Biomedical subjects

R Fisher

Publications and source records attributed to R Fisher.

At least 19 recordsLinked to original sources

PubMed2006

Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR genotype.

Few studies of gene-environment interactions for the serotonin transporter promoter polymorphism (5-HTTLPR), life stressors and depression have considered women separately or examined specific types of stressful life events. None have looked at depression during pregnancy. In the Pregnancy Outcomes and Community Health (POUCH) Study, women were queried about history of stressful life events and depressive symptoms at the time of enrollment (15-27 weeks gestation). Stressful life events were grouped a priori into "subconstructs" (e.g. economic, legal, abuse, loss) and evaluated by subconstruct, total subconstruct score and total stressful life event score. The effect of genotype on the association between stressful life events and elevated depressive symptoms was assessed in 568 white non-Hispanic participants. The relationship between exposure to abuse and elevated depressive symptoms was more pronounced in the s/s group (OR = 24.5) than in the s/l group (OR = 3.0) and the l/l group (OR = 7.7), but this significant interaction was detected only after excluding 73 (13%) women with recent use of psychotropic medications. There was no evidence of gene-environment interaction in analytic models with other stressful life events subconstructs, total subconstruct score or total stressful life events score. These data offer modest support to other reports of gene-environment interaction and highlight the importance of considering specific stressful life events.

Adaptation, Psychological↗

PubMed2005

Menkes disease: a rare cause of bilateral inguinal hernias.

This case of Menkes disease presented with the uncommon association of bilateral inguinal hernias at the age of 4 months. Further investigation demonstrated classical skeletal and neurological changes of this rare neurodegenerative disorder.

Diagnosis, Differential↗

PubMed2004

Clinical verification of the superiority of the current International Union Against Cancer staging criteria in an Australian population of patients with nasopharyngeal carcinoma.

The purpose of this study is to assess the prognostic abilities of the fourth and fifth edition International Union Against Cancer (UICC) staging systems for nasopharyngeal carcinoma (NPC) in Australian patients. All patients planned for curative treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. There were 181 patients eligible for this study. The median follow up was 7.6 years. Histological subgroups were World Health Organization (WHO) 1 (23), WHO 2 (12), and WHO 3 (146). Presentation with stage IV disease was 83% by UICC fourth edition staging and 34% by UICC fifth edition staging. The 5 years failure-free survival (FFS) rates for stage 1, 2, 3 and 4 disease by the fourth edition was 77, 100, 93, and 49% respectively,and by the fifth edition was 85, 76, 57 and 36%, respectively. The 5 years overall survival (OS) for stage 1, 2, 3, and 4 disease by the fourth edition was 77, 100, 100 and 61%; respectively, and by the fifth edition was 85, 82, 67 and 53%, respectively. Stage 4 patients by the fourth edition were reclassified as stages 2, 3 and 4 by the fifth edition with hazard ratios of 0.77, 1.01 and 1.79, respectively. In multifactor analysis, the fifth edition staging system was significantly related to FFS and OS after allowing for the fourth edition (FFS: P = 0.002; OS: P = 0.005), but the fourth edition was not significantly related to FFS or OS after allowing for the fifth edition (FFS: P = 0.96; OS: P = 0.96). This study confirms the prognostic superiority of the fifth edition UICC staging system over the fourth edition staging system in an Australian NPC population.

Adolescent↗

PubMed2003

Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis.

