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Biomedical subjects

R B Mitchell

Publications and source records attributed to R B Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Subglottic stenosis complicating cardiac surgery in children.

OBJECTIVE: To highlight the incidence of subglottic stenosis (SGS) as a complication of surgery for congenital heart disease and the role of single-stage laryngotracheoplasty in treating this complication. DESIGN: Retrospective case series. SETTING: University-based referral center specializing in surgery for congenital heart disease and complex airway problem management. INTERVENTION: Laryngotracheal reconstruction (LTR). MAIN OUTCOME MEASURE: Successful airway expansion. RESULTS: At last follow-up, 87.5% (7 of 8) of patients remain free of obstructive airway symptoms. CONCLUSION: SGS can complicate surgery for congenital heart disease in children. Single-stage LTR is an effective treatment modality for this problem.

Acute Disease↗
PubMed1997

Relationships between in situ protein degradability and grass developmental morphology.

The objective of this research was to determine the relationships between the morphological development and in situ ruminally degradable protein (RDP), ruminally undegradable protein (RUP), and microbial protein of two cool season grasses (intermediate wheatgrass and smooth bromegrass) and two warm season grasses (switchgrass and big bluestem). The initial growth of grass tillers grown near Mead, Nebraska was clipped at ground level six times during the 1992 growing season and morphologically classified. Mean stage was calculated. Forage was ground to pass a 2-mm screen and was incubated in ruminally fistulated steers for 16 h. The RUP was adjusted for microbial protein and acid detergent insoluble N. The mean stage of cool season grasses was higher than that of warm season grasses throughout the growing season. The RDP decreased as plant maturity increased for all species. The RUP expressed as a percentage of crude protein for the cool season grasses was lower than that for warm season grasses. The RUP for intermediate wheatgrass, smooth bromegrass, and switchgrass remained constant across maturities, but RUP for big bluestem decreased as maturity increased. Microbial augmentation of RUP decreased as crude protein decreased in all species. The RUP corrected for acid detergent insoluble N and microbial protein was relatively constant across plant maturities. The quantification of RUP across a range of plant maturities provided information for incorporating RUP content of forage grasses into the diets of animals.

Analysis of Variance↗
PubMed1997

Pseudoaneurysm of the right lingual artery: an unusual cause of severe hemorrhage during tonsillectomy.

Profuse intraoperative hemorrhage is an uncommon complication of tonsillectomy. We present a three-year-old girl who underwent a routine adenotonsillectomy during which massive bleeding occurred from a large vessel in the right tonsillar fossae. Angiography revealed an aberrant right lingual artery with a pseudoaneurysm. The right lingual artery was embolized with multiple coils and the bleeding was halted. The causes and treatment of extracranial carotid artery pseudoaneurysms are discussed.

Aneurysm, False↗
PubMed1997

The management of asymptomatic firearm injuries in children.

Paediatric firearm injuries in the UK are uncommon. We present two children with BB-gun pellets in the parapharyngeal space who were managed conservatively and remained asymptomatic 6 months after the gunshot injury. The management of asymptomatic firearm injuries in children is discussed and a literature review included.

Accidents↗
PubMed1996

Campomelic syndrome--laryngotracheomalacia treated with single-stage laryngotracheal reconstruction.

The campomelic syndrome is a rare osteochondrodysplasia which frequently leads to early death from pulmonary insufficiency. We describe a patient with anatomic compromise of the upper airway due to diffuse laryngotracheomalacia and a moderate subglottic stenosis, treated successfully with single-stage laryngotracheal reconstruction using a rib graft. To our knowledge this has not been previously described. A review of the current literature is included.

Airway Obstruction↗
PubMed1996

Day-stay tonsillectomy: is hospital stay reduced at the expense of increased community care?

