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Biomedical subjects

J F Fowler

Publications and source records attributed to J F Fowler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Vascular targeting of solid tumours: a major 'inverse' volume-response relationship following combretastatin A-4 phosphate treatment of rat rhabdomyosarcomas.

Tumour-specific vascularisation may be therapeutically approached in two different ways: by antiangiogenic treatments specifically directed to dividing and migrating endothelial cells, or by agents that target principally the inadequate and ill-structured tumour vasculature. Combretastatin A-4 phosphate (combreAp), a recently synthesised prodrug (OXiGENE, Lund, Sweden), is a vascular targeting agent of the latter kind. We evaluated the effect of a single intraperitoneal (i.p.) combreAp injection on the growth of rhabdomyosarcomas syngeneic in WAG/Rij rats. Different tumour volume groups, ranging between 0.1 and 27 cm(3), were selected to assess the relationship between the size at treatment time and the response to combreAp. A double combreAp treatment (2x25 mg/kg) was investigated within the same overall aim: the relationship between growth delay and tumour size. Our results show that the systemic administration of combreAp induces a clear-cut differential growth delay in the solid rat rhabdomyosarcomas: with very large tumours (>/= 14 cm(3)), a 17.6-fold stronger effect was measured than with very small tumours (<1 cm(3)). This is the 'inverse' of the volume-response seen with the conventional therapeutic approaches (radiotherapy, chemotherapy or surgery). These combreAp antitumour responses were observed without treatment limiting systemic toxicity in the rats. With clinical digital subtraction angiography, using microsurgical cannulation of a major tumour draining vessel, and with histopathology, we demonstrate that growth delay is related to an early (within 3-6 h) and extensive breakdown of tumour blood vessels. The experiments involving a second injection also indicate a volume-dependent effect of combreAp in reducing the regrowth rate of small or large rhabdomyosarcomas. This significant differential volume-response obtained with 'selective' vascular targeting, stronger in larger tumours than smaller ones, suggests the potential of broadening the therapeutic window.

Angiography, Digital Subtraction↗
PubMed2000

Efficacy of a skin-protective foam in the treatment of chronic hand dermatitis.

BACKGROUND: Irritant and/or allergic hand dermatitis in individuals who are unable to avoid causative exposures is difficult to control. Usefulness of protective creams has been generally unsatisfactory. OBJECTIVE: To determine if hand dermatitis, primarily of an occupational nature, could be improved by the use of a protective foam containing dimethicone and glycerin. METHODS: Adult male and female subjects with chronic hand dermatitis for at least 12 months, felt to be either allergic, irritant, or combined in nature were given the study foam for routine application after a 2-week observation period. At 2 and 6 weeks the skin was evaluated by the investigator and subject for parameters including redness, scaling, fissuring, blistering, and pruritus on a numerical scale. A global evaluation also was performed. Photographs were taken at each visit. Usage of topical corticosteroids was recorded. No systemic therapies other than antihistamines were allowed. RESULTS: Thirty-one subjects were enrolled in the study and 28 completed it. The physician and subject's initial global evaluations averaged 6.13 and 5.48, respectively (0-10 scale). The final scores were 3.68 and 4.75, respectively (P < .001 for physician rating; P = .259 for subject rating). Topical corticosteroid usage was reduced in 16 of 30 (53.6%) subjects. Twenty-one of 30 subjects (70.0%) had improved over the course of the study. No adverse effects were noted. CONCLUSION: This protective foam greatly or moderately improved chronic hand dermatitis in a sizable number of individuals with previously uncontrolled dermatitis despite continuing in their regular occupation.

Administration, Topical↗
PubMed2000

Systemic contact dermatitis caused by oral chromium picolinate.

Although nickel is the metal most commonly implicated in systemic contact dermatitis, other metals such as chromate have also been known to cause dermatitis when ingested. Chromium picolinate has been espoused as a nutritional supplement. Allegedly, it helps control blood sugar in diabetes and may reduce cholesterol and blood pressure levels.

Administration, Oral↗
PubMed1999

Medium-dose-rate brachytherapy of cancer of the cervix: preliminary results of a prospectively designed schedule based on the linear-quadratic model.