BACKGROUND: Conventional measures of the severity of alveolar proteinosis (AP) include alveolar-arterial oxygen gradient ([A - a]DO(2)), vital capacity (VC), and carbon monoxide transfer factor (TLCO), but alternative serological measures have been sought. Granulocyte-macrophage colony stimulating factor (GM-CSF) neutralising autoantibody is found in patients with idiopathic acquired AP. We have investigated the interrelationships between the levels of this antibody and those of surfactant protein (SP)-A and -B, lactate dehydrogenase (LDH), and conventional measures of disease severity, and the capacity of these parameters to predict the response to rhGM-CSF treatment. METHODS: Blood levels of anti-GM-CSF antibodies, SP-A, SP-B, LDH, and [A - a]DO(2), VC, and TLCO were measured before rhGM-CSF treatment and every 2 weeks thereafter in 14 patients with AP. RESULTS: At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83%. SP-A was highly correlated with [A - a]DO(2), VC, and TLCO (p</=0.02), but other markers were not. Only a normal LDH level was predictive of a response to rhGM-CSF treatment (p=0.03). During treatment a correlation between conventional and serological variables within patients was seen only between SP-A and [A - a]DO(2) (p=0.054), LDH levels and [A - a]DO(2) (p=0.010), and LDH levels and VC (p=0.019). CONCLUSIONS: Of the serological parameters studied, only SP-A and LDH levels were correlated with conventional measures of disease severity, with LDH most accurately reflecting [A - a]DO(2) and vital capacity. Only a normal LDH level predicted a higher likelihood of response to treatment with GM-CSF.

Adolescent↗

PubMed2002

Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system.

Duchenne muscular dystrophy results from the absence of dystrophin, a cytoskeletal protein. Previously, we have shown in a transgenic mouse model of the disease (mdx) that high levels of expression of the dystrophin-related protein, utrophin can prevent pathology. We developed a new transgenic mouse model where muscle specific utrophin expression was conditioned by addition of tetracycline in water. Transgene expression was turned on at different time points: in utero, at birth, 10 and 30 days after birth. We obtained moderate levels of expression, variable from fibre to fibre (mosaicism) but sufficient to induce a correct localization of the dystro-sarcoglycan complex. Histology revealed a reduction of necrotic foci and of the percentage of centronucleated fibres, which remained still largely above the normal level. Isometric force was not improved but the resistance to eccentric contractions was significantly stronger. When utrophin expression was activated 30 days after birth, improvements were marginal, suggesting that the age at which utrophin therapy is initiated could be an important factor. Our results also provide an unexpected insight into the pathogenesis of the dystrophinopathies. We observed a complete normalization of the characteristics of the mechano-sensitive/voltage-independent Ca(2+) channels (occurrence, open probabilities and Ca(2+) currents), while the classical markers of dystrophy were still abnormal. These observations question the role of increased Ca(2+) channel activity in initiating the dystrophic process. The new model shows that utrophin therapy, initiated after birth, can be effective, but the extent of correction of the various symptoms of dystrophinopathy critically depends on the amount of utrophin expressed.

Animals↗

PubMed2002

Influence of the embryonic preplate on the organization of the cerebral cortex: a targeted ablation model.

Transgenic mice were generated to permit the targeted ablation of cortical preplate cells at the time they are born. In these mice, the 1.3 kb golli promoter of the myelin basic protein gene was used to drive the herpes simplex virus thymidine kinase (TK) transgene in cortical preplate cells. Heterozygous transgenic pairs were bred, and pregnant dams were treated with ganciclovir at embryonic days 11-12 to ablate preplate cells at the time the preplate was forming. This paradigm exposed control (TK-) and experimental (TK+) littermates to exactly the same conditions. Embryological ablation of preplate cells led to an early disruption of the radial glial framework and subplate structure in the developing cortex and dramatically altered the cellular lamination and connectivity of the cortical plate. The disturbed radial glial network contributed to an impaired radial migration of neurons into the cortical plate from the ventricular zone. The cortical plate became dyslaminated, and there was a substantial reduction in short- and long-range cortical projections within the cortex and to subcortical regions. Cell death within the cortical plate and the proliferative zones was substantially increased in the ablated animals. After birth, a cortical lesion developed, which became exacerbated with the secondary onset of hydrocephaly in the second postnatal week. The results underscore the critical importance of the preplate in cortex formation, mediated through its guidance of the formation of radial glial scaffolding, subsequent neuronal migration into the incipient cortical plate, and the final arrangement of its vertical organization and cellular connectivity.

