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Biomedical subjects

M J Griffin

Publications and source records attributed to M J Griffin.

At least 19 recordsLinked to original sources
PubMed2006

Acute effects of force and vibration on finger blood flow.

OBJECTIVES: To investigate the effects of contact force at the finger on acute changes in finger circulation during exposure to vibration. METHODS: Each of 10 subjects attended 11 sessions in which they experienced five successive experimental 5-minute periods: (i) no force and no vibration; (ii) force and no vibration; (iii) force and vibration; (iv) force and no vibration; (v) no force and no vibration. During periods (ii) to (iv), the intermediate phalanx of the right middle finger applied one of two forces (2 N or 5 N) on a platform that vibrated during period (iii) at one of two frequencies: 31.5 Hz (at 4 or 16 ms(-2) r.m.s.) or 125 Hz (at 16 or 64 ms(-2) r.m.s.). Finger blood flow was measured in the exposed right middle finger, the unexposed right little finger, and the unexposed left middle fingers throughout the 25 minutes of each session. RESULTS: The application of force alone caused a reduction in finger blood flow in the exposed finger, but not other fingers. There were additional reductions in finger blood flow caused by vibration, with greater reductions at the higher vibration magnitudes at both frequencies but no difference between the two frequencies when using unweighted acceleration. The vibration caused a similar vasoconstriction in vibrated and non-vibrated fingers. CONCLUSIONS: Modest levels of force applied by a finger can have a large effect on the finger blood flow, possibly due to the constriction of local blood vessels. The acute vascular effects of vibration cause additional reductions in finger blood flow that are not limited to the finger experiencing force and vibration. In all fingers (exposed and not exposed to vibration), the greater the magnitude of vibration, the greater the reduction in finger blood flow. In all fingers (exposed and not exposed to vibration), when the vibration was frequency weighted according to current standards, 125 Hz vibration caused greater reductions in finger blood flow than 31.5 Hz vibration.

Adult↗
PubMed2005

Phase I study of temozolomide plus paclitaxel in patients with advanced malignant melanoma and associated in vitro investigations.

The purpose of this study was to determine activity of temozolomide combined with paclitaxel or epothilone B in vitro, and to investigate the combination of temozolomide with paclitaxel in a Phase I clinical trial. Melanoma cell lines A375P and DX3 were treated with temozolomide and either paclitaxel or epothilone B. Combination indices were determined to assess the degree of synergism. In a clinical study, 21 patients with malignant melanoma were treated with increasing doses of temozolomide (orally, days 1-5), in combination with a fixed dose of paclitaxel (i.v. infusion day 1), followed by dose escalation of the latter drug. Cycles of treatment were repeated every 3 weeks. Pharmacokinetics of both agents were determined on day 1, with temozolomide pharmacokinetics also assessed on day 5. All three compounds were active against the melanoma cell lines, with epothilone B being the most potent. There was a strong degree of synergism between temozolomide and either paclitaxel or epothilone B. In the clinical study, no pharmacokinetic interaction was observed between temozolomide and paclitaxel. Dose escalation of both drugs to clinically active doses was possible, with no dose-limiting toxicities observed at 200 mg m(-2) day(-1) temozolomide and 225 mg m(-2) day(-1) paclitaxel. There were two partial responses out of 15 evaluable patients. One patient remains alive and symptom-free at 4 years after treatment. Temozolomide and paclitaxel may be administered safely at clinically effective doses. Further evaluation of these combinations in melanoma is warranted.

Adult↗
PubMed2004

Minimum health and safety requirements for workers exposed to hand-transmitted vibration and whole-body vibration in the European Union; a review.

In 2002, the Parliament and Commission of the European Community agreed "minimum health and safety requirements" for the exposure of workers to the risks arising from vibration. The Directive defines qualitative requirements and also quantitative requirements in the form of "exposure action values" and "exposure limit values". The quantitative guidance is based on, but appears to conflict with, the guidance in International Standards for hand-transmitted vibration (ISO 5349) and whole-body vibration (ISO 2631). There is a large internal inconsistency within the Directive for short duration exposures to whole-body vibration: the two alternative methods give very different values. It would appear prudent to base actions on the qualitative guidance (i.e. reducing risk to a minimum) and only refer to the quantitative guidance where there is no other reasonable basis for the identification of risk (i.e. similar exposures are not a suspected cause of injury). Health surveillance and other precautions will be appropriate wherever there is reason to suspect a risk and will not be restricted to conditions where the exposure action value is exceeded.

