Clinical Characteristics and Outcomes in a Population With Disseminated Herpes Zoster: A Retrospective Cohort Study. / Características clínicas y evolutivas de una población con herpes zoster diseminado: un estudio de cohorte retrospectiva.

INTRODUCTION: Shingles is the cutaneous expression of the reactivation of latent varicella zoster virus infection in sensory ganglia. It presents as vesicles in the corresponding dermatome. The condition is called disseminated herpes zoster (DHZ) when more than 2 contiguous dermatomes are affected, more than 20 vesicles are observed outside the initial dermatome, or involvement is systemic. DHZ is rare and most frequently occurs in immunocompromised patients. OBJECTIVES: To describe the epidemiology, predisposing factors, clinical presentation, laboratory findings, and clinical course of patients with DHZ, and to compare the findings in immunocompromised and immunocompetent patients. METHODOLOGY: We analyzed a retrospective case series of adults hospitalized between February 2010 and October 2015. RESULTS: Forty-one patients with virologically confirmed manifestations of DHZ were included. Stress as a trigger factor was detected in 39% and immunodepression in 58.5%. Immunocompromised patients were younger than the immunocompetent patients (mean ages, 60.5 vs 82 years, P<.01). The 8 immunocompetent patients with no detectable trigger factors were older (mean age, 85 years). In 95% of cases, DHZ was initially limited to a single dermatome and then spread to other dermatomes or became disseminated. Thrombocytopenia was detected in 56% of cases. Complication rates were similar in immunocompromised and immunocompetent patients (54% vs 59%, P>.01). Six patients died; there was no difference in mortality between the 2 groups. CONCLUSION: This study provides evidence on the relationship between DHZ, the presence of underlying immunodepression, and complications. Immunosenescence may play an important role in the onset of this disease in older immunocompetent patients.

Basic and Meal Stimulated Plasma GIP Levels are Higher in Lean PCOS Women with FAI over 5.

OBJECTIVE: Glucose dependent insulinotropic peptide (GIP) belongs to the incretins which are responsible for 70% of the insulin release after oral glucose intake. Its impaired secretion was noted in several conditions involving insulin resistance, including polycystic ovary syndrome (PCOS), known as the state with increased testosterone level. This paper considers a possible relationship between the free androgen index (FAI) and basal as well as meal stimulated level of GIP in lean women affected by PCOS. To our knowledge, no previous study has evaluated the matter so far. DESIGN: cross-sectional study METHODS: 50 age-matched lean women (BMI=20.76±1.83) were enrolled to the study and divided into 2 groups. Patients with phenotype with FAI<5 were classified as group 1, PCOS patients with FAI>5 formed group 2. All subjects underwent standard meal test. Serum GIP concentration was determined both at fasting and at 60 min of the test. Calculations were carried out using Statistica 10. RESULTS: Mann-Whitney test indicated a statistically significant difference in medians values of GIP plasma levels between groups on fasting (36.4 pg/ml vs. 59.6 pg/ml; p=0.0007) and at 60 min after meal test (50.1 pg/ml vs. 72.5 pg/ml; p=0.006). Spearman test indicated significant positive correlation between FAI and GIP levels at 0' and 60' in total study population (0':R=0.37;p=0.008; 60':R=0.28; p=0.049). CONCLUSION: Excess androgen activity might be a factor contributing to alter secretion of incretins in lean PCOS women. However it could not be ruled out that it is also possible that increased GIP levels might induce hyperandrogenemia in PCOS. An increased GIP levels may induce hyperinsulinemia and play an additive to insulin resistance role in progression to diabetes mellitus type 2 (DMT2).

Calea zacatechichi dichloromethane extract exhibits antidiarrheal and antinociceptive effects in mouse models mimicking irritable bowel syndrome.

