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Biomedical subjects

J A Allen

Publications and source records attributed to J A Allen.

At least 37 records · Page 2Linked to original sources

Absence of mutagenic activity in Salmonella and of clastogenic activity in CHO cells of Caramel Colours I, II, III and IV.

A total of 15 caramel colours were examined for genotoxic activity using the Salmonella typhimurium plate incorporation assay (Ames test). Five bacterial strains, TA1535, TA1537, TA1538, TA98 and TA100 were used in all the plate incorporation tests. Caramel colours can be divided into four classes, classification depending on the preparative method used. In this study, representatives of all four classes of caramel colour were tested for genotoxic potential in the Ames test, some of the caramel colours being tested both with and without a pre-incubation stage. None of the 15 caramel colours tested exhibited genotoxic potential in any of the five bacterial tester strains. The last two caramel colours tested, in the series of 15 [203-23-4 (Class II) and 311 (Class III)] were also assessed for clastogenic potential. For this test, cultures of CHO cells were exposed to the two caramel colours and metaphase preparations from these cultures examined for evidence of chromosomal aberrations. No evidence of chromosome damaging activity was observed.

Animals↗

Assessment of the genotoxic potential of Caramel Colour I in four short-term tests.

A battery of three short-term tests in vitro and one in vivo was used to determine the genotoxicity of Caramel Colour I. The results of the bacterial mutation assay, using five strains of Salmonella typhimurium, and the mouse micronucleus assay in vivo showed no evidence of genotoxic activity. Results from both the cytogenetics assay in vitro, using CHO cells, and the mouse lymphoma assay indicated that there was some genotoxic activity associated with Caramel Colour I but only in the absence of S-9 and at very high dose levels.

Animals↗

An objective test for the diagnosis and grading of vasospasm in patients with Raynaud's syndrome.

1. Reliable objective tests for the diagnosis and grading of vasospasm would be helpful in the assessment of patients with Raynaud's syndrome. 2. Measurements of finger blood flow at local finger temperatures from 32 degrees C down to 20 degrees C did not reliably distinguish between patients with Raynaud's syndrome and matched control subjects. 3. Using laser Doppler flowmetry to detect blood cell flux in fingertip skin, there was no significant difference (Wilcoxon's signed rank test) in the finger systolic blood pressure of 28 patients with Raynaud's syndrome and their matched controls when the fingers were warm at 32 degrees C. 4. Absence of flux was considered to indicate complete vasospasm and the degree of cooling required to abolish flux indicated the severity of the vasospastic condition in an individual patient. 5. Finger cooling for 5 min did not significantly alter finger systolic blood pressure in the control subjects, but abolished blood cell flux in the fingertip skin of 27 of the 28 patients with Raynaud's syndrome. 6. A grading scale was derived from the flux measurements. There was a significant correlation (r = 0.75, P less than 0.001) between the grading of disease severity as judged by the flux test and the clinical grade as assessed before the laboratory visit. 7. There was one false-negative result in the 28 patients with Raynaud's syndrome tested and no false-positive results in 28 matched control subjects. 8. This type of testing may prove helpful in the diagnosis and grading of vasospastic disorders.

Adolescent↗

Objective testing for vasospasm in the hand-arm vibration syndrome.

Since vibration white finger (VWF) became a prescribed industrial disease in 1985, objective testing for the diagnosis and grading of the severity of the condition has become desirable. Measurements have been made of finger blood flow and finger systolic pressure before and after cold challenge in 22 healthy control subjects and 34 men presenting for medical examination in connection with compensation claims for VWF. This type of testing has previously produced one false negative result in 35 patients with an established clinical diagnosis of Raynaud's syndrome and no false positives in 40 control subjects. Finger blood flow was not significantly different in the claimants and controls in either warm or cool environments at local finger temperatures from 32 degrees C down to 20 degrees C. Finger systolic pressure in the claimants was not significantly different from that in the controls when the fingers were warm at 32 degrees C. After five minutes middle phalangeal cooling to 15 or 10 degrees C, finger systolic pressure was 0 mm Hg in 22 of the claimants indicating that vasospasm had occurred. No vasospasm occurred in the remaining 12 claimants or in any of the 22 control subjects. By clinical assessment alone, 26 of the 34 claimants had been thought to have VWF and 21 (81%) of these exhibited vasospasm in the laboratory. Of the eight considered not to have VWF, only one exhibited vasospasm in the laboratory.

Adult↗

Treatment of newly diagnosed state D2 prostate cancer with leuprolide and flutamide or leuprolide alone, phase III, intergroup study 0036.

