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. (C) 2001 Elsevier Science Inc.

Repeatability of maximal voluntary force and of surface EMG variables during voluntary isometric contraction of quadriceps muscles in healthy subjects

The repeatability of initial values and rate of change of EMG signal mean spectral frequency (MNF), average rectified values (ARV), muscle fiber conduction velocity (CV) and maximal voluntary contraction (MVC) was investigated in the vastus medialis obliquus (VMO) and vastus lateralis (VL) muscles of both legs of nine healthy male subjects during voluntary, isometric contractions sustained for 50 s at 50% MVC. The values of MVC were recorded for both legs three times on each day and for three subsequent days, while the EMG signals have been recorded twice a day for three subsequent days. The degree of repeatability was investigated using the Fisher test based upon the ANalysis Of VAriance (ANOVA), the Standard Error of the Mean (SEM) and the Intraclass Correlation Coefficient (ICC). Data collected showed a high level of repeatability of MVC measurement (normalized SEM from 1.1% to 6.4% of the mean). MNF and ARV initial values also showed a high level of repeatability (ICC > 70% for all muscles and legs except right VMO). At 50% MVC level no relevant pattern of fatigue was observed for the VMO and VL muscles, suggesting that other portions of the quadriceps might have contributed to the generated effort. These observations seem to suggest that in the investigation of muscles belonging to a multi-muscular group at submaximal level, the more selective electrically elicited contractions should be preferred to voluntary contractions. (C) 2001 Elsevier Science Ltd. All rights reserved.

Congenital thyrotoxicosis in premature infants

OBJECTIVES Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex. DESIGN and PATIENTS The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays. RESULTS Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25-36 week) and median B Wt was 1.96 kg (0.50-2.62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1-16 days) and mean age at commencement of treatment was 12 days (7-26 days). Two infants received propylthiouracil and five received a combination of carbimazole and propranolol. Pour became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supplementation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort. CONCLUSIONS This is a large series of extremely small and premature infants with neonatal thyrotoxicosis. Presentation was nonspecific. The diagnosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme law birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recognition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.

Safety and efficacy of low anterior en bloc resection as part of cytoreductive surgery for patients with ovarian cancer

Objective. To examine the feasibility and safety of a low anterior resection of the rectosigmoid plus adjacent pelvic tumour as part of primary cytoreduction for ovarian cancer. Methods. This study included 65 consecutive patients with primary ovarian cancer who had debulking surgery from 1996 through 2000. All patients underwent an en bloc resection of ovarian cancer and a rectosigmoid resection followed by an end-to-end anastomosis. Parameters for safety and efficacy were considered as primary statistical endpoints for the aim of this analysis. Results. Postoperative residual tumour was nil, 1 cm in 14, 34, and 14 patients, respectively. The median postoperative hospital stay was 11 days (range, 6 to 50 days). Intraoperative complications included an injury to the urinary bladder in one patient. Postoperative complications included wound complications (n=14, 21.5%), septicemia (n=9, 13.8%), cardiac complications (n=7, 10.8%), thromboembolic complications (n=5, 7.7%) ileus (n=2, 3.1%) anastomotic leak (n=2, 3.1%) and fistula (n=1, 1.5%). Reasons for a reoperation during the same admission included repair of an anastomotic leak (n=1), postoperative hemorrhage (n=1), and wound debridement (n=1). Wound complications, septicemia, and anastomotic leak formation were more frequent in patients who had a serum albumin level of less than or equal to 30 g/L preoperatively. There was one surgically related mortality in a patient who died from a cerebral vascular accident 2 days postoperatively. Conclusions. An en bloc resection as part of primary cytoreductive surgery for ovarian cancer is effective and its morbidity is acceptably low. (C) 2001 Academic Press.

