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Biomedical subjects

W Hanna

Publications and source records attributed to W Hanna.

At least 73 records · Page 4Linked to original sources

Immunotherapy of human leukemia with antibody to pluripotential K-562 stem cells.

Gamma (gamma) globulin was fractionated from the serum of a goat immunized with the pluripotential leukemia cell line K-562. The lyophilized gamma-globulin preparation, termed leukoglobulin, contained about 50% immune IgG and suppressed the proliferation of heterotransplanted leukemia and lymphoma cells of human origin. The main aims of this study were to evaluate the potential therapeutic value of leukoglobulin and to determine its toxicity in humans with terminal leukemia and patients whose disease was unresponsive to current therapy. Two patients with CML, one with AMML, four with ALL, and one with AML were treated once a week for up to 5 weeks with leukoglobulin intravenously at doses ranging from 2 to 29 mg/kg. Leukoglobulin was well tolerated with minimal adverse effects and produced an initial mobilization of blasts from the bone marrow, spleen, and other organs with a parallel increase in the number of blasts in the systemic circulation. Subsequent injections of leukoglobulin led to a sharp decrease and the eventual eradication of blasts from the peripheral blood and bone marrow. Except in patients with CML, immature cells other than blasts also markedly diminished. The results of the clinical trials indicated a synergism with or potentiation of most chemotherapeutic agents used. Two possible uses for a combination of leukoglobulin and antileukemic drugs are indicated by the results we report here; drug-antibody synergism for cases showing no response to chemotherapy alone or leukoglobulin given immediately after chemotherapy is administered to eliminate residual leukemia cells. Alternatively, leukoglobulin can be given as a single therapeutic agent during the induction or maintenance phases of treatment to patients with leukemia resistant to other therapeutic combinations.

Adolescent↗

Steroid receptors in meningiomas. A histochemical and biochemical study.

Meningiomas are more common in females and their course can be affected by changes in the hormonal milieu of the patient. Recently, a few studies have reported the presence of one or more steroid receptors in a small number of meningiomas. We have studied the estrogen and progesterone receptors (ER and PgR) of 11 surgically excised meningiomas. The receptors were assayed biochemically and localized at the cellular level using fluoroceinated estradiol and rhodamine-conjugated progesterone. Considerable amounts of ER were found in 4/11 cases, and PgR was high in 6/11 tumors. Cytoplasmic localization of the steroid binding sites was seen using both tracers. The presence of 10% of cells with two ++ intensity of the fluorescence correlated with tumors having positive ER values (greater than 10 Fm/mg protein). The presence of nuclear fluorescence and the higher level of PgR seen in some tumors indicate that the ER present is functioning. This study confirms the presence of steroid binding sites in meningiomas and suggests that there may be a role for hormonal manipulation in selected patients.

Adult↗

Origin of the desmoplasia in desmoplastic malignant melanoma.

Four cases of desmoplastic malignant melanoma were examined light microscopically and immunohistochemically. Electron microscopy was performed in three cases. Light microscopy showed that all tumors were composed of neoplastic spindle cells that infiltrated between mature collagen bundles in the reticular dermis. Some of the spindle cells had bizarre nuclei, whereas other spindle cells resembled normal fibroblasts. Melanin could not be demonstrated in any of the tumors by histochemical techniques. Electron microscopic examination of the spindle cells showed prominence of rough endoplasmic reticulum, which was dilated and filled with flocculent material and occasional collagen fibrils. The same cells contained aggregates of non-membrane-bound melanin granules and pre-melanosomes. Some cells also showed features of myofibroblasts. Immunoperoxidase staining with anti-S100 protein antibody demonstrated positivity of the spindle cells as well as of melanocytes in the basal layer of the epidermis. Scar tissue and fibroblasts did not stain. These findings show that the desmoplastic component of these malignant melanomas derives from melanocytes that have undergone adaptive fibroplasia. Therefore, in assessing depth of invasion in a malignant melanoma, measurements should include the desmoplastic areas.

Adult↗

Ultrastructure of the esophageal muscle in achalasia and diffuse esophageal spasm.

