Aerosolized pentamidine prophylaxis against AIDS-related Pneumocystis carinii pneumonia and its short- and long-term effects on pulmonary function in the Japanese

 We evaluated the incidence of prophylaxis failure with aerosolized pentamidine (AP) for Pneumocystis carinii pneumonia (PCP) in Japanese patients with human immunodeficiency virus (HIV) infection, and we examined the short- and long-term effects of AP on pulmonary function. The patients inhaled 300 mg of pentamidine by ultrasonic nebulizer, after the inhalation of procaterol (80 μg), every 4 weeks. PCP developed in 2 of 16 patients receiving primary prophylaxis with AP, and in 4 of 13 patients with secondary prophylaxis. The CD4⁺ T-lymphocyte count was very low in the patients with prophylaxis failure. The chest radiographic presentations were atypical in 4 of the 6 patients with prophylaxis failure. There were no significant changes in the vital capacity (VC), VC/predictive VC (%VC), forced expiratory volume in 1 s (FEV_1.0), FEV_1.0/forced vital capacity (FEV_1.0%), and maximum expiratory flow rate at 25% of vital capacity (MEF₂₅)/height comparing values before and after initial AP treatment. However, a reduction of oxygen saturation (SpO₂) of over 3% was noted in 4 patients during the initial AP administration. In 9 patients receiving AP prophylaxis for more than 36 months, we compared the pulmonary function parameters between the baseline and final observations (mean, 52.7 months). There were no changes in VC, %VC, FEV_1.0, FEV_1.0%, and SpO₂, but there was a statistically significant decline in MEF₂₅/height after long-term AP treatment. We concluded that the incidence of prophylaxis failure with AP for PCP in Japanese patients was similar to that in Western patients, and that long-term AP treatment affected MEF₂₅/height in spite of the safe pulmonary effects in short-term AP inhalation. Received: October 17, 2002 / Accepted: January 9, 2003     

Splenic infarction due to Mycobacterium avium complex infection in an HIV-infected patient with immune reconstitution failure: a case report

Splenic infarction is extremely rare in human immunodeficiency virus-infected populations. We report a rare case of splenic infarction involving Mycobacterium avium complex infection in a patient with acquired immune deficiency syndrome with immune reconstitution failure. A young man was initially admitted with cryptococcus meningitis and found to be infected with human immunodeficiency virus. He had anti-cryptococcosis treatment performed in combination with placement of an Ommaya capsule because of persistent intracranial hypertension, and first-line therapy followed by second-line anti-retroviral therapy were performed. Although there was an absence of immune reconstitution, the patient refused to take prophylactic sulfamethoxazole/trimethoprim, isoniazid, and clarithromycin continuously because of gastrointestinal intolerance. Pneumocystis pneumonia then developed. Finally, the patient developed a fever again accompanied by abdominal pain and splenic infarction. M. avium complex infection was verified by a metagenomic next-generation sequencing test using a whole blood sample. M. avium complex infection should be considered as an etiology of splenic infarction in human immunodeficiency virus-infected patients with an extremely low CD₄⁺T-cell count.     

Dapsone-induced methemoglobinemia in pediatric oncology patients: Case examples

Over the last 25 years, significant advances have been made in supportive care of the immunocompromised patient. One significant advance is the use of trimethoprim-sulfamethoxazole (TMP-SMZ) in the prevention of Pneumocystic carinii pneumonia (PCP). Although TMP-SMZ remains the drug of choice for PCP prophylaxis, children who develop or have a history of adverse reactions must be prescribed an alternative treatment. In these instances, medications such as dapsone, aerosolized pentamidine, or atovaquone are prescribed. This report discusses four children with sulfa allergy who were prescribed dapsone and later developed methemoglobinemia. Although methemoglobinemia is associated with dapsone, there was no reference found regarding this link in the pediatric oncology literature. The purpose of these clinical examples is to alert the pediatric nurse and advanced practitioner to the association of dapsone and methemoglobinemia.     