In order to test the hypothesis of complete androgen blockade for advanced prostate cancer (D2CaP), an intergroup trial was instituted in 1985 comparing leuprolide (L) alone to the combination of L with flutamide (F). Eligibility requirements included previously untreated histologically confirmed stage D2CaP, measurable bone or soft tissue metastases, performance status (PS) of 3 or better, acceptable renal and hepatic function, no severe cardiac disease, and no prior or concomitant endocrine therapy. Stratification at entry was on the basis of PS and none or minimal disease (MD) versus severe degree (SD) of bone metastases. Six hundred and seventeen patients were entered into this study between March 1985 and April 1986. At the present time, there is a 3-month difference in the median progression-free survival (13.9 vs 16.9 months; P = 0.039) and a 7.1-month difference in survival (27.9 vs 35.01 months; P = 0.035) favoring L + F. In L + F-treated patients with good PS-MD, the median survival recently has been reached and is 51.9 months vs 39.6 months for L + P patients. The 107 black patients in the study had median survival of 26.4 months vs 33.3 months for whites. Discussions of racial differences in survival as well as other prognostic factors will be presented. The combination of L + F is superior to treatment with L alone. The benefits appear greatest in patients with minimal disease.

Antineoplastic Agents↗

A comparison of peripheral vasoconstrictor responses and cardiovascular autonomic function tests in diabetic patients.

Venous occlusion plethysmography has been used to measure sympathetic vasoconstrictor responses in the feet and hands to a deep breath and body cooling and to assess blood flow variability. Measurements were made in 14 non-diabetic control subjects and 52 diabetic patients, 30 of whom had evidence of peripheral neuropathy. All the measurements were significantly reduced in the feet of patients with neuropathy. Vasoconstrictor responses were not significantly impaired in the hands of these patients. Cardiovascular autonomic function was assessed in the same subjects by standard tests of reflex heart rate responses and compared to sympathetic vasoconstrictor function as determined by the response to a deep breath. Eighteen of the 30 diabetic patients with peripheral neuropathy had impairment of both cardiovascular and sympathetic vasoconstrictor function. Five had normal vasoconstrictor but impaired cardiovascular responses and two had normal cardiovascular but impaired vasoconstrictor function. It may therefore be important to assess both systems in diabetic patients.

Blood Pressure↗

Autonomic function in Holmes Adie syndrome.

Autonomic function was studied in a group of 11 patients with Holmes Adie Syndrome. Autonomic function was assessed by the measurement of cardiovascular reflexes. Heart rate responses to respiration, valsalva manoeuvre and standing were studied. The change in systolic blood pressure on moving from the lying to the standing position was measured. Abnormalities of parasympathetic function were found in three patients, compared with matched controls. Autonomic dysfunction in Holmes Adie Syndrome may be more widespread than previously suspected.

Adie Syndrome↗

Frequency-dependent selection by predators.

Sometimes predators tend to concentrate on common varieties of prey and overlook rare ones. Within prey species, this could result in the fitness of each variety being inversely related to its frequency in the population. Such frequency-dependent or 'apostatic' selection by predators hunting by sight could maintain polymorphism for colour pattern, and much of the supporting evidence for this idea has come from work on birds and artificial prey. These and other studies have shown that the strength of the observed selection is affected by prey density, palatability, coloration and conspicuousness. When the prey density is very high, selection becomes 'anti-apostatic': predators preferentially remove rare prey. There is still much to be learned about frequency-dependent selection by predators on artificial prey: work on natural polymorphic prey has hardly begun.

Animals↗

Blood flow in diabetics with foot lesions due to 'small vessel disease'.

Blood flow was measured in the feet and toes of 23 diabetics, 7 controls and 6 non-diabetic neuropathic controls, using venous occlusion plethysmography. All of the diabetics showed a characteristic flow abnormality with mild hyperperfusion of the foot at rest but impaired peak flow following arterial occlusion. When the diabetics were subdivided into those with 'small vessel disease', those with neuropathic ulceration and those with neuropathy but no ulceration, the groups had remarkably comparable blood flows, except that peak great toe blood flow was rather lower in small vessel disease. In small vessel disease, the combination of high resting blood flow and elevated foot venous oxygen saturation suggests that the hyperperfusion is due to arteriovenous shunting. It seems likely that the toe lesions ascribed to small vessel disease were in fact manifestations of severe diabetic neuropathy. The term small vessel disease should be avoided in the context of diabetic foot lesions.

Adult↗

Apostatic selection by humans searching for computer-generated images on a colour monitor.

A computer program was used to generate "populations" of dimorphic "prey" on the screen of a colour monitor. Different subjects were presented with the prey at seven different frequencies and were asked to use a light pen to remove each prey they detected. They all received the same two types of prey but 70 had them presented against a matching background and 49 had them against a background that made them conspicuous. The results showed that apostatic selection occurred when the prey were inconspicuous but not when they were conspicuous. There is evidence that the apostatic selection was caused by some effect of the difficulty in detecting the prey when they were cryptic.

Color↗

Phase I study of carboplatin (CBDCA) in children with cancer.