The pathogenesis of dysphagia in achalasia and diffuse esophageal spasm (DES) is not understood completely, and the primary site of damage in these two entities is not known. This project was undertaken to study the ultrastructural changes present in the muscular wall of the esophagus in eight patients with achalasia and nine patients with DES, compared with seven controls. The ultrastructural alterations in the smooth muscle of all patients were neither pronounced nor consistent. However, nonspecific changes, including filament disarray, mottling of the fiber density in myocytes, thick and long cytoplasmic dense bodies, long dense plaques, and few nexus junctions were seen in both achalasia and DES. In addition, the smooth muscle cells in achalasia exhibited nuclear and cytoplasmic inclusions. Statistical analysis of the number of muscle cells per unit area suggested that the gross thickening of the muscular wall of the esophagus in cases of DES is because of hyperplasia and not hypertrophy of muscle cells. A striking change seen in achalasia esophagi and a few cases of DES, as compared to the controls, was the marked loss of small nerve fibers and the paucity of granules in the remaining fibers. This study points to a neurogenic pathogenesis for dysphagia in achalasia with secondary nonspecific changes in the smooth muscle in these two diseases. No nerve abnormalities were noticed in DES.

Adult↗

Ultrastructural features of epidermolysis bullosa.

Epidermolysis bullosa (EB), a heterogeneous group of hereditary diseases, varies in mode of inheritance, extent, severity, and presence or absence of scarring and dystrophy. Fourteen cases (13 in infants and 1 in a young adult) were studied. Subtyping by ultrastructural findings in normal and blistered skin biopsies was as follows: EB simplex (2), EB letalis (3), EBD dominant (2), and EBD recessive (7). One case diagnosed as recessive dystrophic by electron microscopy (EM) followed a benign course with little scaring and was reclassified clinically and after reviewing the EM as dominant dystrophic. Defining the level of bulla formation by EM allowed accurate diagnosis of subtypes. In 6 patients with EBD recessive, normal and bullous skin showed collagenolysis and no anchoring fibrils. In patients with EBD dominant, rudimentary fibrils were noted in normal skin. Whether absence of anchoring fibrils is primary or secondary in these two types and the role of collagenolysis remain unresolved.

Adult↗

Cellular localization of estrogen binding sites in human breast cancer.

Biopsy specimens from 52 consecutive cases of primary human breast cancer were collected over a period of seven months and included in a study for histochemical localization of estrogen binding sites (EBS), using a fluorescein labelled Estradiol conjugate. Cryostat frozen sections from each tumor were examined to determine the localization of the tracer and to evaluate the percentage of positive cells in a given tumor. Results are correlated with the values of the biochemical assay for the estrogen receptor (ER) protein done on the same tumor. The localization of EBS by a tracer is a simple technique that can be done and interpreted in any surgical pathology laboratory. It was concluded that this method could be a valuable supplementary technique to the biochemical assay; allowing more accurate selection of patients and prediction of their response to endocrine therapy. Clinical follow-ups are extremely necessary to evaluate the suitability and the accuracy of the technique in choosing breast cancer patients for endocrine manipulation.

Breast Neoplasms↗

Decreased antithrombin III level associated with failure of anticoagulation.

A 67-year-old man with adenocarcinoma of the colon had recurrent pulmonary emboli. The patient's level of serum antithrombin III was found to be below normal. Heparin therapy led to further reduction, resulting in failure of adequate anticoagulation. The patient subsequently died of massive pulmonary emboli despite heparin therapy. We believe the antithrombin III level should be routinely determined for patients receiving heparin therapy.

Adenocarcinoma↗

Immunohistochemical localization of prekeratin filaments in benign and malignant cells in effusions. Comparison with intermediate filament distribution by electron microscopy.

