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Biomedical subjects

R Wheeler

Publications and source records attributed to R Wheeler.

At least 37 records · Page 2Linked to original sources
PubMed1988

Fast horizontal electrophoresis. II. Development of fast automated staining procedures using PhastSystem.

The development of equipment for fast automated staining is described. It is possible to handle staining procedures with up to 20 steps and nine different solutions. To increase the reaction rate in the reaction chamber, the gels are rotated and high temperatures are used. The temperature in the reaction chamber is controlled between room temperature and 50 degrees C. Increased temperature, above 20 degrees C, generally results in faster staining and destaining. However, some reactions proceed better at a low temperature, including fixation of proteins with TCA, and the development step in silver staining, where increased temperatures cause a high background stain. Silver staining using acidic silver nitrate solution is preferred, due to easy preparation and good storage stability of the reagents. This method also causes little precipitation of silver on the walls of the reaction chamber. Silver staining is accomplished within one hour. Staining with PhastGel Blue is accomplished within 30 min.

Automation↗
PubMed1988

Simultaneous therapy with high-dose cisplatin and radiation for unresectable squamous cell cancer of the head and neck: a phase I-II study.

Studies using simultaneous radiation therapy and conventional doses of cisplatin have suggested improvement in local control and patient survival. This study was undertaken to determine toxicity and patient tolerance to concomitant high-dose cisplatin (40 mg/m2 per day X 5) and radiation (60 Gy in 6 wk +/- 10-Gy boost to residual tumor). Seventeen patients with advanced, inoperable squamous cell cancer primary tumor in the head and neck were treated (15 males and 2 females; median age, 57 yr). Cisplatin was started on day 1 of radiation therapy and repeated every 28 days for three cycles. Normal saline infusion (250 ml/hr) was started 12 hours prior to the first dose and continued 12 hours after the fifth dose. The daily dose of cisplatin was dissolved in 250 ml of 3% NaCl and given over 30 minutes. The cisplatin dose for subsequent cycles was reduced 10 mg/m2 per day only for a nadir granulocyte count less than 500/mm3 or fever greater than 101 degrees F during leukopenia. Of the 17 patients who started therapy, 15 have completed therapy; 1 patient died after one cycle, and 1 died after two cycles. Eleven patients received three cycles of cisplatin, and 10 patients required one dose reduction (6 at course 2 and 4 at course 3). Seven possible infections were successfully treated. Grade 2 neuropathy occurred in 3 patients, and renal toxicity greater than grade 1 occurred in 1 patient. Additional toxic effects were median WBC count nadir of 1.8 X 10(3)/mm3, platelet count nadir of 128 X 10(3)/mm3, hemoglobin nadir of 9.8 g/dl, and median weight loss of 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Intra-arterial chemotherapy for head and neck cancer. An update on the totally implantable infusion pump.

Intra-arterial chemotherapy for the treatment of localized malignant neoplasms in the head and neck is an appealing approach for several reasons. Perhaps the most important is the possibility of obtaining a regional advantage such that an increased drug concentration is delivered systemically. The patient may, therefore, be spared systemic toxicity. We report our accumulated experience using a totally implantable infusion pump in 37 patients. A total of 42 pumps were implanted: 28 single-catheter pumps and 14 dual-catheter pumps. Radionuclide imaging demonstrated total perfusion of the tumor in all patients. A combination of cisplatin (50 to 100 mg/m2) and floxuridine (0.01 to 0.045 mg/kg/d) was used to treat 26 patients. For these heavily pretreated patients, we observed a 43% complete and partial response rate in the subgroup of patients with squamous cell carcinoma. These results are comparable with those reported for these drugs administered systemically and for other drug combinations tested in the treatment of recurrence disease.

Adolescent↗
PubMed1987

The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite: Part I. Exposure estimates.