Animals↗

PubMed2002

Modulation of synchrony between single motor units during precision grip tasks in humans.

During precision grip, coherence between motor cortex and hand muscle EMG oscillatory activity in the 15-30 Hz range covaries with the compliance of the manipulated object. The current study investigated whether short-term synchrony and coherence between discharges of single motor units (SMUs) in the first dorsal interosseous (1DI) muscle were similarly modulated by object compliance during precision grip. Eight subjects used index finger and thumb to grip two levers that were under robotic control. Guided by visual feedback of the lever force levels, subjects held the levers against a steady force of 1.3 N for 8 s; they then linearly increased the force to 1.6 N over a 2 s period and held for a further 8 s before linearly decreasing the force back to the 1.3 N level over another 2 s period. Subjects performed the task at two different levels of compliance, each with identical grip force levels. Both surface EMG and SMU activity were recorded from the 1DI muscle. Short-term synchrony between the discharges of pairs of SMUs was assessed in the time domain by cross-correlation and in the frequency domain by coherence analysis. Coherence was seen in two frequency ranges: 6-12 Hz and 15-30 Hz. The compliance of the gripped object had a significant effect on both short-term synchronisation and coherence in the 15-30 Hz range between SMUs; both were greater for the more compliant condition. There was no change in the 6-12 Hz coherence.

Adult↗

PubMed2001

Suppression of EMG activity by transcranial magnetic stimulation in human subjects during walking.

1. The involvement of the motor cortex during human walking was evaluated using transcranial magnetic stimulation (TMS) of the motor cortex at a variety of intensities. Recordings of EMG activity in tibialis anterior (TA) and soleus muscles during walking were rectified and averaged. 2. TMS of low intensity (below threshold for a motor-evoked potential, MEP) produced a suppression of ongoing EMG activity during walking. The average latency for this suppression was 40.0 +/- 1.0 ms. At slightly higher intensities of stimulation there was a facilitation of the EMG activity with an average latency of 29.5 +/- 1.0 ms. As the intensity of the stimulation was increased the facilitation increased in size and eventually a MEP was clear in individual sweeps. 3. In three subjects TMS was replaced by electrical stimulation over the motor cortex. Just below MEP threshold there was a clear facilitation at short latency (approximately 28 ms). As the intensity of the electrical stimulation was reduced the size of the facilitation decreased until it eventually disappeared. We did not observe a suppression of the EMG activity similar to that produced by TMS in any of the subjects. 4. The present study demonstrates that motoneuronal activity during walking can be suppressed by activation of intracortical inhibitory circuits. This illustrates for the first time that activity in the motor cortex is directly involved in the control of the muscles during human walking.

Adult↗

PubMed2001

The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial.

PURPOSE: Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. METHODS AND MATERIALS: A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. RESULTS: One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p = 0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p = 0.41), consistency (p = 0.20), flatus (p = 0.25), mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p = 0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p = 0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). CONCLUSION: This study suggests that oral sucralfate taken prophylactically during radiotherapy does not ameliorate the symptoms of acute radiation proctitis and may increase acute bleeding. The cause of the increased bleeding in the sucralfate group is unclear. As the pathogenesis of acute and late reactions are different, late follow-up, which includes sigmoidoscopic evaluation, is currently being performed on this cohort of patients.

Administration, Oral↗

PubMed2001

Sequences in the 5' leader of Mason-Pfizer monkey virus which affect viral particle production and genomic RNA packaging: development of MPMV packaging cell lines.

