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D Larson

Publications and source records attributed to D Larson.

At least 19 recordsLinked to original sources
PubMed2001

Temporary transverse colostomy vs loop ileostomy in diversion: a case-matched study.

HYPOTHESIS: For temporary fecal diversion, transverse colostomy (TC) has superior safety, but loop ileostomy (LI) has superior management qualities. METHODS: Of patients with TC or LI seen between 1988 and 1997, 63 patients were matched for diagnosis, operative procedure, and date of surgery. The 2 groups were then compared for hospital/postoperative mortality and morbidity and stoma complications. RESULTS: Mortality rates were 6.3% for the TC group and 1.6% for the LI group (P =.25). Morbidity rates for stoma creation and for stoma closure were 47.6% and 10% (P =.19), respectively, for the TC group, and 36.5% and 6.3% (P>.99), respectively, for the LI group. Most morbidity events were minor, and neither procedure-related nor other medical complications showed a significant difference between the groups. However, patients with a TC were significantly more likely to experience skin trouble around the stoma (TC vs LI, 15.9% vs 3.2%) and leakage around the stoma (TC vs LI, 12.7% vs 1.6%). CONCLUSIONS: Regarding safety, TC and LI should be considered equivalent options for temporary fecal diversion. We recommend further study comparing the 2 procedures with regard to patient perception and quality of life.

Adult↗
PubMed2001

Heterozygosity for a mutation in Brca1 or Atm does not increase susceptibility to ENU-induced mammary tumors in Apc(Min)/+ mice.

The proteins encoded by BRCA1 and ATM may be important in DNA repair and maintenance of genomic integrity. Women heterozygous for a mutation in BRCA1 have an increased incidence of breast cancer. Some evidence also suggests that female carriers of ATM mutations may be susceptible to breast cancer. However, mice carrying one mutant allele of Brca1 or ATM are not highly susceptible to breast cancer. We proposed that heterozygosity for a mutant allele of Brca1 or ATM may confer a decreased ability to repair DNA damage. Such a defect might lead to a heightened sensitivity to tumor development in susceptible animal models. Therefore, mice predispose to mammary tumor development might show an increased susceptibility if they also carry an ATM or Brca1 mutation. C57BL/6J (B6) MIN/+ mice are predisposed to mammary and intestinal tumors and exposure to the point mutagen ethylnitrosourea (ENU) markedly increases mammary tumor multiplicity and incidence. To test our hypothesis, B6.MIN/+ male mice were crossed with 129S6/SvEvTac females heterozygous for a mutant allele of either Brca1 or ATM. Female progeny from each cross were treated with ENU and followed for tumor development. Only MIN/+ F1 females developed mammary tumors and heterozygosity for a mutant Brca1 or ATM allele had no effect on mammary or intestinal tumor incidence and multiplicity. These results suggest that heterozygosity for a mutation in Brca1 or ATM: does not affect MIN-induced tumorigenesis in mice under these conditions. Additionally, exposure to a somatic point mutagen does not increase tumor development in mice carrying Brca1 or ATM mutations.

Animals↗
PubMed2000

Electro-migration of nitrate in sandy soil.

Migration of nitrate to groundwater has become a serious threat in many agricultural areas. This paper presents the results of experimental laboratory tests studying the nitrate gradient developed in response to an electrical potential. Two systems were tested; the first had no flow (closed system) and the second had flow opposite to the direction of the electrical current. A solution of sodium nitrate in sandy soil was used in both systems. The tests showed that the electro-kinetic process effectively concentrated and retained nitrate close to the anode. The movement of NO(3)(-) through the soil column was significantly influenced by the development of a pH gradient. Statistical analysis was performed to determine best-fit equations relating the nitrate gradient to the electrical input and pH gradient. A simple one-dimensional finite difference model was used to predict the pH gradient developed during the electro-kinetic process. The experimental measurements closely agreed with the predicted spatial and temporal distribution of the nitrate gradient for both closed and open system configurations.

Electrochemistry↗
PubMed2000

Pine bark extract reduces platelet aggregation.

