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1.
Braz J Med Biol Res ; 55: e12376, 2023.
Article in English | MEDLINE | ID: mdl-36629525

ABSTRACT

The aim of our study was to validate the use of the standardized Radiological Society of North America (RSNA) reporting system in individuals with known lung cancer who presented to the emergency department with suspected COVID-19. We included patients aged 18 years or older from the Cancer Institute of the State of São Paulo (ICESP) with a confirmed diagnosis of lung cancer, admitted to the emergency department and undergoing chest computed tomography (CT) for suspicion of COVID-19. Comparison between SARS-CoV2 RT-PCR across RSNA categories was performed in all patients and further stratified by diagnosis of lung cancer progression. Among 58 individuals included in the analysis (65±9 years, 43% men), 20 had positive RT-PCR. Less than a half (43%) had no new lung findings in the CT. Positive RT-PCR was present in 75% of those with typical findings according to RSNA and in only 9% when these findings were classified as atypical or negative (P<0.001). Diagnostic accuracy was even higher when stratified by the presence or absence of progressive disease (PD). Extent of pulmonary inflammatory changes was strongly associated with higher mortality, reaching a lethality of 83% in patients with >25% of lung involvement and 100% when there was >50% of lung involvement. The lung involvement score was also highly predictive of prognosis in this population as was reported for non-lung cancer individuals. Collectively, our results demonstrated that diagnostic and prognostic values of chest CT findings in COVID-19 are robust to the presence of lung abnormalities related to lung cancer.


Subject(s)
COVID-19 , Lung Neoplasms , Male , Humans , Female , COVID-19/diagnostic imaging , SARS-CoV-2 , RNA, Viral , Brazil , Tomography, X-Ray Computed/methods , Lung Neoplasms/diagnostic imaging , North America/epidemiology , Retrospective Studies
2.
Braz. j. med. biol. res ; 55: e12376, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1420744

ABSTRACT

The aim of our study was to validate the use of the standardized Radiological Society of North America (RSNA) reporting system in individuals with known lung cancer who presented to the emergency department with suspected COVID-19. We included patients aged 18 years or older from the Cancer Institute of the State of São Paulo (ICESP) with a confirmed diagnosis of lung cancer, admitted to the emergency department and undergoing chest computed tomography (CT) for suspicion of COVID-19. Comparison between SARS-CoV2 RT-PCR across RSNA categories was performed in all patients and further stratified by diagnosis of lung cancer progression. Among 58 individuals included in the analysis (65±9 years, 43% men), 20 had positive RT-PCR. Less than a half (43%) had no new lung findings in the CT. Positive RT-PCR was present in 75% of those with typical findings according to RSNA and in only 9% when these findings were classified as atypical or negative (P<0.001). Diagnostic accuracy was even higher when stratified by the presence or absence of progressive disease (PD). Extent of pulmonary inflammatory changes was strongly associated with higher mortality, reaching a lethality of 83% in patients with >25% of lung involvement and 100% when there was >50% of lung involvement. The lung involvement score was also highly predictive of prognosis in this population as was reported for non-lung cancer individuals. Collectively, our results demonstrated that diagnostic and prognostic values of chest CT findings in COVID-19 are robust to the presence of lung abnormalities related to lung cancer.

3.
J Med Entomol ; 54(1): 114-124, 2017 01.
Article in English | MEDLINE | ID: mdl-28082638

ABSTRACT

Recording the nycthemeral rhythm of sand flies allows the evaluation of the daily activity in different ecotypes, the period of greatest activity, and their degree of anthropophily. We investigated the fauna and the rhythm of sand fly activity in an ecotourism region in Mato Grosso do Sul (MS) state, Brazil. Sand flies were captured monthly, using a Shannon trap for 24 h periods between July 2012 and June 2014. We collected 1,815 sand flies, in which Lutzomyia whitmani (=Nyssomyia whitmani, sensu Galati) and Lutzomyia longipalpis were the most abundant species during the dry season, with activity from 5 p.m.-7 a.m. and 6 p.m.-5 a.m., respectively. Both species require particular attention as vectors of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum in several regions of Brazil, including MS. However, Lutzomyia dispar was more anthropophilic, and was most active between January and March, from 5 p.m. to 5 a.m. Lutzomyia misionensis (=Pintomyia misionensis, sensu Galati) was present throughout both years, active from 4 p.m. to 5 a.m. Other species were active from 5 p.m. to 6 a.m. Due to intense tourism in the months that coincide with a high number of vectors for leishmaniases in Piraputanga, it is essential to determine vector-monitoring strategies in the area by investigating sand fly rhythm while not neglecting other periods of the year when the insects are present.