PURPOSE: To compare results and complications of our previous low-dose-rate (LDR) brachytherapy schedule for early-stage cancer of the cervix, with a prospectively designed medium-dose-rate (MDR) schedule, based on the linear-quadratic model (LQ). METHODS AND MATERIALS: A combination of brachytherapy, external beam pelvic and parametrial irradiation was used in 102 consecutive Stage Ib-IIb LDR treated patients (1986-1990) and 42 equally staged MDR treated patients (1994-1996). The planned MDR schedule consisted of three insertions on three treatment days with six 8-Gy brachytherapy fractions to Point A, two on each treatment day with an interfraction interval of 6 hours, plus 18 Gy external whole pelvic dose, and followed by additional parametrial irradiation. The calculated biologically effective dose (BED) for tumor was 90 Gy10 and for rectum below 125 Gy3. RESULTS: In practice the MDR brachytherapy schedule achieved a tumor BED of 86 Gy10 and a rectal BED of 101 Gy3. The latter was better than originally planned due to a reduction from 85% to 77% in the percentage of the mean dose to the rectum in relation to Point A. The mean overall treatment time was 10 days shorter for MDR in comparison with LDR. The 3-year actuarial central control for LDR and MDR was 97% and 98% (p = NS), respectively. The Grades 2 and 3 late complications (scale 0 to 3) were 1% and 2.4%, respectively for LDR (3-year) and MDR (2-year). CONCLUSIONS: LQ is a reliable tool for designing new schedules with altered fractionation and dose rates. The MDR schedule has proven to be an equivalent treatment schedule compared with LDR, with an additional advantage of having a shorter overall treatment time. The mean rectal BED Gy3 was lower than expected.

Adult↗
PubMed1999

Caution on the use of altered fractionation for nasopharyngeal carcinoma.

Randomized trials and overviews on the value of altered fractionation for head and neck cancers are reviewed. Attention is drawn to the unexpectedly high incidence of temporal lobe necrosis incurred in patients with nasopharyngeal carcinoma. Preliminary analyses suggest that incomplete repair is likely to be the major factor, even a 6-h interfraction interval may be inadequate if substantial volumes of nervous tissues are included within the target volume.

Carcinoma↗
PubMed1999

Allergic contact dermatitis caused by dialkyl thioureas in a patient with sleep apnea.

Allergic contact dermatitis of the scalp is relatively uncommon. This is a case report of a patient with chronic scalp dermatitis in the distribution of his continuous positive airway pressure (CPAP) mask neoprene rubber strap. Our objective was to identify any relevant contact allergens. Patch testing to the North American Contact Dermatitis Group (NACDG) Standard Allergens, a series of supplemental rubber allergens, and a sample of the neoprene from the patient's mask strap was performed. Relevant allergies to dialkyl thioureas, and the neoprene rubber portion of the CPAP mask strap were identified. Replacement with a cloth strap resulted in clearing of the dermatitis.

Dermatitis, Allergic Contact↗
PubMed1999

Late patch test reaction to acrylates in a dental worker.

A dental technician developed eyelid and hand dermatitis. She had been previously patch-tested elsewhere with a sample of an acrylic material from a nail salon that reportedly was positive only after 1 month. Repeat testing with ethyl acrylate and methyl methacrylate gave no reaction at 48 or 96 hours, but became positive 5 weeks later. This very late reaction is probably a true allergic manifestation and not a case of active sensitization.

Acrylates↗
PubMed1999

A new incomplete-repair model based on a 'reciprocal-time' pattern of sublethal damage repair.

A radiobiological model for closely spaced non-instantaneous radiation fractions is presented, based on the premise that the time process of sublethal damage (SLD) repair is 'reciprocal-time' (second order), rather than exponential (first order), in form. The initial clinical implications of such an incomplete-repair model are assessed. A previously derived linear-quadratic-based model was revised to take account of the possibility that SLD may repair with time such that the fraction of an element of initial damage remaining at time t is given as 1/(1 + zt), where z is an appropriate rate constant; z is the reciprocal of the first half-time (tau) of repair. The general equation so derived for incomplete repair is applicable to all types of radiotherapy delivered at high, low and medium dose-rate in fractions delivered at regular time intervals. The model allows both the fraction duration and interfraction intervals to vary between zero and infinity. For any given value of z, reciprocal repair is associated with an apparent 'slowing-down' in the SLD repair rate as treatment proceeds. The instantaneous repair rates are not directly governed by total dose or dose per fraction, but are influenced by the treatment duration and individual fraction duration. Instantaneous repair rates of SLD appear to be slower towards the end of a continuous treatment, and are also slower following 'long' fractions than they are following 'short' fractions. The new model, with its single repair-rate parameter, is shown to be capable of providing a degree of quantitative explanation for some enigmas that have been encountered in clinical studies. A single-component reciprocal repair process provides an alternative explanation for the apparent existence of a range of repair rates in human tissues, and which have hitherto been explained by postulating the existence of a multi-exponential repair process. The build-up of SLD over extended treatments is greater than would be inferred using a single-exponential repair model and this has important implications in several areas of radiotherapy.

Brachytherapy↗
PubMed1999

An environmental hazard assessment of low-level dermal exposure to hexavalent chromium in solution among chromium-sensitized volunteers.

