Selective necrosis in hamster pancreatic tumours using photodynamic therapy with phthalocyanine photosensitization.

Photodynamic therapy (PDT) is often thought to be able to effect selective tumour necrosis. This therapeutic selectivity, based on transient differences in tumour: normal tissue photosensitizer concentration ratios, is rarely useful clinically in extracranial tumours, although PDT itself may be of value by virtue of the nature of the damage produced and healing of normal tissue by regeneration. This report describes the effects of PDT on normal pancreas and chemically induced pancreatic cancers in the hamster, where a different mechanism of selective necrosis may be seen. Photosensitizer distribution in normal and neoplastic pancreas was studied by chemical extraction and fluorescence microscopy. Correlation of distribution studies with necrosis produced by PDT shows that the photodynamic dose (product of tissue concentration of sensitizer and light dose) threshold for damage is seven times as high for normal pancreas as for pancreatic cancer. Tumour necrosis extended to the point where tumour was invading normal areas without damaging the normal tissue. In rat colonic cancer, photodynamic dose thresholds in tumour and normal tissue are similar and so such marked selectivity of necrosis is not possible. The reason for this selectivity in the pancreas is not clear, but recent evidence has suggested a difference in response to PDT between normal and neoplastic pancreatic cell lines and the presence of a singlet oxygen scavenger in normal pancreas is postulated. Furthermore, the present fluorescence microscopy studies suggest that tumour stroma contains the highest level of photosensitizer and thus receives the highest photodynamic dose during PDT. These results suggest a possible role for PDT in treating small pancreatic tumours or as an adjuvant to other techniques, such as surgery, that reduce the main bulk of tumours localized to the pancreas.     

Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.     

Anaesthesia for Treacher Collins and Pierre Robin syndromes: A report of three cases

We present three patients with Treacher Collins or Pierre Robin syndromes who had historical and physical evidence of airway obstruction, difficulty feeding, and sleep disturbances. These preoperative findings correlated with difficult airway management intraoperatively. Based on this experience, we recommend that children with obstructive symptoms have laryngoscopy prior to anaesthetic induction. If the glottic opening is visualized, inhalational induction can proceed. If the glottic structures cannot be visualized, then the anaesthetist must choose between awake oral or nasal intubation, elective tracheostomy, or fiberoptic intubation. In all cases, a tracheostomy tray should be ready and a surgeon experienced in paediatric tracheostomy should be in attendance. After intubation, anaesthesia is best maintained with oxygen and a potent inhalational agent. Extubation should only be done with the patient fully awake and with emergency airway equipment immediately available. Postoperatively, these patients should be transferred to an intermediate care area or intensive care unit where they can be observed closely since delayed complications of airway obstruction are common in this group of patients.     

Hemorrhagic and nonhemorrhagic brain lesions: evaluation with 0.35-T fast MR imaging

Two fast magnetic resonance (MR) imaging techniques, advanced Fourier and partial-flip imaging, were used at 0.35 T to examine 21 patients with suspected intracranial lesions; the results were quantitatively compared with a conventional spin-echo study. Both of the fast MR techniques yielded a fourfold reduction in imaging time per section. The advanced Fourier sequence showed contrast that was identical to the conventional spin-echo study with signal-to-noise ratios of 58% and 57% for the first and second echoes, respectively. The partial-flip sequence showed a contrast of 109% and 57% for lesions versus substantia alba, and 107% and 78% for substantia grisea versus substantia alba relative to the first and second echoes of the conventional spin-echo study. The partial-flip sequence was particularly sensitive to magnetic susceptibility; this produced artifacts that may undermine the usefulness of partial flip for routine screening in certain parts of the brain. However, this susceptibility significantly improved the detection of intracranial hemorrhage when compared with the spin-echo sequence, particularly when combined with phase mapping of the partial-flip study.     

New pharmacologic developments in physical urticaria--therapeutic consequences

Recent evidence suggests that mast cell derived mediators other than histamine are likely to be involved in the pathogenesis of physical urticarias. Much of the work has been performed in idiopathic cold contact urticaria where the presence of neutrophil and eosinophil chemotactic factors, and platelet activating factor-like lipid substances have been previously demonstrated. Now, an increase in prostaglandin D2 measured by GC-MS has been demonstrated in venous blood draining the cold challenged area. This appeared a few minutes later than histamine, but then both substances paralleled the onset, development and subsidence of the urticarial reaction. There appeared to be no quantitative relationship between histamine and PGD2 release. A similar rise in histamine and PGD2 occurred on heat challenge of a subject with the rare localized form of heat urticaria. This rise of both substances was considerably reduced after combined treatment with induction of tolerance and oral indomethacin. The concentrations of PGD2 measured suggested that it plays an indirect role.     

高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。