Subject(s)
Circadian Rhythm , Psychodidae/physiology , Animals , Behavior, Animal , Biodiversity , Brazil , Feeding Behavior , Female , Male , Psychodidae/classification , Seasons , Species Specificity
4.
J Med Entomol ; 52(5): 925-31, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26336242

ABSTRACT

The understanding of the transmission dynamics of Leishmania spp. Ross as well as the epidemiology and spread of leishmaniasis is related to parasite-vector-host interactions. These interactions can be studied using specimens of a sand fly population reared in the laboratory, exposing individuals to experimental infection for the investigation of vector competence and parameters of the vectorial capacity of the species. The present study sought to describe an alternative method for the implantation of a Lutzomyia (Lutzomyia) cruzi colony with wild specimens captured in the municipality of Corumbá, Brazil. With Method 1, engorged females were individualized for oviposition. The eggs were transferred to an acrylic petri dish with a layer of plaster on the bottom, on which food was placed after hatching of the first larvae. With Method 2, females were kept in groups for oviposition in containers, in which soil and food were placed on their bottom for the larvae. In addition, the exposure time of the larvae to light was reduced in comparison with Method 1. With Method 2, a significantly greater number of specimens of Lu. cruzi was obtained. The ratio between the number of emerged adults and the females followed for oviposition was 0.42 with Method 1 and 2.75 with Method 2. The optimization of the rearing conditions for Lu. cruzi will enable the establishment of a colony providing a sufficient number of specimens to develop experimental infection by Leishmania as well as vectorial competence and some parameters of the vectorial capacity of this sand fly.


Subject(s)
Animal Husbandry/methods , Entomology/methods , Psychodidae/growth & development , Animals , Female , Larva/growth & development , Male , Pupa/growth & development
5.
Parasitology ; 139(4): 516-21, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22309735

ABSTRACT

Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.


Subject(s)
Chagas Disease/epidemiology , Chagas Disease/parasitology , Endemic Diseases , Trypanosoma cruzi/classification , Trypanosoma cruzi/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Argentina/epidemiology , Chagas Cardiomyopathy/epidemiology , Chagas Cardiomyopathy/parasitology , Chagas Cardiomyopathy/physiopathology , Chagas Disease/physiopathology , Child , Child, Preschool , DNA, Protozoan/analysis , DNA, Protozoan/genetics , Female , Genetic Variation , Genotype , Heart/parasitology , Humans , Infant , Male , Middle Aged , Phylogeny , Polymerase Chain Reaction , Trypanosoma cruzi/isolation & purification , Young Adult
6.
Infection ; 38(4): 261-7, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20508967

ABSTRACT

BACKGROUND: Detailed reports on the treatment of visceral leishmaniasis (VL) are scarce, particularly with regard to the utilization of antimoniate of N-methylglucamine. The aim of this study was to analyze the treatment of children admitted to a reference hospital, focusing in particular on the use of antimoniate of N-methylglucamine and on the supportive measures adopted. MATERIALS AND METHODS: Medical records of children treated for VL from January 1998 to February 2005 in the Hospital of the University of Mato Grosso do Sul, Central-West Region of Brazil, were reviewed retrospectively. RESULTS: A total of 116 children were treated, and 111 received antimoniate as the first therapeutic choice. The drug was highly efficient (96.9%) in patients with no signs of gravity on admission, in cases presenting warning signs of potential evolution to gravity, and even in some severely ill children. The most common adverse effects were increases in transaminase (22.5%) and amylase (17.5%) levels, and generally reversible electrocardiogram changes (18%). Some problems were detected during the treatment, such as inadequate prescription (causing an under- or overdose) or inappropriate change to a second-line scheme. Of the 116 children, 80% were given antibiotics, 71.5% needed a transfusion of red blood cells, 10.3% required a transfusion of platelets, fresh frozen plasma was given to 4.3%, albumin was administered in 3.4, and 8.6% needed intensive care support. The mortality rate was about 2.6%. CONCLUSION: Antimoniate of N-methylglucamine remains highly efficient and well tolerated in pediatric patients, which allows its utilization as a first-line therapy in Brazilian children until a better drug for widespread use becomes available; however, it should be used with caution, and special attention is required during its prescription and for the management of adverse effects. The low mortality rate obtained confirms that, in addition, successful treatment demands the correction of serious anemia and thrombocytopenia, the vigorous use of antibiotics to fight intercurrent bacterial infections, and sometimes the availability of intensive care units to treat more severe patients.


