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Biomedical subjects

T R Walters

Publications and source records attributed to T R Walters.

At least 19 recordsLinked to original sources
PubMed1997

Brimonidine tartrate: a one-month dose response study.

BACKGROUND: Brimonidine tartrate is a relatively selective alpha2-agonist that effectively reduces mean intraocular pressure (IOP) and the incidence of IOP spikes after laser trabeculoplasty. The authors were interested in evaluating the dose response of brimonidine when applied topically for a longer duration in patients with elevated IOPs. METHODS: The authors conducted a 1-month, multicentered, double-masked, randomized, placebo-controlled, parallel clinical study in 194 patients with ocular hypertension or glaucoma (mean IOP, 25.6 +/- 3.2 mmHg). The authors administered three concentrations of brimonidine (0.08%, 0.2%, and 0.5%) or placebo bilaterally every 12 hours for 1 month. The authors evaluated the following parameters: IOP, heart rate, blood pressure, visual acuity, pupil size, basal tear secretion as well as patient comfort at baseline, day 1, week 1, week 3, and week 4. RESULTS: All concentrations of brimonidine significantly reduced IOP, compared to baseline and placebo, at all follow-up visits. Maximum mean IOP decreases from baseline of 20.8%, 27.2%, and 30.1% were observed for the 0.08%, 0.20%, and 0.5% treatment groups, respectively. On days 1 and 21, the 0.2% and 0.5% treatment groups exhibited significantly greater IOP decreases than did the 0.08% group. After the initial steep decline in IOP, the effect decreased slightly and stabilized at day 14 at the level that was maintained throughout the study. The most frequent side effects reported were fatigue and dry mouth. No significant changes in heart rate were reported. Statistically significant decreases in mean blood pressure without clinical symptoms were observed within the 0.2% and 0.5% treatment groups. CONCLUSION: Brimonidine 0.2% is well tolerated, efficacious, and shows potential as an agent in the long-term treatment of elevated IOP.

Adrenergic alpha-Agonists↗
PubMed1996

Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies.

Clinical trials were conducted to evaluate brimonidine tartrate, an alpha 2-adrenoceptor agonist, for treating chronically elevated intraocular pressure (IOP) and the prophylactic treatment of acute pressure rises. In normal volunteers, brimonidine administered twice daily for five days at concentrations ranging from 0.08-0.5% lowered IOP 16-22% and was well-tolerated ocularly and systemically. In a 28-day study in 186 patients with glaucoma or ocular hypertension, maximum IOP lowering was 27.2% and 30.1% for brimonidine 0.2% and 0.5%, respectively. The most common adverse events were dry mouth fatigue/drowsiness, and blurring, which occurred significantly more frequently with brimonidine 0.5% than 0.2%. Brimonidine 0.5% was tested in 471 patients undergoing argon laser trabeculoplasty (ALT). One drop administered preoperatively, postoperatively or both pre- and postoperatively significantly reduced the number of postoperative IOP spikes (1-2% of patients compared to 23% receiving only vehicle). Systemic hypotension, dry mouth, lid retraction and conjunctival blanching occurred more frequently in patients who received the drug twice. Brimonidine 0.2% twice daily was compared with three times daily in 101 patients. No significant differences were seen between the two regimens in mean change from baseline IOP with mean decreases ranging from 3.4 +/- 3.23 to 5.2 +/- 3.77 mm Hg (standard deviation) with twice daily dosing, and from 2.8 +/- 3.26 to 4.9 +/- 3.70 mm Hg with three times daily dosing. The most common complaints were blurring and oral dryness. Based upon results of these and other early studies, brimonidine 0.5% was selected for acute therapy for the prevention of postoperative intraocular pressure spikes and brimonidine 0.2% for chronic use in glaucoma and ocular hypertension.

Acute Disease↗
PubMed1990

Thyroid adenoma following treatment of acute lymphocytic leukemia.