We used a series of deletion mutations in the 5' untranslated region of the prototype D type retrovirus, Mason-Pfizer Monkey Virus (MPMV), to analyse RNA encapsidation. A region was identified upstream of the major splice donor which reduced particle production but had a proportionally greater effect on RNA packaging. A small deletion downstream of the splice donor had little effect on RNA production and caused no significant packaging defect. A large deletion encompassing the end of the primer binding site down to the splice donor had a dramatic effect, disrupting viral protein synthesis. Stable cell lines were produced containing packaging-defective virus. These first-generation packaging cell lines were used to package and transfer an MPMV-based vector.

5' Untranslated Regions↗

PubMed2001

Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolated from zidovudine-naive patients experiencing viremia on stavudine-containing regimens.

Studies have demonstrated that HIV-1 isolated from subjects experiencing virologic failure on stavudine (d4T)-containing regimens often contains thymidine analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with zidovudine (ZDV) resistance. In clinical study NZT40012, HIV-1 was isolated from 86 ZDV-naive subjects experiencing viremia on d4T-based therapies (plasma HIV-1 RNA > or =1000 copies/ml) and analyzed to examine the association between RT mutations and phenotypic resistance to d4T. Resistance-associated mutations were analyzed from HIV-1 isolated from 85 subjects. Of these, 24 samples (28%) had TAMs, and 30 samples (35%) had either TAMs and/or the Q151M multinucleoside resistance (MNR) mutation. Phenotypic susceptibility to d4T was determined by two commercially available methods. Statistically significant increases (p < 0.001) in phenotypic fold resistance to d4T were observed in virus with at least one TAM or MNR mutation. However, the mean increases in phenotypic resistance were 4-fold for the Antivirogram assay and 3-fold for the Phenosense HIV assay, only slightly above the levels used to designate decreased susceptibility to d4T. Subjects can experience viremia on d4T-containing regimens with virus exhibiting only small increases in IC(50), suggesting that relatively small changes in viral susceptibility to d4T may influence drug efficacy.

Anti-HIV Agents↗

PubMed2001

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group.

PURPOSE: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. METHODS AND MATERIALS: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. RESULTS: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. CONCLUSION: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications.

Adenocarcinoma↗

PubMed2001

Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer.

PURPOSE: To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and/or N2/3 squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The starting schedule was conventionally fractionated radiotherapy (70 Gy in 7 weeks) with concomitant cisplatin 75 mg/m2 and tirapazamine 290 mg/m2 (before cisplatin) in weeks 1, 4, and 7 and tirapazamine alone 160 mg/m2 three times a week in weeks 2, 3, 5, and 6. Positron emission tomography scans for tumor hypoxia (18F misonidazole) were performed before and during radiotherapy. RESULTS: We treated 16 patients with predominantly oropharyngeal primary tumors, including 10 patients with T4 or N3 disease. Febrile neutropenia occurred toward the end of radiotherapy in three out of six patients treated on the initial dose level. Two of these patients also developed grade 4 acute radiation reactions. Another 10 patients were treated with the same doses, but the week 5 and week 6 tirapazamine doses were omitted. This resulted in less neutropenia and only one dose-limiting toxicity (DLT) (febrile neutropenia), and eight out of 10 patients completed treatment without any dose omissions. In these 10 patients, the acute radiation toxicities were not obviously enhanced compared with chemoradiotherapy regimens using concurrent platinum and fluorouracil. 18F misonidazole scans detected hypoxia in 14 of 15 patients at baseline, with only one patient having detectable hypoxia at the end of treatment. With a median follow-up of 2.7 years, the 3-year failure-free survival rate was 69% (SE, 12%), the 3-year local progression-free rate was 88% (SE, 8%), and the 3-year overall survival rate was 69% (SE, 12%). CONCLUSION: DLT was due unexpectedly to febrile neutropenia, which could be overcome by omitting tirapazamine in weeks 5 and 6. The combination of tirapazamine, cisplatin, and radiotherapy resulted in remarkably good and durable clinical responses in patients with very advanced head and neck cancers. It warrants further investigation.

