Catheter-directed middle hemorrhoidal artery embolization for life-threatening rectal bleeding.

Over the past 10 years, arteriography has become a well-established technique for the diagnosis of acute lower gastrointestinal bleeding, but not particularly for rectal bleeding. However, to the authors' knowledge, the technique of middle hemorrhoidal artery embolization has rarely been reported in the literature. In the present report, three patients with life-threatening rectal bleeding are presented, which was controlled by superselective embolization of the middle hemorrhoidal artery or selective embolization of the internal iliac artery as a last resort.     

Anatomic study of a new axial skin flap based on the cutaneous branch of the medial plantar artery

A new axial skin flap based on the middle cutaneous branch of the medial plantar artery was evaluated in 33 fresh cadaver legs. The vascular pedicle of the skin flap is based on the middle cutaneous artery, its venae comitantes, and segments of the great saphenous vein, if necessary. The middle cutaneous artery is the largest cutaneous branch, arising from the medial plantar artery 2.5 cm distal to its origin. The diameter of its origin is 1.2 mm, and its pedicle is 2 cm long. The midline of the flap runs from the first web space to the heel tip. The upper and lower borders of the flap are 3 to 4 cm on either side of this line. The upper border is medial to the extensor hallucis tendon, and the lower border is medial to the abductor hallucis. Distally, the border begins 2 cm proximal to the metatarsalphalangeal joint; proximally, the border is at the middle of the medial malleolus. The flap diameter can be up to 8 × 12 cm. The middle cutaneous branch of the medial plantar artery was found in all cadaver specimens, except for one with a common trunk. The new flap design leaves the major blood supply to the foot and the plantar aponeurosis intact. It is easy to harvest and may be used either as an island flap or free flap. © 1995 Wiley-Liss, Inc.     

Modeling spheroid growth, PET tracer uptake, and treatment effects of the Hsp90 inhibitor NVP-AUY922.

For a PET agent to be successful as a biomarker in early clinical trials of new anticancer agents, some conditions need to be fulfilled: the selected tracer should show a response that is related to the antitumoral effects, the quantitative value of this response should be interpretable to the antitumoral action, and the timing of the PET scan should be optimized to action of the drug. These conditions are not necessarily known at the start of a drug-development program and need to be explored. We proposed a translational imaging activity in which experiments in spheroids and later in xenografts are coupled to modeling of growth inhibition and to the related changes in the kinetics of PET tracers and other biomarkers. In addition, we demonstrated how this information can be used for planning clinical trials. METHODS: The first part of this concept is illustrated in a spheroid model with BT474 breast cancer cells treated with the heat shock protein 90 (Hsp90) inhibitor NVP-AUY922. The growth-inhibitory effect after a pulse treatment with the drug was measured with digital image analysis to determine effects on volume with high accuracy. The growth-inhibitory effect was described mathematically by a combined E(max) and time course model fitted to the data. The model was then used to simulate a once-per-week treatment; in these experiments the uptake of the PET tracers (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was determined at different doses and different time points. RESULTS: A drug exposure of 2 h followed by washout of the drug from the culture medium generated growth inhibition that was maximal at the earliest time point of 1 d and decreased exponentially with time during 10-12 d. The uptake of (18)F-FDG per viable tumor volume was minimally affected by the treatment, whereas the (18)F-FLT uptake decreased in correlation with the growth inhibition. CONCLUSION: The study suggests a prolonged action of the Hsp90 inhibitor that supports a once-per-week schedule. (18)F-FLT is a suitable tracer for the monitoring of effect, and the (18)F-FLT PET study might be performed within 3 d after dosing.     

Blood alcohol levels of patrons leaving licensed premises in Perth,Western Australia

Abstract: We aimed to determine the alcohol consumption, blood alcohol levels (BALs) and subsequent driving of patrons leaving 15 hotels and taverns in Perth, Western Australia. Of the 414 patrons approached by interviewers on Friday and Saturday evenings, 307 (74 per cent) consented to take part. Self-reported alcohol consumption, driving intentions, perceived levels of fitness to drive and demographic information were collected using an interviewer-administered questionnaire. Observations of subsequent driving were recorded and BALs were measured by breath-alcohol meter. The patrons surveyed were predominantly male (76 per cent) and aged between 18 and 35 (87 per cent). Average reported alcohol consumption was 7.6 standard drinks for males and 4.9 drinks for females, around double the daily amount recommended by the National Health and Medical Research Council. Further, 23 per cent of the sample had consumed more than 10 drinks (male) and 6 drinks (female). With respect to BALs, 37 per cent of patrons exceeded the drink-drive limit then in force of 0.087 and 56 per cent exceeded 0.05. Of greater concern, 23 per cent who were over the 0.08 legal limit were subsequently observed to drive even though they had been informed of their BAL and legal status with respect to driving. The results suggest that most young patrons drinking in Perth metropolitan hotels and taverns consume alcohol on such occasions in excess of limits currently recommended by health authorities and attain blood alcohol levels dangerous for driving. This is likely to remain unchanged without public debate as to the responsibility of licensees in serving a potentially harmful psychotropic drug and effective enforcement of liquor licensing laws.     

Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats

3,4-Methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug-induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 h after each of twice-daily MDMA (10 mg/kg s.c.) or saline injections administered from postnatal days 1–4. Other drug-treated and control litters were maintained at normothermic temperatures following injection. Changes in forebrain serotonergic innervation were assessed at postnatal day 25 (serotonin transporter binding and serotonin levels), postnatal day 60 (serotonin transporter binding), and 9 months of age (serotonin transporter immunohistochemistry). We also determined the influence of MDMA treatment on apoptotic activity by means of immunohistochemistry for cleaved caspase-3 at postnatal day 5. The hippocampus showed significant MDMA-related reductions in serotonergic markers at postnatal day 25 and postnatal day 60. At 9 months, there was no effect of prior MDMA exposure on serotonin transporter-immunoreactive fiber density in the hippocampus; however, significant reductions in fiber density were observed in two neocortical areas and a hyperinnervation was found in the caudate-putamen and nucleus accumbens shell. MDMA treatment also produced a two-fold increase in the number of cleaved caspase-3-immunoreactive cells in the rostral forebrain and hippocampus. All of these effects were completely independent of pup body temperature. These findings demonstrate that neonatal MDMA administration exposure stimulates apoptotic cell death in various forebrain areas and also leads to a long-term reorganization of the forebrain serotonergic innervation. Consequently, offspring of MDMA-using women may be at heightened risk for abnormal neural and behavioral development.