MMed, Ophthalmology, Faculty of Health Sciences, University of the Witwatersrand / Aim To determine and document the demographic profile, clinical features, associations and clinical and visual outcomes in black African patients with idiopathic intracranial hypertension (IIH) attending St John Eye Hospital during 2006 and 2007. Method A retrospective descriptive study was conducted on black African IIH patients. Patient files and data of 21 of 32 IIH patients, seen in the Neuro-ophthalmology clinic at St John Eye Hospital over a two year period (2006 and 2007), were available and this study is based on these 21 patients. All 21 patients fulfilled the modified Dandy criteria for the diagnosis of IIH. Information obtained from files of the 21 patients were recorded on a data capture sheet. The demographics, initial (presenting) and final visual acuities and visual fields, initial and final clinical symptoms and signs, associations and treatment modalities were recorded on the data capture sheet. Visual and clinical outcomes were determined by comparing the final with the initial (presenting) symptoms and signs. The minimum follow-up period between the initial and the final visit was two months. Patients were regarded as legally blind if they had severe to profound visual acuity and/or visual field loss. Results All 21 patients were female and black African. Mean age was 31.2 ± 8.9 years (range 16 – 50 years). Mean period of follow up was 19.9 ± 20.1 months (range 2 – 77 months). 71.4% were obese. All patients presented with symptoms. The commonest presenting symptom was headache (90%) followed by visual loss (67%), transient visual obscurations (38%) and diplopia (29%). The results of the presenting signs were as follows: Seven eyes (17%) had visual acuity loss (most of which were mild [9.5%]), seven patients (33%) had abduction deficits, four patients (9.5%) had unilateral abnormal pupil reactions and all patients had papilloedema. Of the recorded associations seven patients (33%) were hypertensive, six (29%) were on contraception (two [9.5%] were on oral contraception) and two (9.5%) were taking prednisone prior to presentation. After the initial visit, all 21 vi IIH patients were treated with acetazolamide (Diamox) and weight loss was recorded in three patients (14%). Two patients (9.5%) had optic nerve sheath fenestrations (ONSF), two (9.5%) had lumbar-peritoneal shunts (LPS) and six (28.6%) had multiple lumbar punctures (LP’s). The outcome analysis was as follows: Symptoms in 19 patients (90%) improved but 16 patients (76%) still had papilloedema. Two patients (9.5%) had abduction deficits at the final visit. Visual acuity loss occurred in five eyes (12%) at the final visit compared to seven eyes (17%) at the initial visit (presentation). From the initial visit (presentation) to the final visit, visual acuity in seven eyes (16%) improved, 31 eyes (74%) remained stable and four eyes (10%) worsened. Although visual fields in 33 eyes (79%) improved from the initial to the final visit, 36 eyes (86%) still had visual field loss at the final visit. 26% of eyes had severe to profound visual impairment i.e. were legally blind, at the final visit. Conclusion The results of 21 black African IIH patients reported in this study were similar to some other studies with regards to demographics, clinical features and clinical and visual outcomes. An association between IIH and oral contraceptives, steroids and hypertension could not be established. Although symptoms resolved in most patients, a significant number of patients still had papilloedema and visual field loss following treatment. Despite treatment, a quarter of the patients were legally blind at the final visit, indicating that this condition is not benign.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 97-111).

There has been much discussion about the relationship between hormonal contraceptives and the development of pseudotumor cerebri (PTC). Some have claimed that progestin-containing contraceptives, such as levonorgestrel intrauterine devices, are linked to PTC. However, the relationship and mechanism of PTC following the use of progestin-containing contraceptives remain controversial. We present a case of PTC following implantation of Nexplanon® (etonogestrel) (Merck Sharp & Dohme BV, Haarlem, The Netherlands), a progestin contraceptive. Clinicians should be vigilant for visual disturbances, headache, nausea, and other signs of increased intracranial pressure in patients receiving progestin-containing contraceptives.