Subject(s)
Antiprotozoal Agents/therapeutic use , Leishmaniasis, Visceral/drug therapy , Meglumine/therapeutic use , Organometallic Compounds/therapeutic use , Adolescent , Antiprotozoal Agents/adverse effects , Brazil/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/epidemiology , Male , Meglumine/adverse effects , Meglumine Antimoniate , Organometallic Compounds/adverse effects , Retrospective Studies , Surveys and Questionnaires , Treatment Outcome
7.
Exp Parasitol ; 124(3): 253-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19854175

ABSTRACT

In the New World, visceral leishmaniasis (VL), which is a progressive disease and frequently fatal, is caused by Leishmania (Leishmania) infantum/chagasi. It is endemic in many regions of Brazil and occasionally occurs in non-endemic regions when dogs from an endemic area are introduced. The aim of the present study is to compare different skin infection patterns of dogs from two leishmaniasis endemic areas. A histological analysis of dogs from Campo Grande, Mato Grosso do Sul state, a region where epidemic episodes are currently taking place, showed dermic inflammatory infiltrates, composed of numerous vacuolated parasitized macrophages, few lymphocytes, plasma cells and many degranulated mast cells. In the other region of the study, São Luís, Maranhão state, the skin of dogs presented a remarkable inflammatory reaction composed mainly of plasma cells, lymphocytes and very few parasites. We concluded that there is a difference in the skin lesion patterns of dogs with leishmaniasis that is directly related to the endemic area where the animals live.


Subject(s)
Dog Diseases/pathology , Endemic Diseases/veterinary , Leishmania infantum/isolation & purification , Leishmaniasis, Visceral/veterinary , Skin/pathology , Animals , Brazil , Connective Tissue/parasitology , Disease Reservoirs , Dog Diseases/epidemiology , Dog Diseases/parasitology , Dogs , Female , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/pathology , Lymphocytes/parasitology , Lymphocytes/pathology , Macrophages/parasitology , Male , Mast Cells/pathology , Plasma Cells/parasitology , Plasma Cells/pathology , Skin/parasitology
8.
Cytogenet Genome Res ; 125(1): 19-25, 2009.
Article in English | MEDLINE | ID: mdl-19617692

ABSTRACT

Xist non-coding RNA (ncRNA) is essential for X chromosome inactivation (XCI). Some genes can escape from XCI, but how this occurs is unknown. We developed a modified RNA tagging and recovery of associated proteins (TRAP) method to study the association between Xist RNA and its target genes. In mouse cells, Xist RNA was detected on the Uba1 gene, but not on Jarid1c and Utx genes, which escape from XCI. Using this technique we were able to show that the Xist RNA molecule is not present on active genes that escape from XCI, but is present on genes inactivated by XCI, suggesting that this method is a powerful tool for functional analysis of ncRNA.


Subject(s)
Chromatin/genetics , Chromatin/metabolism , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , X Chromosome Inactivation/genetics , X Chromosome/genetics , X Chromosome/metabolism , Animals , Cell Line , Chromatin Immunoprecipitation , DNA/genetics , DNA/metabolism , Female , Gene Expression , In Situ Hybridization , In Situ Hybridization, Fluorescence , Male , Mice , RNA, Long Noncoding , Reverse Transcriptase Polymerase Chain Reaction
9.
Vet Res Commun ; 28(5): 365-74, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15379431

ABSTRACT

Canine visceral leishmaniosis (CVL) may be an important factor preceding human outbreaks of the disease. We report that the prevalence of canine visceral leishmaniosis infection has been increasing in recent years in Anastácio town, located in the central western region of Brazil. Serological investigations showed that 75.3% of dogs presented antibody titres ranging from 1/40 to 1/160 in the indirect immunofluorescence antibody test (IFAT). Bone marrow and lymph node aspirates provided positive cultures and furnished parasites for enzymological and serological typing in 42.5% and 41.1% of the cases, respectively. All the strains were typed as Leishmania (L.) chagasi. This is primarily a canine disease that spills over into the human population as a zoonosis. The study showed the epidemiological features of the infection in a region in which the problem of visceral leishmaniosis has been underestimated.