Calea zacatechichi Schltdl. (Asteraceae alt. Compositae) is a Mexican plant commonly used in folk medicine to treat respiratory and gastrointestinal (GI) disorders. The objective of this study is to characterize the effect of C. zacatechichi extracts in mouse models mimicking the symptoms of irritable bowel syndrome (IBS). Powdered C. zacatechichi herb (leaves, stems, and flowers) was extracted with methanol. Methanolic extract was filtered and evaporated giving methanolic fraction. The residue was extracted with dichloromethane (DCM). Methanolic and DCM (200 mg/kg, per os) extracts were screened for their effect on GI motility in several in vitro tests, and the antidiarrheal and antinociceptive effects were assessed using mouse models. The influence of the DCM extract on motoric parameters and exploratory behaviors was also assessed. Finally, the composition of C. zacatechichi DCM extract was qualitatively analyzed using liquid chromatography-mass spectrometry (LC-MS) method. C. zacatechichi DCM extract significantly inhibited the contractility of mouse colon in vitro (IC50 = 17 ± 2 µg/ml). Administration of the DCM extract in vivo (200 mg/kg, per os) significantly prolonged the time of whole GI transit (46 ± 1 vs. 117 ± 27 min for control and DCM-treated animals, respectively; P = 0.0023), inhibited hypermotility, and reduced pain in mouse models mimicking functional GI disorders. Our findings suggest that constituents of the C. zacatechichi DCM extract exhibit antidiarrheal and analgesic activity. The extract may thus become an attractive material for isolation of compounds that may be used as a supplementary treatment for pain and diarrhea associated with IBS in the future.

[Mohs micrographic surgery for the treatment of basal cell carcinoma]. / Cirugía micrográfica de Mohs en el tratamiento de carcinoma basocelular.

INTRODUCTION: Basal cell carcinoma accounts for 75% of all nonmelanoma skin cancer. Although various treatment modalities are available, the most frequently used option is surgical excision. Here, we evaluate the efficacy of Mohs micrographic surgery for the treatment of basal cell carcinoma. MATERIAL AND METHODS: A retrospective review of cases of basal cell carcinoma treated with Mohs micrographic surgery between October 2003 and June 2009 was performed using patient records from Hospital Italiano in Buenos Aires, Argentina. RESULTS: A total of 2412 basal cell carcinomas treated with Mohs micrographic surgery were identified; 50.5% were in women and 49.5% in men. The mean age of the patients was 70.7 years (range, 8-100 years). The histologic type of the tumor was solid in 65.3% of cases and in 89% of cases the tumor was located on the head or neck. Ten percent of the tumors were recurrent following previous treatment. A mean of 1.74 Mohs stages were used, with a mean of 3.81 sections. The mean size of the initial defect was 0.86 cm² and the mean final defect was 1.88 cm². The ratio of initial tumor size to final defect was estimated at 1.02. Over a mean follow-up of 32 months, there were 9 cases of tumor recurrence (0.37%). CONCLUSIONS: In our experience, Mohs micrographic surgery is effective for the treatment of high-risk basal cell carcinoma.

Cirugía micrográfica de Mohs en el tratamiento de carcinoma basocelular / Mohs Micrographic Surgery for the Treatment of Basal Cell Carcinoma

Introducción: El carcinoma basocelular constituye el 75% de todos los carcinomas cutáneos no melanoma. Para su tratamiento existen múltiples modalidades siendo la escisión quirúrgica la más frecuentemente usada. Se plantea evaluar la eficacia de la cirugía micrográfica de Mohs en el tratamiento del carcinoma basocelular. Materiales y métodos: Revisión retrospectiva en la base de datos del Hospital Italiano de Buenos Aires de los casos de carcinoma basocelular tratados con cirugía micrográfica de Mohs entre octubre del 2003 y junio del 2009. Resultados: Se encontraron 2.412 casos (85,3%); el 50,5% se presentaron en mujeres y el 49,5% en hombres. La media de edad fue de 70,7 años (rango entre 8 y 100 años). El 65,3% de los tumores eran del tipo histológico sólido y la ubicación más frecuente fue la cabeza y el cuello (89%). El 10% de los carcinomas basocelulares eran recidivas de tratamientos previos. El número medio de estadios fue de 1,74 con una media de 3,81 cortes. La media del defecto inicial fue de 0,86cm2 y del defecto final de 1,88cm2. La relación defecto final/defecto inicial se estimó en 1,02cm2. Nueve tumores presentaron recidiva (0,37%) con una media de seguimiento de 32 meses. Conclusión: Consideramos que la cirugía micrográfica de Mohs es eficaz en el tratamiento del carcinoma basocelular de alto riesgo (AU)