The goal of thesis "nursing care of patients with implemented intracranial sensor" was to analyze nursing care of patients on neurosurgical and critical care units in hospitals of the capital city of Prague. Main objectives were to understand whether there are nursing standards for "Nursing care for patients with established intracranial sensor", how nurses care for patients with increased intracranial pressure, if they have an experience with complications with patients with implemented ICP sensor and finally if they know the main complications that can potentially occur. The theoretical part describes the most common causes of brain damage and associated causes of intracranial hypertension, summarizes the types of sensors for monitoring intracranial pressure and ways of their implementation. It also deals with the specifics of nursing care associated with monitoring of intracranial hypertension. Quantitative research was chosen as methodology for this work. Data for the research was collected through anonymous questionnaire with nursing staff. The result was a finding that none of the cooperating departments have prepared a standard of nursing care for patients with an implemented ICP sensor, and that the majority of interviewed staff were not able to answer correctly if that standard in their...

A hidrocefalia ainda é um desafio no que diz respeito ao diagnóstico, tratamento e acompanhamento na população pediátrica. O tratamento, por meio das derivações ventriculares ou ventriculostomias endoscópicas, está bem estabelecido. Contudo, o diagnóstico de mau funcionamento das derivações, associado à hipertensão intracraniana, permanece um problema, especialmente em crianças menores e com fontanelas não patentes. Os exames radiológicos, tais como: ultrassonografia, tomografia computadorizada e ressonância magnética, possibilitam apenas o acesso indireto à pressão intracraniana, enquanto os métodos para sua avaliação direta podem apresentar riscos e raramente são utilizados em crianças. O objetivo deste estudo foi avaliar um dispositivo não invasivo para acessar alguns parâmetros da curva de pressão intracraniana em crianças portadoras de hidrocefalia. Para tanto, foi realizado um estudo descritivo-analítico, não experimental, prospectivo. A amostra foi composta por indivíduos menores de 18 anos, incluindo 28 pacientes portadores de hidrocefalia e 28 crianças em seguimento rotina de puericultura (grupo controle). Os participantes foram divididos em quatro grupos: grupo A: hidrocefalia compensada clinicamente; grupo B: pacientes com hidrocefalia, sem sinais clínicos sugestivos de hipertensão intracraniana e já submetidos à cirurgia para tratamento da hidrocefalia; grupo C: pacientes com hidrocefalia aguda e hipertensão intracraniana; grupo D: crianças sem qualquer doença neurológica (controle). Os dados foram coletados entre 2014 e 2016, por meio da instalação de um sensor extracraniano de deformação, acoplado sobre o couro cabeludo, com registro da curva de pressão intracraniana não invasiva. A análise dos dados foi realizada com software Freemat® 4, Origin Pro® 8 e R® 3.1.3. Foram analisados parâmetros obtidos na curva de pressão intracraniana como \"relação P2/P1\", \"classificação de P1 e P2\" (P1>P2 ou P2>P1) e \"inclinação de P1\". Os resultados apontaram, que na amostra estudada, o índice P2>P1 apresentou sensibilidade de 80% e especificidade de 100%, a \"classificação de P1 e P2\" sensibilidade de 100% e especificidade de 80% para predição de hipertensão intracraniana em hidrocefalia, sendo que a \"inclinação de P1\" não apresentou relação estatística. Conclui-se que, apesar de limitações operacionais, o método de monitorização não invasiva da pressão intracraniana se mostrou útil na detecção de hipertensão intracraniana e apresenta perspectivas de aplicação clínica futura. / Hydrocephalus is still a challenge regarding diagnosis, treatment and monitoring in the pediatric population. Currently, treatments by ventricular or endoscopic ventriculostomies are well established. However, to date, the diagnosis of malfunctioning shunts associated with intracranial hypertension remains a problem, especially in young children and without patent fontanelles. Radiological examinations, such as ultrasonography, computerized tomography and magnetic resonance, allow only an indirect access to the intracranial pressure, whilst methods for direct assessment may present risks and therefore are rarely used in children. The aim of this study was to evaluate a noninvasive device to assess some parameters of the intracranial pressure curve in children with hydrocephalus. For this, we performed a prospective and non-experimental descriptive-analytic study. The sample consisted of children (under 18 years), including 28 patients with hydrocephalus and 28 children following routine child care (control group). Participants were divided into four groups; Group A: children with clinically compensated hydrocephalus; B: patients with hydrocephalus, but with no clinical signs of intracranial hypertension and no history of medical surgery for the treatment of hydrocephalus; C: patients with acute intracranial hypertension due to hydrocephalus, and D: children without neurological disease (control). Data were collected between 2014 and 2016, through the installation of an extracranial deformation sensor, coupled to the children\'s scalp, which allowed registration of non-invasive intracranial pressure curves. Data analysis was performed using Freemat® 4, Origin Pro® 8 and R® 3.1.3 software. Parameters obtained from the intracranial pressure curves were analyzed, such as \"ratio P2 / P1\", \"classification P1 and P2\" (P1> P2 or P2> P1) and \"P1 slope.\" The results showed that P2>P1 index had a sensitivity of 80% and specificity of 100%, while the \"classification of P1 and P2\" had 100% of sensitivity and 80% of specificity for predicting intracranial hypertension. \"P1 slope\" presented no statistical difference. In summary, despite some operational limitations, this study showed an useful and non-invasive method for monitoring intracranial pressure, which was able to indicate the intracranial hypertension in children with hydrocephalus and, thus, should be further investigated for clinical applications.

