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H Nelson

Publications and source records attributed to H Nelson.

At least 19 recordsLinked to original sources

Limits on spin-independent interactions of weakly interacting massive particles with nucleons from the two-tower run of the cryogenic dark matter search.

We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 (12) kg d for the Ge (Si) targets after cuts, averaged over recoil energies 10-100 keV for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10(-43) cm2 from Ge and 3 x 10(-42) cm2 from Si, for a WIMP mass of 60 GeV/c2. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results and constrains predictions of supersymmetric models.

Journal Article↗

First results from the Cryogenic Dark Matter Search in the Soudan Underground Laboratory.

We report the first results from a search for weakly interacting massive particles (WIMPs) in the Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory. Four Ge and two Si detectors were operated for 52.6 live days, providing 19.4 kg d of Ge net exposure after cuts for recoil energies between 10 and 100 keV. A blind analysis was performed using only calibration data to define the energy threshold and selection criteria for nuclear-recoil candidates. Using the standard dark-matter halo and nuclear-physics WIMP model, these data set the world's lowest exclusion limits on the coherent WIMP-nucleon scalar cross section for all WIMP masses above 15 GeV/c2, ruling out a significant range of neutralino supersymmetric models. The minimum of this limit curve at the 90% C.L. is 4 x 10(-43) cm2 at a WIMP mass of 60 GeV/c2.

Journal Article↗

Socioeconomic status and prevalence of allergic rhinitis and atopic eczema symptoms in young adolescents.

Environmental factors are known to influence the development of allergic rhinitis and atopic eczema in genetically susceptible individuals. Socioeconomic status (SES) may be an important indicator of risk for these conditions. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase 1 written questionnaire was used to determine the prevalence and severity of allergic rhinoconjunctivitis and atopic eczema symptoms in 4947 pupils aged 13-14 years attending 30 schools in socioeconomically diverse areas of Cape Town. Home addresses were used to stratify participants into five SES bands. Relationships between symptom prevalence and severity, and SES, recent urbanization and upward socioeconomic mobility were examined. Logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (CI) in order to assess overall trends by SES. The prevalences of self-reported allergic rhinitis symptoms and recurrent itchy rash in the past year were 33.2% and 11.9% respectively. Girls had a significantly higher prevalence of all symptoms than boys. The prevalence of allergic rhinitis symptoms increased from lowest to highest SES (overall OR for rhinitis symptoms in past year = 1.16, 95% CI 1.11-1.21). There was no significant trend in reported eczema symptoms by SES other than for the question, 'Have you ever had eczema' (OR = 0.88, 95% CI 0.83-0.93). Longer period of urbanization was weakly associated only with recurrent itchy skin rash (OR = 1.05, 95% CI 1.01-1.09). 'Socially mobile' pupils, i.e. those resident in the lowest SES areas but attending highest SES schools showed significantly higher prevalences of eczema and some rhinitis symptoms than pupils attending lowest SES schools. These findings may reflect differences in reporting related to language, culture and access to medical care rather than real differences in prevalence.

Adolescent↗

Desmoid tumors in familial adenomatous polyposis: a pilot project evaluating efficacy of treatment with pirfenidone.

OBJECTIVES: Pirfenidone (Deskar, Marnac Inc., Dallas, TX), 5-methyl-1-phenyl-2-(1H)-pyridone, is a broad-spectrum, noncytotoxic, oral antifibrotic agent that is reported to inhibit or block the action of cytokine growth factors: transforming growth factor beta1, platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor, and to prevent formation of new fibrotic lesions. METHODS: We enrolled 10 women and four men with extensive familial adenomatous polyposis (FAP)-associated desmoid disease in a 2-yr open-label treatment trial with oral pirfenidone. Imaging of desmoids was conducted at baseline and 6, 12, and 24 months. RESULTS: No drug toxicity or drug intolerance was encountered. Seven patients dropped out (three because of progressive disease), and seven continued for at least 18 months. Of those that continued, two had partial but significant reduction in the size of all desmoids beginning in the first 6 months of treatment, and two others experienced relief of symptoms without change in desmoid size. Three patients experienced no change in tumor size or symptoms. CONCLUSIONS: Pirfenidone is well tolerated by patients with FAP-associated desmoid tumors. Some patients with FAP/desmoid tumors treated with pirfenidone had regression of tumors, some had progression, and some had no response. Patients with rapidly growing tumors did not respond to pirfenidone. A placebo-controlled trial is needed to determine whether there is a subset of patients for whom pirfenidone may result in partial shrinkage of desmoid tumors, because the natural history of desmoid tumors is not predictable or understood.