The vermiculite ore and concentrate of a mine and mill near Libby, Montana, was found to be contaminated with fibrous tremolite-actinolite. Of 599 fibers (length greater than 5 microns and width greater than 0.45 micron) counted in eight airborne membrane filter samples, 96% had an aspect ratio greater than 10 and 16% had an aspect ratio greater than 50. Additionally, 73% of the fibers were longer than 10 microns, 36% were longer than 20 microns, and 10% were longer than 40 microns. Estimates of exposure before 1964 in the dry mill were 168 fibers/cc for working areas, 182 fibers/cc for sweepers, 88 fibers/cc for skipping, and 13 fibers/cc for the quality control laboratory. In 1964-1971, exposure estimates for these areas were 33, 36, 17, and 3 fibers/cc, respectively. Estimates of exposures in the mine before 1971 ranged from 9-23 fibers/cc for drillers and were less than 2 fibers/cc for nondrilling jobs. All 8-hr TWA job exposure estimates decreased from 1972-1976, and from 1977-1982 were less than 1 fiber/cc.

Air Pollutants, Occupational↗
PubMed1987

The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite: Part II. Mortality.

The vermiculite ore and concentrate of a mine and mill located near Libby, Montana was found to be contaminated with a fiber of the tremolite/acetinolite series. A study was conducted to estimate the exposure-response relationship for mortality for 575 men who had been hired prior to 1970 and employed at least 1 year at the Montana site. Individual cumulative fiber exposure (fiber-years) was calculated. Results indicated that mortality from nonmalignant respiratory disease (NMRD) and lung cancer was significantly increased compared to the U.S. white male population. For those workers more than 20 years since hire, the standard mortality rate (SMR) for lung cancer (ICDA 162-163) was 84.7, 225.1, 109.3, and 671.3 for less than 50, 50-99, 100-399, and more than 399 fiber-years respectively. Corresponding results for NMRD (ICDA 460-519) were 327.8, 283.5, 0, and 278.4. Based on a linear model for greater than 20 years since hire, the estimated percentage increase in lung cancer mortality risk was 0.6% for each fiber-year of exposure. At 5 fiber-years, the estimated percentage was 2.9% from an unrestricted (nonthreshold) linear model and 0.6% from a survival model.

Aluminum Silicates↗
PubMed1987

Intra-arterial cisplatin and FUDR in advanced malignancies confined to the head and neck.

Twenty-seven patients with advanced malignancies confined to the head and neck region were treated with intra-arterial (IA) cisplatin and 5-fluorodeoxyuridine (FUDR) using implantable pumps or injection ports. Tumor histologies were: 16 squamous cell, one mucoepidermoid, one adenocarcinoma, one neuroendocrine, four adenoid cystic, two acinic cell, one fibrosarcoma, and one melanoma. All primaries originated from tissues in the head and neck area. Nineteen patients had received prior treatment, including chemotherapy in 13; eight were newly diagnosed. Responses in 26 evaluable patients were two complete (CR), ten partial (PR), six minor (MR), and eight progressions. The median duration of response was 5 months, with a range of 2 to 11 months. Sites of progression were within the infused volume in 13 patients and to uninfused local-regional or distant sites in eight. The response rate in the subset of 15 patients with squamous cell head and neck cancer was 47%. Toxicity in the 26 patients included stomatitis in 88%, nausea and vomiting in 64%, myelosuppression in 15%, and grade 1 nephrotoxicity in 1%. A regional advantage for IA cisplatin and FUDR can be calculated based on total body clearance rates (CLTB) for these agents and estimates of external carotid artery (ECA) blood flow. However, frequent progression of disease outside the infused volume to regional and distant sites limits the usefulness of this approach in recurrent disease patients.

Adult↗
PubMed1986

Time to conception after IUD removal: importance of duration of use, IUD type, pelvic inflammatory disease and age.

Some investigations of IUD use have demonstrated impaired ability to become pregnant after removal, while others have not. None of these studies, however, have adequately considered such potentially influencing variables as age and a history of pelvic inflammatory disease (PID). To study the effect of length of IUD use, IUD type and the modifying influences of age and PID history on time required to conceive, we followed women trying to become pregnant after removal of their IUD. Five hundred forty women in Ljubljana, Yugoslavia who were first fitted with an IUD between 1964 and 1972 and had their IUD removed in order to become pregnant were followed through 1980. We found no relationship between the duration of IUD use or type of IUD used, but increasing age and a history of PID each decreased the monthly probability of conception. These findings, along with other recent work, indicate that IUDs are a safe and efficacious contraceptive for women at low risk for sexually transmitted diseases.

