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Biomedical subjects

C T Holbrook

Publications and source records attributed to C T Holbrook.

At least 37 records · Page 2Linked to original sources
PubMed1991

Fine-needle aspiration cytology of Langerhans' cell histiocytosis (eosinophilic granuloma) of bone in children.

Fine-needle aspiration (FNA) cytology of three cases of Langerhans' cell histiocytosis (eosinophilic granuloma [EG]) of bone in children (mean age--8.3 yr; range 5-11 yr) is presented. Two patients presented with vertebral lesions and the third had a femoral mass. Cytomorphologic features of EG were seen in all cases including Langerhans' cell histiocytes having oval to reniform shape nuclei with nuclear grooving and abundant pale cytoplasm. The background showed a polymorphic population of cells including neutrophils, lymphocytes, foamy histiocytes, and osteoclasts. Moderate numbers of eosinophils were seen in two cases, while eosinophils were sparse in the third case. Ancillary immunocytochemical (ICC) studies performed on the aspirated material demonstrated positive staining for S-100 protein (all three cases) and T-6 antigen (one case). Ultrastructural examination (EM) performed in one case demonstrated characteristic Birbeck granules in the histiocytes. A specific cytologic diagnosis was made in all cases, enabling proper chemotherapy in one case, surgical excision in another and spontaneous resolution in the third case. Our experience demonstrates that FNA cytology can make a definitive diagnosis of EG, especially when coupled with ancillary studies such as ICC and EM on the aspirated material.

Biopsy, Needle↗
PubMed1991

Pediatric fine-needle aspiration biopsy.

A total of 135 fine-needle aspiration (FNA) biopsies from varying sites were performed in 123 children (mean, 10.5 years; range, one day to 18 years) over a five-year period. One hundred thirty (96.3%) biopsy specimens were satisfactory for evaluation. Seventy-nine cases were nonneoplastic (60.8%); among these cases, a specific diagnosis of infectious disease was made in 17 (13.1%). A diagnosis of neoplastic disease was made in 50 (38.5%) cases, of which 14 (10.8%) were benign, 28 (21.5%) were malignant, and 8 (6.2%) were neoplasms of uncertain biologic potential. The sensitivity of pediatric FNA biopsies was 90.6%, specificity 100%, positive predictive value 100%, negative predictive value 94.7%, and efficiency of the test 96.5%. There were no false-positive diagnoses and there were four false-negative diagnoses, three of which involved aspirates of the central nervous system (CNS). Ancillary studies, including immunocytochemistry (20 cases), electron microscopic examination (18 cases), microbiologic culture (8 cases), cytogenetic studies (7 cases), and flow cytometry (3 cases), were performed on the aspirated material, enabling a more specific diagnosis or supplying additional information in many cases. Definitive diagnosis by FNA biopsy enabled radiation therapy and/or chemotherapy to be administered for unresectable malignant neoplasms, provided material for culture of infectious lesions, identified benign lesions not needing surgery, and aided the surgeon in planning the extent of surgery in resectable malignant neoplasms. These results support the greater use of FNA biopsy in the pediatric population.

Abdominal Neoplasms↗
PubMed1990

Biochemical modulation of 5-fluoropyrimidine toxicity by dehydroepiandrosterone in human colonic adenocarcinoma cells.

Exposure to dehydroepiandrosterone caused a concentration-dependent accumulation of HT-29 human colonic adenocarcinoma cells in S-phase and sensitization toward the cytotoxic effects of fluorouracil deoxyriboside but not 5-fluorouracil. These effects were synergistic at all tested concentrations of dehydroepiandrosterone (25-100 microM) and fluorouracil deoxyriboside (0.1-10 microM). Sterilization of cultures occurred at a fluorouracil deoxyriboside concentration of 1.0 microM in the presence of 50 microM dehydroepiandrosterone, while sterilization in the absence of dehydroepiandrosterone required nearly a 10-fold higher concentration of drug. Even in HT-29 cells selected for the ability to grow in 50 microM dehydroepiandrosterone, a synergistic response with fluorouracil deoxyriboside was observed. Double label experiments to examine the relative rates of incorporation of [14C]thymidine and [3H]uracil into DNA thymidine indicated that dehydroepiandrosterone exposure preferentially enhanced the de novo pathway for thymidylate synthesis, suggesting that this shift may have contributed to the observed synergism with fluorouracil deoxyriboside. Compared to controls, however, the salvage pathway for thymidylate biosynthesis was also stimulated following exposure to dehydroepiandrosterone. These results and the non-toxic nature of this naturally occurring steroid suggest that dehydroepiandrosterone may be useful as a biochemical modulator of fluorouracil deoxyriboside and, perhaps, other nucleoside analogs in cancer treatment.