Introduction: Basal cell carcinoma accounts for 75% of all nonmelanoma skin cancer. Although various treatment modalities are available, the most frequently used option is surgical excision. Here, we evaluate the efficacy of Mohs micrographic surgery for the treatment of basal cell carcinoma. Material and methods: A retrospective review of cases of basal cell carcinoma treated with Mohs micrographic surgery between October 2003 and June 2009 was performed using patient records from Hospital Italiano in Buenos Aires, Argentina. Results: A total of 2412 basal cell carcinomas treated with Mohs micrographic surgery were identified; 50.5% were in women and 49.5% in men. The mean age of the patients was 70.7 years (range, 8–100 years). The histologic type of the tumor was solid in 65.3% of cases and in 89% of cases the tumor was located on the head or neck. Ten percent of the tumors were recurrent following previous treatment. A mean of 1.74 Mohs stages were used, with a mean of 3.81 sections. The mean size of the initial defect was 0.86cm2 and the mean final defect was 1.88cm2. The ratio of intial tumor size to final defect was estimated at 1.02. Over a mean follow-up of 32 months, there were 9 cases of tumor recurrence (0.37%). Conclusions: In our experience, Mohs micrographic surgery is effective for the treatment of high-risk basal cell carcinoma (AU)

Alopecia areata transitoria en pacientes trasplantados / Transient alopecia areata in transplanted patients

La alopecia areata es una enfermedad autoinmune. Entre los fármacos propuestos para su tratamiento se incluyen la ciclosporina y los corticoides sistémicos. Dado que estos fármacos son habitualmente usados en el tratamiento de pacientes trasplantados, la presencia de alopecia areata en este grupo de enfermos es un hallazgo llamativo. Presentamos los casos de 11 pacientes trasplantados que presentaron alopecia areata a placa única entre los 3 y 17 días posteriores al trasplante. Todos los pacientes se encontraban recibiendo tratamiento inmunodepresor cuando se diagnosticó la alopecia y todos ellos presentaron recuperación total de la afección entre los 30 y 60 días posteriores al diagnóstico, sin recibir ningún tratamiento específico. Concluimos que la incidencia de alopecia areata hallada en este grupo de pacientes excede ampliamente la encontrada en la población general. (AU)

Role of adenosine 5'-triphosphate in vasospasm after subarachnoid hemorrhage: human investigations.

OBJECTIVE: Adenosine 5'-triphosphate (ATP) is a vasoactive compound found in high concentrations inside erythrocytes. This compound may contribute to vasospasm after subarachnoid hemorrhage (SAH). We assessed the hypothesis that ATP contributes to vasospasm in humans. METHODS: ATP and hemoglobin concentrations were measured in cerebrospinal fluid (CSF) from humans with SAH and in blood incubated in vitro. The vasoactivity of the human CSF samples and of fractionated (fractions with molecular weight greater than or less than 10 kDa) and unfractionated blood incubated in vitro was assessed by application of samples to canine basilar artery segments under isometric tension. RESULTS: ATP in human CSF declined within 72 hours of SAH to concentrations too low to contract cerebral arteries. Vasoactivity of human CSF correlated with the concentration of hemoglobin. The vasoactivity of incubated erythrocyte hemolysates remained high despite a decline in ATP concentrations. Fractionation of incubated erythrocyte hemolysates showed that for incubation periods up to 7 days, all vasoactivity was in a fraction of molecular weight greater than 10 kDa. CONCLUSION: ATP is unlikely to contribute to vasospasm because the concentrations in CSF after SAH in humans are not high enough to cause vasospasm after 72 hours. The vasoactivity of erythrocyte hemolysate is not related to the ATP or ferrous hemoglobin content but may be related to the total hemoglobin content. Therefore, ATP is unlikely to be a major cause of clinically significant delayed vasospasm.

Hemoglobin increases endothelin-1 in endothelial cells by decreasing nitric oxide.

