X-ray phototherapy for solid tumors.
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Animals↗
Biomedical subjects
A Norman
Publications and source records attributed to A Norman.
A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer.
MVP chemotherapy (mitomycin C 8 mg m(-2), courses 1, 2, 4 and 6, vinblastine 6 mg m(-2), cisplatin 50 mg m(-2)) is an active low-toxicity regimen in non-small-cell lung cancer (NSCLC). Based on the single-agent activity of these agents in SCLC, we have conducted a phase II trial of MVP in SCLC. Fifty chemo-naive patients with SCLC were entered in this trial. There were 33 men and 17 women with median age 66 years (range 46-83 years); 18 patients had limited disease (LD) and 32 extensive disease (ED). WHO performance status (PS) was: three patients PS 0, 33 patients PS 1, ten patients PS 2, four patients PS 3. A maximum of six cycles was given in responding patients. On completion of chemotherapy, patients with LD obtaining complete response (CR)/good partial response (PR) received thoracic irradiation and those obtaining CR were offered entry into the ongoing MRC Prophylactic Cranial Irradiation Trial. The overall response was 79% with 17% CR and 62% PR. For LD patients, 38% obtained CR but for ED only one patient achieved CR. Median response duration for LD patients was 8 months and for ED patients 5 months. Median survival was 10 months for LD patients and 6 months for ED patients. There was complete resolution of symptoms in 24%, partial improvement in 68%, no change in 2% and progressive symptoms in 6%. As regards toxicity, 24% developed WHO grade 3/4 neutropenia, 16% grade 3/4 thrombocytopenia and 6% significant hair loss. Two patients died during the first week of treatment with neutropenic infection. Quality of life using the EORTC questionnaire (QLC-C30) with lung cancer module demonstrated significant improvements from baseline levels in emotional and cognitive functioning, global QOL, of pain, dyspnoea and cough. MVP, an effective palliative regimen for NSCLC, is also active against SCLC with low toxicity and merits comparison with more toxic conventional schedules.
Aged↗
The Royal Marsden experience of a small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil.
The purpose of this study was to review the efficacy of a protracted venous infusion of 5-fluorouracil (PVI 5-FU)-based chemotherapy in advanced small bowel adenocarcinoma. Data on all patients with small bowel malignancy who were seen at a single institution over a 5-year period were retrieved from the gastrointestinal unit and hospital databases, and these cases were reviewed. Eight patients with advanced small bowel adenocarcinoma received PVI 5FU-based chemotherapy. The overall response rate in assessable patients was 37.5% (3/8). The median overall survival was 13 months (range 1-28), and progression-free survival was 7.8 months (range 0-15). Overall, the treatment was well tolerated and symptomatic benefit was seen. In conclusion, PVI 5-FU has activity in this disease. This should be assessed either as a single agent or as part of a combination regimen such as epirubicin/cisplatin/PVI FU (ECF) in a multicentre randomized study.
Adenocarcinoma↗
Management of school leavers given a diphtheria and tetanus vaccine intended for children instead of the intended low dose preparation.
In November 1995, 102 school leavers in two North Staffordshire schools were given high dose diphtheria and tetanus vaccine (intended for primary immunisation of children) rather than a preparation with a low dose of diphtheria vaccine intended for adults and adolescents. We describe the management of the incident and the action taken to minimise the risk of such an error being made again. Pupils who had received the high dose vaccine and a control group were surveyed with a self-administered questionnaire. Thirteen children out of 67 given the higher dose diphtheria vaccine consulted their general practitioner and the same number had time off school, compared with none of 25 from a control school. This excess morbidity was probably attributable to the higher dose of diphtheria vaccine.
Absenteeism↗
X-ray phototherapy for canine brain masses.
Brain masses diagnosed in 47 pet dogs as tumors by CT scans, and confirmed in 12 dogs by necropsies, were injected with iodinated contrast media and treated by a modified CT scanner, the CTRx. Twenty-six dogs that received six or more weekly treatments of about 5.6 Gy per fraction, of which about 25% was contributed by radiation from the iodine, for a median total dose of 39 Gy, had a median survival of 230 days. This compares well with the 150 days reported for 25 dogs given 46-48 Gy of cobalt-60 radiation to the whole brain, and is significantly greater than the 6 to 13 days in untreated historic controls.