Adenocarcinoma↗
PubMed1990

Patient-controlled analgesia pain management for children with sickle cell disease.

Painful episodes account for approximately 60% of all hospitalizations of children and adults with sickle cell disease. Limited information is available on managing pain in these individuals. Increasing attention is being focused on new ways to promote pain control. A new, safe, and effective way to achieve pain relief and control is through patient-controlled analgesia (PCA). This report describes our experiences using PCA in children with sickle cell disease. Over an 18-month period, 61 children considered to have severe or intolerable pain (unassociated with infection or organ-related disease) were treated with PCA. The records of 10 children selected randomly from the 61 were examined and compared with those of 10 children also randomly selected who had been treated using a conventional, fixed-schedule approach. Time in the hospital, time until tapering of narcotic, time until pain relief, and duration of parenteral narcotic therapy were similar between the two groups. Total dose of intravenous narcotic therapy (meperidine equivalent in mg/kg) was greater in the PCA group. Five of 10 children using PCA, however, experienced relief within 6 hours compared with 1 of 10 children in the non-PCA group (P = .052). Patients, families, and hospital staff expressed satisfaction and preferred PCA to conventional management when offered a choice.

Adolescent↗
PubMed1988

Clinical utility of fine needle aspiration in the diagnosis and management of neuroblastoma.

Eleven fine needle aspiration (FNA) biopsies were performed in five children with neuroblastoma, including one patient with peripheral neuroectodermal tumor of the thoracopulmonary region (Askin tumor). Cytologic features in conjunction with immunocytochemistry and electron microscopy on the aspirated material enabled us to make a primary diagnosis in four of the five patients and diagnose local recurrence and metastatic disease in three patients. There were no false-positive or false-negative cytologic diagnoses; therefore, diagnostic accuracy was 100%. FNA is an extremely useful technique for the primary diagnosis and management of neuroblastoma and excludes other small cell malignancies of children. The results of this study and literature review demonstrate that FNA cytology coupled with ancillary techniques of immunocytochemistry and electron microscopy is a rapid, safe, minimally invasive procedure which can aid in the diagnosis and management of patients with neuroblastoma without resorting to more aggressive diagnostic procedures in selective cases.

Biopsy, Needle↗
PubMed1988

Thoracic neuroblastoma presenting as a cystic hygroma.

A case of thoracic neuroblastoma with extension into the supraclavicular fossa is described. By physical examination and ultrasound the patient was thought to have a cystic hygroma with mediastinal extension. A 'cystic' neck mass may be the initial presentation of a mediastinal neuroblastoma.

Diagnosis, Differential↗
PubMed1986

Chronic renal failure presenting as proximal muscle weakness in a child.

A 13-year old boy presented with a three-year history of slowly progressive proximal muscle weakness, particularly involving the lower extremities. Chronic renal failure was uncovered in the course of his evaluation. Urologic investigation showed small and poorly functioning kidneys with a BUN of 118 mg/dL and a creatinine of 10.7 mg/dL. There were no anomalies of the proximal or distal collecting systems or history suggestive of recurrent urinary tract infection. The neurologic examination revealed proximal muscle weakness primarily of the lower extremities and especially of the proximal musculature of the pelvic girdle. Nerve conduction studies were normal. The electromyogram (EMG) showed high-voltage polyphasic potentials consistent with neurogenic muscle disease. A biopsy of the right quadriceps muscle demonstrated type II muscle fiber atrophy with histochemical staining. The patient's clinical findings, EMG studies, and muscle biopsy were not specific for either neurogenic or myopathic disease. Following a period of home peritoneal dialysis and renal transplantation, there was significant clinical improvement of the muscle weakness.

Adolescent↗
PubMed1983

Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster.

We describe a new type of gamma delta beta-thalassemia in four generations of a family of Scotch-Irish descent. The proposita presented with hemolytic disease of the newborn, which was characterized by a microcytic anemia. Initial restriction endonuclease analysis of the DNA showed no grossly abnormal patterns, but studies of polymorphic restriction sites and gene dosage revealed an extensive deletion that removed all the beta- and beta-like globin genes from the affected chromosome. In situ hybridization of chromosome preparations with radioactive beta-globin gene probes showed that only one 11p homolog contained the beta-globin gene cluster in the affected family members.

Adult↗
PubMed1983

Pyruvate kinase isozyme (PK-Greenville) with defective allosteric activation by fructose-1,6-diphosphate: the role of F-1,6-P modulation in normal erythrocyte metabolism.

