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Biomedical subjects

B E Johnson

Publications and source records attributed to B E Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1993

Individualized chemotherapy for patients with non-small cell lung cancer determined by prospective identification of neuroendocrine markers and in vitro drug sensitivity testing.

We attempted to prospectively select individualized chemotherapy for 165 non-small cell lung cancer patients based on in vitro analysis of neuroendocrine (NE) markers and drug sensitivity testing (DST) using fresh tumor. The chemotherapy used for small cell lung cancer (SCLC) was selected when NE marker expression determined by L-dopa decarboxylase assay was documented. Selection of chemotherapy for other patients was guided by DST results using a modified dye exclusion assay when available; otherwise etoposide and cisplatin was administered. A total of 112 of 165 (68%) specimens were assayed for L-dopa decarboxylase and 36 patients (22%) had DST. In vitro data directed management for 27 of 96 (28%) patients given chemotherapy: 6 with NE markers were treated with the SCLC regimen; and 21 (58% of those with DST) received their DST-selected chemotherapy regimen. There were no significant differences in response rate among all 3 treatment arms (P = 0.076). However, response to chemotherapy for the patients treated prospectively with a SCLC regimen was 3 of 6 (50%), marginally better than patients given their DST-selected chemotherapy regimen (2 of 21; 9%; P = 0.056) or those treated with etoposide and cisplatin (10 of 69; 14%; P = 0.061). When patients whose NE markers were identified retrospectively are included, 4 of 9 (44%) responded to administered chemotherapy, compared to 7 of 55 (13%) with no NE markers present (P = 0.04). There were no differences in survival among the three treatment groups. Cisplatin and etoposide comprised the most active regimen in vitro for tumors from 16 of 36 (44%) patients, potentially limiting the benefit of DST since this is often the empiric therapy for non-SCLC. Furthermore, the correlation between in vitro and clinical response is nonsignificant for all drugs tested, highlighting the overall relative resistance of non-SCLC tumors to currently available chemotherapy.

Antineoplastic Agents↗
PubMed1993

IA-1, a new marker for neuroendocrine differentiation in human lung cancer cell lines.

IA-1 is a recently isolated novel complementary DNA which encodes a protein of 510 amino acids that contains both a zinc finger DNA-binding domain and a putative prohormone domain. mRNA expression of IA-1 has been found thus far only in tumors of neuroendocrine origin. In this report we describe the expression of IA-1 mRNA in a panel of 64 human lung cancer cell lines. IA-1 mRNA was detected by Northern blot analysis in 97% (30 of 31) of small cell lung cancer cell lines. In contrast, IA-1 mRNA was detected in only 13% (4 of 30) of non-small cell lung cancer cell lines. Nine of the 30 (30%) expressed either chromogranin A mRNA or produced L-dopa decarboxylase. Four of these 9 (44%) had detectable levels of IA-1 mRNA. In most of the lung cancer cell lines examined, IA-1 showed high concordance with the other neuroendocrine markers, L-dopa decarboxylase, and chromogranin A. The one exception was a variant small cell lung cancer cell line which expressed low or nondetectable levels of L-dopa decarboxylase. IA-1 is a candidate marker of neuroendocrine differentiation of human lung tumors.

Biomarkers, Tumor↗
PubMed1993

Smoking cessation after successful treatment of small-cell lung cancer is associated with fewer smoking-related second primary cancers.