Introdução: Dados sobre a relação entre a farmacocinética do fluconazol (FCZ) e anfotericina B (AMB) no líquido cefalorraquidiano (LCR) e a hipertensão intracraniana (HIC) não se encontram disponíveis na literatura. Objetivos: Avaliar a influência da pressão intracraniana na concentração dos antifúngicos AMB e FCZ no LCR de pacientes com meningite criptococócica internados no Hospital de Clínicas de Porto Alegre (HCPA), no período de 1 ano. Métodos: Foram estudados 15 pacientes com meningite criptococócica durante os primeiros 14 dias de tratamento com AmB (1 mg/kg/dia) e FCZ (800 mg/dia). As amostras de LCR foram obtidas por meio de punções lombares de rotina realizadas nos dias 1, 7 e 14 da terapia antifúngica, respectivamente. Os valores das pressões intracranianas de abertura foram obtidos no momento de cada punção lombar. Os níveis de AmB e FCZ no LCR foram medidos pela metodologia de cromatografia líquida de alta performance (HPLC). A concentração inibitória mínima (CIM) para AmB, FCZ, voriconazol (VRZ) e flucitosina (5-FC) de cada isolado de Cryptococcus sp. foi realizada de acordo com o as normas descritas no documento M27-A3, do CLSI, publicado em 2008. Resultados: Entre os 15 pacientes incluídos no estudo, C. gattii foi isolado do LCR de 2 pacientes e C. neoformans foi isolado do LCR de 13 pacientes apresentaram. A condição de imunossupressão encontrada foi a AIDS, seguida de transplante de órgão sólido. Nove pacientes apresentaram cultura negativa de LCR no 14º dia de terapia antifúngica. Os níveis de AmB no LCR foram indetectáveis para a maioria das amostras de LCR durante os 14 dias de terapia antifúngica. Os níveis de FCZ no LCR aumentaram progressivamente do dia 1 ao dia 14 de terapia. Seis pacientes apresentaram HIC no dia 1, com variação da pressão de abertura entre 100 mmH2O e 650 mmH2O no respectivo dia. A pressão intracraniana não interferiu nas concentrações de FCZ no LCR. Não observamos correlação entre a HIC e as concentrações de AMB e FCZ no LCR de acordo com a correlação de Spearman (Spearman p= 0.122). Conclusão: São necessários mais estudos para avaliar o papel da HIC na eficácia terapêutica de diferentes agentes antifúngicos em pacientes com meningite criptococócica. / Introduction: Data considering the relationship between pharmacokinetics of fluconazole (FCZ) and amphotericin B (BPA) in cerebrospinal fluid (CSF) and intracranial hypertension (IH) are not available in the literature. Objectives: To evaluate the influence of intracranial pressure on the concentration of the antifungals AMB and FCZ in the CSF of patients with cryptococcal meningitis admitted at the Hospital de Clínicas de Porto Alegre (HCPA), within a period of one year. Methods: Fifteen patients with cryptococcal meningitis were studied during the first 14 days of treatment with AmB (1 mg / kg / day) and FCZ (800 mg / day). CSF samples were obtained by means of routine lumbar punctures performed on days 1, 7 and 14 of antifungal therapy, respectively. The values of intracranial opening pressures were obtained at the time of each lumbar puncture. The levels of AmB and FCZ in the CSF were measured by high performance liquid chromatography (HPLC) methodology. The minimum inhibitory concentration (MIC) for AmB, FCZ, voriconazole (VRZ) and flucytosine (5-FC) of each isolate of Cryptococcus sp. was performed according to CLSI guideline M27-A3, published in 2008. Results: Among the 15 patients included in the study, C. gattii was isolated from the CSF of 2 patients and C. neoformans was isolated from the CSF of 13 patients presented. The immunosuppressive condition found was AIDS, followed by solid organ transplantation. Nine patients presented negative CSF culture on the 14th day of antifungal therapy. AmB levels in the CSF were undetectable for most of the CSF samples during the 14 days of antifungal therapy. CSF FCZ levels increased progressively from day 1 to day 14 of therapy. Six patients presented IH on day 1, with variation of the opening pressure between 100 mmH2O and 650 mmH2O on the respective day. Intracranial pressure did not interfere with CSF on FCZ concentrations. We did not observe a correlation between IH and the concentrations of AMB and FCZ in the CSF according to the Spearman correlation (Spearman p = 0.122). Conclusion: Further studies are needed to evaluate the role of IH in the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.

