiderosis, as attested by pathology data and the demonstration in vivo of nonstimulable follicle-stimulating hormone and luteinizing hormone release and secretion after the exogenous administration of gonadotropin-releasing hormone or its agonistic analogs. Ovulation can be achieved with the use of exogenous gonadotropins provided that the ovary has no siderosis (as seen in neglected patients) or damage induced by drugs used for bone marrow transplantation. Once pregnancy is achieved, it should be considered high risk and be dealt with or cared for by an expert team to ensure a successful outcome.

Adolescent↗

Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry.

PURPOSE: Diamond-Blackfan anemia (DBA) is a congenital pure red cell aplasia, usually presenting in infancy or early childhood. A review of the literature strongly supports a predisposition to hematopoietic malignancy. Recently, solid tumors have been reported, some attributable to hemosiderosis and/or androgen therapy. Two cases of osteogenic sarcoma have also been documented. An analysis from the Diamond-Blackfan Anemia Registry was performed to evaluate the cancer risk in patients with DBA. METHODS: The Diamond-Blackfan Anemia Registry of North America (DBAR) is a comprehensive database of patients with DBA enrolled, after informed consent, through outreach to pediatric hematologists and family groups. The patients and/or their families complete a detailed questionnaire, and a review of medical records and telephone interviews are performed to complete and clarify the information provided. RESULTS: Of the 354 patients registered in the DBAR, there were six patients meeting the accepted diagnostic criteria for DBA who were found to have malignancies. Three patients had osteogenic sarcoma diagnosed, one with myelodysplastic syndrome, one with colon carcinoma, and one with a soft tissue sarcoma. CONCLUSION: There appears to be an association of osteogenic sarcoma with DBA. A young age at presentation may be a feature of DBA-associated osteogenic sarcoma. Because of the immaturity of the database, the actuarial risk for osteogenic sarcoma and other cancers in individuals with DBA cannot be ascertained. Speculation is made regarding the nature of the molecular defect leading to the association of DBA and osteogenic sarcoma.

Adolescent↗

Transfusion practice for patients with sickle cell disease.

The practice of transfusion for patients with sickle cell disease is changing. Diminished childhood mortality is resulting in greater patient longevity and a higher prevalence of chronic systemic complications. Many of these chronic complications, as well as several acute ones, are treatable with erythrocyte transfusion. Proactive or preventive uses for transfusion are being considered for selected patients. Immunologic phenomena, hemosiderosis, and risk for transmission of infectious agents are the three most noticeable risks associated with repetitive transfusion. Evolving work with alternative oxygen carriers and surface modification of erythrocytes is also promising and relevant for patients with sickle cell disease.

Adult↗

Pediatric fiberoptic bronchoscopy: Clinical experience with 2,836 bronchoscopies.

OBJECTIVE: To report 21 yrs of experience with pediatric flexible fiberoptic bronchoscopy in infants and children, explore newer applications, delineate potential complications, and make recommendations for its future application. DESIGN: Retrospective review. SETTING: A 20-bed pediatric critical care unit in a tertiary care, university-based children's hospital. PATIENTS: A total of 2,836 pediatric and infant fiberoptic bronchoscopies, performed over a course of 21 yrs, were reviewed. Measurement and MAIN RESULTS: A total of 2,836 children (1,536 girls) were subjected to flexible fiberoptic bronchoscopy. Of those, laryngeal mask airway was incorporated in 92 procedures (3.2%) and general anesthesia was applied in 198 cases (7%). The youngest subject was a 1-wk-old, 600-g, premature infant. The procedure resulted in diagnoses that modified patient care, particularly in tracheostomized infants and those with upper airway obstruction, plastic bronchitis of acute chest syndrome, dyskinetic cilia syndrome, immunocompromised individuals, and those with unexplained chronic cough and recurrent pulmonary infiltrates. Microbiologic and cytologic data from bronchoalveolar lavage helped confirm the diagnoses of pulmonary hemosiderosis and gastroesophageal reflux and validated the presence, or lack of, bacterial or viral pathogens. A total of 21 patients (<1%) experienced life-threatening hypoxemia, prompting termination of the procedure. Laryngospasm or bronchospasm was observed in 17 individuals (<1%) undergoing bronchoalveolar lavage, and 4% of the total population experienced mild nasopharyngeal bleeding. No fatalities were encountered. CONCLUSIONS: Pediatric flexible fiberoptic bronchoscopy is a safe diagnostic and interventional tool, even in young or extremely premature infants. Although the rate of serious complications in this report is low, general anesthetic agents and incorporation of laryngeal mask airway is advocated for severe mucoid impaction, transbronchial biopsy, and chronic pulmonary infiltrates, which may necessitate extensive bronchoalveolar lavage.

Journal Article↗

Severe anemia owing to occult pulmonary hemorrhage: a diagnostic pitfall.

