Criterios broncoscópicos, laboratoriales y anatomopatológicos de enfermedad de la vía aérea en pacientes diagnosticados con granulomatosis con poliangitis / Bronchoscopic, laboratory and anatomopathological criteria for airway disease in patients diagnosed with granulomatosis with polyangiitis

Introducción: los pacientes con granulomatosis con poliangitis (GPA) pueden presentar compromiso de la vía aérea superior (VAS) o inferior (VAI). Objetivos: describimos las manifestaciones endoscópicas de las vías respiratorias, los hallazgos histológicos y los anticuerpos anticitoplasma de neutrófilos (ANCA) en un grupo de pacientes con GPA. Métodos: estudio retrospectivo de historias clínicas de pacientes con GPA sometidos a broncoscopia entre 2012 y 2019. Se analizaron hallazgos de la vía aérea, biopsias y ANCA. Resultados: se incluyeron 40 pacientes, con una edad media de 46,92±17,61 años, predominantemente del sexo femenino (67,5%). Se observó afectación de la vía aérea en el 90% (n=36). El C-ANCA fue reactivo en el 63,9%, P-ANCA en el 25%, ANCA doblemente reactivo en el 8,33% y no reactivo en el 20%. Los hallazgos comunes en la vía aérea superior (VS) fueron sinusitis crónica (41,7%), destrucción del tabique nasal (16,7%); y en la vía aérea inferior (AI): estenosis traqueobronquial (38,9%), traqueobronquitis (25%). Los hallazgos más frecuentes de las biopsias broncoscópicas fueron proceso inflamatorio polimorfonuclear (61,9%) y necrosis geográfica (47,6%). Conclusión: la vía aérea está comprometida hasta en un 90% de los pacientes con GPA. ANCA no reactivos no descartan esta posibilidad. La sinusitis crónica y los procesos fibroestenóticos traqueobronquiales fueron los hallazgos endoscópicos más comunes. La vasculitis en biopsias se encontró en una minoría de casos.

Introduction: patients with granulomatosis with polyangiitis (GPA) may present upper airway (UA) and lower airway (LA) involvement. Objectives: we describe the endoscopic manifestations of the airways, histological findings from biopsied tissue and antineutrophilic cytoplasm antibody (ANCA) in a group of patients with GPA. Methods: retrospective study of medical records of patients with GPA undergoing bronchoscopy between 2012 and 2019. Airway findings, results of biopsies performed and ANCA results were analyzed. Results: 40 patients were included, with a mean age of 46.92±17.61 years and predominantly female (67.5%). Airway involvement was observed in 90% (n=36). The C-ANCA was reactive in 63.9%, P-ANCA in 25%, doubly reactive ANCA in 8.33% and non-reactive in 20%. The findings in upper airway (UA) were: chronic sinusitis (41.7%), destruction of the nasal septum (16.7%); and in lower airway (LA) were: tracheobronchial stenosis (38.9%) and tracheobronchitis (25%). The pathological findings most common of bronchoscopic biopsies were: polymorphonuclear inflammatory process (61.9%) and geographic necrosis (47.6%). Conclusion: the airway is involved in up to 90% of patients with GPA. Non-reactive ANCA does not rule out this possibility. Chronic sinusitis and tracheobronchial fibrostenotic processes were the most common endoscopic findings. Vasculitis in biopsies was found in a minority of cases.

Testing the efficacy and safety of BIO101, for the prevention of respiratory deterioration, in patients with COVID-19 pneumonia (COVA study): a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacydata, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Diacerein decreases visceral pain through inhibition of glutamatergic neurotransmission and cytokine signaling in mice.