Adenomatous Polyposis Coli↗

Laparoscopic colectomy for colon cancer.

Surgical resection is the primary treatment for colon cancer. The introduction and acceptance of laparoscopic colectomy for cancer has been gradual for a number of reasons including the fact that it is technically challenging, has less than dramatic patient benefits, and perhaps most significantly it could theoretically represent a compromise as an oncologic procedure. Preliminary evidence suggests that laparoscopic colectomy for colon cancer is safe, feasible, and can be performed with acceptable operative times and conversion rates. Furthermore, it may offer important patient-related advantages and the same extent of resection as in open surgery can be achieved. It may result in improved outcomes when performed by experienced surgeons. The early experience with high rates of wound recurrences has not been realized in current reports. Ongoing prospective, randomized trials should establish whether laparoscopic colectomy is as effective as open colectomy in preventing recurrence and death from colon cancer; until then this procedure is not considered standard for patients with curable colon cancer.

Adenocarcinoma↗

Socioeconomic deprivation and asthma prevalence and severity in young adolescents.

This study used the international study of asthma and allergies in childhood (ISAAC) to investigate the association between asthma and socioeconomic deprivation among young adolescents in Cape Town, South Africa. The completed ISAAC written and video questionnaires of 4,706 13-14-yr-old school pupils were used. The prevalence of asthma symptoms was analysed by a local index of socioeconomic deprivation, based on residential location and defined on a 10-category scale from least to most deprived. Linear trends were examined visually and the prevalence odds ratio was used to summarize overall trends. In general, the least socioeconomically deprived pupils reported higher prevalences of asthma symptoms "ever" and "in the last 12 months". In contrast, the most socioeconomically deprived pupils reported higher asthma-symptom occurrence monthly or more frequently in the previous 12 months. A subgroup of pupils from low-income areas commuting to better-off schools showed the highest symptom prevalences. The findings are consistent with a model in which an increase in the incidence of asthma is driven by factors associated with improved social circumstances, whereas severity is determined by factors associated with poverty. The impact of social mobility on asthma, including reporting of symptoms, deserves closer study.

Adolescent↗

Impact of surgical and pathologic variables in rectal cancer: a United States community and cooperative group report.

PURPOSE: Substantial and successful effort has been focused on decreasing the risk of local failure after rectal cancer surgery through the use of adjuvant therapies. Our study examined data from studies conducted by United States cooperative groups to investigate the impact of surgical and pathologic variables in rectal cancer outcomes. PATIENTS AND METHODS: Surgical and pathologic reports from 673 patients with stage II/III rectal cancer enrolled onto three adjuvant clinical trials were reviewed for tumor and surgical variables. Additional information on individual institutions and operating surgeon was collected. Variables were tested for association with 5-year local recurrence and survival after adjustment for adjuvant treatments and other important prognostic factors. RESULTS: Five-year local recurrence and survival rates were 16% and 59%, respectively. Surgeons treating more than 10 study cases had lower local recurrence rates than those treating < or = 10 (11% v 17%, P =.02). Free radial margins also correlated with local recurrence (P =.01). Type of surgery, distal margins, and tumor radial spread were not significant. Tumor adherence to adjacent structures predicted local recurrence (35% v 14%, P <.001) and survival (30% v 63%, P <.001), regardless of en bloc resection. Although T and N classification predicted survival (P <.001), only N classification correlated with local recurrence. The number and percentage of positive nodes correlated with survival, but only the percentage independently predicted local recurrence. Several pathologic and surgical variables were reported suboptimally. CONCLUSION: Moderate variability in outcomes among surgeons was detected in this high-risk population. Efforts to improve surgical results will require changes in reporting practices to allow for more accurate assessment of the quality of surgery.

Clinical Trials as Topic↗

Features of V-ATPases that distinguish them from F-ATPases.

The general structure of F- and V-ATPases is quite similar and they may share a common mechanism of action that involves mechanochemical energy transduction. Both holoenzymes are composed of catalytic sectors, F1 and V1 respectively, and membrane sectors, F(o) and V(o) respectively. Although we assume that a similar mechanism underlies ATP-dependent proton pumping by F- and V-ATPases in eukaryotic cells, the latter cannot catalyze pmf-driven ATP synthesis. The loss of this ability is probably due to a proton slip that is a consequence of alterations in its membrane sector. The major events include gene duplication of the proteolipids and the presence of three distinct proteolipids in each complex.

Adenosine Triphosphate↗

The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas.

