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R Walters

Publications and source records attributed to R Walters.

50 records · Page 3Linked to original sources

Identification of molecular variants of p210bcr-abl in chronic myelogenous leukemia.

The aberrant abl protein product of a chronic myelogenous leukemia (CML) blast crisis cell line (K562) and of five Philadelphia chromosome-positive CML patients in blast crisis were analyzed by an immune complex kinase assay using two antipeptide sera generated against the hydrophilic domain of v-abl and a region within the third exon of the breakpoint cluster region (bcr) respectively. Both the anti-abl and anti-bcr sera detected a 210 kd band in extracts derived from K562 cells and from two CML patients with myeloid blast crisis. p210 was detected by the anti-abl but not the anti-bcr sera in three CML patients with myeloid (one patient) and lymphoid (two patients) blast crisis, indicating the absence of bcr exon 3 in this protein. Southern blot analysis on DNA derived from one of the patients in the latter group was consistent with the break on chromosome 22 occurring 5' to bcr exon 3. Our observations demonstrate that the Philadelphia translocation results in the generation of a chimeric bcr-abl protein with at least two molecular variants, both of which are enzymatically active as protein kinases.

Blast Crisis↗

Therapy of chronic myelogenous leukemia with recombinant interferon-gamma.

Recently, we reported that recombinant interferon-alpha (rIFN-alpha) can induce hematologic remissions and cytogenetic improvement in newly diagnosed Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) patients. Although IFN-gamma is a structurally distinct molecule, this agent suppresses in vitro hematopoietic progenitor cells in a fashion similar to that of IFN-alpha. Therefore, we initiated a study of rIFN-gamma at doses of 0.25 to 0.5 mg/m2/d intramuscularly in patients with Ph-positive benign-phase CML. Twenty-six of 30 patients entered in the study were evaluable. Six patients have achieved a complete hematologic response; four, a partial hematologic response. The median follow-up period of patients who are in complete remission is 7.5 months (range, 5 to 12 months). No relapses have occurred among the complete responders. So far, five patients have had cytogenetic improvement with emergence of 5% to 45% diploid cells in the bone marrow. Fever and flulike symptoms were the most common side effects, with partial tolerance often developing after about 1 week. The majority of patients tolerated therapy with minimal change in performance status. In conclusion, rIFN-gamma has demonstrated clinical activity in CML. On the basis of these observations and the in vitro synergistic growth-inhibitory effects of IFN-alpha and IFN-gamma, we have started trials of combination IFN therapy in CML patients.

Adult↗

Old age: a sign of poor prognosis in patients with chronic myelogenous leukemia.

Fifty-four patients aged 60 years or older with a diagnosis of chronic myelogenous leukemia were referred to University of Texas M. D. Anderson Hospital between 1965 and 1982. Patients in this age group had a significantly shorter median survival than that of the 249 patients younger than 60 seen during the same period (26 vs 42 months; P = .01). Old age was associated with a higher incidence of poor performance status, hepatomegaly, and anemia. Fourteen other patient characteristics were correlated with poor prognosis, including black race, weight loss, symptoms, hepatomegaly, splenomegaly, anemia, thrombocytopenia or thrombocytosis, increased peripheral blast cells and promyelocytes or basophils, increased blasts or basophils in the bone marrow, decreased megakaryocytes, and additional cytogenetic abnormalities. A multivariate analysis that accounted for the interactions of these factors identified old age as being of primary adverse prognostic significance in patients with chronic myelogenous leukemia, suggesting a biologic difference in the disease in older patients. The poor prognosis in elderly patients receiving present available therapy justifies promising and well tolerated investigational approaches such as interferons in patients in this age group.

Age Factors↗

Does melatonin deficiency cause the enlarged genitalia of the fragile-X syndrome?

Melatonin profiles were studied in five males with cytogenetic and clinical features of the fragile-X syndrome including megalo-orchidia and macrogenitosomia. In comparison with age-matched normal controls, the fragile-X group showed lower melatonin values and a significant impairment of the nocturnal rise in this hormone. Melatonin deficiency may thus be responsible for some of the phenotypic features of this disorder.

Aged↗

Percutaneous drainage of abscesses in the postoperative abdomen that is difficult to explore.