We determined whether ferrous hemoglobin increases endothelin-1 (ET-1) secretion from bovine cerebral artery endothelial cells and the mechanisms involved. Exposure of endothelial cells to hemoglobin caused dose-dependent increases in pre-proET-1 mRNA and peptide. The increase in ET-1 peptide was inhibited by cycloheximide or actinomycin D whereas only cycloheximide decreased basal ET-1 release. N(G)-nitro-l-arginine significantly increased ET-1 concentration and reduced hemoglobin stimulation of ET-1 release. 8-Bromo-cGMP did not alter basal ET-1 concentration but suppressed hemoglobin-induced ET-1 production. Methemoglobin and S-nitrosylated methemoglobin were less potent inducers of ET-1 release. In summary, hemoglobin increases ET-1 in cerebral endothelial cells by mechanisms that involve transcription and translation. Nitric oxide production inhibits ET-1 production. Ferrous hemoglobin increases ET-1 by binding nitric oxide and abolishing this inhibitory pathway although other mechanisms are involved since N(G)-nitro-l-arginine reduces hemoglobin-induced ET-1 release.

[Plasma concentration of leptin, neuropeptide Y and tumor necrosis factor alpha in patients with cancers, before and after radio- and chemotherapy]. / Stezenie leptyny, neuropeptydu Y oraz czynnika martwicy nowotworów alfa u chorych z nowotworami przed- i po radio- lub chemioterapii.

In patients with cancers progressive reduction of body mass is frequently recent. Pathogenesis of cachexia in patients with cancer is multifactorial. Such factors as cytokines, peptides relieved by tumor mass and different forms of treatment as radio or chemotherapy may play a major role in the pathogenesis of cachexia in patients with cancer. The aim of this study was to assess the relationship between body fat and lean mass and plasma leptin, NPY and TNF concentrations in patients with cancer of oral cavity and pharynx, cancer of larynx and non-Hodgkin lymphoma (NIL). 30 patients (10 with cancer of oral cavity and pharynx, 10 with cancer of larynx and 10 with non-Hodgkin lymphoma) were enrolled into this study. Mean age of all cancer patients was 50 +/- 2.9 years (from 18 to 76 years). The control group consisted of 29 healthy subjects with a means age 48 +/- 3.5 years (from 18 to 75 years), properly chosen according to the body weight, BMI, gender and age as above mentioned groups of patients with cancer. In control and study groups body fat and not-fat mass was assessed before and after treatment using the bioelectrical impedance method. Before oncological therapy patients with cancer did not differ from healthy subject with regard to body weight and body mass index. After treatment significant: decrease of body weight, body fat mass and BMI was observed. Serum leptin, NPY and TNF concentrations were analysed in healthy subjects and patients with cancer before and after treatment. Before oncological treatment significantly lower serum leptin concentration in comparison to leptinaemia in control group was found. In contrast to serum leptin, NPY serum concentration was similar in patients with cancer and in control subjects. Serum concentration of TNF was significantly higher in patients with cancer in comparison to subjects of control group. After oncological treatment, serum leptin and NPY concentration did not change significantly. In contrast, serum TNF concentration decreased significantly after oncological therapy. From the results obtained in this study we can conclude, that in patients with cancer secretion of leptin is decreased in relation to body fat mass. However, contribution of this hormone to pathogenesis of cancer induced anorexia seems not to proven. From the other side, the role of TNF in pathogenesis of disregulation of leptin secretion seems to be very likely. After chemo or radiotherapy, serum NPY concentration did not change significantly. After this oncological treatment the relationship between serum leptin concentration and body mass is no longer significant.

Effects of hemoglobin on heme oxygenase gene expression and viability of cultured smooth muscle cells.

Ferrous Hb contributes to cerebral vasospasm after subarachnoid hemorrhage, although the mechanisms involved are uncertain. The hypothesis that cytotoxic effects of ferrous Hb on smooth muscle cells contribute to vasospasm was assessed. Cultured rat basilar artery smooth muscle cells were exposed to pure Hb, dog erythrocyte hemolysate, or Hb breakdown products; and heme oxygenase (HO-1 and HO-2) and ferritin mRNA and protein were measured. Cytotoxicity was assessed by lactate dehydrogenase release and fluorescence assays. Pure Hb or hemolysate caused dose- and time-dependent increases in HO-1 mRNA and protein. Hemin was the component of Hb that increased HO-1 mRNA. Cycloheximide inhibited the increase in HO-1 mRNA in response to hemin. Ferritin protein heavy chain but not mRNA increased upon exposure of cells to Hb. Hemin and ferric but not ferrous Hb were toxic to smooth muscle cells. Toxicity was increased by exposure to Hb plus tin protoporphyrin IX. In conclusion, exposure of smooth muscle cells to Hb induces HO-1 mRNA and protein through pathways that involve new protein synthesis. Hemin is the component of Hb that induces HO-1. Hemin and ferric but not ferrous Hb are toxic.