The purpose of this paper is to increase the awareness about pulmonary hemorrhage as a possible cause of microcytic hypochromic anemia and to delineate diagnostic difficulties and possible pitfalls. An instructive case of anemia of unclear origin referred to our institution for a hematologic workup is presented. Microcytic hypochromic anemia owing to repeated occult alveolar hemorrhages was the only clinical sign of idiopathic pulmonary hemosiderosis in this case. The laboratory finding constellation in such cases may be misleading and may lead to misinterpretation. Awareness about this condition among pediatricians and hematologists can optimize and accelerate the diagnostic process.

Anemia, Hypochromic↗

Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis: a clinicopathologic study of 35 cases.

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension, regarded by some as distinct entities. However, their presentations are similar and both are associated with poor prognoses. We therefore reviewed 38 specimens [autopsies (n=15), surgical biopsies (n=15), explants (n=7), and pneumonectomy (1 case)] from 35 patients diagnosed as either PVOD (n=30; av. age 34 y, range 4 to 68 y; 19M:11F) or PCH (n=5, av. age 42 y, ranging from 9 months to 60 years; 3M:2F) to assess their interrelationship. PCH was identified in 24 (73%) cases diagnosed as PVOD, either as perivenular foci or diffuse involvement of the pulmonary parenchyma. Other features seen in PVOD were arterial medial hypertrophy and/or intimal fibrosis (88%), hemosiderosis (79%), venulitis (12%), infarction (9%), interstitial fibrosis (sometimes as localized scars) (48%), and a mild lymphocytic infiltrate (67%). In cases diagnosed as PCH, 4 showed venous and arterial changes of PVOD. Cases with PCH also all showed a mild interstitial lymphocytic infiltrate but there was no venulitis or infarction. Capillary proliferation was particularly well demonstrated by CD34 immunostaining and predominantly involved the alveoli, but was also seen within walls of bronchi and pulmonary vessels. Our data suggest that in the majority of cases PCH represents a secondary angioproliferative process caused by postcapillary obstruction rather than a separate disease. The cause of the venous obliteration was not identified but the occasional identification of phlebitis suggests this plays a role in venous damage in some cases.

Adolescent↗

Hemispherectomy for seizures.

Hemispherectomy, or hemidecorticectomy as it is more accurately described, has been highly effective in reducing or eliminating medically intractable seizures associated with hemiplegia. Because of late onset postoperative superficial cerebral hemosiderosis and its associated neurologic deterioration, this procedure was all but abandoned for years. With improved surgical techniques and diagnostic testing, some medical centers with a special interest in epilepsy are again using hemispherectomy as a treatment for uncontrolled seizures associated with Rasmussen's encephalitis, as well as other etiologies. Specialized nursing care throughout the hospital course is essential to a positive outcome for the patient and family.

Cerebral Decortication↗

Milk-induced pulmonary disease in infants (Heiner syndrome).

Heiner syndrome (HS) is a food hypersensitivity pulmonary disease that affects primarily infants, and is mostly caused by cow's milk (CM). Only a few reports have been published, which may be due to its misdiagnosis. We review here a series of eight cases. When first diagnosed they were 4-29 months of age. They were fed CM from birth and their chronic respiratory symptoms began at age 1-9 months. The symptoms were in the form of cough in seven, wheezing in three, hemoptysis in two, nasal congestion in three, dyspnea in one, recurrent otitis media (OM) in three, recurrent fever in four, anorexia, vomiting, colic or diarrhea in five, hematochezia in one, and failure to thrive (FTT) in two. All had radiologic evidence of pulmonary infiltrates. High titers of precipitating antibodies to CM proteins were demonstrated in six of six and milk-specific immunoglobulin E (IgE) was positive in one of two. Pulmonary hemosiderosis (PH) was confirmed in one patient who showed iron-laden macrophages (ILM) in the bronchoalveolar lavage (BAL), gastric washing, and open lung biopsy. Additional findings, in a descending frequency, were eosinophilia, anemia, and elevated level of total IgM, IgE or IgA. Milk elimination resulted in remarkable improvement in symptoms within days and clearing of the pulmonary infiltrate within weeks. Parents consented to milk challenge in only three cases, all of whom developed recurrence of symptoms. After 2 yr of milk avoidance in one patient, milk challenge was tolerated for 2 months, and then the patient developed symptoms, serum milk precipitins, pulmonary infiltrate, and ILM. The HS should be suspected in young children with chronic pulmonary disease of obscure cause. The diagnosis is supported with a positive milk precipitin test and improvement on a trial of milk elimination. Severe cases may be complicated with PH, which should be suspected in the presence of anemia or hemoptysis and be confirmed with the demonstration of ILM.

Antibody Specificity↗

Histopathological investigation of DMF-induced hepatotoxicity.

