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Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 163 records · Page 9Linked to original sources
PubMed1994

Proliferative potential and prognostic evaluation of low-grade astrocytomas.

Despite their histological similarity, low-grade astrocytomas vary widely in their clinical behavior. To elucidate this variable behavior, we measured the proliferative potential of 69 primary and 18 recurrent low-grade astrocytomas and correlated the results with the clinical characteristics and outcome. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR); BUdR-labeled nuclei in excised tumor specimens were identified by immunoperoxidase staining. The BUdR labeling index (LI), or S-phase fraction, ranged from < 1 to 9.3%; the LI was < 1% in 64 (74%) patients and > or = 1% in 23 patients (26%). The LI did not appear to be associated with age, sex, tumor location, or whether the tumor was primary or recurrent. A Cox proportional-hazards analysis of the influence of the LI and other variables (age, sex, tumor location, extent of surgery, primary versus recurrent tumor) on survival showed that the LI and extent of surgery (total resection, subtotal resection, biopsy) were significant in predicting both survival and progression-free survival for all patients and for patients with primary tumors. The LI was also significant in predicting progression-free survival for patients with recurrent tumors. The correlation between the BUdR LI and both survival and time to recurrence suggests that the outcome of low-grade astrocytomas varies according to the proliferative potential. The growth rate of these histologically similar tumors should be assessed individually in order to select specific treatment.

Adolescent↗
PubMed1994

The prognostic implications of histologic classification and bromodeoxyuridine labeling index of mixed gliomas.

To clarify the biological and clinical behavior and prognosis of mixed gliomas, 47 patients underwent intraoperative bromodeoxyuridine (BrdU) labeling studies. The mean age was 27.8 years at symptom onset and 31.8 years at labeling (median, 36 years). Forty-five tumors were supratentorial, 30 were frontal, and two were cerebellar; 16 were recurrent at labeling. The median labeling index (LI) was 1% (range, < 1 to 15.1%). Forty-six tumors has oligodendroglial and astrocytic elements, and one had astrocytic and ependymal elements. The median LI was 4.4% in recurrent tumors and < 1% in primary tumors. A higher BrdU LI correlated with an increased risk of recurrence and a shorter time to recurrence. During a median follow-up of 16 months, four patients died; each had a BrdU LI > or = 4.4%. The median time to recurrence was 4.5 months for tumors with BrdU LI's > 5% but was not reached for tumors with LI's < 5% (p < 0.003). The histologic grade of the oligodendroglial component correlated with the median time to recurrence (8 months for Smith Grade C tumors, not reached for Smith Grade B tumors; p < 0.05); there were too few cases to evaluate the median times to recurrence of Smith Grade A and Grade D tumors. The median time to recurrence was not reached for any astrocytic grade, and there were no significant differences in the Kaplan-Meier survival curves. These findings suggest that the BrdU LI and the grade of the oligodendroglial component of mixed gliomas have prognostic significance.

Adolescent↗
PubMed1994

Progress in understanding the Drosophila dnc locus.

The genetic dissection of learning and memory in Drosophila is two decades old. Recently, a great deal of progress has been made towards isolating new mutants as well as towards a better understanding of the originally isolated ones. This paper reviews the recent developments in the understanding of the structure and function of the gene identified by the first and best-characterized of these mutants, the Drosophila dunce mutant.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Cranial computed tomography scans in children after minimal head injury with loss of consciousness.

STUDY OBJECTIVE: To assess the need for cranial computed tomography (CT) in the emergency department evaluation of children with Glasgow Coma Scale (GCS) score of 15 after mild head injury with loss of consciousness. DESIGN: Retrospective case series of children aged 2 to 17 years with documented loss of consciousness after head injury from January 1, 1988, to July 31, 1992. All had a GCS score of 15 on initial ED evaluation and were further categorized according to physical examination findings, neurologic status, and whether the head injury was isolated or nonisolated. Recursive partitioning was used to identify variables predictive of the presence and absence of intracranial hemorrhage. SETTING: ED in two settings: a regional tertiary care trauma center and a community children's hospital. RESULTS: Of the 185 patients who met study criteria, 17 had evidence of depressed or basilar skull fractures on physical examination or had a ventriculoperitoneal shunt in place before head injury. In the remaining 168 patients, recursive partitioning identified two variables (neurologic status and head injury type) associated with intracranial hemorrhage. Overall, 12 of 168 patients (7%) had intracranial bleeding. However, none of the 49 neurologically normal children with isolated head injury had intracranial hemorrhage (95% confidence interval, 0.0 to 6.0). CONCLUSION: The prevalence of intracranial hemorrhage in children with mild closed-head injury appears to vary with the presence of neurologic abnormalities and other noncranial injuries. After isolated head injury with loss of consciousness, children older than 2 years who are neurologically normal and without signs of depressed or basilar skull fracture may be discharged home from the ED without a cranial CT scan after careful physical examination alone.