Subarachnoid hemorrhage as a cause of an adaptive response in cerebral arteries.

OBJECT: It is not known whether the factors responsible for vasospasm after subarachnoid hemorrhage (SAH) cause the cerebral arteries to be narrowed independent of the subarachnoid blood clot or whether the continued presence of clot is required for the entire time of vasospasm. The authors undertook the present study to investigate this issue. METHODS: To distinguish between these possibilities, bilateral SAH was induced in monkeys. The diameters of the monkeys' cerebral arteries were measured on angiograms obtained on Days 0 (the day of SAH), 1, 3, 5, 7, and 9. The subarachnoid blood clot was removed surgically on Day 1, 3, or 5 or, in control animals, was not removed until the animals were killed on Day 7 or 9. The concentrations of hemoglobins and adenosine triphosphate (ATP), substances believed to cause vasospasm, were measured in the removed clots and the contractile activity of the clots was measured in monkey basilar arteries in vitro. If the clot was removed 1 or 3 days after placement, vasospasm was significantly diminished 4 days after clot removal. Clot removal on Day 5 had no marked effect on vasospasm. There was a significant decrease over time in hemoglobin and ATP concentrations and in the contractile activity of the clots, although substantial hemoglobin and contractile activity was still present on Day 7. CONCLUSIONS: The authors infer from these results that vasospasm requires the presence of subarachnoid blood for at least 3 days, whereas by Day 5 vasospasm is less dependent on subarachnoid blood clot. Because the clot still contains substantial amounts of hemoglobin and contractile activity after 5 days, there may be an adaptive response in the cerebral arteries that allows them to relax in the presence of the stimulus that earlier caused contraction.

Heme oxygenase-1 and ferritin are increased in cerebral arteries after subarachnoid hemorrhage in monkeys.

Hemoglobin is a key factor in the production of cerebral vasospasm. Metabolism of hemoglobin involves breakdown of heme by heme oxygenase (HO) and sequestration of the released iron in ferritin. We determined whether subarachnoid hemorrhage induces these proteins in cerebral arteries and, if so, in which cells they are produced. Whether the changes correlated with vasospasm also was investigated. Subarachnoid hemorrhage was created in monkeys, and vasospasm was assessed by angiography in cohorts of animals killed 3, 7, or 14 days after the hemorrhage. Ferritin and HO-1 messenger ribonucleic acid (mRNA) and protein were measured by competitive reverse transcription-polymerase chain reaction and Western blotting in hemorrhage-side and control-side cerebral arteries and brain tissue. The location of these proteins was determined by immunohistochemistry. There was significant vasospasm 3 and 7 days but not 14 days after subarachnoid hemorrhage. There were no significant changes in mRNA for HO-1 or ferritin in cerebral arteries or brain tissue at any time. There was a significant increase in HO-1 and ferritin protein in hemorrhage-side compared with control-side cerebral arteries at 3, 7, and 14 days. The increase in HO-1 protein was maximal at 3 days, whereas the increase in ferritin protein was maximal at 7 days. There was no detectable increase in HO-1 or ferritin protein in brain tissue at any time. Immunohistochemistry localized HO-1 protein and ferritin to cells in the adventitia of the arterial wall. We show that subarachnoid hemorrhage is associated with a significant increase in HO-1 and ferritin proteins in cerebral arteries that begins at least as early as 3 days after the hemorrhage and that persists for up to 14 days.

Effect of adenovirus-mediated nitric oxide synthase gene transfer on vasospasm after experimental subarachnoid hemorrhage.