The effects of long-term consumption of the bioflavonoid mixture, French maritime pine bark extract (Pycnogenol(R)), were assessed on aggregation of platelets from cigarette smokers and nonsmokers. Previously we showed that a single dose of Pycnogenol(R) reduced platelet aggregation in cigarette smokers in a dose-response fashion. Cigarette smoking increased platelet reactivity aggregation when measured 2 h after smoking the first cigarette of the day. Blood was collected immediately before and 5 min after smoking three cigarettes each. Smoking increased platelet aggregation (1.17 +/- 0.04). However 200 mg Pycnogenol(R)/day, taken 3 h prior to first cigarette for the day for 2 months, significantly (p <.0023) reduced smoke-induced platelet aggregation (0.98 +/- 0.05) to the level of nonsmokers. In a group of 19 nonsmokers, platelet aggregation was measured during in vitro stimulation by platelet aggregation factor (PAF) after 4 or 8 weeks of 200 mg/day of Pycnogenol(R) consumption. Platelet aggregation was significant when induced in vitro by PAF. However, Pycnogenol(R) consumption did not change platelet aggregation, suggesting that Pycnogenol(R)'s regulation of aggregation is by another mechanism. Thromboxane A2 (TxA2) is increased in smokers by release from platelets and rapidly becomes thromboxane B2 (TxB2). Smoking increased TxB2, which was prevented by Pycnogenol(R), lowering TxB2 levels to those of nonsmokers. However, Pycnogenol(R) had no effect on the lower levels of TxB2 in nonsmokers. These observations suggest that Pycnogenol(R) supplementation reduces a risk factor for cardiovascular diseases, that is, platelet aggregation in smokers. The bioflavonoids in Pycnogenol(R) reduced platelet aggregation stimulated by tobacco smoke.

Journal Article↗
PubMed2000

ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation.

We previously generated a mouse model with a mutation in the murine Atm gene that recapitulates many aspects of the childhood neurodegenerative disease ataxia-telangiectasia. Atm-deficient (Atm-/-) mice show neurological defects detected by motor function tests including the rota-rod, open-field tests and hind-paw footprint analysis. However, no gross histological abnormalities have been observed consistently in the cerebellum of any line of Atm-/- mice analyzed in most laboratories. Therefore, it may be that the neurologic dysfunction found in these animals is associated with predegenerative lesions. We performed a detailed analysis of the cerebellar morphology in two independently generated lines of Atm-/- mice to determine whether there was evidence of neuronal abnormality. We found a significant increase in the number of lysosomes in Atm-/- mice in the absence of any detectable signs of neuronal degeneration or other ultrastructural anomalies. In addition, we found that the ATM protein is predominantly cytoplasmic in Purkinje cells and other neurons, in contrast to the nuclear localization of ATM protein observed in cultured cells. The cytoplasmic localization of ATM in Purkinje cells is similar to that found in human cerebellum. These findings suggest that ATM may be important as a cytoplasmic protein in neurons and that its absence leads to abnormalities of cytoplasmic organelles reflected as an increase in lysosomal numbers.

Animals↗
PubMed2000

Ileal pouch-anal anastomosis in patients with indeterminate colitis: long-term results.

PURPOSE: Patients with chronic ulcerative colitis who undergo proctocolectomy and are found intraoperatively to harbor histologic signs suggesting Crohn's disease have indeterminate colitis; nonetheless, ileal pouch-anal anastomosis is usually performed. The aim of this study was to determine the long-term outcome of ileal pouch-anal anastomosis in patients with indeterminate colitis compared with a cohort of patients with chronic ulcerative colitis. METHOD: Review of an ileal pouch-anal anastomosis registry identified 1,437 patients with chronic ulcerative colitis and 82 patients with indeterminate colitis who underwent an ileal pouch-anal anastomosis between 1981 and 1995. The median follow-up was 83 (range, 1-192) months. Demographic data and functional outcomes were compared by chi-squared and Wilcoxon's rank-sum tests. Probabilities of complications and pouch failure were analyzed using Kaplan-Meier and log-rank techniques. Finally, Bonferroni adjustments were used for multiple comparisons. RESULTS: Patients with indeterminate colitis and chronic ulcerative colitis were comparable in terms of gender and length of follow-up. The mean age of the chronic ulcerative colitis group was higher (34 vs. 31; P < 0.01). At ten years patients with indeterminate colitis had significantly more episodes of pelvic sepsis (17 percent indeterminate colitis vs. 7 percent chronic ulcerative colitis; P < 0.001), pouch fistula (31 vs. 9 percent; P < 0.001), and pouch failure (27 vs. 11 percent; P < 0.001). Importantly, during follow-up fully 15 percent of patients with indeterminate colitis, but only 2 percent of patients with chronic ulcerative colitis, had their original diagnosis changed to Crohn's disease (P < 0.001). When the outcomes of these patients newly diagnosed with Crohn's disease were considered separately, the rate of complications for the remaining patients with indeterminate colitis was identical to that of patients with chronic ulcerative colitis. Functional outcomes were comparable among all three groups. CONCLUSION: After ileal pouch-anal anastomosis patients with indeterminate colitis who did not develop Crohn's disease subsequently experienced long-term outcomes nearly identical to patients with chronic ulcerative colitis. Crohn's disease, whether it develops after surgery for chronic ulcerative colitis or indeterminate colitis, is associated with poor long-term outcomes.