Animals↗
A prospective analysis of 949 long-term central venous access catheters for ambulatory chemotherapy in patients with gastrointestinal malignancy.
We present a prospective analysis of the insertion complications and longevity of 949 cuffed, tunnelled central venous catheters used for ambulatory chemotherapy. Mean catheter life span was 121.8 days, 13.4% had complications at insertion, 17.7% had complications not necessitating removal and 18.6% had complications requiring removal. The more experienced operators had fewer complications inserting catheters (P < 0.0001). Late-onset shoulder pain occurred in 4.8% and was associated with an increased incidence of venous thrombosis (P < 0.0001) and infection (P = 0.06). Complications necessitating removal were not predicted by patient' age, site of insertion or malignancy, chemotherapy regimen, insertion platelet and fibrinogen counts, insertion complications, leucocyte count or cuff distance from the exist site. Catheters inserted with their tip in the superior vena cava were more at risk of removal (2.57 times) than those in the right atrium (P = 0.003).
Adolescent↗
Residual mass following chemotherapy of seminoma.
BACKGROUND: The residual mass so frequently found after chemotherapy of advanced seminoma may consist entirely of benign tissue or may contain residual disease amenable to adjuvant therapy. PATIENTS AND METHODS: A detailed retrospective analysis was performed on 45 patients treated with cisplatin based chemotherapy for advanced seminoma between 1978 and 1994. RESULTS: The probability of a residual mass after chemotherapy was higher if the pre-treatment mass diameter was > 5 cm (78% versus 15%, P = 0.0009). Of 33 patients with residual masses following cisplatin chemotherapy, 4 were explored surgically showing fibrosis only, 15 were treated by adjuvant radiotherapy and 14 were managed by observation alone. Recurrence occurred in 2 of 14 patients managed by observation and in 2 of 15 managed by radiotherapy. There was no evidence that risk of recurrence was related to diameter of residual mass. CONCLUSION: Residual masses persisted following cisplatin based combination chemotherapy for seminoma in 73% of cases. In our study, recurrence was rare and there was no evidence that this was influenced by either the size of the residual mass or the use of adjuvant therapy.
Antineoplastic Combined Chemotherapy Protocols↗
A prospective randomised trial of protracted venous infusion 5-fluorouracil with or without mitomycin C in advanced colorectal cancer.
BACKGROUND: To compare protracted venous infusion (PVI) 5-fluorouracil (5-FU) with and without mitomycin C (MMC) in a prospectively randomised study and analyse for tumour response, survival, toxicity and quality of life (QL). PATIENTS AND METHODS: Two hundred patients with advanced colorectal cancer received PVI 5-FU 300 mg/m2/day for a maximum of 24 weeks and were randomised to PVI 5-FU alone or PVI 5-FU + MMC 10 mg/m2 (7 mg/m2 from June 1995) 6 weekly for 4 courses. RESULTS: Overall response was 54% (95% confidence interval [CI] 44.1%-63.9%) with PVI 5-FU + MMC compared to 38% (95% CI: 28.3%-47.7%) for PVI 5-FU alone (P = 0.024). The median failure free survival was 7.9 months in PVI 5-FU plus MMC and 5.4 months with PVI 5-FU alone (P = 0.033) and at one year 31.9% for the combination compared to 17.7% for PVI 5-FU alone. Median survival was 14 months with MMC and 15 months in 5-FU alone; one-year survival 51.7% vs. 57.2%. PVI 5-FU + MMC caused more overall haematological toxicity but CTC grades 3/4 was increased only for thrombocytopaenia. Two patients treated with a cumulative dose of MMC of 40 mg/m2 developed haemolytic uraemic syndrome warranting the reduction in cumulative MMC dose to 28 mg/m2. The global QL scores were better for PVI 5-FU + MMC arm at 24 weeks, but the remaining QL data showed no differences. CONCLUSIONS: PVI 5-FU + MMC results in failure-free survival and response advantage, tolerable toxicity and better QL when compared to PVI 5-FU alone but no overall survival advantage. There is no irreversible toxicity with MMC at a cumulative dose of 28 mg/m2.