Subject(s)
Dog Diseases/epidemiology , Leishmaniasis, Visceral/veterinary , Animals , Brazil/epidemiology , Dog Diseases/parasitology , Dogs , Geography , Leishmaniasis, Visceral/epidemiology , Prevalence
10.
Fungal Genet Biol ; 34(2): 107-21, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11686676

ABSTRACT

Using a green fluorescent protein (GFP)-tubulin fusion protein, we have investigated the dynamic rearrangement of microtubules during appressorium formation of Colletotrichum lagenarium. Two alpha-tubulin genes of C. lagenarium were isolated, and GFP-alpha-tubulin protein was expressed in this fungus. The strain expressing the fusion protein formed fluorescent filaments that were disrupted by a microtubule-depolymerizing drug, benomyl, demonstrating successful visualization of microtubules. In preincubated conidia, GFP-labeled interphase microtubules, showing random orientation, were observed. At conidial germination, microtubules oriented toward a germination site. At nuclear division, when germ tubes had formed appressoria, mitotic spindles appeared inside conidia followed by disassembly of interphase microtubules. Remarkably, time-lapse views showed that interphase microtubules contact a microtubule-associated center at the cell cortex of conidia that is different from a nuclear spindle pole body (SPB) before their disassembly. Duplicated nuclear SPBs separately moved toward conidium and appressorium accompanied by astral microtubule formation. Benomyl treatment caused movement of both daughter nuclei into 70% of appressoria and affected appressorium morphogenesis. In conidia elongating hyphae without appressoria, microtubules showed polar elongation which is distinct from their random orientation inside appressoria.


Subject(s)
Microtubules/metabolism , Mitosporic Fungi/cytology , Mitosporic Fungi/physiology , Amino Acid Sequence , Benomyl/pharmacology , Cell Division/drug effects , Cell Division/physiology , Cell Nucleus/drug effects , Cell Nucleus/physiology , Gene Expression , Green Fluorescent Proteins , Luminescent Proteins/analysis , Luminescent Proteins/genetics , Mitosporic Fungi/drug effects , Mitosporic Fungi/growth & development , Molecular Sequence Data , Morphogenesis , Phylogeny , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/physiology , Sequence Homology, Amino Acid , Spindle Apparatus/metabolism , Tubulin/chemistry , Tubulin/genetics , Tubulin/physiology
11.
World J Surg ; 25(8): 980-4, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11571979

ABSTRACT

Recent reports have implicated CO2 pneumoperitoneum for laparoscopic surgery in the occurrence of postoperative mesenteric ischemia. With this kind of surgery, the increase in blood lactate levels has been attributed to anaerobic metabolism, probably due to tissue ischemia induced by high intraabdominal pressure (IAP). The aim of this study was to evaluate the metabolic repercussion of CO2 pneumoperitoneum during laparoscopic cholecystectomy (LC). This was a prospective randomized study of CO2 pneumoperitoneum (PP group, n = 19) versus abdominal wall retraction (AWR group, n = 15). Demographic data were collected preoperatively. Four-trocar LC was performed with either a CO2 pneumoperitoneum (IAP of 12 mmHg) or abdominal wall retraction (abdominal wall pressure 6-10 kp). Intraoperative and postoperative blood samples were collected and lactate levels determined by enzymatic analysis. Repeated measures analysis of variance (MANOVA) was used for statistical analysis. Significance was evaluated at p < 0.05. The groups were shown to be homogeneous. Lactate concentration, expressed as mean (SD), went from 25.4 (14.4) mg/dl at baseline to 18.9 (13.6) mg/dl 4 hours after surgery in the PP group and from 19.4 (6.1) mg/dl at baseline to 17.8 (14.7) mg/dl in the AWR group. No significant differences were found between groups intraoperatively (p = 0.116) or postoperatively (p = 0.99). Our study did not show significant differences in blood lactate levels during LC with CO2 pneumoperitoneum compared to the same procedure with abdominal wall retraction.