European Union↗
PubMed2004

Cigarette smoking, occupational exposure to noise, and self reported hearing difficulties.

AIMS: To explore the interaction of smoking and occupational exposure to noise as risk factors for hearing difficulty in the general population. METHODS: A questionnaire was mailed to 21 201 adults of working age, selected at random from the age-sex registers of 34 British general practices, and to 993 members of the armed services, randomly selected from pay records. Questions were asked about smoking habits, years spent in a noisy occupation, difficulty in hearing conversation, and wearing of a hearing aid. Associations of hearing difficulty with smoking habit were examined by logistic regression and compared across strata of noise exposure, with adjustment for potential confounders. RESULTS: Around half of the respondents had ever smoked, and half of these still smoked. Among 10 418 who provided details on hearing, 348 were classed as having moderate and 311 as having severe hearing difficulty. Risk of hearing difficulty was 3-5-fold higher in those employed for >5 years in noisy work compared with those never employed in a noisy job. Within strata of noise exposure (including those who had never worked in a noisy job), ex- and current smokers had a higher risk of hearing difficulty than lifetime non-smokers. The additional risks were small compared with those of long term noise exposure, and the combination of effects was more consistent with an additive than a multiplicative interaction. CONCLUSIONS: Smoking may adversely affect hearing, and workers should be encouraged to refrain from both smoking and exposure to noise. However, the extra risk to hearing incurred by smoking in high ambient noise levels is small relative to that from the noise itself, which should be the main target for preventive measures.

Adolescent↗
PubMed2003

Dose-response patterns for vibration-induced white finger.

AIMS: To investigate alternative relations between cumulative exposures to hand-transmitted vibration (taking account of vibration magnitude, lifetime exposure duration, and frequency of vibration) and the development of white finger (Raynaud's phenomenon). METHODS: Three previous studies have been combined to provide a group of 1557 users of powered vibratory tools in seven occupational subgroups: stone grinders, stone carvers, quarry drillers, dockyard caulkers, dockyard boilermakers, dockyard painters, and forest workers. The estimated total operating duration in hours was thus obtained for each subject, for each tool, and for all tools combined. From the vibration magnitudes and exposure durations, seven alternative measurements of cumulative exposure were calculated for each subject, using expressions of the form: dose = summation operator a(m)(i)t(i), where a(i) is the acceleration magnitude on tool i, t(i) is the lifetime exposure duration for tool i, and m = 0, 1, 2, or 4. RESULTS: For all seven alternative dose measures, an increase in dose was associated with a significant increase in the occurrence of vibration-induced white finger, after adjustment for age and smoking. However, dose measures with high powers of acceleration (m > 1) faired less well than measures in which the weighted or unweighted acceleration, and lifetime exposure duration, were given equal weight (m = 1). Dose determined solely by the lifetime exposure duration (without consideration of the vibration magnitude) gave better predictions than measures with m greater than unity. All measures of dose calculated from the unweighted acceleration gave better predictions than the equivalent dose measures using acceleration frequency-weighted according to current standards. CONCLUSIONS: Since the total duration of exposure does not discriminate between exposures accumulated over the day and those accumulated over years, a linear relation between vibration magnitude and exposure duration seems appropriate for predicting the occurrence of vibration-induced white finger. Poorer predictions were obtained when the currently recommended frequency weighting was employed than when accelerations at all frequencies were given equal weight. Findings suggest that improvements are possible to both the frequency weighting and the time dependency used to predict the development of vibration-induced white finger in current standards.

Adult↗
PubMed2003

The relative importance of whole body vibration and occupational lifting as risk factors for low-back pain.

AIMS: To explore the impact of occupational exposure to whole body vibration (WBV) on low back pain (LBP) in the general population and to estimate the burden of LBP attributable to occupational WBV in comparison with that due to occupational lifting. METHODS: A questionnaire including sections on WBV at work, LBP, and potential risk factors was mailed to a community sample of 22 194 men and women of working age. Sources and durations of exposure to occupational WBV were ascertained for the past week and personal vibration doses (eVDV) were estimated. Analysis was confined to subjects reporting exposures in the past week as typical of their work. Associations of LBP with eVDV, driving industrial vehicles, and occupational lifting were explored by logistic regression and attributable numbers were calculated. RESULTS: Significant associations were found between daily lifting of weights greater than 10 kg at work and LBP, troublesome LBP (which made it difficult to put on hosiery), and sciatica (prevalence ratios 1.3 to 1.7); but the risk of these outcomes in both sexes varied little by eVDV and only weak associations were found with riding on industrial vehicles. Assuming causal associations, the numbers of cases of LBP in Britain attributable to occupational WBV were estimated to be 444 000 in men and 95 000 in women. This compared with an estimated 940 000 male cases and 370 000 female cases of LBP from occupational lifting. CONCLUSIONS: The burden of LBP in Britain from occupational exposure to WBV is smaller than that attributable to lifting at work.