N,N-Dimethylformamide (DMF) has been implicated in the production of hepatotoxicity in male and female F344 rats. Repeated administration of dosages of 0.75 and 1.0 ml/kg DMF for up to 12 weeks produced massive liver necrosis associated with decreased body weight gain. Macroscopically, areas of necrotic change were well pronounced in every hepatic lobe, being yellowish-red in coloration, irregular in shape, and varying in size, but were most striking immediately adjacent to the porta hepatis. Among the lobes, those which were relatively small were most markedly affected, and occasionally an entire lobe was involved. Light and electron microscopic studies revealed the hepatic architecture to be occupied by massive fibrosis. There were, however, sharp lines of demarcation between surviving normal and necrotic areas. Hemosiderosis involving macrophages was accompanied by proliferative bile ductules and a number of multinucleated giant cells. The distribution and quality of the hepatic lesions produced by DMF were discussed.

Administration, Oral↗

Dilated cardiomyopathy complicating a case of epidermolysis bullosa dystrophica.

A child with epidermolysis bullosa dystrophica, recessive type (EBDR) developed significant anemia at 9 years of age and was treated with long-term transfusion therapy. At age 17 he had symptoms of congestive heart failure secondary to dilated cardiomyopathy. Treatment with digoxin and vasodilators for the past year has failed to improve his cardiomyopathy significantly. Chronic iron overload and secondary hemosiderosis may have contributed to his problems, and we propose that chelation therapy be used in any child receiving long-term transfusion therapy.

Adolescent↗

Hippocampal cell loss in posttraumatic human epilepsy.

PURPOSE: We performed this study to determine whether significant head trauma in human adults can result in hippocampal cell loss, particularly in hilar (polymorph) and CA3 neurons, similar to that observed in animal models of traumatic brain injury. We examined the incidence of hippocampal pathology and its relation to temporal neocortical pathology, neuronal reorganization, and other variables. METHODS: Twenty-one of 200 sequential temporal lobectomies had only trauma as a risk factor for epilepsy. Tissue specimens from temporal neocortex and hippocampus were stained with glial fibrillary acidic protein (GFAP) and hematoxylin and eosin (H&E). Eleven hippocampal specimens had additional analysis of neuronal distributions by using cresyl violet and immunolabeling of a neuron-specific nuclear protein. RESULTS: The median age at onset of trauma was 19 years, the median time between trauma and onset of seizures was 2 years, and the median epilepsy duration was 16 years. The length of the latent period was inversely related to the age at the time of trauma (r=0.75; Spearman). The neocortex showed gliosis in all specimens, with hemosiderosis (n=8) or heterotopias (n=6) in some, a distribution differing from chance (p=0.02; Fisher). Hippocampal neuronal loss was found in 94% of specimens, and all of these had cell loss in the polymorph (hilar) region of the dentate gyrus. Hilar cell loss ranged from mild, when cell loss was confined to the hilus, to severe, when cell loss extended into CA3 and CA1. Some degree of mossy fiber sprouting was found in the dentate gyrus of all 10 specimens in which it was evaluated. Granule cell dispersion (n=4) was seen only in specimens with moderate to severe neuronal loss. CONCLUSIONS: Neocortical pathology was universally present after trauma. Neuronal loss in the hilar region was the most consistent finding in the hippocampal formation, similar to that found in the fluid-percussion model of traumatic head injury. These findings support the idea that head trauma can induce hippocampal epilepsy in humans in the absence of other known risk factors.

Adult↗

Reversal of heart failure in thalassemia major by combined chelation therapy: a case report.

In patients with thalassemia major (TM) who are non-compliant with long-term desferrioxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional hemosiderosis. Combined chelation therapy with DFO and deferiprone has maximized the efficacy of the therapy and reduced cardiological complications. The aim of this report is to present the results of this combination in a desperate case of heart failure.

Adult↗

Posttransfusion non-A, non-B hepatitis. A prospective study.

We have prospectively studied the clinical data, prognostic factors and chronic liver sequelae in 68 patients who developed posttransfusion non-A, non-B hepatitis. The mean incubation period was 5.9 weeks with a range from 2.1 to 12 weeks; 63.5% of the patients were asymptomatic and 60.6% anicteric. The chronicity rate (elevated ALT values for a period of more than 6 months) was 67.6%. The chronicity rate of symptomatic hepatitis (95.5%) was significantly higher than that of asymptomatic hepatitis (54.5%) (P less than 0.01). Monophasic hepatitis, characterized by a rapid elevation in serum ALT followed by a rapid decline with no further fluctuations, had a chronicity rate (42.5%) significantly lower than polyphasic hepatitis (86.6%) (P less than 0.05) and plateau type hepatitis (94.4%) (P less than 0.01). Results of 35 liver biopsies carried out among 46 patients with elevated ALT after 6 months were as follows: chronic active hepatitis, 15 cases; prolonged acute hepatitis, 12 cases; chronic persistent hepatitis, 6 cases; posthepatitis liver changes, 1 case; and secondary hemosiderosis, 1 case.

Acute Disease↗