The present study evaluated the antinociceptive effect of the pro-inflammatory cytokines inhibitor diacerein in mice and its possible mechanism of action. The antinociception produced by diacerein was tested at different sites of action, moreover selective antagonists or agonists were used to identify the mechanism that may be involved in its antinociceptive action against acetic acid-induced visceral pain. Diacerein administered systemically (intraperitoneal [i.p.] or intra-gastric [i.g.] routes), supra-spinally (i.c.v.), spinally (i.t.) or peripherally (in association with the irritant agent) inhibited the visceral nociception induced by acetic acid in mice. Interestingly, diacerein treatment (25 mg/kg, i.p. or 50 mg/kg, i.g.) produced long-lasting (for up to 4 h) inhibition of acetic acid-induced nociception. Intraperitoneal treatment of mice with diacerein (25.0 mg/kg) inhibited somatic nociception induced by i.t. injection of glutamate, NMDA, kainate, and trans-ACPD but not that caused by AMPA. Diacerein (5.0-25.0 mg/kg) also produced dose related inhibition of interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) induced nociception. These results indicate that diacerein produces antinociception by inhibiting glutamatergic transmission through both ionotropic and metabotropic receptors as well as activity of pro-inflammatory cytokines.

Impacto da reforma de financiamento de hospitais de ensino no Brasil / Impacto de la reforma del financiamiento de hospitales de enseñanza en Brasil / Impact of the funding reform of teaching hospitals in Brazil

OBJETIVO: Avaliar o impacto da reforma de financiamento na produtividade de hospitais de ensino. MÉTODOS: A partir do Sistema de Informações dos Hospitais Universitários Federais, foram construídas fronteiras de eficiência e produtividade em 2003 e 2006 com técnicas de programação linear, por meio de análise envoltória de dados, considerando retornos variáveis de escala e orientação a input. Calculou-se o Índice de Malmquist para identificar mudanças de desempenho ao longo dos anos quanto à eficiência técnica (razão entre os escores de eficiência em tempos distintos) e eficiência tecnológica (deslocamento da fronteira no período considerado). RESULTADOS: Houve aumento do aporte financeiro em 51% e da eficiência técnica dos hospitais de ensino (de 11, passaram a ser 17 na fronteira empírica de eficiência), o mesmo não ocorrendo com a fronteira tecnológica. O uso de análise envoltória de dados estabeleceu os benchmarks para as unidades ineficientes (antes e depois da reforma) e os escores de eficiência mostraram uma possível correlação entre a eficiência técnica encontrada e a intensidade e dedicação de ensino. CONCLUSÕES: A reforma permitiu o desenvolvimento de melhorias gerenciais, mas é necessário maior tempo de acompanhamento para observar mudanças mais efetivas do modelo de financiamento.

OBJECTIVE: To assess the impact of funding reform on the productivity of teaching hospitals. METHODS: Based on the Information System of Federal University Hospitals of Brazil, 2003 and 2006 efficiency and productivity were measured using frontier methods with a linear programming technique, data envelopment analysis, and input-oriented variable returns to scale model. The Malmquist index was calculated to detect changes during the study period: "technical efficiency change," or the relative variation of the efficiency of each unit; and "technological change" after frontier shift. RESULTS: There was 51% mean budget increase and improvement of technical efficiency of teaching hospitals (previously 11, 17 hospitals reached the empirical efficiency frontier) but the same was not seen for the technology frontier. Data envelopment analysis set benchmark scores for each inefficient unit (before and after reform) and there was a positive correlation between technical efficiency and teaching intensity and dedication. CONCLUSIONS: The reform promoted management improvements but there is a need of further follow-up to assess the effectiveness of funding changes.

OBJETIVO: Evaluar el impacto de la reforma de financiamiento en la productividad de hospitales de enseñanza. MÉTODOS: A partir del Sistema de Informaciones de los Hospitales Universitarios Federales de Brasil, se construyeron fronteras de eficiencia y productividad en 2003 y 2006 con técnicas de programación linear, por medio de análisis envoltorio de datos, considerando retornos variables de escala y orientación a input. Se calculó el Índice de Malmquist para identificar cambios de desempeño a lo largo de los años con relación a la eficiencia técnica (cociente entre los puntajes de eficiencia en tiempos distintos) y eficiencia tecnológica (desplazamiento de la frontera en el período considerado). RESULTADOS: Hubo aumento del aporte financiero en 51% y de la eficiencia técnica de los hospitales de enseñanza (de 11, pasaron a ser 17 en la frontera empírica de eficiencia), no ocurriendo el mismo con la frontera tecnológica. El uso del análisis envoltorio de datos estableció los benchmarks para las unidades ineficientes (antes y después de la reforma) y los puntajes de eficiencia mostraron una posible correlación entre la eficiencia técnica encontrada y la intensidad y dedicación de enseñanza. CONCLUSIONES: La reforma permitió el desarrollo de mejoras gerenciales, pero es necesario mayor tiempo de acompañamiento para observar cambios más efectivos del modelo de financiamiento.