Adult↗

PubMed2001

Genetic markers of survival and liver recurrence after resection of liver metastases from colorectal cancer.

A significant number of patients with liver metastases from colorectal cancer (CRC) achieve 5-year survival after liver resection. Increased expression of genetic markers in the primary tumor are known to predict outcome after colonic resection, but the predictive value of such markers after resection of hepatic metastases is unknown. The objective of this study was to evaluate whether DNA content and multiple genetic markers, separately or expressed together, can predict patient outcome (liver recurrence and survival) after resection of hepatic metastases. We studied the paraffin-embedded liver tissue of 71 consecutive patients who had undergone a potentially curative resection of hepatic metastases from CRC. Using DNA flow cytometry and immunohistochemical staining techniques we determined the DNA content and the level of co-expression of seven tumor-associated proteins: proliferating cellular nuclear antigen (PCNA), epidermal growth factor receptor (EGFr), p53, c-erbB-2, H-ras, c-myc, and nm23. Three endpoints (liver recurrence, cancer specific, overall survival) were correlated with these tumor markers. The 5-year overall survival of the group was 31.2%. There was no correlation detected between the DNA aneuploidy and overall or cancer-specific survival. Similarly, expression of the individual tumor-associated proteins did not predict survival. Patients whose tumors co-expressed multiple markers had survivals similar to those whose tumors expressed fewer markers. However, a significant difference in hepatic recurrence was found between the p53-positive and p53-negative patients (p = 0.007), with marker-negative tumors having decreased recurrence. In conclusion, this study demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of hepatic metastases from CRC. However, the immunoreactivity of p53 may be an important marker of local recurrence in the liver, which may be useful if re-resection of metastatic liver tumors is considered a viable management option in this disease.

Adult↗

PubMed2001

Second trimester corticotropin-releasing hormone levels in relation to preterm delivery and ethnicity.

OBJECTIVE: To assess the relationship between maternal corticotropin-releasing hormone (CRH) levels in second trimester sera, and the risk of preterm delivery in an ethnically heterogeneous sample of pregnant women. METHODS: This nested case-control study included two case groups (97 women who delivered before 35 weeks' gestation, 144 who delivered at 35--36 weeks' gestation), and a control group (244 women who delivered at or after 37 weeks' gestation) frequency matched by ethnicity (black, white) and by alpha-fetoprotein levels (normal, unexplained high). Corticotropin-releasing hormone was evaluated in stored maternal sera collected at 15--19 weeks' gestation from cases and controls. RESULTS: Delivery before 35 weeks' gestation was associated positively with a second trimester, ethnic-specific CRH above 1.5 multiples of the median in white women [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1, 5.1] and black women (OR 5.0, 95% CI 1.8, 13.3). Sensitivity was 29% in whites and 41% in blacks; specificity was 84% in whites and 80% in blacks. We estimated the positive and negative predictive values to be 6% and 97%, respectively, in white women, and 16% and 93%, respectively, in black women. It was also noted that, within case and control groups, black women had consistently lower CRH levels than white women. CONCLUSION: Factors that lead to a premature increase in placental CRH production and are associated with an increased risk of preterm birth are evident as early as 15--19 weeks' pregnancy. When considering potential links between stressors, placental changes, CRH levels, and preterm birth, it might be important to stratify or adjust for ethnicity.

Adult↗

PubMed2001

Effects of neonatal corticosterone treatment on maze performance and HPA axis in juvenile rats.