A phase I study of carboplatin (CBDCA) was performed in 40 children with advanced cancer. A single course of CBDCA consisted of 4 weekly 1-hour infusions followed by a 2-week rest. The starting dose of 100 mg/m2/week was 66% of the maximum tolerated dose in adults. Escalated dose levels given were: 125, 150, 175, and 210 mg/m2. Myelosuppression was dose limiting, with thrombocytopenia more pronounced than leukopenia. There was no evidence of cumulative toxicity. The maximum tolerated dose for children with solid tumors was 210 mg/m2/week X 4. Other side effects included transient nausea and vomiting at the higher dose levels and non-dose-related, reversible changes in creatinine clearance. One patient developed hives. No hepatic toxicity was seen. Among the 28 evaluable patients with solid tumors, one of ten with osteogenic sarcoma had complete disappearance of a lung nodule for 15+ months. Two of four patients with medulloblastoma had partial responses by clinical and computerized tomographic scan for 4 and 10 months. All three responders had received prior cisplatin therapy. CBDCA has major advantages over cisplatin in terms of reduced toxicity. Responses observed in patients previously treated with cisplatin are encouraging. The recommended phase II dose for children with solid tumors is 175 mg/m2/week X 4 with a 2-week rest.

Adolescent↗

Cost containment through therapeutic substitution of aminoglycosides.

A therapeutic substitution policy (TSP) for tobramycin and gentamicin sulfate was implemented at the University of Texas Medical Branch (UTMB). The policy was designed by various physician-chaired hospital committees and clinical departments that collaborated with the pharmacy service. The goal was to encourage the medical house staff to use the most economical yet safe and effective aminoglycoside, without limiting the medical team's prerogative to select among alternatives within this antibiotic group. Cost data from the first 6 months of aminoglycoside use under the new policy projected an annual savings of $139,071 in drug expenditures and $242,472 in patient charges. Following the implementation of the TSP, a concurrent drug utilization review (DUR) was performed in 50 consecutive inpatients prescribed amikacin, tobramycin, or gentamicin sulfate. The objectives were to identify those aspects of prescribing and monitoring of aminoglycosides by house staff that could be improved by specific policy and/or education, and to evaluate those specific cases in which attending physician's approval allowed house staff to prescribe an aminoglycoside other than designated in the TSP. The audit revealed that house staff were compliant with 72% of the DUR criteria; however, at least one instance (mean of 5.04 +/- 2.21) of noncompliance occurred during the treatment of each patient. The most frequently encountered deficiencies were failure to monitor for ototoxicity, incorrect orders for at least one set of serum aminoglycoside concentrations, and improper dosage adjustments for those patients with renal insufficiency. In three cases, the attending physician approved house staff use of tobramycin instead of gentamicin sulfate for reasons of organism resistance, pre-existing renal impairment, and long-term treatment of osteomyelitis.

Aminoglycosides↗

Effect of distance instructions on size judgments.

The proposition that in a reduced-cue setting subjects could use cognitive information about an object's distance to make accurate judgments of its size was tested. An improved paradigm was used to determine the effects of distance instructions per se. This paradigm also allowed independent tests of the effectiveness of cue reduction. The data indicated that cue reduction was successful and that the specific distance tendency governed size judgments when there were no distance instructions. When distance instructions were given, they produced size judgments in precisely the ratio predicted by the size-distance invariance hypothesis. However, there was a large constant error, which reflects a tendency of college students to overestimate the amount of distance signified by a verbal instruction. Hence, cognitive information in the form of verbal distance instructions has precise effects on size judgments, but the latter are not veridical, even in the absence of anchor effects from the specific distance tendency and residual perceptual cues.

Cognition↗

The effect of local temperature on the response of an extremity to indirect heating in man.

Venous occlusion plethysmography was used to measure blood flow through the extremities of five normal subjects before and during exposure to a standard heat load with one extremity maintained at a cold (15 degrees C) and the other at a neutral (35 degrees C) temperature. In the foot, local cold (15 degrees C) delayed the onset and reduced by about 92% the vasodilatation during release of sympathetic vasoconstrictor tone caused by body heating. Similar results were obtained in the hand exposed to cold (15 degrees C) but the suppression of the reflex vasodilatation in response to body heating was about 66%. This difference between the hand and foot did not appear to be related to the greater length of the foot since the distal half of the foot reacted like the total foot: local cooling suppressed the reflex vasodilatation by 88%. The results suggest that sympathetic release tests should not be carried out in a laboratory with an environmental temperature as low as 15 degrees C, especially when the circulation to the foot is under investigation.

Adult↗

Absence of mutagenic activity of WHR-1142A, lidamidine hydrochloride, in 4 short-term tests for mutagenic/carcinogenic potential.

WHR-1142A, lidamidine hydrochloride, an antidiarrhoeal agent, was tested for possible mutagenic/carcinogenic activity in the Ames Salmonella typhimurium/metabolic activation test, the micronucleus test, by analysis of metaphase chromosomes obtained from human lymphocytes grown in culture and in a cell transformation assay. No evidence of mutagenic/carcinogenic activity due to WHR-1142A, lidamidine hydrochloride, was found in any of the 4 tests.

Animals↗