An immunoperoxidase technique employing antibody to prekeratin was used to study distribution and pattern of staining of prekeratin filaments in cytological smears obtained from 42 specimens of pleural and peritoneal effusions (27 benign, 15 malignant). The smears were either air-dried or ethanol-fixed. Both benign and malignant mesothelial cells showed distinctive peripheral or perinuclear staining patterns which differed from the characteristic arborizing pattern in adenocarcinoma cells. The ultrastructure of these 2 cell types studied in 27 body fluids (12 benign, 15 malignant) and in 13 malignant tumors (3 mesotheliomas, 10 adenocarcinomas) showed a distinctive localizaton of intermediate filaments which corresponded to and could explain the pattern of staining obtained using the immunoperoxidase technique. The immunohistochemical and ultrastructural findings appeared characteristic for benign and malignant mesothelial cells as well as for adenocarcinoma cells, and could be used as markers to differentiate mesothelial tumors and reactive mesothelial cells from adenocarcinomas.

Adenocarcinoma↗

Variant von Willebrand's disease and pregnancy.

The clinical course and coagulation profile of a pregnant patient with variant von Willebrand's disease were followed from the second trimester through puerperium. The clinical course was characterized by a normal delivery and absence of abnormal bleeding or need for replacement therapy. The coagulation profile demonstrated an increase in factor VIII procoagulant activity, factor-VIII-related antigen, and platelet aggregation activity in response to ristocetin prior to delivery. Postpartum, these factors decreased to prepregnancy values with distinctly different patterns. Factor VIII procoagulant activity continued to rise for 5 days after delivery and then decreased with a half-life of approximately 6 days. Factor-VIII-related antigen began to decrease just prior to delivery, displaying a half-life or approximately 6 days. Ristocetin cofactor activity, however, dropped immediately postpartum and displayed a half-life of approximately 6 hr. The ristocetin cofactor activity was associated with factor-VIII-related antigen, which displayed a significantly smaller molecular weight than does normal factor-VIII-related antigen. Larger aggregates of factor-VIII-related antigen. Larger aggregates of factor-VIII-related antigen did not appear during the pregnancy, and ristocetin cofactor activity could not be demonstrated in fragments of less than 0,8 x 10(6).

Adult↗

Nemaline rods in cricopharyngeal dysphagia.

Cricopharyngeal dysphagia, a disorder of uncertain pathogenesis, is most frequently found in patients with associated gastroesophageal reflux. Seven patients who had dominant cricopharyngeal dysphagia were evaluated. Manometry showed characteristic motor incoordination. Biochemical profiles and endoscopy were normal. Electronmicroscopic examination of the cricopharyngeal muscle biopsy specimens obtained during myotomy showed significant ultrastructural abnormalities. These included numerous and aberrant mitochondria, increased glycogen, lipid inclusions, and phagolysozomes. A striking finding was the presence of numerous nemaline rods in five of seven biopsy specimens examined. The pathologic changes in this muscle in cryopharyngeal dysphagia have not been reported previously. Structural changes are thought to be a secondary response to reflux injury. Nemaline rods form part of the structural abnormality of muscle in patients who have cricopharyngeal dysphasia with no evidence of underlying generalized disease or myopathy.

Aged↗

General anaesthesia in sickle-cell disease.

General anaesthesia was administered on 284 occasions to 200 patients with sickle-cell disease at one hospital during July 1958 to June 1978. No intraoperative but six postoperative deaths occurred. The management of anaesthesia may have contributed to two of the postoperative deaths. Clinically uneventful anaesthesia did not appear to provoke severe sickling crises or to be responsible for mortality, but a contribution to postoperative morbidity could not be excluded. A simple, careful anaesthetic technique and selective but not routine blood transfusion appears to be associated with minimal anaesthetic morbidity and mortality in patients with sickle-cell disease.

Adolescent↗

Sedation for upper gastrointestinal endoscopy: a comparative study of midazolam and diazepam.

Comparison of the ease of upper endoscopy, patient tolerance, and amnestic effect, using diazepam, midazolam, or no sedation, was performed on 149 patients. Midazolam and diazepam sedation produced better conditions and improved patient acceptability. Midazolam was associated with better patient tolerance, less thrombophlebitis, and more amnesia than diazepam, but shared a similar recovery time. Midazolam should replace diazepam as the drug of choice in those patients requiring sedation for upper endoscopy.

Adolescent↗