Postoperative vaginal vault brachytherapy for node-negative Stage II (occult) endometrial carcinoma

Objective. The aim of this study is to look at the efficacy of extended surgical staging and postoperative vaginal vault brachytherapy in patients with Stage II (occult) endometrial carcinoma. Methods. Between January 1989 and December 1997, there were 30 patients with Stage II (occult) endometrial carcinoma who received postoperative vaginal vault brachytherapy as the only adjuvant treatment. The study group consisted of 15 of these patients who had extended surgical staging (including lymphadenectomy). Results. At a median follow-up of 36 months (range 17 to 113 months), there has been no recurrence. There were no major complications from surgery. Only 1 patient had mild rectal bleeding following vaginal vault brachytherapy and there were no grade 3 or 4 bowel toxicities. Conclusions. Extended surgical staging and postoperative vaginal vault brachytherapy for Stage II (occult) endometrial carcinoma is associated with minimal morbidity and excellent survival. (C) 2001 Academic Press.

Primary fallopian tube carcinoma: the Queensland experience

The purpose of this study was to review the experience with fallopian tube carcinoma in Queensland and to compare it with previously published data. Thirty-six patients with primary fallopian tube carcinoma treated at the Queensland Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective clinicopathologic study. All patients had primary surgery and 31/36 received chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal pain (14/36) were the most common presenting symptoms at the time of diagnosis. Median follow-up was 70.3 months and the median overall survival was 68.1 months. Surgical stage I disease (P = 0.02) and the absence of residual tumor after operation (P = 0.03) were the only factors associated with improved survival. Twenty of the 36 patients (55%) presented with stage I disease and survival was 62.7% at 5 years. No patient with postoperative residual tumor survived. The majority of the patients with fallopian tube carcinoma present with stage I disease at diagnosis, but their survival probability is low compared with that of other early stage gynecological malignancies. If primary surgical debulking cannot achieve macroscopic tumor clearence, the chance of survival is extremely low.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system, While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation, Patients with negative washings had a DFS of 96'7e at 36 months compared with 67% for patients with positive washings (log-rank P < 0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Effect of gender on ownership and income in veterinary practice

Objective To estimate the effect of gender on ownership and income in veterinary practice in Australia. Methods Questionnaire completed by private veterinary practitioners, and analysed using the SAS System for Windows 7.0. Results More than three-quarters (78%) of male but 36% of female private practitioners were partial or sole owners of practices. The median annual income for all male practitioners working more than 40 hours/week was $70K, but that for females was $43K. These disparities existed in both city and country practices, and in the case of income it increased with increasing time in the workforce. Male practice owners also reported higher incomes than female owners. Conclusions Female veterinary practitioners are less likely to own practices, and more likely to earn low incomes than males. These differentials do not appear to be due to location, hours worked or years since graduation or, in the case of income, to whether they are owners or employees. The evidence points to a lower interest by women than men in the business aspects of veterinary practice.

Reduced Red Cell 2,3-Diphosphoglycerate Concentrations in Critical Illness without Decreased In Vivo P50

We investigated whether red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations are reduced in critical illness, whether acidaemia, hypophosphataemia or anaemia influence 2,3-DPG, and whether there is any net effect on in vivo P50. Twenty healthy, non-smoking, male volunteers were compared with 20 male intensive care patients with APACHE 2 scores > 20 on the preceding day. Those transfused in this time were excluded. Venous red cell 2,3-DPG concentrations were measured in both groups. In the patient group, routine multichannel biochemical profile and arterial blood gas analysis were also performed and in vivo P50 calculated. The mean 2,3-DPG concentration was significantly lower in the patient group than in the controls (4.2 +/-1.3 mmoll/l vs 4.9 +/-0.5 mmol/l, P=0.016). The patients were well oxygenated (lowest arterial PO2=75 mm Hg) and showed a tendency to acidaemia (median pH 7.37, range 7.06 to 7.48) and anaemia (median haemoglobin concentration 113 g/l, range 89 to 154 g/l). By linear regression of patient data, pH had a significant effect on 2,3-DPG concentrations (r=0.6, P=0.011). Haemoglobin and phosphate concentrations did not, but there were few abnormal phosphate values. There was no correlation between 2,3-DPG concentrations and in vivo P50 (r(2) less than or equal to 0.08). We conclude that 2,3-DPG concentrations were reduced in a broad group of critically ill patients. Although this would normally reduce the P50, the reduction was primarily linked with acidaemia, which increases the P50. Overall, there was no net effect on the P50 and thus no affinity-related decrease in tissue oxygenation.