Distal embolic protection during percutaneous intervention of aorto-coronary venous bypass grafts: the FIRST Trial.

OBJECTIVE: Interventions in aorto-coronary venous bypass grafts (CABG) can cause acute procedural complications due to distal embolization of debris. In the FIRST (First European Investigation Regarding the Systematic use of the TriActiv device) multicenter trial the distal endovascular protection system TriActiv (Kensey Nash) was evaluated during intervention of CABG. METHODS: 195 patients in 17 centers in Germany with significant disease of a vein graft were enrolled. Inclusion and exclusion criteria were comparable to the SAFER trial. RESULTS: Acute procedural success was achieved in 98% of cases. Aspirated debris was found in 96.5% of patients. Primary endpoints (MACE at 30 days) occurred in 8.7% of all pts. (ITT). No patient died and 7.2% of patients suffered from MI. The rate of early revascularization was 1.5%. Secondary endpoints (MACCE at 30 days) were found in 9.2% and at hospital discharge in 8.7% of patients. CONCLUSIONS: The TriActiv system is safe and effective. Normal post procedural flow can be preserved and the MACE rate is with 8.7% considerably low. The FIRST trial supports the growing belief that PCI of CABG should be performed with protection systems.

Primary screening for cervical cancer through self sampling.

OBJECTIVE: To evaluate the use of community health agents (CHAs) to instruct women living in poor rural areas in obtaining self-collected cervical samples and compare the high-risk HPV (hrHPV) hybrid capture (HC) results obtained to those for gynecologist-collected samples. METHODS: After a one-day training, CHAs visited sexually active women, instructing each in the use of collection brush and the Universal Collection Medium tube. One week thereafter, a gynecologist collected cervical samples from, and performed colposcopies on, the same women. A single reference lab performed all HCs. RESULTS: 878 women (Age: 15-69 years) participated. Among self-collected samples, hrHPV prevalence was 33.9% (95% CI: 30.8%-37%), compared with 28.6% (95% CI: 27%-30%) among gynecologist-collected samples. However, 9.3% of the patients were HPV HC II-positive in the self-collected sample and HPV HC II-negative in the gynecologist-collected samples (95% CI: 7.38%-11.22%), whereas 4% tested positive in gynecologist-collected samples and negative in self-collected samples (95% CI: 2.7%-5.3%) (P<0.01; kappa=0.7). Of 9 cases of histologically-confirmed, high-grade squamous intraepithelial lesion, self-collected and provider-collected samples missed one each. CONCLUSION: Self-collected vaginal sampling could be made an additional CHA function under existing program conditions, improving access to cervical cancer screening in poor rural settings.

Symptoms and signs of an acute myocardial ischemia caused by chemotherapy with Paclitaxel (Taxol) in a patient with metastatic ovarian carcinoma.

INTRODUCTION: Paclitaxel (Taxol) is an anticancer agent used for the treatment of breast and ovarian cancer. The major side effects are bone marrow suppression, alopecia, polyneuropathy and cardiac toxicity like bradycardia, myocardial infarction, congestive heart failure and cardiac death. SETTING: Intensive care unit (ICU) of a university hospital. PATIENT: We report on a 58-years-old woman with a metastatic ovarian carcinoma who had chest pain, nausea and collapse during their first Taxol infusion. The infusion was stopped and the patient was submitted to the intensive care unit (ICU) to exclude an acute coronary syndrome. RESULTS: The electrocardiography (ECG) showed a third-degree heart block and ST elevation in II, III and avF. In the initial and in the control laboratory investigation values of cardiac enzymes (creatininkinase and Troponine T) remained normal. The control ECG after 30 minutes turned back to normal. After one day the patient was submitted back to a normal ward. CONCLUSION: Symptomatic bradyarrhythmia and clinical sign of an myocardial infarction are rare but important cardiac side effects in patients treated with Taxol. Those patients should be under intensive care unit until patients conditions improve and acute myocardial ischemia has been excluded.