A comprehensive analysis of somatic and germline mutations related to DNA mismatch-repair (MMR) genes can clarify the prevalence and mechanism of inactivation in colorectal carcinoma (CRC). In the present study, 257 unselected patients referred for CRC resection were examined for evidence of defective DNA MMR. In particular, we sought to determine the frequency of hereditary defects in DNA MMR in this cohort of patients. MMR status was assessed by testing of tumors for the presence or absence of hMLH1, hMSH2, and hMSH6 protein expression and for microsatellite instability (MSI). Of the 257 patients, 51 (20%) had evidence of defective MMR, demonstrating high levels of MSI (MSI-H) and an absence of either hMLH1 (n=48) or hMSH2 (n=3). All three patients lacking hMSH2, as well as one patient lacking hMLH1, also demonstrated an absence of hMSH6. DNA sequence analysis of the 51 patients with defective MMR revealed seven germline mutations-four in hMLH1 (two truncating and two missense) and three in hMSH2 (all truncating). A detailed family history was available for 225 of the 257 patients. Of the seven patients with germline mutations, only three had family histories consistent with hereditary nonpolyposis colorectal cancer. Of the remaining patients who had tumors with defective MMR, eight had somatic mutations in hMLH1. In addition, hypermethylation of the hMLH1 gene promoter was present in 37 (88%) of the 42 hMLH1-negative cases available for study and in all MSI-H tumors that showed loss of hMLH1 expression but no detectable hMLH1 mutations. Our results suggest that, although defective DNA MMR occurs in approximately 20% of unselected patients presenting for CRC resection, hereditary CRC due to mutations in the MMR pathway account for only a small proportion of patients. Of the 257 patients, only 5 (1.9%) appear to have unequivocal evidence of hereditary defects in MMR. The epigenetic (nonhereditary) mechanism of hMLH1 promoter hypermethylation appears to be responsible for the majority of the remaining patients whose tumors are characterized by defective DNA MMR.

Adaptor Proteins, Signal Transducing↗

Guidelines 2000 for colon and rectal cancer surgery.

BACKGROUND: Oncologic resection techniques affect outcome for colon cancer and rectal cancer, but standardized guidelines have not been adopted. The National Cancer Institute sponsored a panel of experts to systematically review current literature and to draft guidelines that provide uniform definitions, principles, and practices. METHODS: Methods were similar to those described by the American Society of Clinical Oncology in developing practice guidelines. Experts representing oncology and surgery met to review current literature on oncologic resection techniques for level of evidence (I-V, where I is the best evidence and V is the least compelling) and grade of recommendation (A-D, where A is based on the best evidence and D is based on the weakest evidence). Initial guidelines were drafted, reviewed, and accepted by consensus. RESULTS: For the following seven factors, the level of evidence was II, III, or IV, and the findings were generally consistent (grade B): anatomic definition of colon versus rectum, tumor-node-metastasis staging, radial margins, adjuvant R0 stage, inadvertent rectal perforation, distal and proximal rectal margins, and en bloc resection of adherent tumors. For another seven factors, the level of evidence was II, III, or IV, but findings were inconsistent (grade C): laparoscopic colectomy; colon lymphadenectomy; level of proximal vessel ligation, mesorectal excision, and extended lateral pelvic lymph node dissection (all three for rectal cancer); no-touch technique; and bowel washout. For the other four factors, there was little or no systematic empirical evidence (grade D): abdominal exploration, oophorectomy, extent of colon resection, and total length of rectum resected. CONCLUSIONS: The panel reports surgical guidelines and definitions based on the best available evidence. The availability of more standardized information in the future should allow for more grade A recommendations.

Colonic Neoplasms↗

Intraoperative irradiation for locally recurrent colorectal cancer in previously irradiated patients.

