Biomedical subjects

H Kozakewich

Publications and source records attributed to H Kozakewich.

At least 19 recordsLinked to original sources

PubMed2004

[Skeletal vascular lesions in childhood and adolescence].

Currently, vascular lesions are being classified either as tumors with inherent proliferative potential or as vascular malformations with early manifestation and growth commensurate with the growth of the child. This new classification is also applicable to skeletal vascular lesions. 30% of all skeletal vascular lesions manifest in the first two decades of life, with a preponderance of malformations. They are attributed to disturbances in the complex cascade of angiogenesis and a minority may be hereditary. Multiple cutaneous vascular malformations are associated with mutations of the TIE2- and Glomulin-Genes. Vascular malformations with involvement of multiple skeletal elements may pursue an aggressive course and manifest as massive osteolysis. Among the epithelioid vascular tumours of bone, also in young patients, benign epithelioid hemangioma can be distinguished on a morphological basis from epithelioid hemangioendothelioma as an entity with low malignant potential.

Adolescent↗

PubMed2001

Pulmonary dysplasia, Denys-Drash syndrome and Wilms tumor 1 gene mutation in twins.

While a genetic basis for the association of developmental lung and kidney defects has been suspected, the involvement of specific genes in this process is under active investigation. We report such a possible genetic linkage present in identical twins with a mutant Wilms tumor (WT1) gene. Twin girls, born at 35 weeks gestation, manifested symptoms of congenital nephrotic syndrome, renal failure, and severe respiratory abnormalities refractory to assisted ventilation. Both died at 1 month of age. Renal biopsies and autopsy kidney tissue from both the girls revealed diffuse mesangial sclerosis (DMS). Autopsy lung tissue revealed pulmonary dysplasia and hypoplasia in both twins. The WT1 gene from renal tissue in both twins was analyzed for mutations using polymerase chain reaction (PCR) amplification and the single-strand conformation polymorphism (SSCP) technique. Both twins possessed an identical missense mutation in exon 8 of the WT1 gene, resulting in replacement of arginine by histidine at amino acid 366 (arg366his) in the WTI protein. This mutation has previously been described in Denys-Drash syndrome. The WT1 gene plays a role in mesenchymal epithelial (ME) interactions in the developing urogenital system, and possibly has a similar role during lung morphogenesis. We propose that this WT1 gene mutation contributes to both DMS and developmental pulmonary abnormalities by altering ME interactions in both organs.

Female↗

PubMed2000

Clinical course of postinfectious bronchiolitis obliterans.

We performed a prospective observational study to define the clinical course and the prognostic factors of 31 patients with postinfectious bronchiolitis obliterans. All patients presented with an episode of acute bronchiolitis in the first 2 years of life, and respiratory symptoms and signs persisted since then. Other diseases which may cause chronic airflow obstruction were excluded. The patients were followed after their inclusion in the study and the clinical findings were recorded in a standardized questionnaire and form. Repeated chest radiographs and lung perfusion scans were obtained in all 31 patients and semiannual spirometry was performed in 8 older patients. Eight patients had lung biopsies. The clinical course varied in the 31 patients during a mean of 3.5 years of follow-up. The outcome of the patients included clinical remission (22.6%), persistence of respiratory symptoms and signs (67.7%), and death (9.7%). An older age at onset of illness and presence of atopy as suggested by an elevated serum IgE appeared to predispose to a poor prognosis.

Acute Disease↗

PubMed2000

Pulmonary hypertension associated with nonketotic hyperglycinaemia.

Nonketotic hyperglycinaemia (NKH) is an autosomal recessive disorder characterized by defective glycine degradation by the mitochondrial glycine cleavage system. The clinical features include lethargy, hypotonia, apnoea, seizures and severe psychomotor retardation, all attributed to the accumulation of glycine in the nervous system. Pulmonary hypertension (PHN) has not been reported in NKH. We describe four patients with NKH who had PHN in addition to the characteristic manifestations of NKH. This newly recognized association might provide additional insight into the underlying pathophysiology of PHN.

Amino Acid Metabolism, Inborn Errors↗

PubMed1998

The use of expandable metallic stents for acute tracheal stenosis in the growing lamb.