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit: risk factors for infection and colonization.

An outbreak of extended spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBLKp) infections in a neonatal intensive care unit (NICU) prompted a prospective investigation of colonization and infection with this pathogen. From August 1, 1997 to May 30, 1999, neonates admitted to the NICU for more than 24 h were screened for ESBLKp acquisition. Neonatal gastrointestinal screening was performed by means of faecal sampling within 48 h of admission and then weekly until discharge. Isolates were typed using pulsed-field gel electrophoresis (PFGE). Time-dependent proportional hazard models were used to identify independent effects of invasive procedures and antimicrobials after controlling for duration of stay at the NICU. During the study period, 464 neonates were admitted and 383 were regularly screened. Infections occurred in 13 (3.4%) neonates and 206 (53.8%) became colonized. Independent risk factors for colonization during the first nine days in the NICU were the antimicrobial combination cephalosporin plus aminoglycoside [hazard rate (HR)=4.60; 95% CI: 1.48-14.31], and each NICU-day was associated with a 26% increase in the hazard rate for colonization (HR=1.26; 95% CI: 1.16-1.37). Previous colonization (HR=5.19; 95% CI: 1.58-17.08) and central vascular catheter use (HR=13.89; 95% CI: 2.71-71.3) were independent risk factors for infection. In an outbreak setting the proportion of neonates colonized with ESBLKp was observed to increase with the duration of stay and antimicrobial use, and once colonized, infants exposed to invasive devices may become infected.

Endoluminal beta-radiation therapy for the prevention of coronary restenosis after balloon angioplasty. The Dose-Finding Study Group.

BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement.

Pericardiocentesis: differential aspects of a common procedure.

OBJECTIVE: To evaluate the risk and effectiveness of pericardiocentesis in primary and repeat cardiac tamponade. DESIGN: Retrospective analysis. SETTING: Intensive care unit in a medical university hospital. PATIENTS: Sixty-three consecutively admitted patients with cardiac tamponade. INTERVENTIONS: In all patients pericardiocentesis was performed via the subxiphoid pathway after echocardiographic detection of the pericardial effusion. MEASUREMENTS AND RESULTS: There was no adverse event in patients undergoing primary pericardiocentesis, which was sufficient to resolve pericardial effusion in 51 of 63 patients (81%). However, repeat pericardiocentesis necessitated by the recurrence of symptomatic pericardial effusion yielded suboptimal results in 10 of 12 patients (83%). CONCLUSION: Pericardiocentesis is the treatment of choice for primary symptomatic pericardial effusion. In recurrent pericardial effusion surgical approaches appear to be preferable.

Case report. Histoplasmosis in an AIDS paediatric patient.

Histoplasmosis has been little reported among HIV-infected children. We report a case of a 4-year old boy with AIDS who presented with disseminated histoplasmosis diagnosed by lung biopsy. The patient had a good clinical response to amphotericin B followed by itraconazole oral solution.

[Endomyocardial biopsy--helpful in differential diagnosis between myocarditis and dilated cardiomyopathy. A case report]. / Endomyokardbiopsie--Hilfreich in der Differentialdiagnostik zwischen Myokarditis und dilativer Kardiomyopathie. Ein Fallbericht.

Endomyocardial biopsy is an established technique to distinguish between myocarditis and dilated cardiomyopathy. Even when clinical symptoms for myocarditis are lacking, immunohistologic findings may establish a clear diagnosis. For treatment, however, an early diagnosis is mandatory. We report on a 44 year old patient who was admitted with the echocardiographic diagnosis of dilated cardiomyopathy. He underwent diagnostic angiocardiography and endomyocardial biopsy. The latter demonstrated an active myocarditis. At the time of read-mission, 2 weeks later, the patient had deteriorated. Now, additional to a symptomatic therapy, prednisolone, azathioprine and human immunoglobulin G were given and patient conditions improved dramatically. The use of endomyocardial biopsy seems recommendable in order to define patients diagnosis and their results may be necessary to decide patients therapy.

