The role of ¹8fluoro-deoxy glucose combined position emission and computed tomography in the clinical management of anal squamous cell carcinoma.

AIM: Anal squamous cell carcinoma (SCC) is uncommon in the western world but continues to increase in incidence. Optimal treatment and outcome are dependent upon pretreatment staging strategies. We evaluate the role of ¹8fluoro-deoxyglucose (¹8FDG) combined position emission and computed tomography (PETCT) in the management of anal SCC. METHOD: Patients with a histologically confirmed anal SCC underwent standard staging investigations, including computed tomography, Magnetic resonance imaging and examination under anaesthetic. A tumour, node, metastasis (TNM) system was used. All patients subsequently underwent additional whole-body ¹8FDG PETCT scanning. Management was planned accordingly, blinded to ¹8FDG PETCT findings, at a multidisciplinary meeting, and reviewed again following disclosure of PETCT results. RESULTS: Forty patients (24 men), with a median age of 57 years (range 38-87 years), were prospectively recruited. All primary tumours were ¹8FDG avid. PETCT did not alter the T stage but did result in disease upstaging (N and M stages). Management was altered in five (12.5%) patients: one patient was identified to have an isolated distant metastasis, and four patients had ¹8FDG-avid lymph nodes not otherwise detected, all of which were tumour-positive on fine needle aspiration cytology/biopsy. CONCLUSION: PETCT upstages anal SCC and influences subsequent management. PETCT should be considered in the staging of anal SCC, although the definitive benefit of such a strategy requires further evaluation.

Concurrent daily cisplatin and radiotherapy in locally advanced squamous carcinoma of the head-and-neck and bronchus.

In order to exploit the cytotoxic and radiosensitising actions of cis-platinum, we have treated 35 patients with locally advanced squamous cell carcinoma of the bronchus or head-and-neck. Each patient underwent radical irradiation (60 Gy/30 fractions over 6 weeks) with daily low-dose intravenous cisplatin (10 mg absolute dose per day) administered within 30 min of each daily radiation fraction. Total dose of cisplatin was 300 mg over 6 weeks. Although treatment was complicated by nausea in almost all patients and transient renal dysfunction in the majority, 27 patients completed treatment and renal function returned to normal or near normal in almost all cases. There was no obvious enhancement of pulmonary or skin toxicity, beyond what would have been expected from treatment with radical radiotherapy alone. There were two treatment-related deaths from renal failure. The response rate was high: all patients achieved at least a partial response, and in head-and-neck sites, there were nine complete responders and seven partial responders. Of the initial 35 patients, of whom all but two had advanced inoperable disease, 11 have died and 21 remain in continuous remission, 8-120 weeks from the start of treatment (median 55 weeks).

Hemibody irradiation in multiple myeloma.

Eighteen patients with multiple myeloma were treated by hemibody irradiation using large single fractions, usually to a dose of 10 Gy (lower half) and 7.5 Gy (upper half). All except one patient had previously been treated by multiple courses of conventional chemotherapy with melphalan and prednisone, and were considered to be resistant to further chemotherapy. In most cases, local field irradiation had also been given for symptomatic bone pain. Of the 13 patients who had symptoms at the start of hemibody irradiation, 11 improved sufficiently for their analgesia requirement to be reduced. In eight patients, there was a significant fall in circulating immunoglobulin but no patient with Bence-Jones proteinuria had complete resolution of this biochemical abnormality. Although thrombocytopenia and neutropenia were common, only two patients required platelet transfusion and the treatment was in general extremely well tolerated. Survival following hemibody irradiation was similar to the survival reported from the use of "second-line" chemotherapy and we feel that hemibody irradiation is a more acceptable alternative for most patients.

Study of metabolism of psychotomimetic indolealkylamines by rat tissue extracts using liquid chromatography.