A hidrocefalia ainda é um desafio no que diz respeito ao diagnóstico, tratamento e acompanhamento na população pediátrica. O tratamento, por meio das derivações ventriculares ou ventriculostomias endoscópicas, está bem estabelecido. Contudo, o diagnóstico de mau funcionamento das derivações, associado à hipertensão intracraniana, permanece um problema, especialmente em crianças menores e com fontanelas não patentes. Os exames radiológicos, tais como: ultrassonografia, tomografia computadorizada e ressonância magnética, possibilitam apenas o acesso indireto à pressão intracraniana, enquanto os métodos para sua avaliação direta podem apresentar riscos e raramente são utilizados em crianças. O objetivo deste estudo foi avaliar um dispositivo não invasivo para acessar alguns parâmetros da curva de pressão intracraniana em crianças portadoras de hidrocefalia. Para tanto, foi realizado um estudo descritivo-analítico, não experimental, prospectivo. A amostra foi composta por indivíduos menores de 18 anos, incluindo 28 pacientes portadores de hidrocefalia e 28 crianças em seguimento rotina de puericultura (grupo controle). Os participantes foram divididos em quatro grupos: grupo A: hidrocefalia compensada clinicamente; grupo B: pacientes com hidrocefalia, sem sinais clínicos sugestivos de hipertensão intracraniana e já submetidos à cirurgia para tratamento da hidrocefalia; grupo C: pacientes com hidrocefalia aguda e hipertensão intracraniana; grupo D: crianças sem qualquer doença neurológica (controle). Os dados foram coletados entre 2014 e 2016, por meio da instalação de um sensor extracraniano de deformação, acoplado sobre o couro cabeludo, com registro da curva de pressão intracraniana não invasiva. A análise dos dados foi realizada com software Freemat® 4, Origin Pro® 8 e R® 3.1.3. Foram analisados parâmetros obtidos na curva de pressão intracraniana como \"relação P2/P1\", \"classificação de P1 e P2\" (P1>P2 ou P2>P1) e \"inclinação de P1\". Os resultados apontaram, que na amostra estudada, o índice P2>P1 apresentou sensibilidade de 80% e especificidade de 100%, a \"classificação de P1 e P2\" sensibilidade de 100% e especificidade de 80% para predição de hipertensão intracraniana em hidrocefalia, sendo que a \"inclinação de P1\" não apresentou relação estatística. Conclui-se que, apesar de limitações operacionais, o método de monitorização não invasiva da pressão intracraniana se mostrou útil na detecção de hipertensão intracraniana e apresenta perspectivas de aplicação clínica futura. / Hydrocephalus is still a challenge regarding diagnosis, treatment and monitoring in the pediatric population. Currently, treatments by ventricular or endoscopic ventriculostomies are well established. However, to date, the diagnosis of malfunctioning shunts associated with intracranial hypertension remains a problem, especially in young children and without patent fontanelles. Radiological examinations, such as ultrasonography, computerized tomography and magnetic resonance, allow only an indirect access to the intracranial pressure, whilst methods for direct assessment may present risks and therefore are rarely used in children. The aim of this study was to evaluate a noninvasive device to assess some parameters of the intracranial pressure curve in children with hydrocephalus. For this, we performed a prospective and non-experimental descriptive-analytic study. The sample consisted of children (under 18 years), including 28 patients with hydrocephalus and 28 children following routine child care (control group). Participants were divided into four groups; Group A: children with clinically compensated hydrocephalus; B: patients with hydrocephalus, but with no clinical signs of intracranial hypertension and no history of medical surgery for the treatment of hydrocephalus; C: patients with acute intracranial hypertension due to hydrocephalus, and D: children without neurological disease (control). Data were collected between 2014 and 2016, through the installation of an extracranial deformation sensor, coupled to the children\'s scalp, which allowed registration of non-invasive intracranial pressure curves. Data analysis was performed using Freemat® 4, Origin Pro® 8 and R® 3.1.3 software. Parameters obtained from the intracranial pressure curves were analyzed, such as \"ratio P2 / P1\", \"classification P1 and P2\" (P1> P2 or P2> P1) and \"P1 slope.\" The results showed that P2>P1 index had a sensitivity of 80% and specificity of 100%, while the \"classification of P1 and P2\" had 100% of sensitivity and 80% of specificity for predicting intracranial hypertension. \"P1 slope\" presented no statistical difference. In summary, despite some operational limitations, this study showed an useful and non-invasive method for monitoring intracranial pressure, which was able to indicate the intracranial hypertension in children with hydrocephalus and, thus, should be further investigated for clinical applications.