Adult↗
PubMed1986

Phase I clinical trial of CO17-1A monoclonal antibody.

Twenty patients with metastatic gastrointestinal cancer received one or more weekly infusions of 400 mg CO17-1A monoclonal antibody. The most common side effect was mild gastrointestinal symptoms in 9/20 patients. Two of five patients receiving three weekly infusions had reversible anaphylactic reactions at the time of their third infusion. The pharmacokinetics of the antibody were similar at the first, second or third infusion. Human antibody to 17-1A occurred in 17/20 patients with 11/20 having antibody detectable by 8 days following initial infusion. Thus, one or two infusions (weekly) of large doses of 17-1A were well tolerated but allergic responses limit ability to administer therapy by 15 days post-initial infusion.

Animals↗
PubMed1984

Experimental studies of the pathogenesis of infections owing to Pseudomonas aeruginosa: elastase, an IgG protease.

Pseudomonas aeruginosa elastase, but not alkaline protease, degraded pooled, normal, human IgG in vitro and this degraded IgG lost its protective effect when used to treat burned, P. aeruginosa infected mice. Plasma IgG levels in burned, uninfected mice declined immediately postburning, but remained relatively constant thereafter; the levels in burned, P. aeruginosa infected mice continued to decline until death ensued. Infection of burned mice with an elastase+ strain caused the IgG decline, while infection with an elastase- strain did not, suggesting that elastase production caused the in vivo decline in plasma IgG. Local treatment with the protease inhibitor alpha 2-macroglobulin, of burned mice infected with an elastase+ organism, reduced the IgG decline observed in control mice. These data support the hypothesis that P. aeruginosa elastase acts as an IgG protease both in vitro and in vivo and gives insight into how this enzyme may act as a virulence factor in P. aeruginosa.

Animals↗
PubMed1984

Effect of furosemide on urinary acidification in distal renal tubular acidosis.

Furosemide stimulates urinary acidification in normal humans probably by increasing distal Na delivery and transport, thus creating a favorable electric gradient for H+ and K secretion. Therefore, furosemide should stimulate urinary acidification in patients with distal renal tubular acidosis, provided the distal nephron is capable of transporting Na and the H+ pumps can respond to the favorable electric gradient. We examined the effect of short-term furosemide administration on urinary acidification in five normal participants and 12 patients with normokalemic, hypokalemic, or hyperkalemic distal renal tubular acidosis. In controls, furosemide decreased urine pH and increased net acid and K excretion. In six of eight patients with normokalemic or hypokalemic renal tubular acidosis, furosemide decreased urine pH and increased net acid and K excretion to levels not significantly different from control values. The patients that had normal responses were interpreted as having a rate-dependent or gradient distal renal tubular acidosis, and thus increased distal Na delivery created a favorable electric gradient for H+ and K secretion. The normokalemic patients who did not have a response were considered to have a defect in the pumps (secretory defect). Of the four hyperkalemic patients, two had a voltage-dependent defect and the other two had aldosterone deficiency. The patients with selective aldosterone deficiency had low baseline urine pH values that did not change with furosemide administration, but net acid and K excretion did increase significantly. The patients with voltage-dependent defect did not lower urine pH or increase net acid and K excretion. Our data demonstrate that administration of furosemide enhances urinary acidification in certain patients with distal renal tubular acidosis. We suggest that furosemide administration may be useful in the characterization of the mechanism responsible for distal renal tubular acidosis and in the treatment of distal renal tubular acidosis in selected patients.

Acidosis, Renal Tubular↗
PubMed1983

T lymphocyte subpopulations in idiopathic thrombocytopenic purpura (ITP).