Adolescent↗
PubMed2002

A previously undescribed nonsense mutation of the HFE gene.

A patient with clinically manifest hereditary hemochromatosis was found to be heterozygous for the c.845 A-->G (C282Y) mutation. As simple heterozygotes for this mutation do not develop the hemochromatosis phenotype, the coding region of the patient's HFE gene was sequenced and a previously undescribed nonsense mutation was identified at c.211 C-->T (R74X). The patient's brother who also had the hemochromatosis phenotype shared his HFE genotype. To determine how common such mutations might be, the coding and 5' region of the HFE genes of 11 subjects who had been found in a large population survey to be heterozygous for the C282Y mutation and had elevated ferritin levels were sequenced. No mutations were found. Sequencing of the HFE gene also revealed two polymorphisms that had not previously been noted, -467 C-->G and -970 T-->G. Neither of these mutations appear to cause an abnormality in iron metabolism.

Codon, Nonsense↗
PubMed2002

Topotecan in combination with carboplatin: phase I trial evaluation of two treatment schedules.

BACKGROUND: Topotecan and cisplatin combinations have shown schedule-dependent toxicity, which may in part be due to cisplatin nephrotoxicity. As carboplatin is less nephrotoxic and increasingly replacing cisplatin in clinical practice, the aim of this study was to define the optimal sequence and dose for topotecan in combination with carboplatin. PATIENTS AND METHODS: Two parallel phase I trials, with pharmacokinetic studies, were conducted administering carboplatin on day 1 with topotecan on days 1-5 (schedule A) or days 8-12 (schedule B). repeated every 3 weeks. RESULTS: Twenty-one patients were treated over two dose levels, carboplatin AUC 4 [glomerular filtration rate (GFR) calculated from 51Cr-EDTA clearance] with topotecan 0.5 or 0.75 mg/m2. At the first dose level, six patients were evaluable for each schedule. With schedule A, from 34 cycles, there were two dose reductions and 10 treatment delays due to myelosuppression. With schedule B from 25 cycles, there was one reduction and 10 delays. At dose level 2, both patients in schedule A had dose-limiting neutropenia. In contrast, there was no dose-limiting toxicity with schedule B in six patients, although the majority of cycles were delayed. CONCLUSION: The combination of topotecan and carboplatin using these 3-weekly schedules lead to significant myelotoxicity with attendant dose reductions and delays; the optimal scheduling of these agents remains to be defined.

Adult↗
PubMed2002

Occupational exposure to noise and the attributable burden of hearing difficulties in Great Britain.

AIMS: To determine the prevalence of self reported hearing difficulties and tinnitus in working aged people from the general population, and to estimate the risks from occupational exposure to noise and the number of attributable cases nationally. METHODS: A questionnaire was mailed to 22 194 adults of working age selected at random from the age-sex registers of 34 British general practices (21 201 subjects) and from the central pay records of the British armed services (993 subjects). Information was collected on years of employment in a noisy job; and whether the respondent wore a hearing aid, had difficulty in hearing conversation, or had experienced persistent tinnitus over the past year. Associations of hearing difficulty and tinnitus with noise exposure were examined by logistic regression, with adjustment for age, sex, smoking habits, and frequent complaints of headaches, tiredness, or stress. The findings were expressed as prevalence ratios (PRs) with associated 95% confidence intervals (CIs). Attributable numbers were calculated from the relevant PRs and an estimate of the prevalence of occupational exposure to noise nationally. RESULTS: Some 2% of subjects reported severe hearing difficulties (wearing a hearing aid or having great difficulty in both ears in hearing conversation in a quiet room). In men, the prevalence of this outcome rose steeply with age, from below 1% in those aged 16-24 years to 8% in those aged 55-64. The pattern was similar in women, but severe hearing loss was only about half as prevalent in the oldest age band. Tinnitus was far more common in subjects with hearing difficulties. In both sexes, after adjustment for age, the risk of severe hearing difficulty and persistent tinnitus rose with years spent in a noisy job. In men older than 35 years with 10 or more years of exposure, the PR for severe hearing difficulty was 3.8 (95% CI 2.4 to 6.2) and that for persistent tinnitus 2.6 (95% CI 2.0 to 3.4) in comparison with those who had never had a noisy job. Nationally, some 153 000 men and 26 000 women aged 35-64 years were estimated to have severe hearing difficulties attributable to noise at work. For persistent tinnitus the corresponding numbers were 266 000 and 84 000. CONCLUSIONS: Significant hearing difficulties and tinnitus are quite common in men from the older working age range. Both are strongly associated with years spent in a noisy occupation--a predominantly male exposure. The national burden of hearing difficulties attributable to noise at work is substantial.