Adolescent↗
PubMed2000

Effect of complete response on outcome following autologous stem cell transplantation for myeloma.

We studied the effect of complete response (CR) among 126 consecutive patients who underwent stem cell transplantation (SCT) for myeloma. The CR rate with SCT was 33%. Median overall survival (OS) from diagnosis of myeloma was 56 months. OS following SCT was 22 months. Progression-free survival (PFS) was 12 months. OS was not different between patients who achieved CR and those who did not, median survival 25 vs 24 months, P = 0.5. Corresponding median times for PFS were 15 and 11 months, P = 0.2. The plasma cell labeling index (PCLI) was high (> or = 1%) in 36% (high risk group) and was associated with poor OS and PFS (P < 0.001). Achieving CR did not influence OS or PFS in either the high or the low risk group. In contrast, OS and PFS were significantly influenced by high PCLI both in patients who achieved CR and those who did not. OS was poor (< 30 months) in high risk patients regardless of CR status and in low risk patients who did not achieve CR, compared to low risk patients achieving CR (57 months), making them candidates for novel post-transplant treatment options. Outcome following SCT is dependent more on biological variables such as the PCLI than on CR status.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis.

OBJECTIVE: To assess long-term outcomes after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (CUC) with specific emphasis on patient sex, childbirth, and age. SUMMARY BACKGROUND DATA: Childbirth and the process of aging affect pelvic floor and anal sphincter function independently. Early function after IPAA is good for most patients. Nonetheless, there are concerns about the impact of the aging process as well as pregnancy on long-term functional outcomes after IPAA. METHODS: Functional outcomes using a standardized questionnaire were prospectively assessed for each patient on an annual basis. RESULTS: Of the 1,454 patients who underwent IPAA for CUC between 1981 and 1994, 1,386 were part of this study. Median age was 32 years. Median length of follow-up was 8 years. Pelvic sepsis was the primary cause of pouch failure irrespective of sex or age. Functional outcomes were comparable between men and women. Eighty-five women who became pregnant after IPAA had pouch function, which was comparable with women who did not have a child. Daytime and nocturnal incontinence affected older patients more frequently than younger ones. Incontinence became more common the longer the follow-up in older patients, but this was not found in younger patients. Poor anal function led to pouch excision in only 3 of 204 older patients. CONCLUSIONS: Incontinence rates were significantly higher in older patients after IPAA for CUC compared with younger patients. However, this did not contribute to a greater risk of pouch failure in these older patients. Patient sex and uncomplicated childbirth did not affect long-term functional outcomes.

Adult↗
PubMed2000

A preliminary study of the prognostic value of proton magnetic resonance spectroscopic imaging in gamma knife radiosurgery of recurrent malignant gliomas.