Absolute T cell counts and the relative distributions of antibody-defined helper and cytotoxic/suppressor T lymphocytes are reported in 26 patients with chronic idiopathic thrombocytopenic purpura (ITP). T cell numbers are generally normal in ITP and alterations in relative helper (OKT4 positive) and suppressor (OKT8 positive) T cell numbers show no consistent patterns, although 35% of the cases examined showed inverted distributions. The combined percentages of helper and suppressor T cells consistently exceeded 100% in ITP indicating the presence of increased OKT4+8+ cells in these patients. A cell population, previously defined as SRBC positive and OKT3 negative, was found in the normal group and in ITP patients following splenectomy but was absent in those patients with intact spleens. The role of these changes in the pathogenesis of ITP is discussed.

Adolescent↗
PubMed1983

Metabolic acidosis.

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Acid-Base Equilibrium↗
PubMed1982

Improved regional selectivity of hepatic arterial BCNU with degradable microspheres.

Starch microspheres 40 micrometers in diameter, which are rapidly degraded by serum amylase, have been administered through hepatic arterial catheters to five patients with primary and metastatic liver cancer to determine whether (1) arterial blood flow through the liver could be temporarily blocked, and (2) such occlusion at the level of the arteriolar capillary bed would enhance regional uptake and catabolism and decrease systemic exposure to simultaneously administered hepatic arterial bischlorethylnitrosourea (BCNU). It was possible with 10 ml of microspheres (9 X 10(6) microspheres/ml) injected into the hepatic artery to transiently (for 15-30 minutes) reduce hepatic flow by 80-100% in the five patients. When BCNU (50 mg/m2 in one minute) was given with microspheres there was a 30-90% reduction in systemic nitrosourea exposure and in peak levels. No myelosuppression was noted and hepatic toxicity consisted of acute pain due to BCNU and 1.5-2.0 fold transient enzyme elevations. One patient with cholangiocarcinoma showed a partial response lasting three months; three patients had stable disease and one patient with colon carcinoma had progressive disease. Thus, this pilot study suggests that concurrent intra-arterial microspheres and BCNU may have the potential to improve selective regional drug effect with marked diminution in systemic toxicity.

Carmustine↗
PubMed1982

Totally implanted system for intravenous chemotherapy in patients with cancer.

A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphomas) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.

Antineoplastic Agents↗
PubMed1982

Development and evaluation of an inhibitor-releasing matrix for intrauterine devices.

Antifibrinolytic agents when released into the uterine cavity decrease menorrhagia associated with IUD use. Our objective was to develop a matrix that could be incorporated onto an IUD and release anti-fibrinolytic agents. The copolymer ethylene-vinyl acetate (EVA) was selected for detailed study because it has the advantage over other materials in that it can release large molecular weight substances for more than 100 days, and allows incorporation of large amounts of anti-fibrinolytic agents with different molecular weights. Two compounds, tranexamic acid (AMCA, MW=157) and Trasylol (Kunitz pancreatic trypsin inhibitor, (MW=6,500) were incorporated into the EVA matrix and their release rates measured. In vitro studies with AMCA showed that after the initial burst, a constant high release rate was obtained over a prolonged period of time. The in utero release rate of AMCA from the EVA matrix in rabbits was similar to that obtained in vitro. By contrast, the release rate of Trasylol decreased to low levels during incubation in vitro. The release rate of Trasylol in utero however, appeared to be higher than that in vitro.

Animals↗
PubMed1982

Flagellar preparations from Pseudomonas aeruginosa: animal protection studies.

Recent reports have suggested that motility is associated with virulence in Pseudomonas aeruginosa. We have confirmed this observation by showing that groups of mice immunized with P. aeruginosa flagellar-antigen preparations display enhanced survival when they are subsequently burned and challenged locally in the burned area with strains of P. aeruginosa. The protection appears to be due to the immobilization of the microorganisms in the burned skin tissue. Liver elongation factor 2 is also protected. The protection afforded by immunization with flagellar-antigen preparations is independent of the somatic antigenic type of the challenging strain but is flagellar-antigen specific. These data suggest that vaccination with flagellar-antigen preparations may provide a viable prophylactic or therapeutic alternative to antibiotic therapy for use in compromised patient population in which P. aeruginosa poses a serious infection threat.

Animals↗