The use of a series of liquid chromatographic techniques involving cation-exchange, reverse-phase and normal-phase chromatography has permitted the separation and characterisation of a number of metabolites of the psychotomimetic indolealkylamines N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine which were isolated following incubation of these compounds with rat tissue extracts. In liver, kidney and brain tissue extracts the routes of metabolism identified included oxidative deamination, N-demethylation, O-demethylation and N-oxidation. The quantitative significance of individual routes of metabolism in these tissues was assessed using N,N-dimethyltryptamine as a substrate.

In vivo metabolism of 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine in the rat.

Following intraperitoneal administration, 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine are subject to both a very rapid uptake into, and clearance from, all tissues examined. The current studies in vivo confirm previous in vitro observations that the routes involved in the metabolism of these compounds include oxidative deamination, N-demethylation, O-demethylation, and N-oxidation. The analysis of metabolic profiles in various tissues led to the identification of the N-oxides as major metabolites. The successful inhibition and redirection of metabolism away from the indole acids towards the parent compounds and their structurally unique metabolites were demonstrated in animals pretreated with iproniazid.

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma.

In view of increasing controversy regarding the role of double hemibody irradiation (DHBI) in the treatment of multiple myeloma, we have analysed the use of this technique at our institution over a 6-year period. Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemoresistant to initial therapy. Fifteen patients received alpha IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week, as part of a randomized trial. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. alpha IFN did not appear to prolong survival (OS or PFS) post-DHBI. Cytopenia was a significant problem, such that only 60% of patients had counts adequate enough to be eligible for alpha IFN. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Resistance of the sheep blowfly Lucilia cuprina to insecticides in the Republic of South Africa.

Laboratory tests on larvae of nine strains of the sheep blowfly, Lucilia cuprina, and one of the hairy blowfly, Chrysomia albiceps, taken from the field are reported. Results indicate resistance to arsenic in one strain and to diazinon in the remainder and in Chrysomia albiceps. Field evidence corroborates the presence of resistance in the blowfly maggots to current flystrike insecticides with reduced protection resulting in more frequent treatment.

A new era in outpatients'.

In reply to the article and letters about outpatients (Nursing Standard June 19 and July 3), I must make a point that not all outpatients' departments are the same.

Medical malpractice statutes of limitation: a review of the law and its application.

A medical malpractice statute of limitation fixes the period within which a lawsuit must be filed. In recent year exceptions have been made to these proscribed limitations. States now allow a patient to file suit when he or she discovers the injury even if this occurs after the statutory time period. Similarly, many courts have held that this period does not even begin until treatment is terminated or the physician-patient relationship ends. Likewise, a patient will not be barred from bringing suit if there is evidence of deceit or fraud by the health care provider. Finally, some states are attempting to revise the traditional rule that the limitations period does not begin to run with respect to a minor until he or she reaches the age of majority regardless of when the injury occurred.

Chemoradiotherapy with or without induction chemotherapy for locally advanced pancreatic cancer: a UK multi-institutional experience.

AIMS: The optimal management for patients with unresectable locally advanced adenocarcinoma of the pancreas (LAPC) is unclear. The aim of this study was to determine the outcome of patients treated with chemoradiotherapy (CRT) with or without induction chemotherapy. MATERIALS AND METHODS: We conducted a multi-centre retrospective analysis of 48 patients with biopsy-proven LAPC treated with CRT in four regional oncology centres in the UK between March 2000 and October 2007. The prescribed radiotherapy dose was 4500-5040 cGy in 25-28 fractions and was given concurrent with gemcitabine (n=37), gemcitabine/cisplatin (n=9), 5-fluorouracil (n=1) or capecitabine (n=1). RESULTS: Four patients (8.3%) did not complete the intended treatment due to CRT-related toxicities. The disease control rate (Objective response rate (ORR) and stable disease (SD)) was 81.3%. The median overall survival was 17 months (range 5-66 months). In subgroup analysis, a trend towards improved survival was seen in patients who completed the intended treatment (17.1 months vs 11.0 months, P=0.06) and in patients undergoing surgery (27 months vs 16 months, P=0.023). CONCLUSIONS: This is the largest reported series from the UK focussing on patients who received CRT for pancreas cancer. It shows that it is possible to deliver pancreatic CRT with acceptable toxicity. Induction chemotherapy followed by gemcitabine-based CRT shows promising activity and should be evaluated in phase III studies.