OBJECTIVE: To determine the incidence of second primary cancers developing in patients surviving free of cancer for 2 or more years after treatment for small-cell lung cancer and to assess the potential effect of smoking cessation. DESIGN: Retrospective review of 540 patients from a single institution with a median follow-up of 6.1 years. SETTING: A single government institution (the National Cancer Institute). PATIENTS: Consecutive sample of 540 patients with histologically confirmed small-cell lung cancer treated from 1973 through 1989 on therapeutic clinical trials. MEASUREMENTS: The relative risk for second primary cancers and death were calculated in patients who remained free of cancer for 2 years after initiation of therapy. The relation of these end points to smoking history was also determined. RESULTS: Fifty-five patients (10%) were free of cancer 2 years after initiation of therapy. Eighteen of these patients developed one or more second primary cancers, including 13 who developed second primary non-small-cell lung cancer. The risk for any second primary cancer compared with that in the general population was increased four times (relative risk, 4.4; 95% CI, 2.5-7.2), with a relative risk of a second primary non-small-cell lung cancer of 16 (CI, 8.4-27). Forty-three patients discontinued smoking within 6 months of starting treatment for small-cell lung cancer, and 12 continued to smoke. In those who stopped smoking at time of diagnosis, the relative risk of a second lung cancer was 11 (CI, 4.4 to 23), whereas, in those who continued to smoke, it was 32 (CI, 12 to 69). CONCLUSIONS: Patients with small-cell lung cancer who survive cancer-free for more than 2 years have a significantly increased risk for development of a second primary smoking-related cancer. Cigarette smoking cessation after successful therapy is associated with a decrease in risk for a second smoking-related primary cancer.

Aged↗
PubMed1993

Human small cell lung cancer cell lines express functional atrial natriuretic peptide receptors.

Small cell lung cancer cell (SCLC) lines, NCI-H82, NCI-H660, and NCI-H1284, and HeLa cells were analyzed for the presence of atrial natriuretic peptide (ANP) receptors. In these SCLC cell lines and HeLa cells, ANP A receptor mRNA was identified by Southern blot analyses of polymerase chain reaction products and RNase protection assays using poly(A)(+)-selected RNA. Saturable binding assays revealed that HeLa cells had 2000 to 5000 high affinity atrial natriuretic peptide receptors per cell with a dissociation constant of 140 pM. In the SCLC cell lines, the binding was saturable but too low to accurately estimate the number of binding sites. After addition of human ANP, radioimmunoassays revealed accumulation of cyclic GMP in SCLC cells as well as HeLa cells in a dose-dependent fashion. The half-maximal stimulation concentration of cyclic GMP accumulation in HeLa and these SCLC cell lines was approximately 2 nM. Tetrazolyl blue assays and tritiated thymidine incorporation did not show any remarkable growth inhibition or growth stimulation of SCLC cell lines after addition of human ANP up to 3.3 microM, more than 1000-fold greater than the half-maximal stimulation concentration of cyclic GMP accumulation. Our results indicate that human SCLC cells express functional ANP receptors but ANP addition produced no detectable change in their growth pattern.

Atrial Natriuretic Factor↗
PubMed1993

Application of an algorithm for staging small-cell lung cancer can save one third of the initial evaluation costs.

OBJECTIVE: Design of a cost-effective algorithm for staging disease in patients with small-cell lung cancer. DESIGN: An algorithm was constructed by analyzing all permutations of a sequence of procedures required to stage disease in patients with small-cell lung cancer. Procedural costs were determined, and the model was applied to the small-cell lung cancer patient population treated at the National Cancer Institute, Bethesda, Md, from 1973 to 1989. The final algorithm was derived from the permutation with the lowest cost per accurately staged patient. SETTING: A single government institute, the National Cancer Institute. PATIENTS: Four hundred fifty-one patients with previously untreated, consecutive histologically documented small-cell lung cancer entered into therapeutic protocols at the National Cancer Institute from April 1973 through July 1989. Data were obtained from small-cell lung cancer protocol databases and patients' medical records. MAIN OUTCOME MEASURE: The cost per patient of each sequence of staging procedures when applied to the patient population. RESULTS: The least expensive sequence of procedures saved $1418 per patient when compared with application of a standard set of staging procedures to all patients. The major factor in reducing costs was the concept of stopping the staging procedures after a site of distant metastatic disease had been identified. CONCLUSIONS: An algorithm consisting of a set of sequential staging procedures can accurately stage disease in patients with small-cell lung cancer and save more than one third of the costs of an inclusive standard set of staging procedures.