Subject(s)
Abdominal Muscles/surgery , Cholecystectomy, Laparoscopic , Lactic Acid/metabolism , Pneumoperitoneum, Artificial , Adult , Aged , Aged, 80 and over , Carbon Dioxide , Female , Humans , Intraoperative Period , Male , Middle Aged
12.
Surg Endosc ; 15(12): 1448-51, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11965463

ABSTRACT

BACKGROUND: Although abdominal wall retraction is said to be advantageous in laparoscopic cholecystectomy (LC), many surgeons have found that, when this option is chosen, more time is needed to prepare for and carry out the surgical procedure. Our aim was to determine the time required for surgical preparation and operation in patients undergoing LC with carbon dioxide (CO2) pneumoperitoneum (CO2 PP) vs abdominal wall retraction (AWR). METHODS: We performed a prospective randomized study of a CO2 PP LC group (n = 19) vs an AWR LC group (n = 15). Demographic data were collected preoperatively. LC was performed with either CO2 PP (12 mmHg) or AWR (6-10 kps). Two phases were considered: (a) time employed to create the surgical field (phase 1) and (b) operating time (phase 2). The chi-square test was used to compare the medians of the two groups. RESULTS: The two groups were homogeneous. Phase 1 required 35 min in the CO2 PP group vs 25 min in the AWR group (p = 0.24). Phase 2 required 60 min in both groups (p = 0.76). CONCLUSION: We found no statistically significant difference between the PP CO2 and AWR groups in either time spent to create the surgical field or actual operating time.


Subject(s)
Carbon Dioxide/therapeutic use , Cholecystectomy, Laparoscopic/methods , Pneumoperitoneum, Artificial/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Random Allocation , Time Factors
13.
Cir. Esp. (Ed. impr.) ; 68(4): 304-308, oct. 2000. tab
Article in Es | IBECS | ID: ibc-5595

ABSTRACT

La cirugía laparoscópica es una nueva vía de abordaje quirúrgico que posee una serie de características diferenciales con la cirugía convencional: creación de una cavidad real mediante la introducción de gas y el impacto de éste sobre los órganos intraabdominales, utilización de material sofisticado (óptica, cámara, etc.) y modificación de los sentidos del cirujano en cuanto a su interrelación con la intervención. Se incrementa el detalle y se magnifica el campo, pero se pierde la tercera dimensión. El tacto se modifica de forma sustancial por el tipo de instrumentos, con la pérdida de la sensibilidad estereognóstica (reconocimiento de objetos por el tacto). A la vez, el movimiento manual para la realización de cualquier maniobra quirúrgica es totalmente diferente al de la cirugía convencional. Todo ello significa que la cirugía laparoscópica debe ser aprendida y, por tanto, enseñada de forma diferente a la convencional. La formación del cirujano en cirugía laparoscópica debe realizarse desde los ámbitos teórico, práctico y clínico. Esto incluye el conocimiento del aparataje y de la fisiopatología, el desarrollo de las habilidades en técnicas de disección y sutura en el simulador y el animal de experimentación y, finalmente, en el quirófano, en un inicio como ayudantes para progresar hasta la realización completa de la intervención. Este planteamiento es aplicable tanto a cirujanos formados como a residentes en formación. Los hospitales y servicios de cirugía con responsabilidad en la formación de especialistas deben garantizar la adecuada enseñanza de la cirugía laparoscópica a los nuevos cirujanos para que ésta sea una técnica habitual y no la técnica excepcional (AU)


Subject(s)
Education, Medical/methods , Education, Medical/trends , General Surgery/education , Laparoscopy/classification , Laparoscopy/methods , Laparoscopy/trends , Certification/standards , Internship and Residency/standards , Societies, Scientific/standards
14.
Rev Soc Bras Med Trop ; 33(3): 277-80, 2000.
Article in Portuguese | MEDLINE | ID: mdl-10967597

ABSTRACT

The purpose of this study was to establish the prevalence of Cryptosporidium parvum among infants of less than 5 years of age, resident in the urban area of Campo Grande, Mato Grosso do Sul State, Brazil, 1996/97, through parasitological examinations and epidemiological analysis of the diagnosed cases. It was a transverse study with domiciliary inquiry and we evaluated 1051 fecal samples processed by the Blagg method, and a modified Ziehl-Neelsen staining was used for research of oocysts of C. parvum. We can concluded that the prevalence of C. parvum (1.1%) was not statistically significant; 58.3% of the children with positive diagnosis presented diarrhea, suggesting an association between this sign and the presence of the parasites; C. parvum was more frequent among children aged between 25 to 36 months (50%), but this was not statistically significant; sex did not have a differential role in relation to the cryptosporidiosis; out of the 12 children with cryptosporidiosis, 10 had contact with domestic animals (dogs and or cats).