Previous research has indicated that administering corticosterone to dams' drinking water for 21 days produced persistent alterations in physiology and behavior. We investigated whether 4 days of corticosterone exposure would have similar effects, and whether greater effects would be found when corticosterone was administered early in neonatal life than later in neonatal life. Sprague-Dawley dams were given either corticosterone (250 microg/ml) in their water bottles for postnatal days (PND) 5-9 (early corticosterone treatment: ECT), PND 13-17 (late corticosterone treatment: LCT) or no treatment (NT). At the end of treatment, corticosterone levels were higher in pups of corticosterone drinking dams. However, at weaning, ECT and LCT pups had lower basal corticosterone levels than NT pups. As juveniles, ECT pups learned to navigate to a visible and then to a nonvisible platform in a Morris water maze more quickly than did LCT and NT pups. Among females, ECT pups had higher corticosterone release in response to stress than LCT and NT pups. There were no differences in hippocampal corticosteroid receptor levels among the groups. The pattern of results is similar to, but not identical to, that found for pups exposed to corticosterone for 21 days. The results also suggest that there is a critical or sensitive period for corticosterone treatment in that early treatment was more effective than later treatment.

Age Factors↗

PubMed2001

Combined modality treatment using concurrent radiotherapy and pharmacologically-guided carboplatin for inoperable and incompletely resected non-small cell lung cancer.

BACKGROUND: In our previous randomised trial, radiotherapy (RT) was given concurrently with carboplatin 350 mg/m(2). We wanted to show that the safety and efficacy of the drug could be improved by pharmacologically-guided dosing based on renal function. PATIENTS AND METHODS: Patients were eligible if they had unresectable or incompletely resected NSCLC, good performance status (ECOG 0-2), weight loss < 10%, no distant metastases and adequate haematology and biochemistry. Radiotherapy was given to the primary site and regional lymph nodes to a total dose of 60 Gy in 30 fractions over 6 weeks. Two cycles of carboplatin were given in divided doses of 1-h infusions daily for 5 days before RT weeks 1 and 6. A total plasma AUC of 7 mg/ml per minute per cycle was targeted. The total dose was calculated by using Calvert or Chatelut formulae. RESULTS: Forty-nine patients were treated. Patient characteristics included: 78% male; mean age 66 (range: 38--78); 80% stage 3A or 3B; incomplete resection in six patients. The median dose of carboplatin administered per cycle was 850 mg (range 435--1650); 89% of patients received a higher carboplatin dose compared with BSA-calculated dose (mean increase 41%). Forty-two patients (86%) completed treatment as planned. Myelosuppression > or = grade 3 occurred in 14 patients (29%) (one patient died of pneumonia while neutropenic); two patients developed > or = grade 3 acute oesophagitis and two patients had > or = grade 3 acute pulmonary toxicity. Late pulmonary toxicity > or = grade 3 occurred in two patients. The mean potential follow-up time was 2.7 years. The estimated proportion of patients alive and free of local or distant progression at 1 year was 42% and the median survival duration was 16 months (95% CI: 11--21 months). CONCLUSIONS: Radical chest irradiation can be combined with two cycles of pharmacologically-guided full-dose carboplatin, however because our study demonstrated significant haematologic toxicity, we recommend carboplatin dosing according to renal function at less than full dose (i.e. AUC 6 mg/ml per minute per cycle).

Adult↗

PubMed2001

Estimation of pediatric patient weight by EMT-PS.

To determine paramedics' experience, comfort, and accuracy in the estimation of pediatric weights, paramedics were surveyed regarding their experience and training in estimating pediatric weights and then were presented with four children and asked to estimate their weights and to calculate the first round of i.v. epinephrine dose for asystole according to protocol. Twenty paramedics participated, with 55% stating they were uncomfortable on pediatric calls; 15 of 20 (75%) stated they were uncomfortable estimating children's weights. The majority of estimations were within 50% of the actual weights. Based on weight estimations, the epinephrine doses were calculated correctly in 88% of all cases. In 10% of cases, the epinephrine dose was incorrect by a factor of 10 times the appropriate dose. The weight range using the Broselow tape was determined correctly by all participants, with 95% correctly reporting the correct dose of epinephrine. Overall, paramedics were accurate in estimating pediatric weights, and use of the Broselow tape improved the precision of these estimations.

Attitude of Health Personnel↗