PURPOSE: Expandable metallic stents (Palmaz stents) have been used in the treatment of tracheobronchial obstruction in children and adults. The authors investigated their utility in the management of acute airway stenosis in a growing animal model. METHODS: A model for tracheal stenosis was developed in young lambs (mean age, 4 weeks; mean weight, 8.6 kg). Via an anterior tracheotomy, a circumferential mucosal injury to the trachea was produced with electrocautery in 31 lambs. In the control group (n = 10) no further intervention was used. In the treatment groups, either serial balloon dilatation of the stricture was performed (n = 6), or expandable metallic stents were inserted across the stricture (n = 15). All animals were monitored daily for signs of respiratory distress. Body weights, fluoroscopic airway measurements and rigid bronchoscopy were performed at least weekly. RESULTS: The average weekly rate of airway growth was 8.2% +/- 5.5% of the tracheal cross-sectional area (CSA). All animals displayed severe stenosis (mean, 90.2% +/- 7.5% of CSA) within 13.1 +/- 4 days after the injury. All animals in the control group had severe respiratory distress, weight loss and died within 14.6 +/- 2.8 days after injury. Serial balloon dilatation of the stricture alone failed to relieve symptoms in all six animals in this group, who died within 20 +/- 1 days after the injury, despite two to three dilatations each. With placement of expandable metallic stents, only 3 of 15 lambs died (two of pneumonia, one of iatrogenic perforation). The remaining 12 remained symptom-free and gained weight during a 2-month follow-up period. However, fluoroscopic examination showed partial collapse of the stents in all of these animals (mean, 44.7% +/- 21.6% of CSA) requiring an average of 2 +/- 0.7 bronchoscopic dilatations. Pathological evaluation showed more pronounced granulation tissue in the stented animals. CONCLUSIONS: The authors conclude that expandable metallic stents provide an effective tool in the management of acute tracheal stenosis. However, airway growth, tissue reaction, and the mechanical properties of the stent require close monitoring and stent adjustment.

Animals↗

PubMed1997

Disparities in mean age and histopathologic grade between human papillomavirus type-specific early cervical neoplasms.

Noninvasive squamous and glandular precursor lesions associated with human papillomavirus (HPV) types 16 and 18 have been reported to vary in morphology. HPV 16 is associated predominantly with high-grade squamous intraepithelial lesions (HSIL; cervical intraepithelial neoplasia (CIN 2 and 3), and HPV 18 is associated with low-grade squamous intraepithelial lesions (condyloma/CIN 1) and CIN 3/adenocarcinoma in situ (ACIS). This study explored the relationship of morphologic growth pattern in these precursor groups with age of presentation. One hundred fourteen CIN lesions (including those with ACIS), associated with HPV 16 or 18, were subdivided into well-differentiated low- and high-grade SIL (CIN 1 and 2, respectively), poorly differentiated HSIL (CIN 3) with or without ACIS. HPV was detected by polymerase chain reaction (PCR) amplification with L1 consensus or type-specific E7 primers and typed by restriction fragment length polymorphism (RFLP) analysis. Age of the patient was obtained from the pathology report. Mean age for each group was as follows: Low-risk HPVs, 25 years; HPV 18 CIN 1-2, 21.6 yrs; HPV 18 CIN 3/ACIS, 35.2 yrs; HPV 16 CIN 1,2, 25.9 yrs; and HPV 16 CIN 3, 29.8 yrs. There were significant differences in mean ages between HPV 18 CIN 1 and 2 and HPV 16 CIN 1 to 2 (P = .04), HPV 16 CIN 1-2 and CIN 3 (P = .01) and HPV 18 CIN 1 to 2 and HPV 18 CIN 3/ACIS (P = .00001). None of the cases of HPV 18-associated CIN3/ACIS was associated with a CINI lesion. The disparity in mean ages between well and poorly differentiated HPV 16/18 related that precursor lesions could reflect factors such as morphologic progression with increasing age, different rates of lesion persistence, depending on grade, or efficiency of detection between the two groups. The marked difference in mean age between HPV 18-associated CIN 1-2 and CIN 3/ACIS, combined with their lack of coexistence in the same cervix, raises alternate possibilities that specific viral or host factors may determine the morphological phenotype associated with some HPV 18 infections. In the latter, the possibility that age independently confers an increased risk for higher-grade lesions should be considered.

Adenocarcinoma↗

PubMed1996

Segmental defect of the intestinal musculature of a newborn: evidence of acquired pathogenesis.

Two cases of premature newborns with a segmental defect of the intestinal musculature are presented. The clinical diagnoses were intestinal obstruction and perforation, respectively. Emergency laparotomy was performed. In the first case, this showed a dilated loop of ileum and proximally dilated small bowel. The second case had ileal perforation with marked pneumoperitoneum. Pathological examination showed multifocal partial or complete absence of the muscularis propria, with relative preservation of the remaining components of the bowel wall in both cases. In addition, foci of recent muscular necrosis was noted in case 1, and early replacement fibrosis in case 2. These findings suggest that the muscle defect was secondary to muscle injury rather than a primary absence of muscle. The different theories of pathogenesis are discussed.