Subject(s)
Cryptosporidiosis/epidemiology , Cryptosporidium parvum , Animals , Brazil , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Urban Population
15.
Int Surg ; 84(3): 246-50, 1999.
Article in English | MEDLINE | ID: mdl-10533786

ABSTRACT

The mechanical properties and macroscopic behaviour of non-absorbable materials have been widely studied. Nevertheless, biological tissue response to contact with these prostheses is not well-known. Our purpose was to compare the microscopic behaviour of two non-absorbable materials. Polypropylene and mersilene meshes were implanted on 36 female Wistar rats each (PPL and ME groups) . Six animals per group were sequentially sacrificed at 1, 2, 3, 5, 10 and 15 weeks. Global cell density and number of polymorphonuclear leukocytes, giant cells, fibroblasts and histiocytes were compared for every studied phase. The polypropylene group showed higher cell density and polymorphonuclear response in the initial phases, while scores for giant cells were higher in the mersilene group. Fibrohistiocytic reaction was increased in the polypropylene group. Polypropylene tends to provoke higher acute inflammatory reaction and connective tissue formation than mersilene. The latter induces higher foreign body reaction.


Subject(s)
Abdominal Muscles/surgery , Surgical Mesh , Abdominal Muscles/pathology , Animals , Female , Foreign-Body Reaction/pathology , Polyethylene Terephthalates , Polypropylenes , Rats , Rats, Wistar
16.
Stroke ; 30(1): 140-7, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9880402

ABSTRACT

BACKGROUND AND PURPOSE: The chronic phase of vasospasm after an aneurysmal subarachnoid hemorrhage may be mediated in part by early leukocyte-endothelial cell interactions. Ibuprofen is an anti-inflammatory agent that inhibits expression of certain cell adhesion molecules and therefore disrupts leukocyte-endothelial cell interactions. Its systemic administration, however, has dose-limiting side effects. We evaluated the effect of the periadventitial delivery of ibuprofen using controlled-release polymers in the rat femoral artery model of chronic posthemorrhagic vasospasm. METHODS: Before the animal studies, the release pharmacokinetics of the ibuprofen-loaded ethylene-vinyl acetate polymers were determined in vitro. Subsequently, the femoral arteries (n=266) of Fischer 344 rats (n=133) were enclosed in latex pouches bilaterally. In the toxicity study (n=15 rats), the animals were randomized into 5 dose groups in which 0%-, 10%-, 20%-, 30%-, or 50%-loaded ibuprofen polymers were evaluated. In the efficacy study, the animals were randomized into 5 time groups in which 50%-loaded ibuprofen polymers were inserted at 0 (n=58 rats), 6 (n=16), 12 (n=13), 24 (n=11), or 48 hours (n=12) after blood injection into the pouch. The rats were killed 12 days after blood exposure, at the time of maximal vasospasm in this model. Vasospasm was expressed as percent lumen patency. To evaluate the effect of ibuprofen on leukocyte migration, 8 rats were randomized into 2 groups. Macrophages and granulocytes were stained by immunohistochemistry with the use of a mouse OX-41 monoclonal antibody and counted in the periadventitial space 24 hours after blood exposure. RESULTS: In vitro pharmacokinetics showed that the 50%-loaded ibuprofen polymer released its total drug load over a 12-day period. In the toxicity study, a nonsignificant arterial vasodilatation with ibuprofen treatment was seen at higher doses, and no deleterious effects were noted on the vessel wall histologically. In the efficacy study, ibuprofen treatment resulted in significant vasospasm inhibition when treatment was initiated at 0 hour (73.7+/-4.9% versus 94.5+/-3.3% [mean+/-SEM percent lumen patency]; P<0.001) and 6 hours (69.2+/-5.7% versus 98.0+/-3.9%; P=0. 002) after blood exposure, but not at 12, 24, or 48 hours. Leukocyte immunohistochemistry showed that ibuprofen treatment resulted in significantly lower periadventitial macrophage and granulocyte counts of 25.0+/-3.9 cells per high-powered field compared with counts of 140.5+/-18.2 cells per high-powered field in the untreated vessels (P<0.001). CONCLUSIONS: The periadventitial, controlled release of ibuprofen from surgically implanted polymers significantly inhibits chronic posthemorrhagic vasospasm in this model when treatment is initiated within 6 hours of blood exposure. Vasospasm inhibition with ibuprofen correlates with a significant decrease in the number of macrophages and granulocytes in the periadventitial space. This study supports the hypothesis that inflammation mediates in part the chronic phase of posthemorrhagic vasospasm and suggests a potential alternative treatment for this condition.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Ibuprofen/pharmacokinetics , Vasoconstriction/drug effects , Animals , Cell Adhesion Molecules/physiology , Delayed-Action Preparations , Endothelium, Vascular/chemistry , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Femoral Artery/cytology , Femoral Artery/drug effects , Femoral Artery/physiology , Granulocytes/physiology , Leukocyte Count , Macrophages/physiology , Male , Rats , Rats, Inbred F344 , Tunica Intima/drug effects , Tunica Intima/physiology
17.
Gastroenterol Hepatol ; 21(9): 445-8, 1998 Nov.
Article in Spanish | MEDLINE | ID: mdl-9882936