To evaluate the potential for elicitation of allergic contact dermatitis from contact with standing water in the environment, 26 persons known to be allergic to hexavalent chromium [Cr(VI)] were exposed to 25 to 29 mg/L Cr(VI) by immersion of one arm for 30 minutes per day on 3 consecutive days in a potassium dichromate bath. Sixteen of the 26 volunteers demonstrated either no or an equivocal response to the Cr(VI) challenge. Ten of the volunteers developed a few papules or vesicles (1 to approximately 15), mild redness, and pruritus on the Cr(VI)-challenged arm. Histopathological examination of the papules revealed spongiosis and perieccrine and perivascular inflammation. The responses were diagnosed as acute perieccrine reactions. It was concluded that exposure to similar concentrations of Cr(VI) in the environment does not pose an allergic contact dermatitis hazard, even to Cr-sensitized persons.

Biopsy↗
PubMed1999

Is repair of DNA strand break damage from ionizing radiation second-order rather than first-order? A simpler explanation of apparently multiexponential repair.

The purpose of this paper is to suggest the hypothesis that repair of radiation damage might be largely a second-order process (binary), as well as or instead of first-order (monoexponential). Second-order means that the rate of repair is proportional to n(2) instead of to n, where n is the number of repairable breaks. Integrating this equation gives a linear plot of the reciprocal proportion of unrepaired lesions, n(0)/n(t), as a function of repair time. This is in contrast to mono- or biexponential processes which give rise to reciprocal plots not consistent with such linearity, except with specially selected distributions with multiple T((1/2))'s. There is the advantage of only one parameter (the first half-time) instead of (2n - 1) parameters for n components. At times greater than 2tau of the longest exponential component, a larger proportion of damage would be incompletely repaired than in a mono- or biexponential model of repair. Data on DNA repair from published laboratory experiments were reanalyzed. Results are presented as graphs of the reciprocal of the proportion of damage remaining as a function of time after irradiation of DNA. If the second-order process is correct, these graphs should be straight lines, even though traditional semilog plots of the same data are markedly concave upward, showing the well-noted slowing down of repair with time after irradiation. All the data sets found in the literature showed a good fit to a straight line representing reciprocal repair. Repair of single-strand breaks in DNA fitted very well, from 1.0 down to 1/40 of the initial damage remaining, with tau values of 5-10 min. Repair of DSBs fitted almost as well. One set of data showed a strong dependence on temperature in the range 10-37 degrees C, with each curve fitting the straight reciprocal plot. The tau values for DSBs were 10-100 min, of similar magnitude to those for repair of animal tissues. The second-order process with a single time parameter could explain the data showing "apparently slowing down" repair previously analyzed by multiexponential formulae requiring more parameters. It appears that second-order repair may play a larger part in repair processes than has usually been assumed. It is suggested that analysis of data on repair of radiation-induced damage could test the second-order (one-parameter reciprocal) analysis, as well as using bi-or multiexponential analyses. If repair in DNA is relevant to recovery in mammalian tissues, there may be serious clinical implications, to be discussed elsewhere.

DNA↗
PubMed1998

Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models. METHODS AND MATERIALS: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976-1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18-84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5-4.2 Gy, total dose 45.6-60 Gy, and overall time 38-75 days. RESULTS: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%, p < 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor: p = 0.0022, hazard ratio (HR) = 1.044 per Gy2. Overall time and age were both insignificant. The alpha/beta ratio calculated from our data was 2.9 Gy (95% CI: -1.8, 7.6 Gy). Biological effective dose (BED(Gy3)), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (p < 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates. CONCLUSION: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an alpha/beta ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.

Adolescent↗
PubMed1998

North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens.

BACKGROUND: Allergic contact dermatitis is a significant cause of cutaneous disease affecting many individuals. Patch testing, when used properly, often provides support for the diagnosis of allergic contact dermatitis. OBJECTIVE: This article reports patch testing results from July 1, 1994, to June 30, 1996, by the North American Contact Dermatitis Group (NACDG). METHODS: Patients evaluated in our patch test clinics were tested with the same screening series of allergens by the use of a standardized patch testing technique. The data from these patients were recorded on a standard computer entry form and analyzed. RESULTS: Forty-nine allergens were tested on 3120 patients. Budesonide was added to the series in July 1995 and tested on 1678 patients. Of these patients, 66.5% had positive allergic patch test reactions, and 57% had at least one allergic reaction that was felt to be clinically relevant to the present or past dermatitis. The 20 screening allergens commercially available to United States dermatologists in the Allergen Patch Test Kit, accounted for only 54.1% of the patients with positive allergic reactions. The additional 30 allergens on the NACDG screening series accounted for 47% of patients with positive allergic reactions. Had the Allergen Patch Test Kit alone been used, 12.4% of all patients tested may have had their disease misclassified as a nonallergic disorder, and an additional 34.4% of all tested patients would not have had their allergies fully defined. Among those patients with positive responses to the supplemental allergens, 81% of the responses were of present or past relevance. The 12 most frequent contact allergens were nickel sulfate, fragrance mix, thimerosal, quaternium-15, neomycin sulfate, formaldehyde, bacitracin, thiuram mix, balsam of Peru, cobalt chloride, para-phenylenediamine, and carba mix. The present relevance varied with the specific allergen from 10.7% (thimerosal) to 85.7% (quaternium-15). Among newer allergens, methyldibromoglutaronitrile/phenoxyethanol (cosmetic preservative) caused positive allergic reactions in 2% of the patients; tixocortol-21-pivalate and budesonide (corticosteroids), in 2.0% and 1.1% of the patients, respectively; and ethylene urea/melamine formaldehyde mix (textile resin), in 5% of the patients. CONCLUSION: The usefulness of patch testing is enhanced with the number of allergens tested, because allergens not found on the commercially available screening series in the United States frequently give relevant allergic reactions.

