Immunolocalization of tripeptidyl peptidase II, a cholecystokinin-inactivating enzyme, in rat brain.

Tripeptidyl peptidase II (EC 3.4.14.10) is a serine peptidase apparently involved in the inactivation of cholecystokinin octapeptide [Rose C. et al. (1996) Nature 380, 403-409]. We have compared its distribution with that of cholecystokinin in rat brain, using a polyclonal antibody raised against a highly purified preparation for immunohistochemistry at the photon and electron microscope levels. Tripeptidyl peptidase II-like immunoreactivity was mostly detected in neurons, and also in ependymal cells and choroid plexuses, localizations consistent with a possible participation of the peptidase in the inactivation of cholecystokinin circulating in the cerebrospinal fluid. Immunoreactivity was mostly detected in cell bodies, large processes and, to a lesser extent, axons of various neuronal populations. Their localization, relative to that of cholecystokinin terminals, appears to define three distinct situations. The first corresponds to neurons with high immunoreactivity in areas containing cholecystokinin terminals, as in the cerebral cortex or hippocampal formation, where pyramidal cell bodies and processes surrounded by cholecystokinin axons were immunoreactive. A similar situation was encountered in many other areas, namely along the pathways through which cholecystokinin controls satiety, i.e. in sensory vagal neurons, the nucleus tractus solitarius and hypothalamic nuclei. The second situation corresponds to cholecystokinin neuronal populations containing tripeptidyl peptidase II-like immunoreactivity, as in neurons of the supraoptic or paraventricular nuclei, axons in the median eminence or nigral neurons. In both situations, localization of tripeptidyl peptidase II-like immunoreactivity is consistent with a role in cholecystokinin inactivation. The third situation corresponds to areas with mismatches, such as the cerebellum, a region devoid of cholecystokinin, but in which Purkinje cells displayed high tripeptidyl peptidase II-like immunoreactivity, possibly related to a role in the inactivation of neuropeptides other than cholecystokinin. Also, some areas with cholecystokinin terminals, e.g., the molecular layer of the cerebral cortex, were devoid of tripeptidyl peptidase II-like immunoreactivity, suggesting that processes other than cleavage by tripeptidyl peptidase II may be involved in cholecystokinin inactivation. Tripeptidyl peptidase II-like immunoreactivity was also detected at the ultrastructural level in the cerebral cortex and hypothalamus using either immunoperoxidase or silver-enhanced immunogold detection. It was mainly associated with the cytoplasm of neuronal somata and dendrites, often in the vicinity of reticulum cisternae, Golgi apparatus or vesicles, and with the inner side of the dendritic plasma membrane. Hence, whereas a fraction of tripeptidyl peptidase II-like immunoreactivity localization at the cellular level is consistent with its alleged function in cholecystokinin octapeptide inactivation, its association with the outside plasma membrane of neurons remains to be confirmed.     

Percutaneous catheter thrombus aspiration for acute or subacute arterial occlusion of the legs: how much thrombolysis is needed?

OBJECTIVE: To evaluate the role of a combined percutaneous endovascular approach including thrombus aspiration, catheter thrombolysis, and percutaneous transluminal angioplasty (PTA) to treat acute and subacute occlusions of native leg arteries. MATERIALS AND METHODS: Retrospective evaluation of the effectiveness and safety of this catheter therapy in 89 consecutive patients (93 legs) in a single centre. RESULTS: Treatment was initially successful in 90% of legs. Mortality at 30 days was 8%, and at 12 months 19%. Amputation-free survival at 12 months was 78%. Aspiration alone was sufficient in 31% of cases, urokinase (mean dose 112 500+/-55 900 IU) was used in 22%, PTA was added in 69%. There was no major bleeding except for one false aneurysm treated by ultrasound-guided compression. Secondary interventions within 12 months were required in 30% of cases (14 endovascular, 16 open surgical procedures). CONCLUSIONS: Catheter thrombus aspiration in combination with thrombolysis and/or PTA is highly effective. Only in a minority of patients are thrombolytics in modest doses necessary, and serious bleeding complications are rare. We recommend this procedure as first-line treatment for acute or subacute infrainguinal arterial occlusions.     