Algorithms↗
PubMed1993

Phase I trial of dihydrolenperone in lung cancer patients: a novel compound with in vitro activity against lung cancer.

Antitumor activity of the butyrophenone dihydrolenperone in non-small cell lung cancer was initially suggested by in vitro screening against tumor cells derived from fresh surgical samples using the human tumor colony-forming assay. We have completed a directed phase I trial in patients with lung cancer. Thirty-two patients with lung cancer have completed 25 courses of therapy at doses of 10 to 60 mg/square meter orally on a twice daily schedule. Twenty-three men and 9 women with a median age of 55 (range 24-69) were entered. Twenty-four were performance status 0 or 1 and 8 were 2. The maximum tolerated dose was 50 mg/square meter orally twice daily and the dose limiting toxicity was somnolence. Of the 32 patients, 18 developed symptomatic hypotension (grade 1 or 2). There was no significant hematologic, renal, or hepatic toxicity. In vitro drug testing using the MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (thiazolyl blue)] assay confirmed 50% inhibition of non-small cell and small cell lung cancer cell line growth at 70-450 micromolar concentrations. Plasma dihydrolenperone levels were at least 75-fold less than levels at which in vitro activity was observed. We conclude: 1) the maximum tolerated dose in our study is 50 mg/square meter orally twice daily, 2) the dose-limiting side effect of dihydrolenperone is somnolence, and 3) the concentrations of dihydrolenperone observed in plasma are significantly lower than those associated with in vitro activity.

Adult↗
PubMed1993

Medicine on British television: a content analysis.

Fifty-four British television programs on medical topics were viewed and analyzed during a four-month period in the winter of 1988-89. Medical programs of a nonfictional, nondramatic variety were represented on all four channels of British television with 75% appearing on the BBC. The primary format was that of a documentary; most offerings were during peak television viewing hours and were 30-50 minutes in length. Principal settings were within the realm of clinical medicine or health care delivery. The location of filming was in hospitals rather than outpatient areas. Doctors were presented as experts, but general practitioners were infrequently represented. The health care team was generally treated in a sympathetic manner. Psychiatric/behavioral and neurologic topics appeared frequently, with common medical problems and preventive medicine rarely emphasized.

Attitude to Health↗
PubMed1993

Evaluation of the vertical forces generated by the cervical biteplate facebow.

The biteplate facebow has been recommended for use in the correction of Class II malocclusions with deep overbites. This facebow is similar in design to the conventional cervical facebow with the addition of an inner bow metal plate. The plate presses against the maxillary incisors and prevents the patient from fully closing, thus acting as a biteplate. A test apparatus was constructed to simulate the force system present during application of the facebow. In this study, high resolution force transducers were used to measure the intrusive forces on the maxillary and mandibular incisors. Static force analysis techniques were then used to calculate the vertical force component of the first molars. Analyses were performed using a wide range of relative bow angles, neck strap tensions of 200 grams and 400 grams, and various mandibular incisor occluding forces. The molar eruptive forces of the biteplate facebow are found to exceed those of the standard cervical facebow by a low of 158% to a high of 537%, depending on the neck strap tension and the inner bow/outer bow angle. While the intrusive forces on the maxillary incisors were excessive, no intrusion is anticipated because the biteplate disarticulates the posterior teeth and the eruption of the unopposed maxillary molars would likely cause the occlusal plane to tip in a counter-clockwise direction. Consequently, the overbite correction would be obtained through maxillary molar eruption accompanied by occlusal plane tipping. Before considering use of the biteplate facebow, a patient's anticipated growth pattern, the magnitude of the intrusive forces and the treatment objectives should be evaluated.

Activator Appliances↗
PubMed1993

Force generation by orthodontic coil springs.