Allergens↗
PubMed1998

Methyldibromoglutaronitrile (Euxyl K400): a new and important sensitizer in the United States?

BACKGROUND: Methyldibromoglutaronitrile (MDGN) is a component of Euxyl K400, a preservative used in many skin care products in Europe. MDGN has been used in skin care products in the United States for the last 5 years. Contact allergy from MDGN has been reported from Europe. OBJECTIVE: The purpose of this study was to determine the frequency of MDGN as a sensitizer in patients undergoing routine patch testing. METHODS: We reviewed the results in 163 patients who underwent patch testing during a 4-month period to determine the number who had any reaction to MDGN at two different concentrations (0.2% and 0.5%). Tests were graded with the use of the North American Contact Dermatitis Group criteria (0 to 3+), and readings were performed at 48 and 96 hours (all positive reactions were evaluated at a follow-up visit or by telephone interview). RESULTS: In the 4-month period, 45 of the 163 patients showed some reaction (+/- to 3+) at one or more readings. Of these, the results for 23 patients were considered to be irritant false-positive reactions; for 3 patients, the results were classified as uncertain; and for 19 patients, the results were classified as allergic. Of these, the results for eight patients were of definite relevance; the results for five patients were of probable relevance, and the results for six patients were of doubtful relevance to the problem condition. Other positive patch tests to a variety of allergens were frequently seen in persons positive to MDGN. CONCLUSION: MDGN is a sensitizer in skin products and, with the increase of its use, should be considered in the patch test evaluation of patients with persistent dermatitis. Optimum patch test concentrations are yet to be determined.

Allergens↗
PubMed1998

Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593.

PURPOSE: To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS: Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION: HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.

Aged↗
PubMed1998

Allergy to cocamide DEA.

Three cases are reported of individuals allergic to cocamide DEA, also known as coconut diethanolamide. In two cases, multiple other cutaneous allergies were present. In both instances, cocamide DEA was present in several personal care products used by the patients. In the third case, occupational exposure was suspected. Cocamide DEA is an unusual allergen that may cause contact dermatitis in individuals who often have multiple other skin allergies.

Adult↗
PubMed1998

An economic evaluation of patch testing in the diagnosis and management of allergic contact dermatitis.

BACKGROUND: A previous retrospective study indicated that patch testing is cost-effective and well accepted by patients. OBJECTIVE: The objective of this observational prospective study was to show the cost-effectiveness of patch testing in patients suspected of allergic contact dermatitis (ACD) and to determine the order in which different severity groups rank in terms of cost-effectiveness. METHODS: This observational study was conducted in 567 patients from 10 investigator sites over a period of 1 year. All patients with a suspicion of contact allergy who exhibited at least moderate disease activity were included in the study and were stratified according to disease severity and whether or not they were patch tested. In each severity category, the cost-effectiveness of patch testing was evaluated. Patients who were ruled out for contact allergy by the first 6 months after admission were excluded. A validated dermatology-specific quality of life instrument was administered to all the patients at entrance into the study and at 6 and 12 months after that. The cost-effectiveness analysis is shown using a decision analysis model. RESULTS: Patch testing was performed on 22% of patients with mild disease, 41% of patients with moderate disease, and 50% of patients with severe disease. As a result of changes made in their lifestyle, 66% in the patch-tested group and 51% in the non-patch-tested group reported 75% or more improvement in disease symptoms after 6 months. Early confirmation of diagnosis helped reduce the prediagnosis costs of treatment, which was mostly based on preliminary diagnosis. The greatest quality of life benefits from patch testing, relative to no patch testing, occurred in subjects with recurrent or chronic ACD. CONCLUSION: Patch testing is most cost-effective and reduces the cost of therapy in patients with severe ACD.

Chronic Disease↗