Localization of components of glycinergic synapses during rat spinal cord development

The sequence of events leading to the chemical matching of presynaptic neurotransmitters and postsynaptic transmitter receptors is investigated here in vivo for the spinal glycine receptor (GlyR) by using immunocytochemical methods. In the ventral horn of adult rat spinal cord, GlyRs are only present at glycinergic postsynaptic differentiations where they are stabilized by the associated protein gephyrin. With quantitative confocal microscopy, we found that gephyrin is detected before GlyRs at embryonic day (E)13–E14 and at E15, respectively, inside the cytoplasm and at plasmalemmal loci. Around the time of birth, the number of cell surface gephyrin-immunoreactive (-IR) spots exceeds that of GlyR. They first match 10 days after birth. The densities of postsynaptic gephyrin- and GlyR-IR were quantified between birth and the adult stage with post-embedding immunogold staining. Immunostaining for gephyrin and GlyR was not detected in the extrasynaptic membrane. The density of staining in postsynaptic membrane increased progressively with development. The inhibitory amino-acid content of the presynaptic terminal boutons opposed to gephyrin-IR sites was also analyzed. In the newborn, postnatal day 10, and adult, more than 90% of these boutons were immunostained for glycine. As seen with serial sections, 38% and 51.2% of the terminals also contained γ-aminobutyric acid (GABA) in neonate and adult, respectively. These data indicate that around the time of birth, most glycine-containing boutons, some also containing GABA, are opposed to gephyrin-IR postsynaptic densities, whereas GlyRs are not present. Our results suggest that gephyrin determines subsynaptic loci on the plasma membrane where GlyR will subsequently accumulate. J. Comp. Neurol. 398:359–372, 1998. © 1998 Wiley-Liss, Inc.     

A crosstalk between β1 and β3 integrins controls glycine receptor and gephyrin trafficking at synapses

The regulation of glycine receptor (GlyR) number at synapses is necessary for the efficacy of inhibition and the control of neuronal excitability in the spinal cord. GlyR accumulation at synapses depends on the scaffolding molecule gephyrin and is linked to GlyR synaptic dwell time. However, the mechanisms that tune GlyR synaptic exchanges in response to different neuronal environments are unknown. Integrins are cell adhesion molecules and signaling receptors. Using single quantum dot imaging and fluorescence recovery after photobleaching, we found in rats that β1 and β3 integrins adjust synaptic strength by regulating the synaptic dwell time of both GlyRs and gephyrin. β1 and β3 integrins crosstalked via calcium/calmodulin-dependent protein kinase II and adapted GlyR lateral diffusion and gephyrin-dependent trapping at synapses. This provides a mechanism for maintaining or adjusting the steady state of postsynaptic molecule exchanges and the level of glycinergic inhibition in response to neuron- and glia-derived signals or extracellular matrix remodeling.     

Endovascular treatment of arterial injury as an uncommon complication after orthopedic surgery

PURPOSE: To evaluate selective and superselective catheter therapy of serious arterial damage associated with orthopedic surgery of the pelvis, hip joint, femur, and knee. MATERIALS AND METHODS: Between 1989 and 2005, 16 consecutive patients with arterial damage after orthopedic surgery (seven women, nine men; mean age, 62 years; age range, 21-82 y) underwent angiographic exploration. Seven patients were in hemodynamically unstable condition. Initial orthopedic procedures were iliac crest internal fixation (n = 1); total hip prosthesis (n = 3); revision of total hip prosthesis (n = 4); revision of acetabular cup prosthesis (n = 1); gamma-nailing, nail-plate fixation, or intramedullary nailing (n = 3); and total knee prosthesis (n = 4). RESULTS: Angiography showed pseudoaneurysms (n = 11), vascular lacerations with active extravasation (n = 3), and arteriovenous fistulas with extravasation (n = 2). After angiographic documentation of serious arterial injury, 14 patients were treated with a single or coaxial catheter technique in combination with coils alone, coils and polyvinyl alcohol particles, coils and Gelfoam pledgets, or Gelfoam pledgets; or balloon occlusion with isobutyl cyanoacrylate and coils. Two patients were treated with covered stents. In all, bleeding was effectively controlled in a single session in 16 patients, with immediate circulatory stabilization. Major complications included death, pulmonary embolism, and postprocedural hematoma. CONCLUSION: Selective and superselective catheter therapy may be used for effective, minimally invasive management of rare but potentially life-threatening vascular complications after orthopedic surgery.     

