Various lipid anchors on amphiphilic polyoxazolines to reach efficient intracellular delivery.

This work aimed at evaluating the potential of amphiphilic polyoxazolines bearing lipid chain called lipopolyoxazolines to reach efficient intracellular delivery. Four lipid chains: linear saturated, linear unsaturated and two branched one of various length were associated to poly(2-methyl-2-oxazoline) block. The evaluation of their physicochemical features and their impact on cell viability and internalization capacity indicated that the linear saturated gathered the highest cell internalization with a good cell viability. Its intracellular delivery capacity was compared to the PEG reference (DSPE-PEG) after being formulated in liposomes and loaded with fluorescent probe. Both POxylated and PEGylated liposomes showed similar characteristics regarding size distribution, drug loading and cell viability. However, their intracellular delivery was dramatically different, with an improved delivery by 30 folds for the POxylated ones. This significantly better performance highlighted the difficulty of PEGylated liposomes to enter the cells by endocytosis, contrary to POxylated liposomes. This study promotes the value of lipopoly(oxazoline) as a lipopoly(ethylene glycol) alternative for effective intracellular delivery and holds great promises for development of nanoformulations for intravenous administration.

Rehabilitation and surgical management of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease which, if untreated, may progress to severe damage of the spine with functional impairment, disability and poor quality of life. An increased mortality has been reported in AS patients compared to the general population. AS requires combined management (pharmacological and non-pharmacological) and advice by different health professionals. Even the pharmacological treatment in the last decade has dramatically changed the outcome, the severity of the disease might require a surgical approach for the hip involvement with total hip replacement, or the corrective spinal surgery. However, this surgery deserves some careful approaches since the complexity of the disease. Rehabilitation still represents a cornerstone of the global management of AS patients. The present review summarizes the state of art of surgical management of these two diseases.

Reactive oxygen: its sources and significance in Alzheimer disease.

Over the past decade, oxidative stress has been established as the earliest cytological feature of Alzheimer disease and an attractive therapeutic target. The major challenges now are establishing the source of the reactive oxygen and what oxidative stress tells us about the etiology of Alzheimer disease. These are complex issues since a variety of enzymatic and non-enzymatic processes are involved in reactive oxygen formation and damage to macromolecules. In this review, we consider disease mechanisms that show the greatest promise for future research.

[Preliminary experience with O.P.A.T. (Outpatient parenteral antimicrobial-drug therapy) in infective endocarditis]. / Esperienze preliminari di trattamento delle endocarditi infettive in OPAT.

The authors evaluated the efficacy and safety of an OPAT program in a small group of patients affected by infective endocarditis. Three patients were considered eligible for the treatment; i.e. they had a stable hemodynamic balance and no embolic events. Streptococcus spp. grew in blood cultures of two patients, while blood cultures were negative in the third patient. Long-acting antibiotics were used and all patients recovered from the infection without adverse events. The treatment was efficacious and safe. This preliminary experience suggests that OPAT programs can be promoted in infective endocarditis with advantage. Strictness and caution are necessary in screening and monitoring patients.

[Infective endocarditis: a retrospective analysis of inpatient cases]. / Endocardite infettiva: analisi retrospettiva di una casistica ospedaliera.

The authors analysed retrospectively the clinical and laboratory features of patients hospitalised in a unit of infectious diseases in the period from 1996-99. In particular, the etiology, the antimicrobial susceptibility of responsible microorganisms, criteria utilized for diagnosis, antibiotic courses and outcomes were evaluated and discussed. Echocardiography is an essential tool in the diagnosis. Infective endocarditis remains a serious infection and is still associated with high morbidity and mortality rate, despite appropriate treatment. Seriously ill patients may require prompt surgery.

Fatores associados ao aborto espontâneo recorrente / Recurrent spontaneous abortion associated factors

Objetivo: identificar fatores mais freqüentemente associados ao aborto espontâneo recorrente. Casuística: no período de março de 1993 a março de 1997, 175 pacientes foram avaliadas no Ambulatório de Aborto Recorrente do CAISM/UNICAMP. Os critérios de seleção foram: história de três ou mais abortos espontâneos consecutivos em pacientes com idade inferior a 35 anos e/ou dois abortos e idade superior a 35 anos. Métodos: o protocolo de investigação incluiu: cariótipo; histerossalpingografia; dosagem seriada de progesterona e/ou biópsia de endométrio; pesquisa sorológica de infecções: toxoplasmose, listeriose, brucelose, sífilis e citomegalovírus e pesquisa para Mycoplasma hominis e Chlamydia trachomatis na secreção cérvico-uterina. A investigação também incluiu dosagem de hormônios tiroideanos e da glicemia de jejum; pesquisa de fator auto-imune por meio de painel de auto-anticorpos; pesquisa de fator aloimune mediante anticorpos contra antígenos leucocitários humanos (anti-HLA), prova cruzada por microlinfocitotoxicidade e cultura mista unidirecional de linfócitos, em que se comparam as respostas maternas diante das células paternas e de um doador não-relacionado para pesquisa de fator inibidor destas respostas no soro materno. O exame dos parceiros incluiu: exame físico geral e especial, sorologias para sífilis, doença de Chagas, hepatite B e C e síndrome da imunodeficiência adquirida (AIDS), além da prova cruzada por microlinfocitotoxicidade e da cultura mista de linfócitos. Resultados: o fator mais freqüentemente encontrado foi o aloimune (86,3 por cento dos casos), representado por prova cruzada negativa e inibição na cultura mista de linfócitos inferior a 50 por cento. O segundo fator mais freqüentemente encontrado foi a incompetência istmo-cervical (22,8 por cento), seguido pelo fator hormonal (21,2 por cento), representado principalmente pela insuficiência lútea. Algumas pacientes apresentavam mais de um fator concomitantemente. Conclusão: para uma investigação completa dos fatores associados ao aborto espontâneo recorrente faz-se necessária a inclusão do fator aloimune, sem a qual a maior parte dos casos não terá etiologia esclarecida.