A child with chronic hemolytic anemia since birth was found to have erythrocyte pyruvate kinase (PK) in a highly unusual form relative to other mutant isozymes when characterized by International Committee for Standardization in Hematology criteria. Most properties of the partially purified isozyme (designated PK-Greenville) were altered minimally, if at all, except for nearly total insensitivity to allosteric activation by fructose-1,6-diphosphate (F-1,6-P). One parent appeared to be heterozygous for a null gene and the other for an allele governing production of the mutant isozyme. Apparent restriction of the molecular defect to ineffective activation kinetics suggests that the F-1,6-P binding site on erythrocyte PK is functionally as well as physically allosteric. The magnitude of the metabolic block at the PK step and the clinical severity indicate that allosteric modulation by F-1,6-P is a crucial property of PK in normal erythrocyte metabolism.

Adenosine Diphosphate↗
PubMed1980

Vasoactive intestinal peptide secreting tumors of childhood.

A 2-year-old boy with failure to thrive, watery diarrhea, abdominal distention, hypokalemia, metabolic acidosis, and episodes of hypertension and sweating was found to have a calcified right lower quadrant mass. Blood levels of vasoactive intestinal peptide (VIP) and norepinephrine (NE) were elevated. Presurgical management with phenoxybenzamine hydrochloride and metyrosine was associated with an absence of expected postoperative hypotension, and resection of a benign ganglioneuroma resulted in prompt relief of all symptoms and return to normal of VIP and NE levels. Evidence supports the theory that VIP is the substance responsible for the diarrhea that accompanies some neural crest tumors.

Abdominal Neoplasms↗
PubMed1980

Dysgranulopoietic neutropenia and abnormal monocytes in childhood vitamin B12 deficiency.

Neutropenia and/or leukopenia (associated with elevated serum lysozyme levels) in three children with vitamin B12 deficiency were evaluated using soft agar culture and ultrastructural and cytochemical techniques. In two patients a marked increase in peripheral myeloid colony forming cells (CFC) was observed; whereas a marginal increase in CFC was present in the third, less symptomatic, patient. Marrow CFC was normal or slightly increased. Serum colony stimulating activity (CSA) was normal but elaboration of CSA by white blood cells was low. Normal maturation of the progenitors was present in vitro and serum inhibitors of myelopoiesis were absent. Megaloblastic neutrophils and monocytes with nuclear-cytoplasmic asynchrony were observed ultrastructurally in directly sampled marrow specimens. These cells contained autophagic and/or heterophagic vacuoles and an increase in cytoplasmic granules. Both monocytes and neutrophils also contained enlarged-disrupted centrioles. Many marrow macrophages contained phagocytic vacuoles, which enclosed disrupted neutrophils and cellular debris.

Adolescent↗
PubMed1980

Successful chemotherapy for childhood metastatic embryonal cell carcinoma of the testicle: a preliminary report.

A child with widespread metastases successfully treated with chemotherapy alone is described. One course of combination chemotherapy using cis-platinum, vinblastine, and bleomycin produced disappearance of multiple pulmonary metastatic lesions. Four courses of therapy produced shrinkage and tumor sterilization of an abdominal mass. Twenty-six months after initiation of chemotherapy the patient is well, off of all therapy for fourteen months, and free of disease or drug related complication with normal creatinine clearance and alphafetoprotein determinations. The published adult experience demonstrates that this therapy is extremely effective for the treatment of metastatic embryonal cell carcinoma of the testis in young adults, and our case report extends this favorable experience into childhood. Toxicity is substantial, but justifiable considering the poor outlook associated with widespread metastatic disease. Collectively, the reviewed data suggest that further trials of this type of therapy are indicated in children.

Abdominal Neoplasms↗
PubMed1979

Bilateral Wilms tumor presenting with acute renal failure and clinical findings mimicking cardiac failure.

A six-year-old girl presented with clinical signs and symptoms of right-sided heart failure. Cardiac catheterization demonstrated filling defects in both pulmonary arteries felt to represent metastatic lesions or thromboemboli. Intravenous pyelogram revealed bilateral renal masses and intrarenal obstruction. Acute renal failure was unresponsive to standard therapy. An open renal biopsy revealed Wilms tumor with favorable histology. Aggressive chemotherapy and irradiation were undertaken and renal function returned. This case adds to the heterogeneity of presentations described for Wilms tumor, and review of the literature reveals no other cases with similar presenting signs.

Acute Kidney Injury↗
PubMedDate not supplied

Influence of penicillin prophylaxis on antimicrobial resistance in nasopharyngeal S. pneumoniae among children with sickle cell anemia. The Ancillary Nasopharyngeal Culture Study of Prophylactic Penicillin Study II.

PURPOSE: To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia. METHODS: Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents. RESULTS: Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant. CONCLUSIONS: The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday.

Anemia, Sickle Cell↗
PubMedDate not supplied

Fine needle aspiration cytology of primitive neuroectodermal tumors. A report of these cases.