Sequelae of the treatment of children with acute lymphocytic leukemia (ALL) include multiple effects on the endocrine system, especially as it relates to growth and puberty. Thyroid dysfunction, and in particular, the occurrence of thyroid neoplasia, has been only rarely described. We report the development of benign thyroid neoplasms in two patients 9 years following the diagnosis and treatment of ALL. Both patients were clinically and biochemically euthyroid with noncystic "cold" nodules found on thyroid scan. In light of these observations, and along with previous reports of malignant thyroid neoplasia in children with ALL, long-term careful observation of children successfully treated for ALL is indicated.

Adenoma↗
PubMed1988

Restriction of tumor growth in mice by sodium-deficient diet.

Generalized malnutrition results in inhibition of tumorigenesis and tumor growth in experimental animal models. Neither the specific nutrient deficiency nor the mechanism has been definitely elucidated. We have shown previously that dietary sodium deprivation in rapidly growing rats retards protoplasmic growth. This effect was correlated to the extracellular fluid (ECF) volume expansion which is dependent on sodium accumulation. Since solid tumors are composed of a large quantity of ECF (which includes plasma volume) it was postulated that preventing the accumulation of new ECF by means of sodium restriction would influence tumor growth. The present study was designed to determine the effects of salt restriction on tumor growth and to relate these effects to ECF volume. Approximately 10(6) viable B16 melanoma cells were injected into C57BL/6 x DBA/2 F1 and C57 mice. A salt restricted diet (sodium less than 3 microeq/g) was provided ad libitum. The drinking solution was distilled water for the experimental group and 0.45% saline solution for the controls. There was a significant decrease in tumor growth rates during sodium restriction. The total body ECF volume increased when dietary sodium was supplied but did not change during salt restriction. Therefore, the only source for the ECF in the tumor mass was from nontumorous tissue. We conclude that during dietary sodium restriction solid tumor growth is retarded and can proceed only to the extent that ECF is released from cachectic body tissues.

Animals↗
PubMed1988

The effect of long-term marrow culture on the origin of colony-forming cells in acute myeloblastic leukemia: studies of two patients heterozygous for glucose-6-phosphate dehydrogenase.

Long-term marrow cultures (LTMCs) provide a selective growth advantage for cytogenetically normal cells in patients with acute and chronic myeloid leukemias. In the present study, LTMCs were established from two patients with newly diagnosed acute myeloid leukemia (AML) who were heterozygous for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). Initially only leukemic clusters grew from cells plated in semisolid medium, but after 1 or more weeks in LTMC, morphologically normal granulocyte-macrophage colonies were detected. Nonetheless, in one of the patients, more than 80% of these colonies expressed the G6PD type observed in the leukemic blast cells, indicating a probable neoplastic derivation for many of them. In the second patient, colonies cultured during the first 3 weeks of the LTMC were predominantly derived from clonal progenitors, whereas after week 4 the colonies were derived from normal stem cells. Colonies derived from clonal or normal stem cells were not morphologically distinguishable. These data support the conclusion that LTMC has a selective anti-leukemic effect on marrow cells from some patients. However, normalization of colony growth is by itself not a sufficient criterion for determination of whether committed progenitor cells from patients with AML are derived from normal or leukemic stem cells.

Bone Marrow↗
PubMed1986

Atypical mesoblastic nephroma. Pathologic characterization of a potentially aggressive variant of conventional congenital mesoblastic nephroma.

A case of an aggressive variant of conventional congenital mesoblastic nephroma (CMN) occurred in a 10-month-old male infant. The tumor proved to be fatal, with two abdominal recurrences, but no metastases were found. Of the various terms used to designate the tumor, atypical mesoblastic nephroma (AMN) is preferred. We reviewed 17 previously reported cases to attempt pathologic characterization of AMN. The features that distinguish AMN from CMN are as follows: (1) atypical gross features consisting of one or more of the following: fleshy areas, foci of hemorrhage, necrosis, involvement of adjacent structures other than connective tissue; and (2) high cellularity and mitotic index. Aggressive behavior was noted at surgery or on follow-up in seven of the 18 cases. It was characterized by one or more of the following: (1) invasion of adjacent structures, such as adrenal gland, spleen, colon, and diaphragm (three cases); (2) one or more recurrences (four cases); and (3) metastasis (two cases). Atypical mesoblastic nephroma should be recognized as a potentially aggressive lesion separate from CMN.