There is concern about the burden day-stay surgery created upon community services. We have followed 128 children and 38 adults undergoing day-stay tonsillectomy and a similar cohort of adults and children undergoing tonsillectomy as inpatients and looked at the demands made on general practice and casualty services over the 2 weeks after discharge. Twelve adults (18%) and four children (3%) required overnight admission after day-stay surgery. Within the first 2 weeks, 27 adults (48.2%) and 62 children (50%) visited their GP and 13 adults (23.2%) and six children (4.8%) visited the casualty department. There was no statistically significant difference for either adults or children when comparing the day-stay and inpatient cohorts. Adult day-stay tonsillectomy is associated with a high admission rate. Both adult and paediatric tonsillectomy lead to considerable demand for general practice and casualty services, but this demand is high regardless of whether the day-stay or inpatient route is chosen.

Adolescent↗
PubMed1996

Bilateral fat graft myringoplasty in children.

The results after simultaneous bilateral fat graft myringoplasties in children have not been previously reported in the literature. We report on 28 children who underwent bilateral fat graft myringoplasties as outpatient procedures under general anesthesia. The success rate was 91% at final follow-up, with only 16% of children requiring insertion of pressure-equalizing (PE) tubes following surgery. No complications were documented. We concluded that bilateral fat graft myringoplasties are safe to perform, with an excellent success rate, and are suitable as outpatient procedures.

Adipose Tissue↗
PubMed1994

Sequential therapy with dacarbazine and carmustine: a phase I study.

Depletion of the DNA-repair protein O6-alkylguanine-DNA alkyltransferase (AGT) increases the sensitivity of cells in culture and of human tumor xenografts to chloroethylnitrosoureas such as carmustine (BCNU). We have previously demonstrated that dacarbazine (DTIC) can deplete AGT activity in cells in culture and in human tumor xenografts. A phase I trial of DTIC followed immediately by BCNU was conducted to determine the DTIC dose resulting in maximal depletion of AGT in the peripheral blood mononuclear cells (PBMC) of cancer patients and to determine the maximally tolerated dose of DTIC given as a 4-h infusion immediately prior to a fixed dose of BCNU. A 4-h infusion of DTIC followed by a 2-h infusion of BCNU was given to 42 patients with refractory solid tumors. Complete depletion of AGT activity was not achieved at DTIC doses of up to 750 mg/m2. The dose-limiting toxicity was hematologic, although at higher doses of BCNU (> or = 100 mg/m2) we observed significant nonhematologic toxicity. Our recommended phase II doses are 1,000 mg/m2 DTIC followed by 75 mg/m2 BCNU. AGT activity in PBMC of the 28 patients studied decreased to a mean of 62% +/- 11% (SE) of the baseline value at 4 h after initiation of the DTIC infusion. At 24 h after initiation of the DTIC infusion, AGT activity in PBMC was depleted to a mean of 65% +/- 14% of the baseline value. There was no direct correlation between the DTIC dose and the extent of AGT depletion. Baseline PBMC AGT levels varied widely among patients.

Adult↗
PubMed1993

Effect of temozolomide and dacarbazine on O6-alkylguanine-DNA alkyltransferase activity and sensitivity of human tumor cells and xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea.

We investigated the ability of 5-(dimethyltriazeno)imidazole-4-carboxamide (DTIC, decarbazine) and an analogue, temozolomide, to deplete cells or tumors of O6-alkylguanine-DNA alkyltransferase (AGT) and to enhance the antitumor effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Human colon cancer (HT29) cell survival was decreased by almost 1 log when treated with 500 microM temozolomide prior to 150 microM BCNU. Administration of the maximal tolerated dose of DTIC (300 mg/kg) to nude mice carrying HT29 xenografts resulted in complete depletion of AGT activity in tumors at 4 h and 16 h. Administration of 150 mg/kg DTIC caused a 76% reduction in AGT activity at 4 h, but only a 28% reduction at 16 h. The maximally tolerated doses of DTIC and BCNU, alone and in combination, were used to treat nude mice bearing HT29 xenografts. No difference in tumor growth occurred when animals were treated with either BCNU alone (50 mg/kg), DTIC alone (300 mg/kg), DTIC (150 mg/kg) followed by BCNU (12.5 mg/kg), or BCNU (25 mg/kg) followed by DTIC (150 mg/kg). These data suggest that methylating agents such as DTIC may be too toxic to be used in combination with BCNU to deplete tumor alkyltransferase levels effectively and increase the therapeutic index of BCNU.