Adolescent↗
PubMed1994

Statistical considerations for design and analysis of a multiperiod crossover study to compare two treatments for migraine headache.

The purpose of this paper is to discuss a long-term, multiperiod crossover study to compare two treatments for migraine headache. Principal attention is given to the analysis of an example in which patients randomly received a treatment sequence with test drug for three migraine headaches and placebo for one. An issue that requires attention for this example is the influence of a carryover effect for test drug that was greater when placebo was the subsequent treatment than when test drug was the subsequent treatment. A way to address this issue without excessive loss of power is to consider tests of "total treatment effects," which are weighted averages across headaches of differences between average response to test drug and average response to placebo. Since these weighted averages are linear combinations of treatment effects and carryover effects, their use requires an argument that carryover effects are at least partly a further form of treatment effects. For the example in this paper, this argument is realistic because the test drug could have provided much better relief to migraine headache than other treatment patients might have previously used. A second purpose of the paper is to present some alternative designs for situations like that represented by the example. The structure of variances for alternative specifications for treatment comparison is provided for models of interest for these designs.

Cross-Over Studies↗
PubMed1994

Hepatitis following treatments with famotidine and then cimetidine.

OBJECTIVE: To report a case of hepatitis induced by two histamine (H2)-receptor blockers, famotidine and cimetidine. CASE SUMMARY: A 51-year-old obese woman with a duodenal ulcer developed symptomatic, famotidine-induced hepatitis. Other causes for hepatitis were ruled out. Famotidine was discontinued and the patient took omeprazole for a month without incident. Cimetidine therapy was then initiated and shortly thereafter, the patient developed another episode of symptomatic hepatitis that resolved upon drug discontinuation. Two abdominal ultrasound examinations six months apart and an abdominal computed tomography scan obtained later showed what appeared to be a stable, fatty liver. DISCUSSION: This appears to be the first reported case of clinical hepatitis related to famotidine and the first reported case where clinical hepatitis followed the administration of two different H2-receptor blockers. The fatty liver probably was secondary to obesity and incidental to the hepatitis episodes. CONCLUSIONS: Famotidine can cause clinical hepatitis, and drug-induced hepatitis can occur after the administration of two different H2-receptor blockers.

Chemical and Drug Induced Liver Injury↗
PubMed1994

Intracranial meningiomas of the first two decades of life.

Meningiomas arising in the first two decades of life are uncommon and their characteristics are controversial. Some authors believe meningiomas in younger patients occur in different locations, have more malignant histological features, and have a worse prognosis than those in adults. To address this controversy, the authors retrospectively reviewed 23 cases of meningiomas in patients under 21 years of age at diagnosis who were operated on at the University of Turin (1948 to 1990) or at the University of California, San Francisco (1970 to 1989). These tumors represented 2.9% of all tumors in this age group and 1.8% of all meningiomas during the study period at the two institutions. There were 14 males and nine females. The mean age at surgery was 13.3 +/- 5.6 years; nine cases occurred in the first decade and 14 in the second. The most common neurological symptoms were a focal neurological deficit (33%) and seizures (25%). Seventy percent of the tumors were supratentorial. A gross total resection was performed in 60% of the cases. Histologically, the majority (74%) of the tumors were meningothelial or mixed. An increased number of mitoses was observed in 33% of the tumors, focal necrosis in 29%, and invasion of adjacent brain in 14%; however, none of the tumors was classified as a Grade III (anaplastic) meningioma. All patients are alive without evidence of recurrent disease 3 to 22 years (mean +/- standard deviation: 10 +/- 7.3 years) after surgery. This study confirms the rarity of meningiomas of the first two decades of life and the absence of the female predominance associated with meningiomas in adults. The location and histological features of these tumors are similar to those in adults; they have a low recurrence rate, and the outcome and survival rate are excellent.

Adolescent↗
PubMed1993

A new method for analyzing the cell kinetics of human brain tumors by double labeling with bromodeoxyuridine in situ and with iododeoxyuridine in vitro.