PURPOSE: Information in the literature regarding salvage treatment for patients with locally recurrent colorectal cancer who have previously been treated with high or moderate dose external beam irradiation (EBRT) is scarce. A retrospective review was therefore performed in our institution to determine disease control, survival, and tolerance in patients treated aggressively with surgical resection and intraoperative electron irradiation (IOERT) +/- additional EBRT and chemotherapy. METHODS AND MATERIALS: From 1981 through 1994, 51 previously irradiated patients with recurrent locally advanced colorectal cancer without evidence of distant metastatic disease were treated at Mayo Clinic Rochester with surgical resection and IOERT +/- additional EBRT. An attempt was made to achieve a gross total resection before IOERT if it could be safely accomplished. The median IOERT dose was 20 Gy (range, 10--30 Gy). Thirty-seven patients received additional EBRT either pre- or postoperatively with doses ranging from 5 to 50.4 Gy (median 25.2 Gy). Twenty patients received 5-fluorouracil +/- leucovorin during EBRT. Three patients received additional cycles of 5-fluorouracil +/- leucovorin as maintenance chemotherapy. RESULTS: Thirty males and 21 females with a median age of 55 years (range 31--73 years) were treated. Thirty-four patients have died; the median follow-up in surviving patients is 21 months. The median, 2-yr, and 5-yr actuarial overall survivals are 23 months, 48% and 12%, respectively. The 2-yr actuarial central control (within IOERT field) is 72%. Local control at 2 years has been maintained in 60% of patients. There is a trend toward improved local control in patients who received > or =30 Gy EBRT in addition to IOERT as compared to those who received no EBRT or <30 Gy with 2-yr local control rates of 81% vs. 54%. Distant metastatic disease has developed in 25 patients, and the actuarial rate of distant progression at 2 and 4 years is 56% and 76%, respectively. Peripheral neuropathy was the main IOERT-related toxicity; 16 (32%) patients developed neuropathies (7 mild, 5 moderate, 4 severe). Ureteral narrowing or obstruction occurred in seven patients. All but one patient with neuropathy or ureter fibrosis received IOERT doses > or =20 Gy. CONCLUSION: Long-term local control can be obtained in a substantial proportion of patients with aggressive combined modality therapy, but long-term survival is poor due to the high rate of distant metastasis. Re-irradiation with EBRT in addition to IOERT appears to improve local control. Strategies to improve survival in these poor-risk patients may include the more routine use of conventional systemic chemotherapy or the addition of novel systemic therapies.

Adult↗

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↗

Laparoscopic ultrasonography: a training model.

PURPOSE: The purpose of this study was to develop a surgical training program and to test the accuracy of laparoscopic ultrasound in detecting injected lesions in pig livers. METHODS: Pig livers were divided into eight segments and injected with Surgilube "malignant" and silicone "benign" lesions. All were examined by laparoscopic ultrasound followed by liver explantation to confirm results. First, a pilot study was conducted on six swine by injecting Surgilube lesions and performing laparoscopic ultrasound through 3 different ports (left upper quadrant (I), umbilicus (II), and right lower quadrant (III)) to determine per-segment accuracy and to optimize port placement. Second, blinded injection of Surgilube and silicone implants was done on 18 pigs with laparoscopic ultrasound conducted through the two most accurate ports from the pilot study. This model was then tested during a resident training workshop. RESULTS: In the pilot study, per-lesion and per-segment sensitivity was 96 percent, with no difference among the three ports used. Ports I and II were chosen for the blinded study for their convenience in performing laparoscopic colectomy. In the blinded study, per-segment sensitivity, specificity, and accuracy were 97 percent, 94 percent, and 96 percent and 99 percent, 94 percent, and 97 percent for ports I and II, respectively. At the conclusion of a pilot workshop, trainee per-segment sensitivity, specificity, and accuracy were 60 percent, 80 percent, and 70 percent, respectively. The major difficulty was differentiating benign from malignant lesions. CONCLUSIONS: A useful liver laparoscopic ultrasound training model for surgeons was developed with good preliminary results. It is anticipated that further training will enhance laparoscopic ultrasound accuracy rates before application of this modality in humans.

Animals↗

Adenosquamous and squamous carcinoma of the colon and upper rectum: a clinical and histopathologic study.

PURPOSE: Squamous and adenosquamous carcinoma of the colon and proximal rectum are rare neoplasms in which the clinicopathologic behavior and the most appropriate management are unknown. The purpose of this study was to review the histology and clinical course of the largest series of cases ever reported from a single center on this rare condition. METHOD: The Mayo Clinic tissue registry was searched for all primary cases of squamous and adenosquamous carcinoma of the colon or rectum proximal to 8 cm from the dentate and presenting before December 31, 1992. Of the 52 identified cases there was adequate histologic material for review in 44 cases. These cases were divided into pure squamous-cell carcinoma (n = 11), mixed adenosquamous carcinoma (n = 31), and adenocarcinoma with benign-appearing squamous metaplasia (adenoacanthoma; n = 2). Squamous-cell carcinomas were examined for evidence of human papilloma virus by in situ hybridization. A retrospective review of medical records was undertaken in all 52 cases with respect to predisposing factors, clinicopathologic behavior, prognostic features, and treatment with adjuvant therapy. RESULTS: The charts of 52 patients (20 females), with a mean age of 58.6 (range, 19-90) years, were reviewed. Right-sided lesions were the most common (43 percent). Metastatic disease was evident at presentation in 49 percent of patients, the most common sites in order being liver, peritoneal, and lung. The five-year overall survival rate was 34 percent, Stage I to III disease had a 65 percent five-year survival rate, and Stage IV mean survival time was 8.5 months. For node-positive and node-negative disease, 23 and 85 percent, respectively, survived five years. There was no evidence of human papilloma virus in the six squamous-cell carcinomas examined. CONCLUSION: Squamous and adenosquamous carcinomas of the colon and rectum are rare neoplasms. Although a poor prognosis can be expected for node-positive disease, patients with negative nodes do generally the same as patients with adenocarcinoma histology. Based on advances made with multimodality therapy of squamous-cell cancer of the anus and adenocarcinoma of the rectum, further studies should define the role of postoperative therapies for these lesions.