Early postoperative flow rates after internal thoracic artery grafting for the left coronary artery system.

OBJECTIVE: The low perioperative flow rates of internal thoracic artery (ITA) conduits have been regarded as a limitation of their use in critical coronary situations with a high myocardial blood demand. To clarify whether these restrictions are justified, early postoperative flow rates were determined. METHODS: Following bilateral ITA grafting, 48 of 106 patients (April 1993-September 1994) underwent recatheterization. Subsequent to control angiography between days 8 and 12, 20 of these patients were studied by intravascular Doppler techniques applied for ITA grafts supplying the left anterior descending artery (LAD) and branches of the circumflex system (CX) (n = 20). Doppler spectral analysis allowed for determination of the average peak velocity and diastolic-systolic velocity ratio. Vascular diameters were assessed by simultaneously performed quantitative angiography and mean flow rates were calculated. All parameters were recorded at rest and following selective stimulation with nitroglycerin (0.2 mg) and papaverine (12.5 mg) to evaluate the graft flow capacity. RESULTS: Baseline values of average peak velocity at rest were 24.6 +/- 11.5 cm/s for ITA-LAD conduits and 21.9 +/- 6.8 cm/s for ITA-CX pedicles. Following dilative stimulation with papaverine, a significant increase in average peak velocities were obtained for both locations (ITA-LAD: 47.3 +/- 17.1 cm/s, ITA-CX: 42.3 +/- 11.8 cm/s). The application of nitroglycerin had a similar effect (ITA-LAD: 42.6 +/- 15.3 cm/s, ITA-CX: 40.3 +/- 10.7 cm/s). The vascular diameters of ITA conduits remained unchanged on nitroglycerin stimulation, whereas papaverine effected significant dilatation in both locations. Flow rates at rest were not significantly different (ITA-LAD: 51.0 +/- 34.2 ml/min, ITA-CX: 44.7 +/- 16.4 ml/min) and maximal flow increase was observed following papaverine stimulation of the LAD conduits (116.1 +/- 90.6 ml/min). Dilative stimulation effected an increase in diastolic-systolic velocity ratios from average values at rest in a range between 34% and 41.7% for both groups and substances. CONCLUSIONS: The basic blood flow in functioning ITA grafts appears to be similar in conduits supplying the LAD and marginal branches. Flow rates between 50 and 60 ml/min at rest should meet myocardial demands, even in the LAD position. Increased flow rates were predominantly based on higher flow velocities with an increased diastolic flow proportion. Enlargement of the graft diameter may exert additional effects, at least following papaverine stimulation at a particular concentration.

Foreign body masquerading as a ruptured globe.

Low density orbital foreign bodies may not be detected on plain x-ray. In this case, a large anterior orbital foreign body was seen by examiners, but was misinterpreted as a ruptured globe. This misdiagnosis was supported by conventional x-rays which failed to show the object. It was later easily visualized on CT scan.

Identificacao de hemoglobinopatias na populacao do Distrito de Sibauma- Rio Grande do Norte, Brasil. / Determination of hemoglobinopathies in the population of Distrito de Sabauma - Rio Grande do Norte, Brasil

Os autores investigaram a frequencia de hemoglobinas anormais em 93 individuos do Distrito de Sibauma - Estado do Rio Grande do Norte, Brasil, utilizando eletroforese em acetato de celulose, teste de falcizacao e de solubilidade. Foram identificados tres portadores de hemoglobina S (HbAS) dois dos quais eram pardos e um branco, correspondendo a uma frequencia de 3,2%

Estenose aórtica supravalvar (sindrome de Williams-Beuren). Apresentacao de um caso / Supravalvular aortic stenosis (Williams-Beuren syndrome).Report of a case

Os autores apresentam um caso de estenose aortica supravalvar associada a anomalia facial e a retardo mental, caracterizando a sindrome de Williams-Beuren. Sao abordados os aspectos etiologicos, o quadro clinico, os metodos de exames complementares de diagnostico e o tratamento cirurgico