Anastomosis, Surgical↗

PubMed1996

Localization of Tc-99m MDP in neuroblastoma metastases to the liver and lung.

Localization of skeletal tracer in a neuroblastoma primary is common but localization in extraskeletal metastatic sites has not received recognition. Tc-99m MDP concentration in hepatic or pulmonary metastases was noted in three of ten patients with such metastases. Lesion size appears to be important for demonstrating these metastases with Tc-99m MDP. This was particularly true for hepatic metastases, which were identified only when they were 5 cm or greater in diameter.

Bone and Bones↗

PubMed1996

Percutaneous biopsy for prognostic testing of neuroblastoma.

PURPOSE: To determine whether percutaneous biopsy can provide the diagnostic and prognostic information necessary to treat children with advanced neuroblastoma. MATERIALS AND METHODS: From 1991 through 1995, 21 percutaneous biopsies were performed in 20 children with advanced neuroblastoma by using 15- or 16-gauge core biopsy needles. An average of six samples were obtained. Since September 1994, fresh tissue was sent to the reference laboratory, where touch preparations were prepared for N-myc evaluation. RESULTS: Histologic confirmation and prognostic information (Shimada classification) were obtained in all cases. Genetic prognostic information was obtained in 19 patients (95%), DNA index (ploidy) in 18 (90%), N-myc gene expression in 14 (70%), and cytogenetic analysis in 10 (50%). N-myc and ploidy determinations were successful in all five biopsy specimens obtained since September 1994. CONCLUSION: Percutaneous biopsy of advanced neuroblastoma is a feasible alternative to open biopsy.

Adolescent↗

PubMed1995

Hepatic venous blood and the development of pulmonary arteriovenous malformations in congenital heart disease.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are a known complication after some types of cavopulmonary anastomoses (CVPAs). Their cause is unknown, but they may be related to the absence of pulsatile flow or the presence or absence of circulating factors. These PAVMs are diffuse and are presumed to be progressive and irreversible. METHODS AND RESULTS: All patients with congenital heart disease (CHD) seen at Children's Hospital, Boston, Mass, between 1970 and 1993 were reviewed. We report on the 10 patients with CHD who were found to have developed PAVMs, as diagnosed by cardiac catheterization. Diagnoses included heterotaxy syndrome/polysplenia, with interrupted inferior vena cava and hepatic veins draining to the right atrium (n = 6); heterotaxy/asplenia (n = 1); corrected transposition with pulmonary stenosis (n = 1); and biliary atresia and associated CHD (n = 2). PAVMs were diagnosed 0.1 to 7.0 years (median, 3.5 years) after creation of a CVPA that resulted in exclusion of hepatic venous flow from one or both lungs in 8 of the 10 patients; the remaining 2 patients had normal drainage of hepatic veins to the lungs but had biliary atresia. In all, the common anatomic feature was the exclusion of normal hepatic venous return from the affected pulmonary arterial circulation. All patients with interrupted inferior vena cava, azygous continuation to the superior vena cava, and hepatic veins draining to the right atrium (polysplenia syndrome) were reviewed to determine the incidence of PAVMs in those with CVPA (ie, hepatic venous flow excluded from the pulmonary arteries) and without CVPA. Six of 28 (21%) of those with versus 1 of 56 (1.8%) of those without CVPA developed PAVMs (P = .004). The 1 patient without CVPA who had PAVMs also had biliary atresia. Among patients with CVPA, the probability of developing PAVMs was 15% and 28% at 3 and 5 years, respectively, after CVPA. The histological and angiographic appearances of PAVMs after CVPA are similar to those seen in PAVMs associated with hepatic cirrhosis. CONCLUSIONS: We postulate that PAVMs after CVPA are related to the diversion of normal hepatic venous flow from the pulmonary circulation. In this sense, these PAVMs may be analogous to those associated with liver disease, which have been found to resolve after liver transplantation. Redirection of hepatic flow to the pulmonary bed in some patients with CHD and PAVMs may lead to reversibility of the PAVMs.

Adult↗

PubMed1994

Histologic correlates of vulvar human papillomavirus infection in children and young adults.