Adenocarcinoma↗
A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.
Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).
Adenocarcinoma↗
Postnatal development of the collagen matrix in rabbit tibial plateau articular cartilage.
Changes in the 3-dimensional arrangement of the articular cartilage matrix during growth of the rabbit tibial plateau were studied. Knees from newborn, and 1, 2 and 6 wk-old rabbits were compared with those of adults by light and electron microscopy. The specimens were fixed, embedded en bloc in epoxy resin and sectioned vertically/coronally through the point where the articular cartilage was thickest in the adult medial tibial plateau. At birth, the proximal tibial epiphysis was cartilaginous, but nascent articular cartilage was recognisable as a densely cellular layer covering the tibial condyle. Within 30 microns of the articular surface, the chondrocytes were flattened and collagen fibres ran among these cells in a direction parallel to the surface. Deeper in the articular cartilage, rounded cells were evenly distributed within a random collagen fibril network. At the centre of the plateau, the tangential layer changed little during growth, whereas the subjacent cellular layer grew in thickness and steadily achieved a more vertical character in the organisation of its constituent collagen and cellular elements. At 1 wk, cells were separated into clusters by acellular regions filled with collagen fibrils. At 2 wk, cells within the forming radial zone were aligned in columns bracketed by vertical collagen fibres. Continuity of these vertical fibres with those in the tangential surface layer was evident at this age. The chondrocytes were surrounded by fibrous capsules typical of chondrons. By 6 wk, the bases of the radial collagen fibres in the very centre of the condyle had calcified, as had the adjacent hypertrophic hyaline cartilage. A solid subchondral plate and tidemark did not appear until skeletal maturity. From birth to age 6 wk, maximum thickness of the layer identified as primordial articular cartilage increased from 0.13 mm to 0.70 mm, and was 1.5 mm in the adult. Throughout growth, however, the thickness of the tangential layer in the centre of the plateau never exceeded 0.05 micron. In the patella, femoral head and peripheral tibial plateau, cartilage development followed the same general sequence. In contrast to the central tibial plateau, the tangential layer also grew in thickness, but at a slower rate than that of the radial zone. At all ages, the developing articular cartilage was structurally distinct from the deeper hyaline cartilage which contributed to growth of the ossification centre through enchondral ossification. The collagen matrix of articular cartilage acquires a characteristic, orderly 3-dimensional structure soon after birth. Growth in cartilage thickness occurs primarily through enlargement of the radial zone.
Animals↗
99Tcm-MDP blood-pool phase in the assessment of repetitive strain injury.
We reviewed three-phase bone scans of the limbs of 7 patients suffering from limb pain suggestive of occupational repetitive strain injury (RSI) and compared them with 13 patients with limb pain due to various aetiologies. Doppler ultrasound measurement of blood flow had been performed in 13 of the 20 patients. The bone scan results showed increased blood flow and pooling (second phase) in the affected limbs of patients with RSI as compared to those with algodystrophy or non-specific limb pain (sensitivity 86%, specificity 85%). Doppler ultrasound also demonstrated increased blood flow to the affected limbs (sensitivity 83%) but failed to differentiate between the different aetiologies of pain (specificity 14%). We conclude that the blood-pool phase of three-phase bone scans can play a potential role in screening RSI patients.
Adolescent↗
Radiation doses in radiation therapy are not safe.
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Biophysical Phenomena↗
Fertility after chemotherapy for testicular germ cell cancers.