Adenocarcinoma↗

Effective control of asthma with hydrofluoroalkane flunisolide delivered as an extrafine aerosol in asthma patients.

BACKGROUND: Inhaled corticosteroids are established as maintenance therapy for persistent asthma. A new aerosol formulation of flunisolide delivers a small particle size by using a hydrofluoroalkane (HFA) propellant with a built-in spacer. OBJECTIVE: To compare efficacy and safety of two different flunisolide formulations, HFA and chlorofluorocarbon (CFC), with placebo treatment over a range of doses. METHODS: The multicenter, randomized, double-blind, placebo-controlled trial consisted of a 2-week, active run-in phase with CFC flunisolide 500 microg, twice daily, followed by 12 weeks of double-blind treatment with placebo, HFA flunisolide (85, 170, or 340 microg, twice daily), or CFC flunisolide (250, 500, or 1,000 microg, twice daily). Patients (N = 669) were nonsmokers, at least 12 years of age, with mild to moderate asthma who were being treated with inhaled corticosteroids. Outcome measures were change from baseline in forced expiratory volume in 1 second (FEV1), peak expiratory flow rate, as needed albuterol use, nocturnal awakenings, and asthma symptoms. RESULTS: After 12 weeks of treatment, patients receiving 170 microg, twice daily, and 340 microg, twice daily, of HFA flunisolide showed a significant (P < 0.01) improvement in percentage increase in FEV1 (12.22% at 170 microg, twice daily, and 14.69% at 340 microg, twice daily) compared with the placebo group (5.35%). At one-third the dose of CFC flunisolide, HFA flunisolide provided similar improvement in pulmonary function versus placebo. Both formulations demonstrated comparable linear dose dependency for the change from baseline in FEV1 without any evidence of cortisol suppression. Outcome values for all seven secondary efficacy measures were numerically superior in patients receiving HFA flunisolide compared with the CFC formulation. Both formulations seemed to be safe and well tolerated. CONCLUSIONS: HFA flunisolide provides comparable efficacy and safety at one-third the dose of CFC flunisolide.

Administration, Inhalation↗

Laparoscopic colectomy for colon cancer--a trial update.

OBJECTIVES: A prospective randomized trial was designed to test the hypothesis that disease-free survival and overall survival are equivalent regardless of whether patients receive laparoscopic assisted colectomy (LAC) or open colectomy. Secondary and tertiary aims will test the safety of LAC and the impact of LAC on quality of life and costs, respectively. METHODS: 1200 patients will be accrued and randomly assigned to LAC or open colectomy. Consenting adults with primary colon cancer without previous or concurrent malignancies and with tumors considered resectable for cure are eligible for enrollment. Patients will be followed postoperatively for evidence of recurrence and for survival and perioperatively for morbidity, mortality, quality of life, and cost end points. RESULTS: Over 800 patients have been enrolled to date. Early trial results are available for 408 patients, 203 open and 205 LAC. As anticipated, patients are evenly distributed within the two treatment arms according to age, gender, and anesthesia risk (ASA classification). In the open arm, the mean age is 69 with 52 percent females, 87 percent ASA I/II and 13 percent ASA III. In the laparoscopic arm, the mean age is 67, with 48 percent females, 87 percent ASA I/II, and 13 percent ASA III. A total of 160 right and 117 sigmoid colectomies have been performed. Extent of resection data is also available and all parameters tested show no difference between the LAC and open cases: for the laparoscopic vs open colectomy, total bowel length 26 cm vs 27 cm; proximal margins 12 cm vs 11 cm; distal margins 10 cm vs 12 cm; mesenteric length 9 cm vs 8 cm. Similarly, the number of nodes resected for laparoscopic colectomy is essentially the same (mean 12 lymph nodes) to that for open surgery (mean 13 nodes). CONCLUSIONS: Although this study is ongoing; preliminary results suggest that open and LAC provide for the same extent of resection. The quality of life portion of the study is now complete and data will soon be available.

Aged↗