We have evaluated our experience with computerized tomography and ultrasonography guided percutaneous drainage of extrahepatic abdominal fluid collections in a group of 22 patients. The most common goal was to avoid or delay surgery on abdomens in which reoperation would be difficult, mainly in high-risk patients. Drainage of pancreatic fluid collections or abscesses was also attempted in a small number of the patients. Percutaneous drainage was curative in 69 percent of those with nonpancreatic abscesses but in only 33 percent of those with abscesses associated with the pancreas. There were no complications attributable to the procedure or to delays in subsequent surgical drainage. Two patients died from problems not directly related to the use of percutaneous drainage. Percutaneous catheter drainage of nonpancreatic abdominal abscesses can play a useful role in patients who are carefully selected because they possess a complex abdominal anatomy distorted by previous surgery and infection or they are at high risk if surgical exploration is carried out.

Abdomen↗

A characteristic pattern of leukemic cell differentiation without cytoreduction during remission induction in acute promyelocytic leukemia.

While differentiation of leukemic cells in vitro is well established, the role of differentiation in vivo is not defined and is generally attributed to differentiation inducers. In five patients with acute promyelocytic leukemia (APL) an unusual pattern of a slow and progressive decrease of immature blasts with a concomitant increase in mature cellular elements was observed following intensive combination chemotherapy. All patients eventually achieved complete remission, four of them without an intermediate phase of marrow hypoplasia. This morphologic pattern of response suggests that leukemic cellular differentiation rather than cytotoxicity was one mechanism involved in remission induction. Cytogenetic studies of remission revealed disappearance of the cytogenetic marker, the balanced translocation between the long arms of chromosomes 15 and 17. This remission induction process appears to be due to the cellular biologic characteristic rather than the therapy used as it occurs in a substantial proportion of patients with APL. It should be considered for optimal diagnostic and therapeutic decisions.

Acute Disease↗

Fragile X chromosome: clinical and cytogenetic studies on cases from seven families.

Results of detailed clinical and cytogenetic studies on 13 mentally retarded males and two heterozygous females (one normal and one retarded) are reported. Reference is made to technical modifications to enhance the incidence of expression of the fragile X. The addition of excess methionine to the fibroblast cultures (final concentration of 115 mg/l medium TC 199) was found to be particularly valuable, increasing the incidence of expression up to four-fold, and enabling the demonstration of the fragile X in fibroblasts when it could not be demonstrated in blood cultures in at least one case. Studies on replication patterns of the X chromosomes in the two heterozygous females showed that the fragile X chromosome was genetically active in a significantly greater proportion of cells (74%) in the mentally retarded female, whereas the normal X was active in a similar proportion (72%) in the carrier with normal intelligence.

Adult↗

Midwifery: episiotomy.

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Attitude of Health Personnel↗

The mandibular dental arch: part III. Buccal expansion.

The tendency toward relapse in intercuspid width has been examined with those cases having final intercuspid width less than 27 mm showing significantly less relapse than those cases with final intercuspid width of 28 mm or more. The point of contact between the cuspid and first premolar has been introduced as a key point on the arch, determining arch width. An individualized norm has been derived for this measurement as a function of the patient's tooth size, facial pattern, and other variables based upon stable normal occlusions in treated cases. Those cases expanded to a dimension exceeding the norm by more than 1 mm showed a greater propensity toward relapse. The group following the norm was significantly more stable than the over- and underexpansion groups at the .025 significance level. An individual norm for intermolar width based upon the patient's facial pattern (using frontal and lateral X-rays) has been established. Cases showing relapse showed considerably less space between the lower molar and the JAG plane, and greater lower face height than stable cases. The results show that the space available for the permanent dentition can be estimated in advance of treatment based on the patient's own skeletal measurements, thus minimizing unnecessary extractions, relapse, and extended treatment time due to errors in diagnosis.

Adolescent↗

Long-term followup of knee injuries in high school football players.

Twenty-three American football participants were studied 20 years after high school competition, as well as 11 age-matched controls, to assess the development of knee osteoarthritis. No statistically significant increase in osteoarthritis could be demonstrated radiographically, subjectively, or objectively. A significant increase in knee joint osteoarthritis was found in the subgroup of football players who had sustained a knee injury.

Adolescent↗