获得性免疫缺陷综合征的消化系统临床表现和肠镜特点分析（附109例报告）

目的总结合并消化系统病变的获得性免疫缺陷综合征(AIDS)患者的主要临床表现和肠镜特点,以提高对合并消化系统疾病的AIDS患者的认识。方法收集和分析2013年1月-2019年10月柳州市人民医院109例行结肠镜检查的人类免疫缺陷病毒(HIV)确诊感染者和116例HIV阴性行肠镜检查患者的临床资料,将HIV感染者(试验组)和HIV阴性患者(对照组)的临床表现和肠镜特点进行比较。同时根据CD4~+T淋巴细胞计数将HIV感染者分为两组进行对照分析,其中A组CD4~+细胞 200×10~6/L (n=34)、B组200×10~6/L(n=75)。结果试验组肠镜下结直肠溃疡检出率和总体病变检出率明显高于对照组,两组比较,差异有统计学意义(P 0.05);B组肠镜下肠黏膜充血、糜烂和总体病变检出率明显高于A组,两组比较,差异有统计学意义(P 0.05)。结论 AIDS患者比普通患者更容易出现结直肠溃疡,随着CD4~+细胞计数下降,肠道炎症病变发生率和肠道病变总体发生率升高。     

Prophylaxis with lactoferrin,a novel antimicrobial agent,in a neonatal rat model of coinfection

Lactoferrin has broad-spectrum antimicrobial activity, and the authors hypothesized that recombinant human lactoferrin (Talactoferrin alfa [TLF]) would reduce mortality and morbidity in a coinfection model. The MIC₅₀ (minimum inhibitory concentration required to inhibit the growth of 50% of organisms) of TLF againstCandida albicans andStaphylococcus epidermidis was determined. Neonatal Wistar rats were infected withCalbicans orS epidermidis or both, at doses of 2 × 10⁸ colony-forming units (CFUs) given subcutaneously. Rat pups in each group were randomly given TLF intraperitoneally at 40 mg/kg/dose or 300 mg/kg/dose, or saline in 0.2 mL, once a day for 4 d and were monitored for mortality, weight gain, and blood culture positivity. Trough serum levels of TLF were measured at 24, 48, 72, 96, and 144 h. MIC₅₀ of TLF was 30 μg/mL and 500 μg/mL forC albicans and Sepidermidis, respectively. TLF prophylaxis significantly improved survival in the coinfection group at 40 mg/kg/dose (by 16.1%; P=.019) and at 300 mg/kg/dose (by 15.1%; P=.027) and in the Sepidermidis group at a dose of 40 mg/kg/dose (by 1 8.6%; P=.04). Weight gain was not affected by TLF prophylaxis. Serum trough levels of TLF were 1000-fold lower than in vitro MIC₅₀. The authors conclude that lactoferrin prophylaxis significantly enhanced survival in coinfection and in the subgroupof S epidermidis infection (40 mg/kg/dose) through indirect mechanisms.     

Pentagalloylglucose, an antisecretory component of Paeoniae radix, inhibits gastric H, K-ATPase

We purified a compound with strong inhibitory effect on H⁺, K⁺-ATPase from Paeoniae radix, which has been used in Japan for the treatment of gastritis and peptic ulcers. The compound was identified as 1,2,3,4,6,-penta-o-galloyl-β- -glucose by proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and fast atomic bombardment mass spectrometry. The IC₅₀ of the compound for H⁺, K⁺-ATPase was 166 nmol/l. Kinetic analyses indicated that the inhibition of the enzyme by pentagalloylglucose was noncompetitive with respect to K⁺. Pentagalloylglucose had relatively weak inhibitory effects for Mg⁺-ATPase (IC₅₀: >10 μmol/l) and Na⁺, K⁺-ATPase (IC₅₀: 2.7 μmol/l). Pentagalloylglucose also inhibited the accumulation of [¹⁴C]aminopyrine in parietal cells that had been isolated from guinea pig stomach and stimulated by 10 μmol/l histamine (IC₅₀: 7.8 μmol/l) and 1 mmol/l dbc-AMP (IC₅₀: 10 μmol/l). These results suggest that pentagalloylglucose is a potent inhibitor of H⁺, K⁺-ATPase and may be responsible for inhibition of acid secretion by Paeoniae radix.     

Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies

BackgroundNegative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required.MethodsHundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1^highT cells, CD8+PD‐1+T cells, and CD4+CD25^high Tregs was also analyzed to explore their effects on disease progression and intercorrelation.ResultsThe percentages of CD4⁺PD‐1⁺T cells and CD4⁺CD25^highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4⁺PD‐1⁺T cells; however, the percentage of CD4⁺CD25^highTregs only increased in the patients with late‐stage disease. In addition, CD4⁺PD‐1⁺T cells but not CD4⁺CD25^highTregs were negatively correlated with the absolute CD4⁺T cell count. Spatially, no correlations between CD4⁺PD‐1⁺T cells and CD4⁺CD25^highTregs were observed, which suggests these Tregs function differently during immunosuppression.ConclusionsThis study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4⁺CD25⁺Tregs and CD4⁺PD‐1⁺T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression.     

The effects of Lyprinol(®) on delayed onset muscle soreness and muscle damage in well trained athletes: a double-blind randomised controlled trial

Objectives

The aim of the study was to determine if Lyprinol^® is effective in reducing pain, indicators of inflammation and muscle damage, and in turn improving performance in well trained athletes suffering from delayed onset muscle soreness (DOMS).

Design

A double blind randomised placebo controlled trial.

Setting

Twenty well trained male volunteers, matched by VO_{2 max} were randomly assigned to consume 200 mg of Lyprinol^® or an indistinguishable placebo daily for 8 weeks prior to a downhill treadmill running episode designed to induce DOMS.

Main outcome measures

Performance measures (Kin-Com, counter movement and squat jump), pain assessments (visual analogue scale, algometer) and blood analyses (Interleukin-1, Interleukin-6, Interleukin-10, tumour necrosis factor-α, C-reactive protein, myoglobin, creatine kinase) were assessed at 7 time points over 5 days (pre, post, 4, 24, 48, 72 and 96 h after the downhill run).

Results

No statistically significant differences were identified in any parameters between the active and placebo groups at any time point.

Conclusion

After 2 months ingestion of Lyprinol^® at the currently recommended dosage (200 mg/day) and a demanding eccentric exercise intervention, Lyprinol^® did not convincingly affect DOMS and indicators of muscle damage.     

Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study

Objective To assess renal dysfunction and outcome in patients treated exclusively with colistin vs. other antibiotics.Design and setting Prospective cohort study in a mixed ICU in a university-affiliated hospital.Patients 185 patients infected with Acinetobacter baumannii and Pseudomonas aeruginosa after an ICU stay longer than 48 h: 55 in the colistin group and 130 in the noncolistin group, similar in age, APACHE II, medical status, and SOFA score.Measurements and results We recorded data on epidemiology and severity of illness, site of infection, renal function before and after treatment, clinical cure, and mortality. Clinical cure was defined as simultaneous normalization of central temperature (38°), leukocyte count (10,000/mm³), and PaO₂/FIO₂ ratio (>187). Before treatment creatinine was 0.9±0.2 in the colistin group and 0.9±0.1 in the noncolistin group; after treatment the value was 1.0±0.3 in both groups. The most frequent infection was ventilator-associated pneumonia: 53% vs. 66% in colistin and noncolistin groups, respectively, Acinetobacter was the cause in 65% and 60% and Pseudomonas in 35% and 53%. In the noncolistin group 81% of patients were treated with carbapenems. Inadequate empirical antimicrobial treatment was more frequent in the colistin group (100% vs. 8%), but there were no differences in the frequency of clinical cure on day 6 of treatment (15% and 17%) or in mortality (29% and 24%).Conclusions Colistin appears to be as safe and as effective as other antimicrobials for treatment of sepsis caused by Acinetobacter and Pseudomonas in critically ill patients.     

