Continuous infusional topotecan in advanced breast and non-small-cell lung cancer: no evidence of increased efficacy

Two open, phase II studies were performed to evaluate the activity and toxicity of infusional topotecan in patients with advanced non-small-cell lung carcinoma (NSCLC) and advanced breast cancer who had not received previous chemotherapy for metastatic disease. Twenty-five patients with an ECOG performance score < 2 were treated with infusional topotecan administered as a daily, continuous intravenous infusion starting at 0.6 mg m(-2) day(-1) (NSCLC) and 0.5 mg m(-2) day(-1) (breast cancer) for 21 days every 4 weeks. Three patients achieved a partial response as defined by WHO criteria: one with NSCLC (8%; 95% CI 0-39%) and two with advanced breast cancer (15%; 95% CI 2-45%). The major toxicities were neutropenia and thrombocytopenia, with one episode of neutropenic sepsis. These data suggest that topotecan delivered as a continuous intravenous infusion over 21 days as single-agent therapy does not appear to offer a clinical advantage over conventional 5-day schedules against advanced NSCLC and advanced breast cancer.     

Relationship between volumes and areas from single transverse scans of intra-abdominal fat measured by magnetic resonance imaging

OBJECTIVE: To determine the level of a single transverse scan of intra-abdominal fat between L1 and L5 vertebrae that best predicts intra-abdominal fat volumes. SUBJECTS: Sixteen male and seven female patients with non-insulin-dependent diabetes mellitus, aged 44-74 y. OUTCOME MEASURES: Volumes and areas from single scans of intra-abdominal fat measured by magnetic resonance imaging with a 1.5 Tesla magnetic field strength. RESULTS: Intra-abdominal fat volumes and were calculated from fat areas from eight cross-sectional transverse single scans (nine scans in eight men) of 20 mm thickness. Men and women, respectively, had mean body mass index (BMI) of 27.9 (s.d. 3.0) and 31.6 (s.d. 4.7) kg/m2, and intra-abdominal fat of 2.3 (s.d. 0.5) and 2.5 (s.d. 0.6) kg. Intra-abdominal fat area of the fourth scan (in the direction of L1 to L5) gave the highest prediction of total intra-abdominal fat both in men (r = 0.959, P < 0.001) and in women (r = 0.973, P < 0.001). The intra-abdominal fat area of the third scan gave almost as good a prediction. These third and fourth scans corresponded to L2 and L3 vertebrae. The intra-abdominal fat areas from the sixth and seventh scans, corresponded to the frequently used L4-L5 and had lower correlations with intra-abdominal fat. There were no gender differences in the prediction of volumes from areas of intra-abdominal fat. Intra-abdominal fat areas of the fourth scan explained 93% of variance (SEE = 0.14 kg) of total of intra-abdominal fat for both genders: intra-abdominal fat (kg) = 0.0108 x intra-abdominal fat area of the fourth scan (cm2) + 0.244. CONCLUSIONS: In large studies of intra-abdominal fat, using magnetic resonance imaging (MRI) or computerised tomography scanning, a single intra-abdominal fat area at the intervertebral disc between L-2 and L-3 vertebrae offers a cheaper, faster and safer method, with high prediction of total intra-abdominal fat volumes and masses.     

Obstetric analgesia in Norwegian hospitals]

We report the results of a questionnaire sent to anaesthetists and midwives on the use of obstetric analgesia and anaesthesia in Norwegian hospitals in 1996. 95% of the 49 hospitals involved responded to the questionnaire, representing a total of 56,884 births. The use of epidural analgesia in labour varied from 0 to 25% in the different hospitals with a mean value of 15%. Epidural analgesia was much more widely used in university and regional hospitals than in local hospitals (p < 0.001). Five of the local hospitals did not offer epidural analgesia during labour at all. The combination of low-dose local anaesthetic and an opioid (either sufentanil or fentanyl) had not been introduced in nine of the hospitals (20%). The optimal use of epidural analgesia to relieve labour pain was judged to be more frequent by the anaesthetists than by the midwives (19% versus 11%, p < 0.01). In response to what factors limited the frequency of epidural analgesia, the anaesthetists specified factors related to the attitude of the midwife, and the midwives specified factors related to the anaesthetist. Only five of the hospitals provided written information on the various analgesic methods that could be employed during labour. The majority of midwives considered the analgesic methods employed on their maternity ward to be good or excellent. The frequency of Caesarean section was 12%; spinal anaesthesia was used in 55%, epidural anaesthesia in 17%, and general anaesthesia in 28% of the cases.     

Familial partial epilepsy with variable foci: a new partial epilepsy syndrome with suggestion of linkage to chromosome 2

Traditional T2-based imaging techniques are geared toward imaging long-T2 species. Traditional techniques are, therefore, not optimal in clinical situations where the information of interest lies in the short-T2 species. T2-selective RF excitation (TELEX) is a technique for obtaining a T2-based contrast that highlights short-T2 values while suppressing long-T2 values-opposite to traditional T2 contrast. Previously, TELEX has been demonstrated qualitatively to highlight only very short-T2 values (T2 approximately 0.001 s). When applied to longer T2 values (T2 > or = 0.01 s), TELEX becomes sensitive to deltaB0 non-uniformities. This restricts its application to problems in which the T2 of interest is very short. In this study, TELEX is characterized quantitatively. Furthermore, a bandwidth broadening scheme is developed that reduces the deltaB0 sensitivity of TELEX. This permits the technique to be applied to longer T2 values. The capabilities and limitations of a practical implementation of TELEX are discussed.     