PURPOSE: To analyze the probability of recovery of spermatogenesis after orchidectomy and cisplatin-based chemotherapy (CT) for testicular germ cell cancer. PATIENTS AND METHODS: One hundred seventy-eight patients treated between 1979 and 1991 were selected by the requirement of sperm count both pre-CT and post-CT. Counts were classified as normospermic (NS) if more than 10 x 10(6)/mL, oligospermic (OS) if 1 to 9 x 10(6)/mL, and azoospermic (AS) if less than 1 x 10(6)/mL. The median follow-up time after CT before sperm analysis was 30 months. RESULTS: Analysis of 170 patients whose spermatogenesis was reassessed at least 1 year after CT showed that of 89 patients whose pre-CT counts were NS, the post-CT count was NS in 64%, OS in 16%, and AS in 20%. There was clear evidence for continued recovery beyond 1 year; the probability of spermatogenesis increased to 48% by 2 years and 80% by 5 years. There was a significantly higher probability of recovery to OS and NS count levels in the 54 patients treated with carboplatin-rather than cisplatin-based therapy. There was an independent and similar effect of normal pre-CT count. There was a reduced probability to recover to OS in the 26 patients treated with more than four cycles of CT. A prognostic model identified three groups with 25%, 45%, and 82% probabilities of recovering spermatogenesis by 2 years after CT. CONCLUSION: Analysis of pre-CT sperm count together with details of planned treatment can be used to predict recovery of spermatogenesis following germ cell CT.
Adolescent↗
Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.
PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL). RESULTS: The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained. CONCLUSION: The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.
Adenocarcinoma↗
Elimination of theophylline metabolites in healthy adults.
The metabolism of theophylline (TP) (540 mg per os) was determined by measuring plasma and saliva concentrations of TP and its metabolites, 0-24 h after loading, and urinary excretion 0-48 h after loading. TP and its five metabolites were separated and quantified by combining high-performance liquid chromatography and capillary electrophoresis. In addition to TP, 1,3-U, 3-X and 1-U were consistently found in plasma and saliva. The area under the plasma concentration-time curve (AUC) showed that TP accounted for 91 +/- 4% (mean +/- SD) of the total AUC in plasma with 1,3-U accounting for 3.1 +/- 1.4%, 3-X for 3.4 +/- 1.8% and 1-U for 2.5 +/- 1.5%. The urine analyses showed that unchanged TP accounted for 19 +/- 5% of total excretion, the remainder being 1, 3-dimethyluric acid (1,3-U, 41 +/- 6%), 1-methylxanthine (1-X, 2 +/- 0.8%), 1-methyluric acid (1-U, 26 +/- 6%), 3-methylxanthine (3-X, 11 +/- 3%) and 3-methyluric acid (3-U, 1 +/- 0.3%). Highest excretion rates were observed for 1,3-U (70 +/- 29 mumol/h), 1-U (40 +/- 26 mumol/h) and 3-X (20 +/- 15 mumol/h) 6-9 h after TP ingestion suggesting the high excretion of 1,3-U, 1-U and 3-X by the kidneys. The highest excretion rate of TP (50 +/- 8 mumol/h) occurring at 0-6 h after the load and rapidly declining thereafter, indicated the lower excretion of TP compared with its metabolites. N3-demethylation of TP accounted for 34 +/- 6% of the urinary metabolites, N1-demethylation of TP for 15 +/- 3% and C8-oxidation of TP for 51 +/- 9%. C8-oxidation of 1-X and 3-X was 93 +/- 4%, and 9 +/- 4%, respectively, of the excreted amount of monomethylxanthine plus formed monomethylurate. Since the extent of all metabolic reactions remained constant during the load, it is suggested that TP is metabolized by hepatic reactions that occurred simultaneously and not sequentially.
Administration, Oral↗
Evaluation of the lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid/14C-mannitol methods for intestinal permeability.