OBJECTIVE: The goal of this study was to investigate the use of proton magnetic resonance spectroscopic imaging as a prognostic indicator in gamma knife radiosurgery of recurrent gliomas. METHODS: Thirty-six patients with recurrent gliomas were studied with proton magnetic resonance spectroscopic imaging at the time of radiosurgery, and with conventional magnetic resonance imaging examinations at regular time intervals until the initiation of a new treatment strategy. Patients were categorized on the basis of their initial spectroscopic results, and their performance was assessed in terms of change in contrast-enhancing volume, time to further treatment, and survival. RESULTS: The trends in the overall population were toward more extensive increase in the percent contrast-enhancing volume, a decreased time to further treatment, and a reduced survival time for patients with more extensive initial metabolic abnormalities. Statistical analysis of the subpopulation of patients with glioblastoma multiforme found a significant increase in relative contrast-enhancing volume (P < 0.01, Wilcoxon signed-rank test), a decrease in time to further treatment (P < 0.01, log-rank test), and a reduction in survival time (P < 0.01, log-rank test) for patients with regions containing tumor-suggestive spectra outside the gamma knife target, compared with patients exhibiting spectral abnormalities restricted to the gamma knife target. Further studies are needed to establish statistical significance for patients with lower-grade lesions and to confirm the results observed in this study. CONCLUSION: The pretreatment spectroscopic results provided information that was predictive of outcome for this patient pool, both in local control (change in contrast-enhancing volume) and global outcome (time to further treatment and survival). This modality may have an important role in improving the selection, planning, and treatment process for glioma patients.

Adult↗
PubMed2000

The role of nitric oxide synthase/nitric oxide in vascular smooth muscle control.

Vascular compliance is dependent on endogenous and exogenous sources of nitric oxide (NO). In a discussion of therapeutics and NO derived via nitric oxide synthase (NOS) enzymes, it is necessary to examine the pathways of each drug to provide the clinical perfusionist with a greater understanding of the role of NOS/NO in vascular function. Endothelial-derived NO is a contributor in the vasoregulation of vascular smooth muscle. Therapeutics seek to mimic the vasodilatory effects of the endogenous NO. The therapeutics included in this review are nitroglycerin, nitroprusside, amyl nitrite, and inhalation of NO. L-Arginine supplementation provides additional substrate for the endogenous pathway that can augment NO production. NO is a small bioactive molecule involved in various biochemical pathways. Dysregulation of NO production can impair normal physiologic control of vascular compliance. Therefore, the purpose of this review is to provide the perfusionist with an understanding of the biochemical and pharmacological aspects of NOS/NO associated with vascular function.

Administration, Inhalation↗
PubMed1999

Pretreatment factors predict overall survival for patients with low-grade glioma: a recursive partitioning analysis.

PURPOSE: Three databases were pooled and analyzed to determine which groupings of prognostic factors best predicted overall survival for patients with low-grade gliomas treated with surgery and immediate or delayed radiotherapy. METHODS AND MATERIALS: Databases of patients with low-grade gliomas compiled at the London Regional Cancer Centre (LRCC), the Norwegian Radium Hospital (NRH), and the University of California, San Francisco (UCSF) were merged. Inclusion criteria for the pooled analysis included: age > or =18 years and histologically confirmed low-grade (World Health Organization Grade II) supratentorial fibrillary astrocytoma, oligodendroglioma or mixed oligoastrocytoma. Factors analyzed for prognostic significance included: age at diagnosis, gender, seizures at presentation, presence of enhancement on computed tomography (CT) or magnetic resonance imaging (MRI), Karnofsky Performance Status (KPS) at diagnosis, histology, extent of surgical resection, timing of radiotherapy, and treating institution. Univariate and multivariate analysis of overall survival for these factors was performed. Recursive partitioning was performed to generate prognostic groups using these factors. RESULTS: From the combined databases, 401 patients were eligible for analysis. Median survival for the entire group was 95 months/7.9 years. On univariate analysis age 18-40, presence of seizures at presentation, KPS > or =70, treating institution, and absence of contrast enhancement were associated with improved overall survival. On multivariate analysis, these factors remained independent predictors of improved overall survival. Recursive partitioning analysis yielded four prognostic groups with statistically different median survivals (MS): Group I (n = 41: KPS <70, age >40) MS 12 months; Group II (n = 34: KPS > or =70, age >40, enhancement present) MS 46 months; Group III (n = 138: KPS <70, age 18-40 or KPS > or =70 age >40, no enhancement) MS 87 months; Group IV (n = 188: KPS > or =70, age 18-40) MS 128 months. CONCLUSION: Clusters of pretreatment prognostic factors described subgroups of low-grade glioma patients with divergent overall survivals. Consideration of these prognostic subgroups may be important when considering timing of interventions for these patients and in the stratification of patients for clinical trials.