Adolescent↗
PubMed2002

Raynaud's phenomenon, vibration induced white finger, and difficulties in hearing.

BACKGROUND: An association has previously been reported between finger blanching and hearing difficulties, but only in workers with exposure to noise and hand transmitted vibration (HTV). AIMS: To explore the association in a community sample, including cases who lacked occupational exposure to noise or HTV. METHOD: A questionnaire was mailed to 12 606 subjects aged 35-64 years, chosen at random from the age-sex registers of 34 British general practices. Inquiry was made about years of employment in noisy jobs, lifetime exposure to HTV, hearing difficulties and tinnitus, and lifetime history of cold induced finger blanching. Subjects were classed as having severe hearing difficulty if they used a hearing aid or found it difficult or impossible to hear conversation in a quiet room. Associations of finger blanching with hearing difficulties and tinnitus were analysed by logistic regression. RESULTS: Among 8193 respondents were 185 who reported severe hearing difficulty and 1151 who reported finger blanching. After adjustment for age and years of work in noisy jobs, hearing difficulty was about twice as common in men and women who reported finger blanching, including those who had never been importantly exposed to noise and in those never exposed to HTV. CONCLUSIONS: These data support an association between finger blanching and hearing loss, which is not explained by confounding occupational exposure to noise, and suggest that it may extend to causes of blanching other than vibration induced white finger. Further investigations are warranted to confirm the association and explore possible mechanisms, such as sympathetic vasoconstriction in the cochlea.

Adult↗
PubMed2001

Factors affecting static seat cushion comfort.

To improve the understanding of factors affecting automobile seat cushion comfort in static conditions (i.e. without vibration), relationships between the static physical characteristics of a seat cushion and seat comfort have been investigated. The static seat comfort of four automobile cushions, with the same foam hardness but different foam compositions, was investigated using Scheffe's method of paired comparisons. The comfort judgements were correlated with sample stiffness, given by the gradient of a force-deflection curve at 490 N (= 50 kgf). Samples with lower stiffness were judged to be more comfortable than samples with greater stiffness. A similar comfort evaluation was conducted using five rectangular foam samples of the same composition but different foam hardness (and a wider range than in the first experiment). There was no linear relationship between the sample stiffness and seat comfort for these samples. Static seat cushion comfort seemed to be affected by two factors, a 'bottoming feeling' and a 'foam hardness feeling'. The bottoming feeling was reflected in the sample stiffness when loaded to 490 N, while the foam hardness feeling was reflected in foam characteristics at relatively low forces. The pressures underneath the buttocks of subjects were compared with the comfort judgements. The total pressure over a 4 cm x 4 cm area beneath the ischial bones was correlated with static seat comfort, even when the differences among samples were great; samples with less total pressure in this area were judged to be more comfortable than samples with greater total pressure. It is concluded that the pressure beneath the ischial bones may reflect both comfort factors: the bottoming feeling and the foam hardness feeling.

Adult↗
PubMed2001

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.

Adolescent↗
PubMed2001

Risk of hand-arm vibration syndrome according to occupation and sources of exposure to hand-transmitted vibration: A national survey.

BACKGROUND: Although some occupational sources of hand-transmitted vibration (HTV) have been extensively investigated, the risks associated with others are poorly characterized. METHODS: A questionnaire was mailed to a community sample of 12,240 men aged 16- 64 years and 906 men from the armed forces. Questions covered current occupation, sources of HTV, numbness or tingling in the fingers in the past week, and finger blanching. In the 5,364 respondents who had been at work in the past week, associations between symptoms and exposures were examined by logistic regression, with odds ratios converted into prevalence ratios (PRs). RESULTS: Altogether, 513 men (10%) reported cold-induced finger blanching and 769 (14%) sensory symptoms in the fingers. The risk of blanching was increased in builders (PR 2.4, 95% CI 1.0-5.2), carpenters and joiners (PR 1.9, 95% CI 1.0-3.4), motor mechanics (PR 2.3, 95% CI 1.1-4.6), and laborers (PR 2.8, 95% CI 1.3-6.0); while the risk of sensory symptoms was elevated in laborers (PR 4.0, 95% CI 2.3-6.6) and plant operatives (PR 3.5, 95% CI 1.9-5.9). Use of hand-guided mowers, concrete breakers, chain saws, and jig saws was significantly associated with symptoms. CONCLUSIONS: Little attention has been paid to the risks of vibration injury in construction workers, woodworkers, motor mechanics, and laborers, or to the risks from mowers, jig saws and several other common vibratory tools. These should be a focus for further investigation and preventive measures.