Nickel titanium (NiTi) coil springs are a new development in orthodontics, designed to produce light continuous forces. This study compares the force delivery by NiTi open and closed coil springs during unloading (de-activation) to that provided by comparable stainless steel (SS) springs. Open-coil springs (0.010 x 0.035 inch) were compressed from their initial length of 15 mm to 6 mm and the forces generated with spring recovery recorded. Closed-coil springs (0.009 x 0.035 inch) were distracted from their initial length of 3 mm to 9 mm and the force recorded as the spring recovered. The closed-coil NiTi springs produced light continuous forces of 75-90 g over the distraction range of 6 mm while the open-coil springs produced forces of 55-70 g within the 9 mm compression range. SS springs produced heavier forces, ca. 200 g, for an activation of 1 mm and the generated force increased rapidly as the activation was increased. The findings indicate that NiTi coil springs deliver optimal forces for orthodontic tooth movement over a longer activation range than comparable SS springs.

Humans↗
PubMed1993

An analysis of orthodontic force systems applied to the dentition with diminished alveolar support.

Many more adults are undergoing orthodontic therapy than in the past. Since adult dentitions often exhibit diminished alveolar support, it is important to recognize the related apical migration of the dental centre of resistance when applying force systems to the teeth. The force system compensations necessary to produce controlled movement in this circumstance are analysed in a model of a maxillary canine undergoing translation.

Adult↗
PubMed1993

Narrow-band (TL-01) UVB air-conditioned phototherapy for chronic severe adult atopic dermatitis.

In an open study of 21 severely affected adult atopic dermatitis patients, air-conditioned narrow-band UVB phototherapy using the Philips TL-01 lamp three times weekly for 12 weeks resulted in a 68% reduction in atopic dermatitis severity scores, with a concomitant 88% reduction in potent topical steroid use. Follow-up at 24 weeks revealed that six patients had relapsed to > 70% of pre-phototherapy severity scores; the remaining 15 continued to derive long-term benefit. The mean value of potent topical steroid use remained 50% below pre-phototherapy needs. Narrow-band UVB (TL-01) phototherapy appears an effective, steroid-sparing treatment for chronic severe atopic dermatitis, offering long-term benefits in the majority of those treated.

Adult↗
PubMed1993

Clinical and laboratory studies of the photosensitizing potential of norfloxacin, a 4-quinolone broad-spectrum antibiotic.

Cutaneous photosensitivity reactions are a consistent although uncommon feature of the fluoroquinolone group of antibiotics, which are related to nalidixic acid. Objective laboratory and clinical data are now routinely required by regulatory bodies for new drugs suspected of being photosensitizers, but no clear recommendations exist. A series of in vitro tests ranging in complexity revealed a UVA-dependent phototoxic potential for the fluoroquinolone norfloxacin similar to that for ciprofloxacin, and less than that of nalidixic acid. Controlled monochromator phototesting, designed to reveal the clinical characteristics, wavelength dependence and severity of cutaneous reactions in normal subjects showed both norfloxacin and ciprofloxacin to have a weak phototoxic potential which clears within 4 weeks of stopping the drug. UVA wavelengths (335 +/- 30 nm; 365 +/- 30 nm) appear most responsible for producing an asymptomatic erythema which is maximal at 24 h. The clinical study differs from those used previously in being blind, containing positive and negative controls, and phototesting after cessation of drug intake. The methodology has the anticipated limitation of failing to detect idiosyncratic photosensitivity responses.

Adolescent↗
PubMed1993

A comparison of narrow band phototherapy (TL-01) and photochemotherapy (PUVA) in the management of polymorphic light eruption.

Twenty-five patients suffering from severe polymorphic light eruption (PLE) were randomized to either photochemotherapy (PUVA) or narrow-band phototherapy (TL-01 UVB) treatment in early spring; patients receiving UVB were given placebo tablets to achieve a matching therapy procedure. During the 4 months following treatment, patient exposure to solar UVB was monitored with polysulphone badges. PLE occurrence, severity, and restriction of outdoor activity were recorded, using weekly diary-sheets. Analysis of covariance on this data, using the logarithm of UVB exposure as the explanatory variable, showed no significant differences between the treatments. TL-01 UVB is an effective alternative to PUVA in the management of PLE.