Primitive neuroectodermal tumor (PNET) is a small round cell malignancy arising in soft tissue and bone, predominantly in older children and adolescents. We report the cytomorphologic features and findings of ancillary studies of eight fine needle aspiration (FNA) biopsies from three patients (7-year-old male, 12-year-old female, 9-year-old female). Two of the biopsies suggested the initial diagnosis of PNET of the chest wall, while the remaining six documented recurrent or metastatic disease. In one of these cases the primary diagnosis made by FNA biopsy enabled the pediatric oncologists to give specific therapy for the unresectable tumor and achieve remission. Local recurrences included the chest wall (two cases), pleura (one case) and pericardium (one case), while metastatic disease involved the supraclavicular lymph node and breast. All the cases consisted of small malignant cells with a high nuclear/cytoplasmic ratio and hyperchromatic nuclei without prominent nucleoli. Homer Wright rosettes were seen in only two of the aspirates, and neuropil and ganglion cells were not present. Ancillary studies, including electron microscopy (two cases), immunocytochemistry (four aspirates from two cases) and cytogenetics (11/22 translocation, one case) performed on the aspirated material were aids in making a specific diagnosis and excluded other small round cell tumors of childhood, such as malignant lymphoma, rhabdomyosarcoma and Ewing's sarcoma. The differential diagnosis between PNET and neuroblastoma can be difficult on the basis of an FNA biopsy alone, although light microscopic morphologic differences exist. Clinical features (e.g., age, primary site, metastatic patterns), catecholamine levels, electron microscopy and cytogenetics are necessary in establishing the correct diagnosis.

Biopsy, Needle↗
PubMedDate not supplied

Chemotherapy of murine colorectal carcinoma with cisplatin and cisplatin plus 3'-deoxy-3'-azidothymidine.

In light of the discouraging results obtained with conventional chemotherapy of human colon cancer using 5-fluorouracil, we examined the effects of cis-diamminedichloroplatinum (cisplatin) alone and combined with 3'-deoxy-3'-azidothymidine (AZT) on chemotherapy of colorectal adenocarcinomas induced by dimethyldrazine in CD-1 mice. Thirteen weeks after a 20 week tumor induction period (15 mg/kg dimethylhydrazine weekly) groups of 19 mice were given either no therapy, or weekly cisplatin (6 mg/kg for 4 wks), AZT (400 mg/kg, wks 3 and 4), or cisplatin and AZT. Animals were autospied at death or after euthanasia on day 99 post initiation of therapy, their colons excised, fixed in buffered formalin and the number and volume of tumors measured. Cisplatin alone or with AZT decreased tumor size by 47-52%, and enhanced survival, leaving 55% of the mice alive at day 99 compared to 18% in controls. These therapeutic effects were amplified when animals were given chemotherapy during recovery from the effects of short-term dietary provision of the anti-carcinogenic steroid, dehydroepiandrosterone (DHEA). Our results suggest cisplatin is an effective chemotherapeutic agent against colon cancer in this murine model, and warrant further studies of its interaction with AZT and DHEA in enhancing this effect.

Animals↗
PubMedDate not supplied

Fine needle aspiration cytology of pancreatoblastoma with immunocytochemical and ultrastructural studies.

The cytologic features of a pancreatoblastoma (infantile adenocarcinoma), a rare pancreatic neoplasm of childhood, are described. Fine needle aspiration (FNA) under ultrasound guidance produced a hypercellular specimen consisting of numerous oval-to-cuboidal cells that had a moderate amount of granular cytoplasm. Spindle-shaped, elongated and triangular-shaped epithelial cells were also seen, along with smaller cells that had a higher nuclear/cytoplasmic ratio and a denser cytoplasm. In addition, there were abundant fragments of stroma present, including some surrounded by epithelial cells. Immunoperoxidase studies performed on the aspirated material revealed positive staining of the epithelial cells for cytokeratin (AE1/3), including high and low molecular weight cytokeratin, carcinoembryonic antigen, neuron-specific enolase and alpha-1-antitrypsin. Ultrastructural examination demonstrated epithelial cells containing either large electron-dense zymogen granules in the range of 400 nm to 600 nm or small dense neuroendocrine granules measuring from 100 nm to 200 nm. This finding, in concert with the immunocytochemical studies, supported a "blastemal" cell origin with bidirectional differentiation for this unusual pancreatic neoplasm and enabled a specific preoperative diagnosis of pancreatoblastoma to be made. The differential diagnosis of pancreatoblastoma from other pediatric neoplasms involving the pancreas, including neuroendocrine tumors and neoplasms of acinar cell derivation, is presented. We believe that the FNA cytologic findings can lead to a correct diagnosis of pancreatoblastoma, especially when coupled with immunocytochemical and ultrastructural studies performed on the aspirated material.

Adenocarcinoma↗