BACKGROUND: Cell kinetics studies performed with immunohistochemical techniques to estimate the S-phase fraction have elucidated the proliferative potential of individual brain tumors. METHODS: The authors developed a new double-labeling method that enables other cell kinetics variables, including the duration of the S-phase (Ts) and the potential doubling time (Tp), to be measured from a single biopsy specimen. Using this method, 100 brain tumors were labeled with bromodeoxyuridine (BUdR) in situ and with iododeoxyuridine in vitro; labeled cells were identified by double staining with immunogold-silver and alkaline phosphatase techniques. RESULTS: Ts was fairly uniform (mean, 9.2 +/- 2.1 hour [+/- standard deviation]); range, 6.0-13.7 hours), but Tp varied from 1 day to more than 2 months. The Tp values correlated closely with the BUdR labeling index (LI), or S-phase fraction, and can be calculated from the equation: Tp = 26.9/LI1.02 (r = 0.98, P < 0.005). CONCLUSIONS: This new method facilitates the quantitation of the proliferative potential of individual brain tumors. The S-phase fraction, Ts, and Tp can be calculated from analysis of a single biopsy specimen. This method can be used to estimate the prognosis of individual patients with brain tumors and to select treatment modalities more directly than is possible with single-labeling studies with BUdR.

Biopsy↗
PubMed1993

Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression.

Meningioma is a common tumor of the central nervous system which displays morphological heterogeneity. In order to determine whether this phenotypic variability is associated with distinct or overlapping genetic lesions, we compared genotypes at several loci defined by allele length polymorphism in tumor and normal tissues from patients with meningioma. In particular, we concentrated on loci on chromosomes 22 and 10 because these genomic regions have previously been shown to be altered in the former in sporadic and familial meningiomas and in the latter as a late stage event in progression of another common brain tumor, astrocytoma. We examined 38 tumors which were classified as benign, atypical, or malignant by morphological criteria, invasive characteristics, or both. We found that loss of heterozygosity (LOH) for loci on chromosome 22 occurred in 5 of 15 benign, 2 of 2 atypical, and 5 of 10 malignant meningiomas. Similar alterations of chromosome 10 were found in 0 of 20 benign, 1 of 2 atypical, and 4 of 13 malignant meningiomas. Among the malignant tumors, LOH for loci on chromosome 10 occurred in 2 of 4 morphologically malignant tumors and in 2 of 4 morphologically and invasively malignant tumors. In contrast, LOH was not observed for any of the 5 informative tumors classified as malignant by invasive characteristics only. LOH for loci on chromosome 22 accompanied (but was not restricted to) allelic loss of loci on chromosome 10. These data suggest that the progression of meningiomas from arachnoidal cells to the morphologically malignant phenotype may, in part, entail the loss of a tumor suppressor gene(s) on chromosome 22 early in the process and that this may be compounded by alterations of chromosome 10, the LOH of which is associated with morphological signs of malignancy.

Adult↗
PubMed1993

Proliferative potential of brain tumors. Analyses with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nuclear organizer region counts.

Histochemical analyses with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies were done, and argyrophilic nucleolar organizer regions (Ag-NOR) were counted to estimate the proliferative potential of 200 brain tumors. The findings were compared with the bromodeoxyuridine labeling index (BrdU LI), or S-phase fraction. The proliferating cell indexes (PCI), determined by Ki-67 and anti-DNA polymerase alpha monoclonal antibodies were higher and Ag-NOR more numerous in medulloblastomas, glioblastomas, and metastatic carcinomas than in astrocytomas or meningiomas. The Ki-67 and DNA polymerase alpha PCI correlated with the BrdU LI (r = 0.87 and r = 0.84, respectively) and with each other (r = 0.94). The number of Ag-NOR correlated less strongly with these indexes in some tumors. These findings suggest that Ki-67 and anti-DNA polymerase alpha monoclonal antibodies may be useful for estimating the proliferative potential of individual tumors in routine clinical practice. The number of Ag-NOR, however, does not always reflect the growth potential of each tumor.

Antibodies, Monoclonal↗
PubMed1993

Cluster of testicular cancer in police officers exposed to hand-held radar.

Within a cohort of 340 police officers, six incident cases of testicular cancer occurred between 1979 and 1991 (O/E 6.9; p < 0.001, Poisson distribution). Occupational use of hand-held radar was the only shared risk factor among all six officers, and all routinely held the radar gun directly in close proximity to their testicles. Health effects of occupational radar use have not been widely studied, and further research into a possible association with testicular cancer is warranted.

Adult↗
PubMed1993

Monitoring of clinical trials and interim analyses from a drug sponsor's point of view.

This paper illustrates aspects of data monitoring of clinical trials in the pharmaceutical industry. Formal interim analyses are performed at least in part to address the question of whether the trial should proceed or whether there should be an early termination of the trial. For formal interim analyses, frequently independent data and safety monitoring committees are utilized for monitoring clinical trials, and adjustments to nominal significance levels for test statistics are required. Various statistical methods developed during the last fifteen years are utilized. Administrative interim analyses are those analyses that are performed without any intention to stop the trial as a consequence of those analyses. For administrative interim analyses, adjustments to significance levels may not be required, but results must still be carefully interpreted. Regardless of the interim analyses performed, it is critical that the plans for interim analyses be identified in the study protocol, and the dissemination of interim results be carefully restricted. The following clinical trials sponsored by Merck Sharp and Dohme Research Laboratories (MSDRL) will illustrate these points: CONSENSUS; CONSENSUS II; 4S; Haemophilus influenza type b efficacy trial; famotidine in upper gastrointestinal haemorrhage, and a phase II analgesic study. It is anticipated that data monitoring and interim analysis activities will increase for future clinical trials due to the availability of appropriate statistical methods and improved data management systems.