Woodstoves uncovered: a paediatric problem

Objectives: To document and describe the effects of woodstove burns in children. To identify how these accidents occur so that a prevention strategy can be devised. Design, Patients and Setting: Retrospective departmental database and case note review of all children with woodstove burns seen at the Burns Unit of a Tertiary Referral Children's Hospital between January 1997 and September 2001. Main outcome measures: Number and ages of children burned: circumstances of the accidents; injuries-sustained, treatment-required and long-term sequelae. Results. Eleven children, median age 1.0 year, sustained burns, usually to the hands, of varying thickness. Two children required skin grafting and five required scar therapy. Seven children intentionally placed their hands onto the Outside of the stove. In all children, burns occurred despite adult supervision Conclusions: Woodstoves area cause of burns in children. These injuries are associated with significant morbidity and financial costs. Through public education, woodstove burns can easily be prevented utilising simple safety measures. (C) 2002 Elsevier Science Ltd and ISBI All rights reserved.

Motorcycle exhaust burns in children

Objectives: To document and describe motorbike exhaust burns on children. Design, Patients and Setting: Departmental database and case note review of all children with motorbike exhaust burns seen at the Stuart Pegg Paediatric Burns Centre, Brisbane between January 1996 and October 2001. Main outcome measures: Number and age of children burned, circumstances of the injury, burns sustained, treatment required and long-term sequelae. Results: Twenty-four children, median age 8 years, sustained thermal burns, most commonly to the right lower leg. Thirteen children required surgery, and 17 required chronic scar management. Conclusions: We have identified motorbike exhausts as a cause of burns in children. The injuries received resulted in significant morbidity to these children and warrants a campaign airned at reducing the incidence of such injuries. (C) 2002 Published by Elsevier Science Ltd. and ISBI.

Determination of the hemispheric character (i.e. southern or northern latitudinal position) of equatorial ionosonde stations as deduced from long-term recordings of the minimum height of the F-region (h ' F)

The virtual (or minimum) height of the F-region (h'F), recorded over a number of solar cycles for I I equatorial and mid-latitude ionosonde stations, was used to deduce the hemispheric (i.e. southern or northern hemisphere) character of equatorial stations. The semi-annual median monthly height (h'F) variations consist of two components: major local summer maximum and winter sub-maximum (about 5 percent of the summer maximum). This hemispheric pattern was most consistently observed for equatorial stations (within 5degrees of the geomagnetic equator) in a period centred on the local midnight (21-03 LT) but was also present, to a lesser extent, at mid-latitude stations and at other time intervals. It is evident that the physical parameter h'F defines the hemispheric character of an equatorial station which has different (sometimes opposite) geographic and geomagnetic latitudes. There is a sharp transition in the latitudinal character of the stations on both sides of the equator leading to hypothesis that the equal maxima in h'F in December and June solstices are observed at a near-equator position labelled as ionosonde deduced equator (IDE). Such a signature was observed for an American equatorial (both geographic and geomagnetic) station Talara (Peru) which is an experimental support of the hypothesis. The IDE can be another useful parameter characterising the equatorial ionosphere. This finding reveals a new application of the standard ionosonde data in defining the geophysical character of equatorial stations, being an important contribution to space climatology. (C) 2002 Elsevier Science Ltd. All rights reserved.

Acute symptoms, not rectally administered sucralfate, predict for late radiation proctitis: Longer term follow-up of a phase III trial - trans-Tasman radiation oncology group

Image : To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy (RT) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity. Image : Eighty-six patients with localized prostate carcinoma were randomized in a double-blind, placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate. The enema began the first day of RT and was continued for 2 weeks after treatment completion. The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) toxicity; however, the patients were followed for an additional 5 years on a 6-month basis. The evaluation included late RTOG/EORTC toxicity and a patient self-assessment questionnaire. Image : With a median follow-up of 5 years, the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12% (95% confidence interval [CI] 2–22%) for placebo and 5% (95% CI 0–12%) for sucralfate (p = 0.26). The probability of late rectal bleeding was 59% (95% CI 45–73%) for placebo and 54% (95% CI 40–68%) for sucralfate. No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self-assessment variables. Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 (95% CI 1.31–5.73) for the development of late toxicity of Grade 1 or greater. Substituting the patient self-assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity, with a hazard ratio of 3.44 (95% CI 1.68–7). Image : The results of this study do not support the use of sucralfate administered rectally as a method for reducing the late toxicity of nonconformal RT for prostate cancer. There appears to be an association between the development of acute and subsequent late toxicity, although the nature of this association remains to be determined