Effects of two cocktails on left ventricular diastolic function in normal men.

The effects of alcohol on diastolic function in normal males are unknown. Therefore, 12 male physicians had a Doppler echocardiogram performed in order to assess left ventricular diastolic performance. They then drank 4 ounces of whiskey, and forty-five minutes later a repeat Doppler echocardiogram was obtained. All the Doppler indexes of diastolic performance differed significantly after the ingestion of alcohol. The mean control D-F interval was 203 +/- 26 ms and after alcohol it was 237 +/- 51 (p less than 0.01). The mean control EF slope was 4.4 +/- 0.35 m/s2 and after alcohol it was 3.2 +/- 0.73 (p less than 0.01). The control E-F interval was 114 +/- 30 ms and it increased after alcohol to 150 +/- 37 (p less than 0.001). The mean control E wave was 0.54 +/- 0.10 m/s and after alcohol it was 0.43 +/- 0.07 (p less than 0.01). The mean control A wave was 0.30 +/- 0.04 m/s and after alcohol it was 0.35 +/- 0.04 (p less than 0.01). The mean control E/A ratio was 1.80 +/- 0.20 and it fell to 1.25 +/- 0.23 after alcohol ingestion (p less than 0.001). Thus, the results suggest that 4 ounces of whiskey can produce, in normal males, a significant impairment in diastolic function.

Pulse generator failure due to blunt trauma.

This case describes a 69-year-old male who had a permanent pacemaker implanted for sick sinus syndrome. He was struck by a car with a resultant failure of the pulse generator. Trauma-related failure of a pulse generator is a rare event. Its recognition is imperative in the overall management of the trauma patient.

Routine reduction of pulse generator voltage.

The porous-tip electrode has led to a significant advancement in pacing system technology. Experience with 38 patients with unipolar tined CPI porous endocardial electrodes, is reported. All patients had programmable pulse generators, CPI model number 531. The voltage in this pulse generator can be reduced from 5 to 2.5 volts. The pulse width threshold (PWT) at implantation was 0.06 ms at 5 volts in all 38 patients, and the PWT at implantation varied between 0.06 and 0.16 ms at 2.5 volts, with a mean PWT of 0.092 +/- 0.026 ms. The 38 patients were restudied six months later. The mean PWT measured at 5 volts was 0.076 +/- 0.018 ms. The PWT measured at 2.5 volts varied between 0.08 and 0.30 ms with a mean PWT of 0.178 +/- 0.067 ms. Twenty-three patients were restudied one year after lead implantation. The PWT measured at 2.5 volts varied between 0.08 and 0.30 ms with a mean PWT of 0.156 +/- 0.061 ms. All of the pulse generators were reprogrammed to 2.5 volts. This permitted a substantial prolongation of the pulse generator life (three to five years) with an improvement in the cost effectiveness of the pulse generator.

The resting cardiointegram: correlation with stress thallium perfusion studies.

The cardiointegram is a noninvasive technique for the analysis of the electrical signals of the heart obtained by a transformation of the voltage versus time format by a series of integrations. The stress thallium perfusion study is a widely used test for the detection of coronary artery disease. In order to evaluate the correlation between the resting cardiointegram and the stress thallium 201 perfusion study, 20 patients with normal resting electrocardiograms underwent stress thallium tests and resting cardiointegrams. The cardiointegram was determined on two resting complexes of leads I, II, V4, V5, and V6 and called abnormal if five of ten complexes deviated outside a normalized template. There was concordance of the cardiointegram and the thallium study in 16 of 20 patients (80%). The sensitivity for the detection of coronary artery disease was 71%, and the specificity was 80%. The overall accuracy was 74%. Thus in patients with normal electrocardiograms, the cardiointegram is a useful noninvasive test for the detection of coronary artery disease.

Aneurysms of the pulmonary arteries--a case report.

A fifty-five-year-old male demonstrated over a three-year period marked enlargement of pulmonary aneurysms. This can be a fatal condition owing to rupture of the aneurysms.