Two clinically important issues in the treatment of vulvar wartlike lesions are the histologic criteria for the recognition of human papilloma virus (HPV)-related lesions and the exclusion of lesions derived from cutaneous rather than genital HPV types. We analyzed a series of 70 biopsies from the vulva or distal vagina of 57 children and 13 young adults for HPV nucleic acids by polymerase chain reaction (PCR) amplification and typed the isolates following isotope labeling and restriction digestion (restriction fragment length polymorphism [RFLP] analysis). Lesions were classified as condyloma, suggestive of condyloma (papillary/verrucous architecture without koilocytotic atypia), or nonspecific epithelial alterations. Three observers independently agreed on the presence of papillary/verrucous architecture and koilocytotic atypia with a high degree of concordance (kappa = 0.74 and 0.71, respectively). By RFLP analysis, 77% of the lesions diagnosed as condyloma and 68% of those diagnosed as suggestive of condyloma contained HPV nucleic acids versus 9% of the nonspecific group. The HPV types identified were HPV 6 (67%), HPV 11 (17%), HPV 16 (3%), and unknown types (14%). No cutaneous HPV types were identified. Three patients with unknown HPV types had a history of sexual abuse, implying a genital source. These findings indicate that verrucopapillary external genital lesions, as defined in this report, are likely to be associated with HPV and that the vast majority contain genital HPV types irrespective of histologic presentation.

Adult↗

PubMed1993

Effects of interleukin-3 and granulocyte-macrophage colony-stimulating factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia.

Amegakaryocytic thrombocytopenia (AMT) is a rare and often fatal disorder of infancy and childhood presenting with isolated thrombocytopenia that progresses to marrow failure. The defect in thrombopoiesis is not well understood nor is the etiology of the progressive marrow failure. No standard modality of treatment exists. Here, we evaluated the capacity of marrow cells isolated from five patients with AMT and progressive marrow failure to generate megakaryocyte progenitor cells (CFU-MK). These in vitro studies demonstrated assayable numbers of CFU-MK from all patient bone marrows that responded in vitro to the addition of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or the combination of both. These findings suggest that the defect in AMT might be partially correctable by the administration of these cytokines. A Phase I/II trial of in vivo administration of these same hematopoietins in the identical patients was conducted in which no significant toxicity was observed. IL-3 but not GM-CSF administration resulted in improved platelet counts in two patients and decreased bleeding and transfusion requirement in the remaining three. No clinical benefit was observed when GM-CSF was administered after IL-3 pretreatment. Prolonged IL-3 administration has resulted in platelet increases in an additional two patients. In vitro responsiveness of CFU-MK to either cytokine did not predict the degree of clinical response. Although the optimal dose and schedule of IL-3 either alone or in combination remains to be established, this study suggests that IL-3 may contribute to the treatment of patients with AMT.

Child, Preschool↗

PubMed1993

Wilms tumor and nephroblastomatosis: imaging characteristics at gadolinium-enhanced MR imaging.

Twelve children with Wilms tumors were prospectively evaluated with 1.5-T magnetic resonance (MR) imaging. Spin-echo images were obtained before and after administration of gadopentetate dimeglumine. Nine of the 12 children had histologically proved nephroblastomatosis or nephrogenic rests involving a total of 14 kidneys. MR imaging depicted involvement in eight of these kidneys, including five of five kidneys with lesions contralateral to the primary Wilms tumor. Overall sensitivity of detection of nephrogenic rests was 43% on nonenhanced images and 58% when gadolinium-enhanced images were added. Nephrogenic rests admixed with Wilms tumors less than 4 mm in diameter were not depicted at MR imaging. On gadolinium-enhanced T1-weighted images, Wilms tumors and hyperplastic were hypointense to normal renal tissue. On T2-weighted images, Wilms tumors and hyperplastic nephrogenic rests were iso- or slightly hyperintense to renal cortex, while sclerotic nephrogenic rests were hypointense to renal cortex. On all images, including gadolinium-enhanced T1-weighted images, the signal intensity of Wilms tumors was inhomogeneous, while the signal intensity of nephrogenic rests was homogeneous.

Child↗

PubMed1993

Prenatal detection of neuroblastoma: a ten-year experience from the Dana-Farber Cancer Institute and Children's Hospital.

OBJECTIVES: To assess the relative frequency of, the clinical and pathological correlates in, and the prognosis of the subset of infants with neuroblastoma who were identified initially by prenatal ultrasonography. DESIGN: Retrospective review of all patients with neuroblastoma evaluated between 1982 and 1992. SETTING: Large, urban, tertiary care children's hospital in Boston, Massachusetts. PATIENTS: Eleven infants with neuroblastoma initially detected with prenatal sonograms were identified. RESULTS: Nine patients had adrenal tumors; two had thoracic paraspinal tumors. Typical diagnostic evidence for neuroblastoma including a palpable abdominal mass and elevations in urinary catecholamines were not commonly seen postnatally. These patients had multiple favorable prognostic indicators including low stage of disease (10/11), favorable biological markers including cellular DNA content (5/5) and N-myc oncogene copy number (5/5), and histopathology suggestive for neuroblastoma in situ (7/11). All patients were treated by surgical resection. One patient exhibited progression of disease postoperatively, but demonstrated a complete clinical response to multiagent chemotherapy. Overall survival in our population was excellent with no deaths seen at a mean follow-up of 37 months (range 3 to 120 months). CONCLUSIONS: Patients with neuroblastoma identified by prenatal ultrasonography generally, although not exclusively, follow a clinically favorable course in which surgical resection is curative. Chemotherapy is not indicated unless substantial progression of disease occurs.