Adolescent↗
PubMed2001

Desflurane, compared to halothane, augments phenylephrine-induced contraction in isolated rat aorta smooth muscle.

PURPOSE: The mechanism responsible for the mediation of hypertension in response to increased desflurane levels is unclear. This study compared the effect of desflurane and halothane on phenylephrine (PE)-induced contraction in rat aorta ring and the effect of desflurane in the presence and absence of nitric oxide (NO) synthase activity. METHODS: Endothelium-free rat aorta rings were exposed serially to 10(-7) M, 10(-6) M and 10(-5) M PE alone and subsequently in the presence of 2 MAC desflurane and halothane. Secondly, endothelium-free preparations were exposed to 10(-6) M PE serially in the presence of 0, 1, 2 and 3 MAC desflurane and halothane. Thirdly, using an endothelium-intact preparation, the effect of desflurane on PE-induced contraction was examined, in the presence or absence of NG-nitro-L-arginine (L-NNA), an inhibitor of constitutive and inducible NO synthase. RESULTS: Contraction amplitudes secondary to 10(-6) and 10(-5) M PE in endothelium-free preparations were increased by 74% and 36% respectively (P <0.05) in the presence of 2 MAC desflurane compared to controls. In endothelium-free preparations, contraction amplitudes secondary to 10(-6) M PE were increased in the presence of 1 and 2 MAC desflurane by 32% and 18% respectively (P <0.05) and reduced by 16% in the presence of 3 MAC halothane (P <0.05). In endothelium-intact preparations an expected absolute increase in contraction amplitude occurred in the presence of L-NNA but the desflurane effect was detectable both in the presence and absence of L-NNA. CONCLUSION: Our results suggest that desflurane may have a local vasoconstrictive effect independent of endothelium and NO synthase activity. The mechanism remains to be determined.

Anesthetics, Inhalation↗
PubMed2001

Interpretation of the finger skin temperature response to cold provocation.

OBJECTIVES: To compare alternative methods of interpreting the response of finger skin temperature (FST) to cold provocation for the detection of the abnormal cold response observed in vibration-induced white finger (VWF). METHOD: The FST response to cold provocation was measured in 36 male subjects: 12 office workers, 12 manual workers and 12 manual workers with symptoms of VWF. The FSTs were monitored continuously on the distal phalanges of all five fingers of a test hand for 2 min before, for 5 min during, and for 10 min following, immersion of the test hand in water at 15 degrees C. Of the fingers investigated, 147 were reported not to exhibit blanching and 33 were reported to exhibit blanching. Twenty-one alternative methods of interpreting the response of FSTs to cold provocation were assessed. These were grouped as: (1) areas above the response profile (i.e. the area above the curve showing the FSTs as a function of time during cooling and recovery), (2) areas below the response profile, (3) absolute temperatures during and following cold provocation, (4) percentage differences in FSTs, (5) the times taken for FSTs to rise by specified amounts and (6) rates of change of FSTs. Differences in the response to cooling between those fingers reported to blanch and the fingers not reported to blanch were tested, and receiver operating characteristics (ROCs) were used to compare the sensitivity and specificity of the various measures to symptoms of VWF. RESULTS: The areas above the response profile, areas below the response profile, percentage FSTs, absolute FSTs and rates of change of FSTs tended to discriminate between healthy and unhealthy subjects on a group basis. However, some of these methods of interpreting the FST response to cold provocation did not show a high sensitivity or specificity to vascular dysfunction on individual fingers. The area above the response profile, the percentage of initial temperature at the fifth minute of recovery and the maximum temperature during the 10-min recovery period, were found to show the highest sensitivity and specificity to symptoms of vascular dysfunction. CONCLUSIONS: The method chosen to interpret the FST response to cold provocation affects the ability of the test to detect an abnormal cold response. The area above the response profile, the percentage of initial temperature at the fifth minute of recovery and the maximum temperature achieved during a 10-min recovery period appear to be the most suitable measures for monitoring vascular function in workers exposed to hand-transmitted vibration. It is suggested that the FST response to cold provocation should be interpreted with respect to the state of initial blood flow.