Introdução: Dados sobre a relação entre a farmacocinética do fluconazol (FCZ) e anfotericina B (AMB) no líquido cefalorraquidiano (LCR) e a hipertensão intracraniana (HIC) não se encontram disponíveis na literatura. Objetivos: Avaliar a influência da pressão intracraniana na concentração dos antifúngicos AMB e FCZ no LCR de pacientes com meningite criptococócica internados no Hospital de Clínicas de Porto Alegre (HCPA), no período de 1 ano. Métodos: Foram estudados 15 pacientes com meningite criptococócica durante os primeiros 14 dias de tratamento com AmB (1 mg/kg/dia) e FCZ (800 mg/dia). As amostras de LCR foram obtidas por meio de punções lombares de rotina realizadas nos dias 1, 7 e 14 da terapia antifúngica, respectivamente. Os valores das pressões intracranianas de abertura foram obtidos no momento de cada punção lombar. Os níveis de AmB e FCZ no LCR foram medidos pela metodologia de cromatografia líquida de alta performance (HPLC). A concentração inibitória mínima (CIM) para AmB, FCZ, voriconazol (VRZ) e flucitosina (5-FC) de cada isolado de Cryptococcus sp. foi realizada de acordo com o as normas descritas no documento M27-A3, do CLSI, publicado em 2008. Resultados: Entre os 15 pacientes incluídos no estudo, C. gattii foi isolado do LCR de 2 pacientes e C. neoformans foi isolado do LCR de 13 pacientes apresentaram. A condição de imunossupressão encontrada foi a AIDS, seguida de transplante de órgão sólido. Nove pacientes apresentaram cultura negativa de LCR no 14º dia de terapia antifúngica. Os níveis de AmB no LCR foram indetectáveis para a maioria das amostras de LCR durante os 14 dias de terapia antifúngica. Os níveis de FCZ no LCR aumentaram progressivamente do dia 1 ao dia 14 de terapia. Seis pacientes apresentaram HIC no dia 1, com variação da pressão de abertura entre 100 mmH2O e 650 mmH2O no respectivo dia. A pressão intracraniana não interferiu nas concentrações de FCZ no LCR. Não observamos correlação entre a HIC e as concentrações de AMB e FCZ no LCR de acordo com a correlação de Spearman (Spearman p= 0.122). Conclusão: São necessários mais estudos para avaliar o papel da HIC na eficácia terapêutica de diferentes agentes antifúngicos em pacientes com meningite criptococócica. / Introduction: Data considering the relationship between pharmacokinetics of fluconazole (FCZ) and amphotericin B (BPA) in cerebrospinal fluid (CSF) and intracranial hypertension (IH) are not available in the literature. Objectives: To evaluate the influence of intracranial pressure on the concentration of the antifungals AMB and FCZ in the CSF of patients with cryptococcal meningitis admitted at the Hospital de Clínicas de Porto Alegre (HCPA), within a period of one year. Methods: Fifteen patients with cryptococcal meningitis were studied during the first 14 days of treatment with AmB (1 mg / kg / day) and FCZ (800 mg / day). CSF samples were obtained by means of routine lumbar punctures performed on days 1, 7 and 14 of antifungal therapy, respectively. The values of intracranial opening pressures were obtained at the time of each lumbar puncture. The levels of AmB and FCZ in the CSF were measured by high performance liquid chromatography (HPLC) methodology. The minimum inhibitory concentration (MIC) for AmB, FCZ, voriconazole (VRZ) and flucytosine (5-FC) of each isolate of Cryptococcus sp. was performed according to CLSI guideline M27-A3, published in 2008. Results: Among the 15 patients included in the study, C. gattii was isolated from the CSF of 2 patients and C. neoformans was isolated from the CSF of 13 patients presented. The immunosuppressive condition found was AIDS, followed by solid organ transplantation. Nine patients presented negative CSF culture on the 14th day of antifungal therapy. AmB levels in the CSF were undetectable for most of the CSF samples during the 14 days of antifungal therapy. CSF FCZ levels increased progressively from day 1 to day 14 of therapy. Six patients presented IH on day 1, with variation of the opening pressure between 100 mmH2O and 650 mmH2O on the respective day. Intracranial pressure did not interfere with CSF on FCZ concentrations. We did not observe a correlation between IH and the concentrations of AMB and FCZ in the CSF according to the Spearman correlation (Spearman p = 0.122). Conclusion: Further studies are needed to evaluate the role of IH in the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.