Animals↗
PubMed1993

Syphilis as AIDS?--A call for research.

Based upon a literature survey, this paper outlines the argument that Treponema pallidum may be the etiologic agent of AIDS. AIDS and syphilis have similar epidemiology, immunology and pathologies. In addition, the current methods of detecting and treating syphilis are inadequate. The similarities between syphilis and AIDS support the need for further research into their relationships, including the role Treponema pallidum may play in AIDS etiology.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effect of O6-benzylguanine on the sensitivity of human tumor xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea and on DNA interstrand cross-link formation.

We have previously shown that O6-benzylguanine can be used to deplete cells of the DNA repair protein O6-alkylguanine-DNA alkyltransferase and to enhance the sensitivity of human glioma (SF767) and colon tumor (HT29) cells to the cytotoxic effects of alkylnitrosoureas. In the present study, the combination of O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was evaluated in vitro to determine the number of DNA interstrand cross-links formed and in vivo to compare the therapeutic index with that of BCNU alone. The number of DNA interstrand cross-links, as measured by alkaline elution, was increased in HT29 cells treated with 10 microM O6-benzylguanine for 2 h prior to BCNU exposure compared to cells treated with BCNU only. The number of single strand breaks was not increased by prior exposure to O6-benzylguanine. To evaluate the therapeutic index, HT29 and SF767 cells were grown as xenografts in nude mice and the tumor growth rate after treatment with BCNU alone was compared with the rate after treatment with O6-benzylguanine and BCNU. Treatment was administered i.p. when tumors reached 100-200 mm3. For animals bearing HT29 xenografts that were treated with 60 mg/kg O6-benzylguanine 1 h prior to 20 mg/kg BCNU, the average time for tumor volume to increase by 200% was 25 days, compared to 10 days for animals treated with 20 mg/kg BCNU alone. For animals bearing SF767 xenografts, the tumor growth of controls was not significantly different from that of animals treated with O6-benzylguanine alone or BCNU alone up to the maximally tolerated dose (50 mg/kg). For these 3 groups, the average time for tumors to reach 300 mm3 was 9-12 days. However, when animals were treated with 80 mg/kg O6-benzylguanine 1 h prior to receiving 20 mg/kg BCNU tumor size did not increase for at least 21 days. Our studies demonstrate that the therapeutic index of BCNU can be increased when given in combination with O6-benzylguanine.

Animals↗
PubMed1992

Changes in HS mouse erythrocyte mass and area with respect to donor age.

Interferometric photographs of blood smears from heterogeneous stock (HS) mice were analyzed for age-related changes in erythrocyte mass using quantitative cytophotometry. Blood smears were obtained from 96 mice (half male/half female) sacrificed at 172, 272, 374, 482, 581, and 664 days of age as part of a larger biomarkers of aging study. Blood smears from each animal were photographed with a Leitz Mach-Zehnder interferometer, and the erythrocyte images on these negatives were measured for dry mass using a Vickers M85a microdensitometer. Cell area measurements were made from a video-microscope image traced with a computer digitizer. Results indicated that animals from middle-age groups (272, 374, and 482 days) have higher red blood cell mass than animals at either young (172 days) or older (581 and 664 days) age groups. Mass changes with respect to age followed similar trends when data were further examined with regard to sex of the animals. Erythrocyte area measurements showed a general age-related decrease in cell size.

Aging↗
PubMed1991

Effect of O6-benzylguanine analogues on sensitivity of human tumor cells to the cytotoxic effects of alkylating agents.