Adult↗
PubMed2001

Pharmacological study of paclitaxel duration of infusion combined with GFR-based carboplatin in the treatment of ovarian cancer.

PURPOSE: To determine the effect on systemic pharmacology and clinical toxicity of dose and mode of administration of paclitaxel combined with carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS: A total of 18 patients were treated with a dose of carboplatin determined by GFR, to attain a target AUC of 6 or 7 mg/ml x min. The paclitaxel dose was 175 or 200 mg/m2 administered over approximately 1 or 3 h. The duration of infusion was randomized, crossing over to the alternative treatment for the second course. Blood samples were analysed for carboplatin, paclitaxel and for the excipients of the paclitaxel formulation, ethanol and Cremophor. RESULTS: Overall the three-weekly schedule of administration of the combination of carboplatin and paclitaxel was well tolerated. There were no clinical differences in the toxicities observed between courses where a 1-h infusion was used compared with those with a 3-h infusion. The target AUC of carboplatin was achieved (mean +/- SD 114 +/- 20% of target). Analysis of paclitaxel pharmacokinetics did not show a difference in the AUC or time above a pharmacological threshold for the two infusion durations. The peak concentration of paclitaxel obtained at the end of the infusion (9.1 vs 4.5 microg/ml), and the plasma ethanol concentration (40.0 vs 20.5 mg/dl) were higher following the shorter duration infusion. Peak concentrations of Cremophor were not different. CONCLUSION: The combination of paclitaxel at a dose of 175 mg/m2 and carboplatin at a target AUC of 6-7 mg/ml min can safely be administered every 3 weeks. Also, a 1-h infusion of paclitaxel has no acute clinical disadvantage over a 3-h infusion and these durations of administration are pharmacologically equivalent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Modelling the response of the spinal system to whole-body vibration and repeated shock.

Back problems are very common and contribute to discomfort and days off work. Some back disorders are attributed to inappropriate loading of the spine that can be combined with other influential factors such a body posture, whole-body vibration and shock. Many models have been developed to predict the forces in the spine associated with vibration and shock. However, the problem is complex due to the incompletely understood dynamic responses of the body, the influence of many variables and the effect of muscle forces. This paper summarises the current state of knowledge relevant to the prediction of forces in the spine associated with whole-body vibration and shock. The paper also introduces presentations at a workshop on the modelling of spinal loads associated with vibration and shock held in Berlin in October 1999. RelevanceBiodynamic models may be used to estimate risks of injury or disease and optimise environments so as to minimise risks. However, the development of useful models requires an understanding of the complex interaction between mechanical forces and the living body. The application of models requires knowledge of their accuracy and limitations.

Humans↗
PubMed2001

Modelling the dynamic mechanisms associated with the principal resonance of the seated human body.

OBJECTIVES: Simple mathematical models have been developed to obtain insights into resonance phenomena observed at about 5 Hz in the dynamic responses of the seated human body exposed to vertical whole-body vibration. DESIGN: Alternative lumped parameter models with a few degrees-of-freedom have been investigated. Rotational degrees-of-freedom, with eccentricity of the centre of gravity of the mass elements, represented responses in the fore-and-aft and pitch axes caused by vertical vibration. BACKGROUND: The causes of body resonance are not fully understood, but this information is required to develop cause-effect relationships between vibration exposures and effects on human health, comfort and performance.Method. The inertial and geometric parameters for models were based on published anatomical data. Other mechanical parameters were determined by comparing model responses to experimental data. RESULTS: Two models, with four and five degrees-of-freedom, gave more reasonable representations than other models. Mechanical parameters obtained with median and individual experimental data were consistent for vertical degrees-of-freedom but varied for rotational degrees-of-freedom. CONCLUSIONS: The resonance of the apparent mass at about 5 Hz may be attributed to a vibration mode consisting of vertical motion of the pelvis and legs and a pitch motion of the pelvis, both of which cause vertical motion of the upper-body above the pelvis, a bending motion of the spine, and vertical motion of the viscera. RELEVANCE: The mathematical models developed in this study may assist understanding of the dynamic mechanisms responsible for resonances in the seated human body. The information is required to represent mechanical responses of the body and assist the development of models for specific effects of vibration.

Humans↗