Fatigue-related changes in torque output and electromyographic parameters of trunk muscles during isometric axial rotation exertion - An investigation in patients with back pain and in healthy subjects

Study Design. A cross-sectional case-control study. Objectives. To examine the effect of fatigue on torque output as well as electromyographic frequency and amplitude values of trunk muscles during isometric axial rotation exertion in back pain patients and to compare the results with a matched control group. Summary of Background Data. Back pain patients exhibited different activation strategies in trunk muscles during the axial rotation exertions. Fatigue changes of abdominal and back muscles during axial rotation exertion have not been examined in patients with back pain. Methods. Twelve back pain patients and 12 matched controls performed isometric fatiguing axial rotation to both sides at 80% maximum voluntary contraction in a standing position. During the fatiguing exertion, electromyographic changes of rectus abdominis, external oblique, internal oblique, latissimus dorsi, iliocostalis lumborum, and multifidus were recorded bilaterally. The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were also measured. Results. No difference in the endurance capacity was found between back pain and control groups. At the initial period of the exertion, back pain patients demonstrated a statistical trend (P = 0.058) of greater sagittal coupling torque as well as lower activity of rectus abdominis and multifidus and higher activity in external oblique. During the fatigue process similar changes of coupling torque were demonstrated in both sagittal and coronal planes, but a smaller fatigue rate for right external oblique, increase in median frequency for latissimus dorsi, and lesser increase in activity for back muscles were found in the back pain group compared with the control group. Conclusions. Alterations in electromyographic activation and fatigue rates of abdominal and back muscles demonstrated during the fatigue process provide insights into the muscle dysfunctions in back pain and may help clinicians to devise more rational treatment strategies.

GH treatment in adults with chronic liver disease: A randomized, double-blind, placebo-controlled, cross-over study

Patients with chronic liver disease (CLD) are catabolic and GH-resistant. The effects of supraphysiological recombinant human GH (rhGH; 0.2 IU.kg(-1).d(-1)) treatment in adults with CLD were assessed in a randomized, double-blind, placebo-controlled cross-over trial (4-wk dietary run-in, 4-wk treatment, and 2-wk wash-out phases). Nine adults with mild- to moderate-severity CLD participated (median age, 49 yr; three males and six females; Child's classification A in six and B in three). Biopsy-proven etiologies were: alcohol (four patients), primary biliary cirrhosis (three patients), non-A, non-B, non-C hepatitis (one patient), and cryptogenic (one patient). Treatment with rhGH increased serum IGF-I (median increase over placebo, +93 mug.liter(-1); P = 0.004), IGF-binding protein-3 (+0.9 mg.liter(-1): P = 0.004), and acid labile subunit (+10.7 nM; P = 0.004). Total body potassium (+8.0 g; P = 0.023), body weight (+1.6 kg; P = 0.008), and total body water (by bioelectrical impedance; +4.9 kg; P = 0.004) increased. Resting metabolic rate (+313 ml.kg(-1).min(-1); P = 0.004) and lipid oxidation (+1072.0 kcal.d(-1); P = 0.032) increased. Metabolic changes included increased fasting plasma glucose (+1.2 mm; P = 0.008), insulin (+33.8 mU.liter(-1); P = 0.004), C-peptide (+0.7 nM; P = 0.004), and free-fatty acids (+0.1 mEq.liter(-1); P = 0.04). Clinical side effects included worsening edema and ascites. Hepatocellular function did not change. Therefore, rbGH treatment in CLD: 1) overcame hepatic GH resistance; 2) may have improved whole-body protein catabolism; 3) increased lipolysis and lipid oxidation; 4) increased insulin resistance; and 5) had potent antinatriuretic effects. Long-term safety and efficacy require further assessment.