OBJECTIVE: Evidence indicates that vasospasm after subarachnoid hemorrhage (SAH) is caused in part by a decrease in the vasodilator nitric oxide (NO), which is produced mainly in endothelial cells. This study tested whether intracisternal injection of adenovirus-expressing endothelial NO synthase (eNOS) would decrease vasospasm in dogs. METHODS: In 12 dogs, baseline cerebral angiography was performed, and then SAH was produced by two injections of blood into the cisterna magna. The dogs were randomized (n = 6/group) to intracisternal injection of adenovirus-expressing lacZ (Ad327beta-Gal) or eNOS (AdCD8-NOS), administered immediately after the first blood injection. Angiography was repeated on Day 7, and then L-arginine (50 mg) was administered intracisternally, and angiography was repeated. Cerebrospinal fluid aspirated from the cisterna magna on Days 2 and 7 was analyzed for levels of NO metabolites. The dogs were killed, and their basilar arteries were removed and studied pharmacologically. Four control dogs underwent angiography on Day 0, followed by virus injection (n = 2/group). Angiography was repeated on Day 7, and the control dogs were killed. Transgene expression was detected in tissue removed on Day 7 by histochemical staining for lacZ, by polymerase chain reaction for messenger ribonucleic acid for eNOS, and by measurement of NO metabolites in cerebrospinal fluid. RESULTS: Angiography showed significant vasospasm in each group (Ad327beta-Gal, -54 +/- 7% reduction in basilar artery diameter; AdCD8-NOS, -53 +/- 7%), with no significant difference between groups. Injection of L-arginine caused an insignificant increase in arterial diameter in each group. In dogs without SAH, Ad327beta-Gal caused a reduction in basilar artery diameter (-13 +/- 10%, P = 0.42; paired t test), whereas injection of AdCD8-NOS caused an increase in diameter (14 +/- 16%, P = 0.77; paired t test). Histological examination and beta-galactosidase staining of dogs given injections of Ad327beta-Gal showed staining in inflammatory cells in the subarachnoid space, in the adventitia of the cerebral vessels, and in the liver and lungs. Messenger ribonucleic acid for eNOS was detected in the leptomeninges of dogs given injections of AdCD8-NOS. Under isometric tension, basilar arteries from each group demonstrated similar relaxation to L-arginine, but arteries exposed to eNOS demonstrated significantly greater relaxation to L-arginine plus tetrahydrobiopterin than arteries exposed to lacZ. Cerebrospinal fluid levels of NO and its metabolites were significantly higher in dogs treated with AdCD8-NOS than those treated with Ad327beta-Gal 2 days after SAH. CONCLUSION: These results demonstrate that adenovirus vectors can be used to transfer genes to cells in the subarachnoid space of dogs. Enough NO can be produced in the absence of SAH to dilate the basilar artery. After SAH, however, NO plus a cofactor can dilate arteries in vitro, but not enough NO is generated in the subarachnoid space to prevent vasospasm, perhaps owing to the scavenging of NO by hemoglobin.

[Mechanisms regulating appetite and energy expenditure]. / Mechanizmy regulujace procesy laknienia i wydatkowania energii.

The nutrition instinct is regulated by central nervous system, hypothalamus, rhinencephalon, lobus limbicus, corpus amygdaloideum and cortex cerebri. These centers constantly get impulses informing about nutrition situation of tissues. There are: psychical, nervous, humoral and metabolic impulses, which are organized in central nervous system. Central nervous system sends the centrifugal impulses to regulate the mechanisms. There is dependence present between neurogenic, momentary and longwave regulation and thermogenesis.

Cutaneous aspergillosis: a report of six cases.

Skin invasion by Aspergillus is infrequent. We here describe six immunocompromised patients with skin manifestations caused by Aspergillus. A heart transplant recipient developed a primary cutaneous aspergillosis; two patients (one with chronic granulomatous disease and another treated with a high dose of corticosteroids) presented with nodular lesions secondary to haematogenous dissemination; and three patients with acute myelogenous leukaemia had skin dissemination by contiguity from orbit and sinus invasion. A. flavus was isolated in the three cases of leukaemia; the infection was due to A. fumigatus in the transplant recipient; A. fumigatus and A. versicolor were isolated in the patients with the secondary aspergillosis. In most cases, amphotericin B was useful, with clinical and mycological remission in four patients. A patient with leukaemia died without undergoing treatment, and a child carrier of chronic granulomatous disease died after only 12 days of treatment.

Randomized comparison of Guglielmi detachable coils and cellulose acetate polymer for treatment of aneurysms in dogs.