Introdução: Dados sobre a relação entre a farmacocinética do fluconazol (FCZ) e anfotericina B (AMB) no líquido cefalorraquidiano (LCR) e a hipertensão intracraniana (HIC) não se encontram disponíveis na literatura. Objetivos: Avaliar a influência da pressão intracraniana na concentração dos antifúngicos AMB e FCZ no LCR de pacientes com meningite criptococócica internados no Hospital de Clínicas de Porto Alegre (HCPA), no período de 1 ano. Métodos: Foram estudados 15 pacientes com meningite criptococócica durante os primeiros 14 dias de tratamento com AmB (1 mg/kg/dia) e FCZ (800 mg/dia). As amostras de LCR foram obtidas por meio de punções lombares de rotina realizadas nos dias 1, 7 e 14 da terapia antifúngica, respectivamente. Os valores das pressões intracranianas de abertura foram obtidos no momento de cada punção lombar. Os níveis de AmB e FCZ no LCR foram medidos pela metodologia de cromatografia líquida de alta performance (HPLC). A concentração inibitória mínima (CIM) para AmB, FCZ, voriconazol (VRZ) e flucitosina (5-FC) de cada isolado de Cryptococcus sp. foi realizada de acordo com o as normas descritas no documento M27-A3, do CLSI, publicado em 2008. Resultados: Entre os 15 pacientes incluídos no estudo, C. gattii foi isolado do LCR de 2 pacientes e C. neoformans foi isolado do LCR de 13 pacientes apresentaram. A condição de imunossupressão encontrada foi a AIDS, seguida de transplante de órgão sólido. Nove pacientes apresentaram cultura negativa de LCR no 14º dia de terapia antifúngica. Os níveis de AmB no LCR foram indetectáveis para a maioria das amostras de LCR durante os 14 dias de terapia antifúngica. Os níveis de FCZ no LCR aumentaram progressivamente do dia 1 ao dia 14 de terapia. Seis pacientes apresentaram HIC no dia 1, com variação da pressão de abertura entre 100 mmH2O e 650 mmH2O no respectivo dia. A pressão intracraniana não interferiu nas concentrações de FCZ no LCR. Não observamos correlação entre a HIC e as concentrações de AMB e FCZ no LCR de acordo com a correlação de Spearman (Spearman p= 0.122). Conclusão: São necessários mais estudos para avaliar o papel da HIC na eficácia terapêutica de diferentes agentes antifúngicos em pacientes com meningite criptococócica. / Introduction: Data considering the relationship between pharmacokinetics of fluconazole (FCZ) and amphotericin B (BPA) in cerebrospinal fluid (CSF) and intracranial hypertension (IH) are not available in the literature. Objectives: To evaluate the influence of intracranial pressure on the concentration of the antifungals AMB and FCZ in the CSF of patients with cryptococcal meningitis admitted at the Hospital de Clínicas de Porto Alegre (HCPA), within a period of one year. Methods: Fifteen patients with cryptococcal meningitis were studied during the first 14 days of treatment with AmB (1 mg / kg / day) and FCZ (800 mg / day). CSF samples were obtained by means of routine lumbar punctures performed on days 1, 7 and 14 of antifungal therapy, respectively. The values of intracranial opening pressures were obtained at the time of each lumbar puncture. The levels of AmB and FCZ in the CSF were measured by high performance liquid chromatography (HPLC) methodology. The minimum inhibitory concentration (MIC) for AmB, FCZ, voriconazole (VRZ) and flucytosine (5-FC) of each isolate of Cryptococcus sp. was performed according to CLSI guideline M27-A3, published in 2008. Results: Among the 15 patients included in the study, C. gattii was isolated from the CSF of 2 patients and C. neoformans was isolated from the CSF of 