Clinical Trials as Topic↗
PubMed1993

Intracranial myxopapillary ependymoma: case report.

The authors report an unusual case of a myxopapillary ependymoma arising from the lateral ventricle. The patient, a 37-year-old woman, developed recurrent symptoms including scotomata, disorientation, and headache during two successive pregnancies before the definitive diagnosis. The causes of this ependymoma variant and its relationship to pregnancy are discussed.

Adult↗
PubMed1993

Gangliogliomas: a clinicopathological study of 25 cases and review of the literature.

The histopathological, clinical, and radiological findings in 25 patients (median age 20.5 years; range 1.7-64.2 years) with gangliogliomas were assessed to correlate degree of astrocytic anaplasia and proliferative potential with recurrence or survival. Most patients (64%) presented with seizures (median Karnofsky Performance Score 90%; range 70-100%). Computerized tomography and magnetic resonance imaging showed nonspecific abnormalities. Neoplastic ganglion cells were defined as heterotopic, irregularly grouped, or having more than one nucleus of bizarre shape or size. The astrocytic component was moderately anaplastic in 15 cases and highly anaplastic (HAA) in 10. Eight patients had gross total resection, 11 had subtotal resection, and six underwent biopsy. Ten patients (five gross total resection, three subtotal resection, two biopsy) had no further treatment, 15 underwent external irradiation, and five had adjuvant chemotherapy. Twenty-four patients are alive 15-394 weeks (median 203.5 weeks) postoperatively; one with ganglioglioma-HAA died at 65 weeks. No tumor recurred after gross total resection. Duration of preoperative symptoms < 1 year, greater anaplasia, and age > 30 years at diagnosis may have increased the risk of recurrence after subtotal resection or biopsy by four, three, and two times, respectively (not significant). Bromodeoxyuridine labeling index (BUdR LI) was < 1% in eight non-recurring tumors and 1.3% in another recurring twice (second recurrence LI = 1.6%). Most patients with ganglioglioma have a good prognosis. After gross total resection, only observation is required. After subtotal resection or biopsy, recurrence is possible. BUdR labeling may guide further therapy.

Adolescent↗
PubMed1993

Preferential expression in mushroom bodies of the catalytic subunit of protein kinase A and its role in learning and memory.

Involvement of the cAMP cascade in Drosophila learning and memory is suggested by the aberrant behavioral phenotypes of the mutants dunce (cAMP phosphodiesterase) and rutabaga (adenylyl cyclase). Line DCO581, isolated via an enhancer detector screen for genes preferentially expressed in the mushroom bodies, contains a transposon in the first exon of the catalytic subunit gene (DCO) of protein kinase A (PKA). RNA in situ hybridization and immunohistochemistry show that DCO is preferentially expressed in the mushroom bodies. The DCO581 insertion and an independently isolated hypomorphic allele (DCOB10) each produce homozygous lethality and a 40% decrease in PKA activity in heterozygotes. This decrease has mild effects on learning but no effect on memory. However, the 80% reduction in activity obtained by constructing heteroallelic yet viable DCO581/DCOB10 animals results in a dramatic learning and memory deficit. These results suggest that PKA plays a crucial role in the cAMP cascade in mushroom bodies to mediate learning and memory processes.

Animals↗
PubMed1993

Genetic dissection of the learning/memory gene dunce of Drosophila melanogaster.

The dunce (dnc) gene of Drosophila melanogaster codes for cAMP phosphodiesterase (PDE) and is required for normal learning/memory and for female fertility. The expression of the gene is elevated in mushroom bodies, brain structures implicated in olfactory learning and memory. In this study several chromosomal deletions and inversions that remove increasingly larger portions of the dnc gene from its 5' end and progressively more of the five known transcription start sites (tss) were used to assess the functions of the various transcriptional units. Surprisingly, the dnc PDE activity, female fertility, mushroom body expression, learning, and memory were unaffected by the removal of tss1 and tss2. tss3 was required for elevated mushroom body expression but not for female fertility nor initial learning. tss4 contributed to learning and the female fertility function, whereas tss5 contributed to female fertility. The results indicate that the structural complexity of the gene is of biological significance, with individual transcriptional units serving different biological functions.

3',5'-Cyclic-AMP Phosphodiesterases↗