BACKGROUND AND PURPOSE: Endovascular treatments for aneurysms are being used more frequently in patients in the absence of a large body of information on their histopathological effects. This study determined the efficacy and histopathological effects of treatment of experimental aneurysms with Guglielmi detachable coils (GDC) or cellulose acetate polymer (CAP). METHODS: Fourteen dogs had 13 terminal and 30 sidewall aneurysms created with venous pouches sutured to the cervical carotid arteries. Two weeks later, dogs had angiography followed by randomization to no treatment (n=2) or to aneurysm occlusion with GDC (n=4) or CAP (n=6). Two months later, angiography was repeated, animals were killed, and aneurysms were excised, fixed, photographed, and examined by light and electron microscopy. RESULTS: Two dogs were excluded because of common carotid artery occlusion at 2-week angiography. There were 11 terminal and 16 sidewall aneurysms available for treatment. The rate of spontaneous thrombosis of untreated aneurysms was 0% (0/5). Treatment with GDC showed complete terminal and sidewall aneurysm obliteration rates of 33% (1/3) and 80% (4/5), respectively. Greater than 90% occlusion occurred in the remaining cases. There were no parent or branch artery occlusions. Treatment with CAP showed complete terminal and sidewall aneurysm obliteration rates of 20% (1/5) and 0% (0/5), respectively, and incomplete sidewall aneurysm obliteration in 1 of 5 cases. Aneurysms reformed at 2 months in 2 of 5 terminal and 1 of 5 sidewall cases. There were parent or branch artery occlusions with CAP in 2 and 4 cases, respectively. The rate of aneurysm occlusion was significantly lower and the rate of arterial occlusion significantly higher with CAP than with GDC (P<.05). Histopathology showed complete endothelialization across the orifice of the aneurysm successfully treated with CAP, whereas aneurysms treated with GDC were significantly more likely to show fresh or organizing thrombus without complete endothelialization (P<.05). CONCLUSIONS: It is concluded that both treatments have limitations. Complete packing of aneurysms with GDC obliterates the aneurysm, but endothelialization does not always occur within 2 months. There are substantial problems with CAP. It is thrombogenic and carries a higher risk of causing arterial thrombosis. Even if an aneurysm is successfully obliterated initially with CAP, the CAP may disappear, leaving the aneurysm completely untreated.

Prevention of vasospasm after subarachnoid hemorrhage in dogs by continuous intravenous infusion of PD156707.

This randomized, blinded study tested the prophylactic effect of PD156707, a nonpeptide competitive antagonist of endothelin A receptors, against vasospasm after subarachnoid hemorrhage in dogs. Twenty-two dogs were allocated on day 0 to undergo cerebral angiography followed by injection of arterial blood (0.5 ml/kg) into the cisterna magna. Dogs had central venous catheters implanted for continuous infusion of drug vehicle (n = 10) or PD156707 (n = 12). Cisternal blood injection was repeated on day 2. Drug levels were measured in plasma on days 2, 4, 6, and 7 and in cerebrospinal fluid (CSF) on days 2 and 7. Angiography was repeated on day 7 to assess vasospasm. After angiography on day 7, acute effects of infusion of PD156707, 100 mg, or drug vehicle on established vasospasm were assessed. Analysis of physiological variables within (analysis of variance) groups across time and between (unpaired t-test) groups at each time showed that drug-treated animals had significantly increased heart rate on day 7 compared to day 0 (p < 0.005). Comparison of basilar artery diameters at day 7 showed that PD156707 significantly decreased the degree of basilar artery vasospasm (placebo: -47 +/- 5% reduction [mean +/- SE] versus PD156707: -28 +/- 7%, p < 0.05, unpaired t-test). There was, however, significant vasospasm when comparing within groups (paired t-test, placebo: p < 0.0001, PD156707: p < 0.005). Mean plasma PD156707 levels (322 +/- 123 ng/ml) were adequate to block responses of endothelin-1 on endothelin A receptors in vitro although CSF levels (11 +/- 7 ng/ml) were substantially lower. Infusion of PD156707 into the basilar artery on day 7 caused a small but significant 10 +/- 3% (paired t-test, p < 0.01) increase in diameter compared to placebo (3 +/- 3% increase, p = 0.32). This infusion also was associated with a substantial increase in CSF drug levels to 19 +/- 9 mg/ml. These results suggest that endothelin A receptors mediate some of the vasospasm that occurs after SAH in dogs and that blockade of these receptors may be a beneficial treatment for vasospasm.