Algorithm for dermocosmetic use in the management of cutaneous side‐effects associated with targeted therapy in oncology

Currently, numerous patients who receive targeted chemotherapy for cancer suffer from disabling skin reactions due to cutaneous toxicity, which is a significant problem for an increasing number of patients and their treating physicians. In addition, using inappropriate personal hygiene products often worsens these otherwise manageable side‐effects. Cosmetic products for personal hygiene and lesion camouflage are part of a patients’ well‐being and an increasing number of physicians feel that they do not have adequate information to provide effective advice on concomitant cosmetic therapy. Although ample information is available in the literature on pharmaceutical treatment for cutaneous side‐effects of chemotherapy, little is available for the concomitant use of dermatological skin‐care products with medical treatments. The objective of this consensus study is to provide an algorithm for the appropriate use of dermatological cosmetics in the management of cutaneous toxicities associated with targeted chemotherapy such as epidermal growth factor receptor inhibitors and other monoclonal antibodies. These guidelines were developed by a French and German expert group of dermatologists and an oncologist for oncologists and primary care physicians who manage oncology patients. The information in this report is based on published data and the expert group's opinion. Due to the current lack of clinical evidence, only a review of published recommendations including suggestions for concomitant cosmetic use was conducted.     

Treatment of renal artery fibromuscular dysplasia with balloon angioplasty: a prospective follow-up study.

OBJECTIVES: to assess restenosis rates and blood pressure response after percutaneous transluminal renal angioplasty (PTRA) in patients treated for fibromuscular dysplastic renal artery stenosis. METHODS: a prospective 12-month follow-up study of 27 patients with 31 treated renal artery stenosis. Follow-up assessment included colour-coded duplex sonography (CCD) of renal arteries, monitoring of blood pressure, antihypertensive medication, and creatinine measurements before discharge and at 3, 6, and 12 months. Primary end point was defined as a haemodynamically significant restenosis >60% assessed by CCD. RESULTS: there was a cumulative 23% restenosis rate at 12 months. Arterial hypertension was cured or improved in 93% of patients immediately after the intervention and remained cured/improved in 74% of patients at 12 months of follow-up. Renal failure present in five patients before PTRA stabilised or improved in all patients. CONCLUSION: although restenosis rate after PTRA in fibromuscular dysplasia is as high as in non-ostial atherosclerotic lesions, there remains a considerable higher therapeutic effect. Profound pressure response and recurrent arterial hypertension with restenosis support the high probability of a renovascular origin of arterial hypertension in this young and otherwise healthy population compared to patients with atherosclerotic renal artery lesions.     

Perkutane Gastrostomie mit Ballon-PEG-Ersatzsonden durch den Radiologen Eine interventionelle Technik zur einfachen Einlage von Ernährungskathetern ohne chirurgischen oder endoskopischen Eingriff

Patients afflicted with stenotic head and neck or esophageal tumors often require artificial enteral feeding. Frequently passage of an endoscope through the esophagus is impossible in these patients. Interventional, fluoroscopically assisted, percutaneous gastrostomy (PG) by balloon replacement tubes is a feasible and successful alternative to percutaneous endoscopic gastrostomy (PEG) and the method of choice in patients where the esophagus cannot be passed with an endoscope anymore. Technical success rate is very high and serious complications are rare. Radiological PG is a feasible, equivalent alternative to PEG also in all other patients. We recommend PG with ballon gastrostomy tubes in conjunction with gastropexy performed with three to four T-fasteners, which are left in place for seven days in order to prevent dislocation and leakage.