Adult↗
PubMed1993

Action spectra for the trans to cis photoisomerisation of urocanic acid in vitro and in mouse skin.

Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans-UCA to cis-UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans-UCA to cis-UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range 270-340 nm. The resulting action spectra were very similar with maximal effectiveness at 300-315 nm and equal activity at 270 nm and 325-330 nm, demonstrating that UVA-II radiation (320-340 nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans-UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis-UCA formation in skin and UV-induced immunosuppression may be complex.

Animals↗
PubMed1993

Comparative potency of broad-band and narrow-band phototherapy sources to induce edema, sunburn cells and urocanic acid photoisomerization in hairless mouse skin.

The Philips TL01 narrow-band (311-313 nm) fluorescent lamp provides effective phototherapy for psoriasis and atopic eczema while emitting less erythemogenic radiation than conventional broad-band (e.g. Philips TL12; 270-350 nm) sources. We studied the potency of TL01 and TL12 radiation to induce edema and sunburn cells (SBC) and to photoisomerize naturally occurring trans-urocanic acid (UCA) to cis-UCA in hairless mouse skin. Cis-UCA has immunosuppressive properties and is a putative mediator of UV-induced suppression of immune responses. For each source, there was UV dose dependence for all three responses. Within the dose ranges used, the potency ratio of TL12:TL01 radiation to induce equivalent edema and SBC was about 6:1. However, the potency ratio to induce cis-UCA was less than 2.3:1. Therefore, at a given level of edema or SBC induction, TL01 was more efficient than TL12 at UCA photoisomerization. The TL01 induction of immunomodulating cis-UCA, while causing minimal skin injury, may relate to the therapeutic efficacy of this source in skin conditions with an immunological component.

Albinism↗
PubMed1993

Overview of genetic and molecular events in the pathogenesis of lung cancer.

Research on dominant oncogenes and tumor suppressor genes has characterized differences in genetic lesions between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and identified associations with clinical parameters. More than one half of all lung cancers contain a mutation of the p53 tumor suppressor gene. There does not appear to be an association between the presence of this mutation and survival. A ras family oncogene was found to be mutated in approximately 20 percent of tumors and tumor cell lines from patients with NSCLC in contrast to none of 45 tumors and tumor cell lines from patients with SCLC. The presence of a K-ras mutation was determined to be an adverse prognostic factor for survival in retrospective studies of patients with NSCLC. Mutations of K-ras are more common in tumors from smokers than nonsmokers and have not been detected in lung cancers resulting from occupational exposure to radon. Mutations in both the p53 gene and K-ras oncogene are most commonly G to T transversions in lung cancer vs G to A transitions in other cancers. Prospective studies of these mutations in resected tumor specimens taken from patients with accurate follow-up may continue to provide important clues about their potential clinical and biologic significance.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

Management of small-cell lung cancer.

SCLC typically presents as a central endobronchial lesion in chronic cigarette smokers with hilar enlargement and disseminated disease. The diagnostic pathology should be reviewed by a pathologist who is accomplished in reading pulmonary pathology and if any doubt exists in the diagnosis, additional special stains and/or diagnostic material should be obtained. Patients with extensive stage disease should be managed by combination chemotherapy, whereas patients with limited stage disease should be treated with combination chemotherapy and chest radiotherapy. The chemotherapy should be administered for 4 to 6 months and discontinued; patients should be retreated with chemotherapy if they relapse. Prophylactic cranial radiation is an appropriate option for patients who achieve a complete remission. The patients who are in complete remission should be carefully observed for second cancers and appropriate therapy should be administered if the cancers appear.

Antineoplastic Combined Chemotherapy Protocols↗