The effect of O6-benzylguanine, O6-(p-chlorobenzyl)guanine, and O6-(p-methylbenzyl)guanine on the sensitivity of various human tumor cell lines to alkylating agents is evaluated. The sensitivity of human colon tumor cells, HT29, to the chloroethylating agents, 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 2-chloroethyl(methylsulfonyl) methanesulfonate (clomesone), and chlorozotocin was increased by pretreatment for 2 h with 25 microM of each analogue. O6-Benzylguanine was slightly more effective as a sensitizer in HT29 cells than the p-chlorobenzyl and p-methylbenzyl analogues. However, all analogues sensitized SF767 glioma cells to the cytotoxic effects of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, and clomesone to the same degree. Both cell lines were sensitized to the methylating agents streptozotocin and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide, the active intermediate of 5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide, by pretreatment with 10 microM O6-benzylguanine for 2 h. The number of Raji cells surviving 50 microM clomesone decreased 3-fold upon pretreatment for 2 h with 1 microM O6-benzylguanine. The degree of enhancement was dependent on the amount of alkyltransferase protein present in cell lines. For example, HT29 cells (alkyltransferase activity, 381 fmol/mg protein) exhibited a greater degree of enhancement when treated with O6-benzylguanine than SF767 (77 fmol/mg protein) and M19-MEL melanoma (36 fmol/mg protein) cells. There was no enhancement observed in mer- cell lines, U251 (less than 2 fmol/mg protein), and BE (3 fmol/mg protein), or with alkylating agents which did not produce a cytotoxic lesion at the O6 position of guanine in DNA such as cisplatin or 4-hydroperoxycyclophosphamide. Our studies suggest that O6-benzylguanine analogues may have utility in mer+ tumors as an adjuvant to a variety of alkylating agents which produce a toxic lesion at the O6 position of guanine.

Alkylating Agents↗
PubMed1990

Modulation of mammalian O6-alkylguanine-DNA alkyltransferase in vivo by O6-benzylguanine and its effect on the sensitivity of a human glioma tumor to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea.

Experiments were carried out in mice and hamsters to determine whether the activity of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, in tissues and tumors was reduced by treatment with O6-benzylguanine in vivo. Following intraperitoneal injection of O6-benzylguanine, there was a rapid and complete loss of alkyltransferase activity in both livers and kidneys of mice and hamsters. The activity in mouse tissues was slowly restored, reaching pretreatment activities at 16 hr and 72 hr after injection of O6-benzylguanine at 10 mg/kg or 126 mg/kg, respectively. The activity in hamster liver was restored at a significantly lower rate, reaching less than 20% pretreatment activity 72 hr after treatment with 100 mg/kg of O6-benzylguanine. The efficient reduction of alkyltransferase activity by O6-benzylguanine was in sharp contrast to the inability of O6-methylguanine to bring about similar reductions. Activities dropped to about 55% of pretreatment activities in several mouse organs 4 hr after treatment with 126 mg/kg of O6-methylguanine compared to a more than 90% reduction in activity in animals after treatment with O6-benzylguanine. The sensitivity of SF767 cells to meCCNU after treatment with O6-benzylguanine was increased substantially. Furthermore, treatment of nude mice carrying SF767 tumor with 60 mg/kg of O6-benzylguanine prior to either 7.5 or 15 mg/kg of meCCNU led to significant inhibition of tumor growth. These studies indicate that O6-benzylguanine is a suitable compound for use in experiments to examine the role of the alkyltransferase protein in vivo in counteracting the effects of alkylating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Syndrome of idiopathic hyperammonemia after high-dose chemotherapy: review of nine cases.