Combined Modality Therapy↗
PubMed1986

Acquired symptomatic inhibitors of plasma clotting factors in nonhemophilic children.

Three children presenting with severe symptomatic bleeding episodes (one child developing a life-threatening subdural hematoma) due to acquired coagulation inhibitors are reported. In two patients, there was a history of an antecedent viral syndrome. None had evidence of drug exposure or an underlying immune disorder. All responded to the administration of corticosteroids, although one patient was steroid-dependent and required immunosuppressive therapy to achieve a complete response. Laboratory characteristics did not clearly distinguish the type of circulating inhibitor present in these children. Since bleeding was a prominent feature, we suggest that the inhibitors noted represent multiple specific coagulation factor inhibitors, rather than a "lupus-like" inhibitor which represents a common antibody to phospholipid-dependent coagulation tests. Such inhibitors may not be as benign as the common lupus anticoagulant seen in adult patients and should be considered in the child with symptomatic bleeding and a prolonged partial thromboplastin time. The true incidence and exact mechanism of action of acquired inhibitors in children has not been established.

Blood Coagulation↗
PubMed1984

Mucoid anaplastic hepatoblastoma. A case report.

A case of an unusual type of hepatoblastoma in a 5-month-old male infant is described. The tumor showed the following unusual features as compared with the epithelial and mixed types of hepatoblastoma: (1) The tumor cells presented a primitive anaplastic appearance without any resemblance in terms of cytologic features or arrangement to embryonal or fetal liver. (2) Abundant mucoid material containing acid mucopolysaccharide was present giving a slimy, gelatinous, gross appearance to the tumor and its metastases. (3) Well-defined tubular structures were present in some foci within the tumor parenchyma. (4) The tumor resulted in a rapidly fatal course, with metastases to the lungs and widespread peritoneal seeding despite complete surgical resection of the primary tumor. Yolk sac carcinoma and undifferentiated (embryonal) sarcoma of the liver were considered in the differential diagnosis. On electron microscopic examination, the tumor cells showed cytoplasmic features and junctional complexes consistent with their epithelial origin. Alpha-fetoprotein in the blood, which was markedly elevated prior to surgery, returned to a normal level postoperatively. Hepatoblastoma with the combination of features described above has not been previously reported. Because of the two striking and easily recognizable features viz. total lack of differentiation of tumor cells and presence of abundant mucoid material, the authors designated the tumor as mucoid anaplastic hepatoblastoma.

Carcinoma, Hepatocellular↗
PubMed1983

Sequential bilateral nephroblastic tumors of different cell types in an infant. Possible effect of chemotherapy versus de novo origin.

A 14-month-old infant had a classical Wilms' tumor of the left kidney and subsequently developed a tumor showing predominantly mature mesenchymal elements and lack of cellular atypia in the right kidney. His father had classical Wilms' tumor of the left kidney. The various possibilities regarding the precise nature and mechanism of the development of the tumor in the right kidney are discussed. The similarities and the differences between this tumor and congenital mesoblastic nephroma are noted. The possible relation of chemotherapy to mesenchymal differentiation and maturation in Wilms' tumor is considered. The possibility of an unusual, histologically benign, mesenchymal variant in the spectrum of infantile nephroblastic neoplasia is also suggested.

Age Factors↗
PubMed1981

Pulmonary fibrosis: a complication of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy.

A pediatric patient is reported who experienced fatal progressive pulmonary fibrosis as a complication of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy. The patient received a cumulative dosage of 1.29 g (1.72 g/m2) over a two-year period as adjuvant therapy for a medulloblastoma. Two and one-half years after cessation of therapy, cough, tachypnea and fatigue were noted. Progressive pulmonary insufficiency developed. Pulmonary pathologic findings included interstitial fibrosis and alveolar dysplasia. Other cases of BCNU pulmonary toxicity are cited from the medical literature.

