Comparison of potency of human carcinogens: vinyl chloride, chloromethylmethyl ether and bis(chloromethyl)ether

The alpha-chloroether carcinogen chloromethylmethyl ether (CME) and its impurity bis(chloromethyl)ether (BCME) are direct-acting alkylating agents. Vinyl chloride (VC) is an indirect-acting carcinogen but its accepted carcinogenic intermediate, chloroethylene oxide, is also an alpha-chloroether. Both CME-BCME and VC have been in industrial use since about 1950. Hence, they were selected for comparison of potency as human carcinogens using numerous epidemiologic reports. There were 115 deaths due to angiosarcoma of the liver among several hundred thousand VC-exposed workers on the basis of reports from 10 countries during 1955 and 1984. Reports from five countries cited a total of 87 respiratory cancer deaths among only 3024 CME-BCME-exposed workers. If a recent court settlement in the United States is taken into account, the number of respiratory cancer deaths due to CME-BCME rises to 117. On the basis of these numbers of cancer deaths, and the levels and durations of exposure, it is concluded that VC is a weak human carcinogen compared to CME-BCME.     

Double-outlet right ventricle and severe systemic outflow tract hypoplasia

Double-outlet right ventricle and severe systemic outflow tract hypoplasia comprises a subset of patients in whom total correction or palliation requires complex surgical procedures in the neonatal period. Our experience with 3 patients illustrates the difficulties associated with treatment and suggests possible surgical options for this otherwise lethal variant of the Taussig-Bing syndrome.     

P6 Complaints of halitosis related to the oral cavity. A preliminary report of 700 consecutive patients

Patients with complaints of halitosis do seek treatment from physicians and dental practitioners, because of the fear that their halitosis may interfere with their social activities. Although the prevalence of halitosis has been reported to be as high as 50%, most physicians and dental practitioners are poorly informed about the causes and treatments of halitosis. In order to care for patients with complaints of halitosis a multidisciplinary team was established at the Erasmus Medical Centre, Rotterdam, The Netherlands. The team included a dental hygienist, an otorhinolaryngologist, and a dentist, who developed a special halitosis programme. One short press release regarding the establishment of the team, was provided to the national press-centre. In the out-patient clinic more than 700 patients were seen by the team. Using a structured questionnaire fed to a PC, patients answered questions regarding complaints about the oral cavity, the upper respiratory tract, the throat, their general health, their cleansing habits of the oral cavity, and prior experiences with general physicians, dental practitioners, and medical specialists. They underwent examinations of the extent of their halitosis, of the perioral and neck region, the oral cavity, the upper respiratory tract, and the upper digestive tract. Finally, the members of the team came to a joint diagnosis and a joint treatment plan for every individual patient. Of the first 700 consecutive patients around 90% had a natural dentition without removable partial dentures. More than 60% were diagnosed as having periodontal disease with pockets of 4 mm or more in the maxilla. This figure was more than 50% in the mandible. Around 95% had tongue coating.     

The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid dispersions of Itraconazole.

Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no Itraconazole peaks were visible; the polymer on the other hand appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly the physical mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.     

Radiation therapy of benign diseases. What's new eight years after?]

The authors present an update version of the indications for radiotherapy in the management of benign diseases. This is based on available randomized trials and recent international meetings. Validated indications remain the prevention of resected heterotopic bone ossifications, kelo?ds scars and pterygium and also treatment of arteriovenous malformations; the place of radiotherapy for malignant exophtalmia is more and more restricted. Randomized trials have demonstrated the efficacy of endobrachytherapy in the prevention of restenosis after angioplasty but the use of embedded stent has replaced this indication. Macular degeneration is no more an indication of radiotherapy. Quality requirements for radiotherapy are identical for benign or malignant indications.     

Comparison between ankle and toe index in patients with peripheral arterial disease

In contrast to the systolic blood pressure at the posterior tibial artery, the evaluation of pressure at the digital artery of the foot before and after exercise in patients with peripheral arterial disease is not well known. Twenty three patients with peripheral vascular disease were examined. The systolic pressure was measured by means of an ultrasound velocity detector at the brachial and posterior tibial artery. Digital artery pressure was determined with photoplethysmography. Pressures were measured before and within 5 and 10 minutes after a treadmill test. Ankle and toe index was calculated. At rest the toe index is lower than the ankle index and after a treadmill test the decrease in toe index occurs in parallel to the ankle index.     

Ultrastructure of aberrant serotonin-immunoreactive fibers in the caudate putamen complex of the aged rat

Degeneration of neurons in the central nervous system is associated with morphological changes. Previous observations made at the light microscopical level indicated degeneration of serotonin-immunoreactive (IR) fibers in the aged rat brain. In this study, a comparison at the ultrastructural level was made between serotonin-IR normal thin and aberrant swollen varicose fibers in the caudate-putamen complex of the aged rat. Ultrastructural features such as the size and content of the thin varicose fibers resembled those in the caudate-putamen complex of the young rat as reported by others. The aberrant profiles were swollen, reaching a size of 6 microns. Their vesicles varied in size and were no longer uniformly round. Moreover, distorted mitochondria and membrane-filled vacuolelike structures were a common feature of the aberrant profiles. These changes are indicative of a degenerative process and give further evidence that, whereas many serotonergic fibers are preserved at high age, other serotonergic fibers are degenerating in the caudate-putamen complex of the aged rat.     

Treatment of nasopharyngeal inlet stenosis following uvulopalatopharyngoplasty with the co2 laser

This report looks at outpatient treatment of nasopharyngeal inlet stenosis, a more commonly seen postoperative complication of uvulopalatopharyngoplasty (UPPP). It does not study the effectiveness of the UPPP for treatment of obstructive sleep apnea syndrome (OSAS). The authors evaluated six patients who had a UPPP for OSAS, all of whom developed stenosis in the nasopharyngeal inlet ranging from 14 mm to complete closure. Two patients had failed rotation flap repairs. The carbon dioxide laser was used to treat these patients in the office under a local anesthesia in a staged manner. We now have patients from 3 months to 12 months follow-up who have had stenosis treated successfully. We believe that the postoperative complication of nasopharyngeal inlet stenosis after UPPP can be treated in a safe and cost-effective manner in the office setting.