Adrenal Gland Neoplasms↗

PubMed1992

Perforation of the augmented bladder.

In 12 of 264 children treated with enterocystoplasty 15 spontaneous perforations occurred. Of the 12 children 9 had myelodysplasia. All segments of the gastrointestinal tract were used for the augmentation and most were detubularized. Surgery to increase bladder outlet resistance was done in 8 cases. At the time of each perforation 9 children had sterile cultures, however, 3 died of overwhelming sepsis. Presenting signs included abdominal pain in 8 cases, septic shock in 4 cases and shoulder pain in 4 older myelodysplastic children with diaphragmatic irritation from escaping urine. Cystography demonstrated a leak in 10 of 11 cases. Urodynamic studies revealed good compliance with low maximum filling pressure in 8 of 10 children. Hyperreflexia was noted in only 5 cases and outlet resistance greater than 85 cm. water was demonstrated in 5. Histological analysis showed changes in the bowel wall consistent with ischemia but suture granulomas were present in areas adjacent to the perforation site or thinned areas in biopsy or autopsy specimens. In addition to the theory that overdistention may cause enterocystoplasty perforation, current detubularization techniques may produce areas of relative ischemia, which become accentuated when the augmented bladder is distended beyond a reasonable volume.

Adolescent↗

PubMed1991

Osteosarcoma in young children.

The clinicopathologic features of osteosarcoma in 12 children younger than 16 years of age treated at The Children's Hospital and Dana-Farber Cancer Institute, Boston, during a 70-year time period are presented. Only one of six children treated before 1972 is a long-term survivor. Four of six children (67%) treated after 1972 are disease-free with an average follow-up of 8.8 years. The year 1972 marked the onset of use of effective chemotherapy in osteosarcoma, namely, high-dose methotrexate and leucovorin rescue. It would appear that the pathologic features and behavior of osteosarcoma in young children is similar to that of osteosarcoma in older children and adolescents. A combination of complete (wide) surgical resection or amputation and aggressive chemotherapy offers the best chance of long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Chronic recurrent multifocal osteomyelitis. Association with vertebra plana.

In seven children who had chronic recurrent multifocal osteomyelitis, the radiographic and histological findings were consistent with those of osteomyelitis, but the results of cultures were negative. We studied the clinical, radiographic, histological, and microbiological findings in these patients, who had a total of thirty-nine lesions. The lesions occurred most frequently in the spine, tibia, and femur; three patients had vertebra plana. The natural history of chronic recurrent multifocal osteomyelitis appears to be slow, spontaneous resolution of the osseous lesions without specific treatment. The diagnosis is one of exclusion. Biopsy is recommended, and results of cultures must be negative before therapy with antibiotics can be withheld.

Adolescent↗

PubMed1988

Characterization of airway mucus from a fatal case of status asthmaticus.

We used density gradient methods to analyze mucus recovered from the airways of a patient who died from status asthmaticus. At postmortem the mucus that plugged the length of the bronchial tree could only be removed by cutting with forceps. It was dispersed in cesium bromide (CsBr) and examined in the analytical ultracentrifuge. Surprisingly, no macromolecular component was seen in the buoyant density region typical of mucus glycoprotein (at 1.5 g/ml). The gelatinous material migrated to the region of lowest density, typical of lipids, and thin-layer chromatography indicated that besides neutral lipids, a variety of phospho- and glycolipids (including gangliosides) were present. The residue left after the lipid extraction contained all sugar components of mucus glycoprotein, and alkaline borohydride cleaved oligosaccharides three to 12 sugars long, indicating that the sugars were O-glycosidically linked as in mucus glycoproteins. Prior desulfation of the residue increased the number of oligosaccharides released by borohydride; analysis showed the presence in these of components (glucose, methylmannuronate) not present in epithelial glycoprotein. A trace component of high buoyant density was also present: Glucose was the predominant component in this, but glycoprotein sugars were also present. The above results suggest that in status asthmaticus plugging of the airways with mucus can occur even in the absence of typical epithelial glycoprotein and that lipids play a crucial role in such plugging.

Adolescent↗