ABSTRACT

Intestinal pneumatosis is an infrequent disease of difficult clinical and radiologic diagnosis. It may be accompanied by pneumoperitoneum in up to 30% of the cases leading to differential diagnosis with pictures of visceral perforation. We herein present 4 cases of intestinal pneumatosis in whom pneumoperitoneum was associated in 3 patients. Diagnosis was intraoperative in 2 patients submitted to emergency surgery because of an associated acute gastrointestinal event (intestinal volvulus and acute cholecystitis). The other 2 cases were diagnosed by computerized tomography and colonoscopy, respectively, and given their satisfactory clinical evolution they received conservative treatment. The course of the disease was favorable in all the patients with the radiologic signs of pneumatosis disappearing.


Subject(s)
Pneumatosis Cystoides Intestinalis/diagnostic imaging , Aged , Aged, 80 and over , Colonoscopy , Emergencies , Female , Humans , Male , Middle Aged , Pneumatosis Cystoides Intestinalis/diagnosis , Pneumatosis Cystoides Intestinalis/surgery , Tomography, X-Ray Computed
18.
Nat Med ; 3(12): 1354-61, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9396605

ABSTRACT

Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase (HSV-TK) gene induces regression of experimental brain tumors in rodents after ganciclovir (GCV) administration. We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors. Antitumor activity was detected in five of the smaller tumors (1.4 +/- 0.5 ml). In situ hybridization for HSV-TK demonstrated survival of vector-producing cells (VPCs) at 7 days but indicated limited gene transfer to tumors, suggesting that indirect, "bystander," mechanisms provide local antitumor activity in human tumors. However, the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach.


Subject(s)
Antineoplastic Agents/therapeutic use , Brain Neoplasms/therapy , Ganciclovir/therapeutic use , Genetic Therapy , Genetic Vectors , Retroviridae/genetics , Thymidine Kinase/genetics , Adult , Animals , Cell Transplantation , Female , Gene Transfer Techniques , Herpesvirus 1, Human/enzymology , Herpesvirus 1, Human/genetics , Humans , Male , Mice , Middle Aged , Thymidine Kinase/biosynthesis , Transplantation, Heterologous
19.
Stroke ; 28(10): 2031-7; discussion 2037-8, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9341715