13 patients presented. The immunosuppressive condition found was AIDS, followed by solid organ transplantation. Nine patients presented negative CSF culture on the 14th day of antifungal therapy. AmB levels in the CSF were undetectable for most of the CSF samples during the 14 days of antifungal therapy. CSF FCZ levels increased progressively from day 1 to day 14 of therapy. Six patients presented IH on day 1, with variation of the opening pressure between 100 mmH2O and 650 mmH2O on the respective day. Intracranial pressure did not interfere with CSF on FCZ concentrations. We did not observe a correlation between IH and the concentrations of AMB and FCZ in the CSF according to the Spearman correlation (Spearman p = 0.122). Conclusion: Further studies are needed to evaluate the role of IH in the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / In humans, intracranial hypertension (ICH) disturbs cardiovascular function and also modifies gastrointestinal physiology as clinically manifested by nausea and vomiting symptoms. Since gastric compliance drives the gastric emptying of liquid which is inhibited by ICH, it was studied the ICH effect on gastric compliance behavior in anesthetized rats and the neuropathways possibly serving this phenomenon. Anesthetized male Wistar rats (N=65, 280-320g) received a carotid cannula to monitor arterial pressure (AP) and heart rate (HR). Under stereotactic guidance a cannula was positioned into each lateral ventricule: one for cerebrospinal fluid simile infusion and the other to record intracranial pressure (ICP in mmHg). All animals received a catheter balloon that was positioned in the proximal stomach and connected to a U shaped barostat filled with standard ionic solution set 4cm above the animals xyphoid appendix. Gastric volume changes transmitted to this communicant vessel system were sensed and recorded by a plethysmometer for 80min After a basal period of 20min the animals were randomly allocated to either experimental protocols: control or ICH. In controls the animals remained untouched while in ICH the ICP was increased from basal to 10, 20, 40, or 60 mmHg, for 30min. In crescent ICP, the pressure was increased in the same animal, at every 20min, from basal to 20, 40 and then 60 mmHg. Separate groups of animals also underwent neurotomy or respective sham operation: subdiafragmatic vagotomy, splancnotomy plus bilateral ganglionectomy and after the basal period were submitted to 10 mmHg of ICP. Brains from other animals (control ICP 10 and ICP 60 mmHg) were removed for histological studies. Data (mean  SEM) were compared to respective basal values after ANOVA and Bonferroniâs test. In controls, hemodynamic parameters and GV remained within stable levels. In ICP 10 mmHg, GV decreased (P<0.05) from basal levels (2.70Â0.12ml) to 2.30Â0.14ml at 30min to remain decreased afterwards, while at ICP 20, 40 and 60mmHg decreased early at 20min of ICH (2.36Â0.18 vs 2.03Â0.19, 2.69Â0.27 vs 2.03Â0.25 e 2.83Â0.12 vs 1.95Â0.11ml, respectively), remaining as such up to the end (P<0.05). In crescent ICP, GV decreased from basal levels (2.94Â0.04ml) at ICP 40mmHg to 2.70Â0.07ml as well as at ICP 60 mmHg to 2.67Â0.06ml (P<0.05). In all groups were observed arterial hypertension and bradycardia, typical findings of Cushingâs reflex. In animals without vagal connection, GV despite beginning from lower basal values (1.82Â0.18ml) decreased (P<0.05) at 30min to 1.69Â0.18ml. After sympathectomy, GV remained stable (P>0.05) throughout the experiment (2.29Â0.21ml vs 2.11Â0.23ml). Moderate