Brain Neoplasms↗
PubMed1980

Olfactory neuroblastoma. Response to combination chemotherapy.

A patient with olfactory neuroblastoma who had bone marrow metastasis at the time of diagnosis is presented. Previous therapy for this disease consisted of surgery and radiation. There is limited information relating to the efficacy of chemotherapy. Our patient was treated with combination chemotherapy (dacarbazine [DTIC-Dome], cyclophosphamide [Cytoxan], doxorubicin hydrochloride [Adriamycin], and vincristine sulfate [Oncovin]) and radiation to the primary site. Objective findings, more than two years after diagnosis, support a good partial response. Although a 50%, five-year survival time has been reported, the five-year cure rate is 18%. This report suggests that the role of combination chemotherapy should be further evaluated in certain patients with olfactory neuroblastoma.

Adult↗
PubMed1979

Slipped capital femoral epiphysis following radiotherapy and chemotherapy.

There may be an increased frequency of slipped femoral epiphysis in pediatric patients who have received radiation to the pelvic area and combination chemotherapy. Previous reports include bilateral slipping of the epiphysis, eight years after radiation, in a patient with a pelvic neuroblastoma and the occurrence in a patient who had received radiation for Hodgkin disease, with a primary site in the pelvic region. No direct correlation was established in either case. This is a report of two patients who received pelvic radiation and combination chemotherapy who subsequently developed slipped femoral epiphysis. Our purpose is to heighten the suspicion in patients who have received radiation and chemotherapy for pelvic tumors. It is recommended that the femoral heads and acetabula be shielded when their inclusion in the treatment fields is not crucial to the treatment of the underlying disease.

Antineoplastic Agents↗
PubMed1979

Childhood acute lymphocytic leukemia with a second primary neoplasm.

The occurrence of de novo cancer in renal transplant patients who have received immunosuppressive therapy has been noted. An increased incidence of second primary neoplasm (SPN) has been reported in adults with various forms of cancer. The incidence of SPN in childhood cancer is lower. Successful therapy in several childhood cancers has resulted in prolonged disease-free survival time with the opportunity for longer patient-years of observation. The development of a SPN, an astrocytoma, in a child with continuous complete remission for more than 6 years is reported. The incidence of SPN in childhood cancer needs to be established.

Adult↗
PubMed1978

Chronic myelocytic leukemia terminating in blast cell crisis with lymphoblastic characteristics.

A child with chronic myelocytic leukemia (CML), Philadelphia chromosome positive, developed a non-T cell, non-B cell, acute lymphocytic leukemia (ALL) during her blast cell crisis. The diagnosis was suggested by light microscopy and supported by histochemical stains and transmission electron microscopy. Immunologic studies showed the presence of a non-T, non-B leukemic blast population--indistinguishable from the most common form of ALL (null cell type). Markedly elevated terminal deoxynucleotidyl transferase (TdT) activity was found. The findings support the hypothesis that the primary cell involved in CML is a stem cell with pluripotential characteristics; frequently the blast cell proliferative phase terminates in acute myeloblastic leukemia, but it may also terminate in ALL. The TdT activity may be evidence of leukemic transformation and not necessarily related to the thymic origin of the lymphocytes.

Bone Marrow↗
PubMed1978

Vitiligo, chronic thrombocytopenia, and autoimmune hemolytic anemia.

A 12-year-old boy with vitiligo, chronic thrombocytopenia, and a Coombs's positive autoimmune hemolytic anemia was treated with oral psoralens and exposure to ultraviolet light. An acute hemolytic crisis developed and he died. The association of autoimmune hemolytic anemia and vitilligo should be looked for in other cases. Until more information is available, patients with vitiligo and thrombocytopenia should not be treated with psoralens and exposure to ultraviolet light.

Anemia, Hemolytic, Autoimmune↗