ABSTRACT

BACKGROUND AND PURPOSE: Inflammation may play a role in delayed chronic vasospasm after aneurysmal subarachnoid hemorrhage. We investigated the role of intercellular adhesion molecule-1 (ICAM-1) and macrophage/granulocyte infiltration in the rat femoral artery model of vasospasm using systemic administration of a murine anti-ICAM-1 monoclonal antibody (MAb). METHODS: The femoral arteries (n = 72) in Sprague-Dawley rats (n = 36) were enclosed in latex pouches bilaterally. Autologous blood was injected into the pouch on one side, and saline was injected on the contralateral side. Chronic vessel narrowing was evaluated with the use of 29 rats, which were randomized into one of three groups for intraperitoneal injections: (1) anti-ICAM-1 MAb (2 mg/kg per dose, n = 10), (2) isotype-matched MAb (2 mg/kg per dose, n = 9), or (3) saline (n = 10), given at 3 hours and 3, 6, and 9 days after blood exposure. These rats were killed 12 days after blood exposure, and femoral artery lumen cross-sectional areas were determined by computerized image analysis. Saturation of ICAM-1 binding sites with this dosing schedule was evaluated by fluorescence-activated cell sorter (FACS) analysis of splenocytes. Immunohistochemical studies with objective cell counts were performed to evaluate macrophage/granulocyte infiltration at 24 hours in 7 rats, comparing anti-ICAM-1 MAb treatment (n = 4) with isotype-matched control MAb (n = 3). RESULTS: Animals treated with anti-ICAM-1 MAb showed a significant inhibition of arterial narrowing at 12 days (P = .0081), with lumen patency of 96.5 +/- 5.3% (mean +/- SEM), compared with 77.3 +/- 5.6% for isotype-matched MAb and 72.2 +/- 5.3% for saline-treated controls. FACS analysis of splenocytes from animals treated with anti-ICAM-1 MAb confirmed saturation of ICAM-1 binding sites. Vessels treated with anti-ICAM-1 MAb showed a significant decrease in inflammatory cell infiltrates, with objective macrophage/granulocyte counts of 31.3 +/- 26.6 (mean +/- SEM) per high-powered field, compared with 171.4 +/- 30.7 for isotype-matched control MAb (P = .0027). CONCLUSIONS: Anti-ICAM-1 MAb administered systemically starting 3 hours after blood exposure results in significant inhibition of chronic vasospasm in the rat femoral artery model and is correlated with a reduction in the number of infiltrating macrophages and granulocytes in the periadventitial region of blood-exposed arteries. We conclude that inflammatory changes associated with ICAM-1-mediated macrophage and granulocyte migration play an important role in the development of posthemorrhagic chronic vasospasm in this model.


Subject(s)
Antibodies, Monoclonal/pharmacology , Intercellular Adhesion Molecule-1/immunology , Vasoconstriction/drug effects , Animals , Blood Physiological Phenomena , Cell Separation , Femoral Artery/metabolism , Femoral Artery/pathology , Flow Cytometry , Granulocytes/pathology , Immunohistochemistry/methods , Intercellular Adhesion Molecule-1/metabolism , Macrophages/pathology , Male , Mice , Mice, Inbred BALB C , Rats , Rats, Sprague-Dawley , Spleen/immunology , Spleen/pathology , Staining and Labeling , Vasoconstriction/physiology
20.
J Neurosurg ; 87(2): 163-9, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9254077

ABSTRACT

In patients with bilateral supratentorial aneurysms, surgical clipping of all aneurysms via a unilateral approach would obviate the need for a second operation. The authors conducted a microsurgical study in human cadaver heads to examine the contralateral exposure for four common aneurysm sites in the anterior circulation: the ophthalmic artery (OA) origin, the posterior communicating artery (PCoA) origin, the internal carotid artery (ICA) termination, and the middle cerebral artery (MCA) bifurcation. Frontotemporal craniotomies were performed in 16 cadavers to evaluate the corridor for exposure of these sites from the contralateral side. Morphometric data, including lengths and diameters of major arterial segments and optic nerves, were documented for anatomical correlation. In this study, the contralateral OA origin was successfully exposed in 62% of specimens, the PCoA origin in 50%, the ICA bifurcation in 100%, and the MCA bifurcation in 62%. Exposure of the OA origin and, in some cases, the PCoA, required incision of the falciform ligament and mobilization of the contralateral optic nerve. Exposure of the MCA bifurcation was dependent on the length of the M1 segment, with successful exposure only when this segment was shorter than 14 mm. Implications for the contralateral approach to aneurysms at these sites are discussed and the microsurgical corridors for exposure are described. For correlation with the anatomical study, a brief clinical review of patients with bilateral supratentorial aneurysms treated at The Johns Hopkins Hospital between 1992 and 1995 is presented. Guidelines for the contralateral approach to aneurysms are discussed with reference to the anatomical study and the clinical review.


Subject(s)
Cerebral Arteries/pathology , Intracranial Aneurysm/pathology , Microsurgery/methods , Adult , Autopsy , Humans
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