BACKGROUND: We earlier compared the lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid (EDTA)/14C-mannitol methods for intestinal permeability We have now investigated an increased number of control subjects, with special regard to the influence of urinary volume, sex, age, and smoking on marker excretion, and patients with intestinal disorders, with special regard to correlations between markers. METHODS: The 0- to 6-h urinary excretion of orally administered markers was measured in 65 control subjects and in 70 patients. RESULTS: In the control group excretion of mannitol and 14C-mannitol (small-pore permeability markers) was strongly correlated to urinary volume, whereas such correlation was weak for lactulose and absent for 51Cr-EDTA (large-pore permeability markers). No sex difference in marker excretion was found, but correlation to urinary volume was more pronounced in males. There was a slightly decreasing excretion of markers with increasing age, reaching significance for 51Cr-EDTA and 14C-mannitol; their excretion ratio was unaffected. Smoking did not significantly affect marker excretion. In the patient group the excretion of large-pore markers tended to be higher and that of small-pore markers to be lower than in the control group; correlation between the large-pore markers, between the small-pore markers, and between the large-pore/small-pore marker ratios was higher than in the control group. CONCLUSIONS: Correction for urinary volume substantially reduces variability in small-pore marker excretion. Excretion of both types of markers tends to decrease with age, the large-pore/small-pore marker ratio remaining unchanged. Smoking does not affect small-intestinal permeability. 14C-mannitol is preferred to chemically determined mannitol owing to lower test variability.
Adolescent↗
Effects of norepinephrine infusion and exercise on blood pressure in rats.
Two experiments were conducted to test the hypotheses that norepinephrine (NE) infusion would increase blood pressure and wheel running activity level, and, secondly, that voluntary exercise would lower NE-induced increases in blood pressure. NE-bitartrate was infused into male Sprague-Dawley rats using an implanted osmotic pump (3.75 micrograms/kg/min in 0.9% saline). Control rats received the vehicle solution. Systolic blood pressure was measured by the tail-cuff method. Voluntary wheel running activity expressed as wheel revolutions per 24 hr was measured on the 5th, 9th, and 13th day. Blood pressure on the 13th day and wheel running activity on the 9th day were significantly higher in NE-infused rats. The NE content of heart tissue was not altered, but urinary excretion of NE and epinephrine was increased in the NE-infused animals. Food intake, body weight gain, and kidney weight per 100 g body wt were not changed but heart weight per 100 g body wt was increased by NE infusion. Urinary total calcium excretion was higher in the NE-infused rats. Spontaneous voluntary exercise in running wheels attenuated increases of blood pressure in NE-infused rats. The results of the present study suggest that rats receiving exogenous NE exhibit increased blood pressure and voluntary wheel running activity. Voluntary wheel running exercise also reduces blood pressure in NE-infused rats.
Animals↗
Clinically occult avascular necrosis of the hip in systemic lupus erythematosus.
OBJECTIVE: To study the natural history of clinically occult avascular necrosis (AVN) of the hip in patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE (without symptoms referable to the hip) receiving at least 5 mg/day prednisone for > or = 6 months were screened by magnetic resonance imaging (MRI) for AVN of the hip. A complete MRI evaluating class and percentage of femoral head involvement, AP and lateral radiographs of the hips, bone scan, and physical examination were performed for patients with positive MRI. Medical records were reviewed for serologic and clinical variables that might predict AVN. Repeat MRI were obtained at 3, 6, and 12 months to assess possible progression or resolution of the lesion. Patients with negative screening MRI underwent repeat screening after one year to assess the one year incidence rate. RESULTS: Eleven asymptomatic hips (8%) in 8 patients (12%) had MRI documented AVN. The percentage of femoral head involvement ranged from 1 to 46%. One lesion was MRI class B, the remaining lesions were class A. The radiographic stage of 10 hips was stage 1, the MRI class B hip was stage 2. Risk factors for clinically occult AVN included Afro-American origin, Raynaud's phenomenon, migraine headaches, and a maximal corticosteroid dose of at least 30 mg/day. After 12 months, 43 of 58 patients with an initially negative MRI underwent repeat screening examinations; no new lesions were observed. CONCLUSION: Clinically occult AVN of the hip is common in patients with SLE. The short term natural history of these lesions appears stable without spontaneous healing or clinical or radiographic progression. Risk factors for these asymptomatic lesions are similar to the risks for symptomatic AVN and surgical intervention appears not to be indicated in these patients.
Adolescent↗