Mitochondrial DNA variable number tandem repeats (VNTRs): utility and problems in molecular ecology

Analysis of mitochondrial (mt)DNA size polymorphism in the form of variable number tandem repeats (mtVNTRs) has become an increasingly popular methodology for addressing questions in molecular ecology. When detected by PCR, mtVNTR analysis can provide a sensitive, rapid, and cost-effective measure of genetic variability that may be exploited in studies of population differentiation and biogeography. Despite the emergence of this approach, there has been little critical evaluation of its success or utility as a practical tool. In this review, we identify problematic methodological, theoretical and interpretive factors that can influence the utility of mtVNTR analysis. The reliability of the procedure is considered in terms of both detection of alleles and scoring of intra-individual allele frequencies. While many of the potential technical problems of the technique do not raise serious practical concerns, this rapid and sensitive methodology is seriously compromised by the difficulty of reliably assessing allele frequencies, of assaying only germline tissue, and in our ignorance of the mechanisms generating mtVNTR diversity. Thus, although there is a considerable potential for mtVNTR pilot studies to assess genetic diversity, the utility of the technique to resolve broader questions in molecular ecology should be treated cautiously until such a time as the system is better understood.     

Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy

Endogenous opioid peptides appear to be involved in acute behavioral effects induced by single doses of ethanol. However, its role in repeated ethanol exposure has not been studied. In the present study ethanol was given to rats at the doses of 2 and 4 g/kg by a stomach gauge for 15 days, and its effects on spontaneous motility, open-field activity, and active avoidance behavior recorded on the 3rd, the 6th and the 15th days. Then the effect of naloxone (0.5 and 2 mg/kg by intraperitoneal route) was tested against a challenge ethanol dose, administrated by oral route, on the 16th day. Control animals received tap water and saline instead of ethanol or naloxone, respectively. Both doses of ethanol induced a decrease in spontaneous motility that was antagonized by naloxone. Open-field ambulations were increased by the high dose of ethanol, low-dose lacking effect; naloxone did not modify these ethanol effects. The low dose of ethanol shortened latency time in shuttlebox, the high dose causing escape and freezing responses; none of these effects were modified by naloxone. Therefore, endogenous opioid peptides appear to play a limited role in the chronic effects of ethanol in rats; particularly its effects in tests inducing an increase in the level of anxiety were resistant to naloxone.     

Kyphosis secondary to tuberculosis osteomyelitis as a cause of ventilatory failure. Clinical features, mechanisms, and management

STUDY OBJECTIVES: To investigate the relationship of thoracic kyphosis following tuberculosis to the development of ventilatory failure and to assess the efficacy on nocturnal noninvasive ventilatory support. DESIGN: Retrospective consecutive case series with crossover from a phase without noninvasive ventilatory support to a phase with this treatment. SETTING: The Respiratory Support and Sleep Centre, Papworth, Hospital, Cambridge, England. PATIENTS: Seven patients with thoracic kyphosis following tuberculous osteomyelitis which had been contracted by the age of 4 years were studied. Their mean age was 53 (SD 7.1) years and the mean angle of kyphosis was 113.60. All patients were in ventilatory failure. INTERVENTIONS: The patients were treated with nocturnal noninvasive ventilation with either an individually constructed cuirass shell and a negative pressure pump or nasal intermittent positive pressure ventilation using a volume preset ventilator. MEASUREMENT AND RESULTS: Each patient underwent an initial clinical assessment along with radiologic studies of the spine, pulmonary function tests, daytime arterial blood gas tensions, and overnight recordings of arterial saturation, and transcutaneous carbon dioxide tension. They were reassessed in detail at a mean of 5 years after starting ventilatory support. Symptoms, vital capacity, daytime carbon dioxide tension, and overnight oximetry had all improved following treatment. Temporary withdrawal of ventilatory support led to severe sleep fragmentation in four patients and the appearance of central apneas and hypopneas in the other three. Six of the 7 patients were alive at a mean of 5.7 years after starting nocturnal ventilation. CONCLUSION: These results show that ventilatory failure may develop, after an interval of many years, in patients with a severe thoracic kyphosis due to tuberculosis in childhood. Noninvasive nocturnal ventilatory support can control the symptoms of ventilatory failure, improve the physiologic abnormalities, and is associated with prolonged survival.     

Bulbous splenic vein as a cause of renal pseudotumor

A number renal and suprarenal pseudotumors have been described during the past two decades, paralleling the development of selective visceral angiography. An apparent left upper pole renal mass in a 71-year-old hypertensive man was found to ba a bulbous portion of the splenic vein during angiography. The anatomical basis of this renal pseudotumor is discussed.