Adult↗
PubMed1999

Five year results of LINAC radiosurgery for arteriovenous malformations: outcome for large AVMS.

PURPOSE: For radiosurgery of large arteriovenous malformations (AVMs), the optimal relationship of dose and volume to obliteration, complications, and hemorrhage is not well defined. Multivariate analysis was performed to assess the relationship of multiple AVM and treatment factors to the outcome of AVMs significantly larger than previously reported in the literature. METHODS AND MATERIALS: 73 patients with intracranial AVMs underwent LINAC radiosurgery. Over 50% of the AVMs were larger than 3 cm in diameter and the median and mean treatment volumes were 8.4 cc and 15.3 cc, respectively (range 0.4-143.4 cc). Minimum AVM treatment doses varied between 1000-2200 cGy (median: 1600 cGy). RESULTS: The obliteration rates for treatment volumes < 4 cc, 4-13.9 cc, and > or = 14 cc were 67%, 58%, and 23%, respectively. AVM obliteration was significantly associated with higher minimum treatment dose and negatively associated with a history of prior embolization with particulate materials. No AVM receiving < 1400 cGy was obliterated. The incidence of post-radiosurgical imaging abnormalities and clinical complications rose with increasing treatment volume. For treatment volumes > 14 cc receiving > or = 1600 cGy, the incidence of post-radiosurgical MRI T2 abnormalities was 72% and the incidence of radiation necrosis requiring resection was 22%. The rate of post-radiosurgical hemorrhage was 2.7% per person-year for AVMs with treatment volumes < 14 cc and 7.5% per person-year for AVMs > or = 14 cc. CONCLUSION: As AVM size increases, the dose-volume range for the optimal balance between successful obliteration and the risk of complications and post-radiosurgical hemorrhage narrows.

Adolescent↗
PubMed1999

A multi-institutional analysis of complication outcomes after arteriovenous malformation radiosurgery.

PURPOSE: To better understand radiation complications of arteriovenous malformation (AVM) radiosurgery and factors affecting their resolution. METHODS AND MATERIALS: AVM patients (102/1255) who developed neurological sequelae after radiosurgery were studied. The median AVM marginal dose (Dmin) was 19 Gy (range: 10-35). The median volume was 5.7 cc (range: 0.26-143). Median follow-up was 34 months (range: 9-140). RESULTS: Complications consisted of 80/102 patients with evidence of radiation injury to the brain parenchyma (7 also with cranial nerve deficits, 12 also with seizures, 5 with cyst formation), 12/102 patients with isolated cranial neuropathies, and 10/102 patients with only new or worsened seizures. Severity was classified as minimal in 39 patients, mild in 40, disabling in 21, and fatal in 2 patients. Symptoms resolved completely in 42 patients for an actuarial resolution rate of 54% +/- 7% at 3 years post-onset. Multivariate analysis identified significantly greater symptom resolution in patients with no prior history of hemorrhage (p = 0.01, 66% vs. 41%), and in patients with symptoms of minimal severity: headache or seizure as the only sequelae of radiosurgery (p < 0.0001, 88% vs. 34%). CONCLUSION: Late sequelae of radiosurgery manifest in varied ways. Further long-term studies of these problems are needed that take into account symptom severity and prior hemorrhage history.

Adrenal Cortex Hormones↗
PubMed1999

Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation.

Cre-mediated excision of exon 11 of the breast-tumour suppressor gene Brca1 in mouse mammary epithelial cells causes increased apoptosis and abnormal ductal development. Mammary tumour formation occurs after long latency and is associated with genetic instability characterized by aneuploidy, chromosomal rearrangements or alteration of Trp53 (encoding p53) transcription. To directly test the role of p53 in Brca1-associated tumorigenesis, we introduced a Trp53-null allele into mice with mammary epithelium-specific inactivation of Brca1. The loss of p53 accelerated the formation of mammary tumours in these females. Our results demonstrate that disruption of Brca1 causes genetic instability and triggers further alterations, including the inactivation of p53, that lead to tumour formation.

Alleles↗