Why should optometry become involved in the hospital setting?

Our nation's hospitals are no longer the private domain of the medical physician. Other "independent" health care providers are justified in applying for clinical privileges. The expanding scope of practice has served to make optometrists more aware of their rights to practice in the hospital environment. Recent changes in the guidelines of the Joint Commission for Accreditation in Health Care Organizations (JCAHO) has further reinforced the concept that no independent health care providers should be denied clinical privileges based solely on the fact that an applicant is not an "MD."

High-performance liquid chromatographic determination of clomiphene using post-column on-line photolysis and fluorescence detection.

A method has been developed for the extraction and quantitation of the ovulatory stimulant drug clomiphene from plasma. The cis- and trans-isomers were separated by normal-phase chromatography using chloroform-methanol as the mobile phase. After eluting from the column, the clomiphene was passed through a PTFE photolysis coil irradiated by a powerful UV lamp, resulting in conversion of the isomers to highly fluorescent species. The derivatised material was then detected using a fluorescence spectrometer. Use of this method enables a substantial improvement of sensitivity over UV detection and has permitted the measurement of plasma clomiphene levels in patients receiving clomiphene therapy.

Aortocaval compression and plasma concentrations of thiopentone at caesarean section.

The venous plasma concentration-time profiles of thiopentone were measured simultaneously over the first 30-40 min after induction of anaesthesia, in blood obtained from an arm vein and a vein in the foot, in nine healthy full-term women undergoing Caesarean section. Patients were tilted laterally to the left by from 8 to 18 degrees during the procedure. In all but two of the patients, the profiles from the arm and foot were virtually identical, suggesting that aortocaval compression was absent or insignificant. Therefore, the large intersubject variability in volume of distribution of thiopentone at Caesarean section is unlikely to be the result of aortocaval compression.

High performance liquid chromatographic determination of phenothiazine residues in sheep tissues.

A high performance liquid chromatographic (HPLC) technique is described for the determination of residue levels of the anthelmintic drug phenothiazine in sheep tissues. Phenothiazine was administered to sheep which were slaughtered after withholding periods of 24, 48, and 72 h. Residues of phenothiazine were then extracted from tissue samples by homogenization in methanol. The HPLC analysis of the extracts involved separation on a 10 micrometer silica column using a mobile phase of 0.3% n-propanol in cyclohexane. The lower limit of detection by ultraviolet absorption at 254 nm was 0.05 ppm.

Radiation enhancement of laser palliation for advanced rectal and rectosigmoid cancer: a pilot study.

Laser palliation for advanced rectal or rectosigmoid cancer requires repeat treatments every four to six weeks. Thirteen patients (seven men, six women) age range 65-91 (median 81) received additional external beam radiotherapy in an attempt to reduce the frequency of laser treatments required. After successful laser recanalisation, patients were treated with a dose of 30-55 Gy in 10-20 fractions. Bowel symptoms were well controlled for prolonged periods in 11 patients (85%) and further laser procedures were only required every 19 weeks median (range 6-53 weeks). The laser energy required after radiotherapy was only 800 J/month (median). Survival was 14 months (median, range 2.5-20 months) for the seven patients who have died. Seven patients received laser treatment only for three months or more (median 14 weeks, range 13-39). In this group control of symptoms required procedures every four weeks (median) before radiotherapy and 20 weeks (median) afterwards. The laser energy required before radiotherapy was 15,000 J/month and 2000 J/month afterwards (Wilcoxon rank sum test, p < 0.01 for both). Radiotherapy was well tolerated in all but one patient. Three patients developed strictures after radiotherapy but all were dealt with endoscopically. There were no complications solely due to endoscopic procedures. Additional radiotherapy enhances laser palliation for inoperable rectal or rectosigmoid cancer.