meningeal edema-coroid plexus- was observed moreover at brains from ICP 60mmHg subset. In conclusion, experimental ICH besides inducing Cushingâs reflex (arterial hypertension and bradycardia) also decreases gastric compliance in anesthetized rats in an ICP dependent manner. Vagotomy had no effect and this phenomenon is likely to be mediated by sympathetic neuropathways. / Em humanos, a hipertensÃo intracraniana (HIC) alÃm de promover distÃrbios hemodinÃmicos, tambÃm provoca alteraÃÃes na funÃÃo gastrintestinal, apresentadas clinicamente com nÃuseas e vÃmitos. Como a HIC em ratos acordados inibe o esvaziamento gÃstrico de lÃquido e este à influenciado pela complacÃncia gÃstrica (CG), estudou-se o efeito da HIC sobre a CG e os mecanismos neurais envolvidos no fenÃmeno. Ratos Wistar (N=65, 280-320g) anestesiados com uretana tiveram a artÃria carÃtida canulada para registro hemodinÃmico. Mediante estereotaxia, cÃnulas-guias foram implantadas bilateralmente nos ventrÃculos laterais, para registro simultÃneo da PIC e compressÃo do sistema ventricular por infusÃo de lÃquido cefalorraquidiano-sÃmile (LCR-sÃmile). Um catÃter com um balÃo na extremidade foi posicionado no estÃmago proximal e conectado a um sistema de vasos comunicantes com barostato. VariaÃÃes do volume do balÃo gÃstrico (VG) transmitidas ao barostato foram detectadas por um sensor eletrÃnico de volume e registradas continuamente por 80min num pletismÃmetro. ApÃs um perÃodo basal de 20min, os ratos foram aleatoriamente submetidos Ãs seguintes condiÃÃes: Controle (PIC espontÃnea), PIC 10mmHg, PIC 20mmHg, PIC 40mmHg, PIC 60mmHg e PIC Crescente. ApÃs a compressÃo ventricular, os animais foram monitorados por mais 30min. Para o estudo dos mecanismos neurais, grupos de ratos, previamente submetidos a laparotomia seguida ou nÃo (falsa cirurgia) de vagotomia subdiafragmÃtica ou esplancnicectomia+gangliectomia celÃaca bilaterais, foram estudados sob PIC de 10mmHg. Um grupo à parte de animais (n=9) PIC controle, PIC 10mmHg e PIC 60mmHg tiveram seus encÃfalos retirados para avaliaÃÃo histolÃgica. Os dados foram expressos em mÃdiaÂEPM e analisados pela ANOVA seguido pelo teste de Bonferroni. No grupo controle, os parÃmetros hemodinÃmicos e de VG se mantiveram constantes. No grupo PIC 10mmHg, em relaÃÃo ao perÃodo basal (2.70Â0.12ml), o VG diminuiu para 2.30Â0.14ml aos 30min de HIC, assim permanecendo por todo o experimento (P<0.05). Jà nos grupos PIC 20mmHg, PIC 40mmHg e PIC 60mmHg, o VG diminuiu em relaÃÃo ao perÃodo basal aos 20min de HIC (2.36Â0.18 vs 2.03Â0.19, 2.69Â0.27 vs 2.03Â0.25 e 2.83Â0.12 vs 1.95Â0.11ml, respectivamente), assim permanecendo atà o final (P<0.05). No grupo PIC crescente, em relaÃÃo ao perÃodo basal (2.94Â0.04ml), o VG diminuiu para 2.70Â0.07ml com PIC 40 mmHg e para 2.67Â0.06ml com PIC 60mmHg (P<0.05). Em todos os grupos observou-se hipertensÃo arterial e bradicardia, efeitos tÃpicos do reflexo de Cushing. Nos animais sem conexÃo vagal, o VG embora partindo de nÃveis basais menores (1.82Â0.18ml) diminuiu (P<0.05) aos 30min para 1.69Â0.18ml. Nos animais submetidos a esplacnicectomia, em relaÃÃo ao perÃodo basal (2.29Â0.21ml), o VG permaneceu inalterado (P>0.05) durante (2.11Â0.23ml) e apÃs a compressÃo ventricular. Nas lÃminas analisadas identificou-se edema parenquimatoso e congestÃes menÃngea, do plexo corÃide e parenquimatosa de graus leve a moderado, principalmente nos animais submetidos a PIC de 60 mmHg. A HIC diminui a CG de ratos anestesiados, sendo o fenÃmeno PIC dependente e possivelmente mediado por via esplÃncnica