PURPOSE: The syndrome of idiopathic hyperammonemia occurs in patients who have received high-dose cytoreductive therapy for the treatment of hematologic malignancy. It is characterized by abrupt alteration in mental status and respiratory alkalosis associated with markedly elevated plasma ammonium levels in the absence of any identifiable cause, and frequently results in intractable coma and death. Our goal was to survey clinical and pathologic manifestations of the disorder and discuss treatment options. PATIENTS AND METHODS: Plasma ammonium levels were measured in patients on the acute leukemia service or on the bone marrow transplant service at The Johns Hopkins Hospital, and a level more than twice normal was considered diagnostic of hyperammonemia. The syndrome was identified in nine patients; in eight, hyperammonemia occurred after administration of intensive cytoreductive therapy that resulted in profound leukopenia. The disorder occurred in the ninth patient two months after allogeneic bone marrow transplantation. RESULTS: Three of the nine patients survived an episode of idiopathic hyperammonemia; one patient subsequently died of leukemia and one of recurrent idiopathic hyperammonemia. The one long-term survivor is currently alive and well without neurologic sequelae 250 days after autologous bone marrow transplantation. CONCLUSION: Because neurologic function can deteriorate rapidly, early recognition of this disorder and close monitoring of the patient's neurologic status are critical.

Adolescent↗
PubMed1985

Differentiation of normal marrow and HL60 cells induced by antithymocyte globulin.

Antithymocyte globulin (ATG) therapy is an important treatment alternative for patients with acquired aplastic anemia. The mechanism by which it exerts its effects on hematopoiesis is unknown. In this report, we describe the ability of horse ATG to induce growth and differentiation of normal bone marrow. A single cell suspension of normal human bone marrow was cultured in methylcellulose medium and examined for the growth and maturation after incubation with ATG (10 micrograms/ml). After 3-4 days of culture, spherical colonies containing mature myeloid elements were found in cultures containing ATG but not in cultures containing medium or preimmunization horse IgG. The addition of 10% colony-stimulating factor increased growth by 40%. The number of spherical colonies is not dependent on the presence of macrophages or T lymphocytes. This property of ATG may be relevant to the mechanism behind the hematologic recovery in some patients with acquired aplastic anemia. We also describe the ability of ATG to induce terminal differentiation in the HL60 leukemic cell line. ATG binds to HL60 cells and at concentrations between 10 and 100 micrograms/ml, 50% of the cells become mature granulocytes, acquire the ability to reduce nitroblue tetrazolium, and lose their proliferative capacity in the clonogenic assay. These new observations of ATG-induced differentiation of normal marrow myeloid elements and terminal differentiation of the HL60 cell line point to different avenues for future search of differentiation-inducing agents.

Antilymphocyte Serum↗
PubMed1982

Histochemical assessment of nuclear protein content and enzyme activity in confluent nonarrested and low-serum arrested WI-38 fibroblasts at mid and late population doubling levels.

Cultures of WI-38 fibroblasts maintained in low-serum medium have little mitotic activity. Such arrested cultures can serve as a useful adjunct to the normal-serum proliferating fibroblast model system of senescence since the reduced cycling activity more accurately reflects in vivo conditions. Normal-serum plateau phase cultures and 17-day low-serum arrested plateau phase cultures were examined at both mid and late population doubling levels (PDL). Acidic, basic and total nuclear protein contents were determined by staining with toluidine blue O, alkaline fast green and acid fast green, respectively. Succinate dehydrogenase and glucose-6-phosphate dehydrogenase were localized with the nitroblue tetrazolium staining reaction. Quantification of individual cell staining was done on a Vickers M85 microdensitometer. Low-serum arrested cells at both mid and late PDL showed a significant increase in acidic protein staining and a decrease in basic protein staining when compared with normal-serum nonarrested cells. Enzyme activities in arrested cells were lower than nonarrested cells at mid PDL but equivalent to nonarrested cells at late PDL. This study demonstrates that the use of selected quantitative histochemical staining in combination with cytophotometry can be employed to differentiate arrested from nonarrested fibroblast populations as well as mid PDL from late PDL cultures.

Blood↗