Potentialization of IL-2 effects on immune cells by oyster extract (JCOE) in normal and HIV-infected individuals

Peripheral blood mononuclear cells (PBMCs) are physiologically activated by interleukin (IL)-2. We found that oyster extract (JCOE) currently used as a functional nutrient enhanced in vitro the IL-2 dependent activation as measured by cell count, ³H-thymidine uptake and up-regulation of a IL-2 receptor. In human immunodeficiency virus (HIV) seropositive individuals, this oyster extract-induced effect was marked in asymptomatic individuals with quasi-normal CD4 cell counts, but was weakly reflected in acquired immunodeficiency syndrome (AIDS) patients.     

Use of the Relationship between Absolute Lymphocyte Count and CD4 Count to Improve Earlier Consideration of Pneumocystis Pneumonia in HIV-positive Emergency Department Patients with Pneumonia

Background

The ability to accurately assess the level of immunosuppression in HIV+ patients in the emergency department (ED) is often limited and can affect management of these patients.

Objective

To evaluate the relationship between the absolute lymphocyte count (ALC) and CD4 count in HIV patients admitted through the ED with pneumonia and how utilization of this relationship may affect early consideration and evaluation of Pneumocystis jiroveci pneumonia (PCP).

Methods

Retrospective multicenter 5-year study of HIV+ patients with an ICD-9 diagnosis of pneumonia. Included patients had an ALC measured on ED presentation and a CD4 count measured in < 24 h. A receiver operator curve (ROC), decision plot analysis, and McNemar test of proportions were used to characterize the relationship between study variables.

Results

Six hundred eighty six patients were enrolled, 23.2% (95% confidence interval [CI] 20.2–26.1) were diagnosed with PCP. The geometric mean CD4 count and ALC were 81 and 1089, respectively. The correlation between ALC and CD4 was r = 0.60 (95% CI 0.55–65, p < 0.01). The ROC was 0.78 (0.75–0.82). An ALC < 1700 cells/mm³ had a sensitivity of 84% (95% CI 80–87) and specificity of 55% (95% CI 48–70) for a CD4 < 200 cells/mm³. An ALC threshold of 1700 cells/mm³ would have identified 86% of patients with PCP but falsely identified 2.5 patients without PCP for every one accurately identified.

Conclusion

The ALC threshold of 1700 cells/mm³ retains significant discriminatory value and would moderately improve identification of patients with a CD4 < 200 cells/mm³ but is not likely to be reliable as the sole method of early recognition and evaluation of PCP.     

Chronic methemoglobinemia: Improving hemoglobin saturation monitoring during anesthesia

Methemoglobin interferes with the accuracy of pulse oximetry data. Methemoglobinemia is caused by many factors, both congenital and acquired. However, the increasing usage of dapsone, which converts hemoglobin to methemoglobin, is increasing the number of patients with methemoglobinemia. We present the case of a patient with dapsone-induced methemoglobinemia who was successfully treated with methylene blue, which converts methemoglobin back to hemoglobin. Methemoglobin interferes with the accurate pulse oximetric monitoring of oxyhemoglobin saturation [1—5]. Generally, in the presence of methemoglobin levels greater than 1 g’dL^-1, pulse oximeter readings above 85% underestimate the saturation of functional hemoglobin (the hemoglobin functioning normally with respect to oxygen); readings below 85% overestimate the saturation [2]. These inaccuracies are exaggerated as methemoglobin levels increase or functional hemoglobin saturation decreases [2]. In addition to other causes of methemoglobinemia, the spread of the HIV epidemic and the increasing number of HIV patients receiving dapsone (diaminodiphenylsulfone) as prophylactic treatment forPneumocystis carinii will expand the population of patients with clinical methemoglobinemia who require anesthesia for surgery [6-8]. Virtually all patients treated with dapsone will have levels of methemoglobin sufficient to interfere with pulse oximetric monitoring [7]. We present a case that illustrates these problems and emphasizes the importance of treating methemoglobinemia before the induction of anesthesia to ensure accurate intraoperative monitoring of oxyhemoglobin saturation.     

Drug-resistant tuberculous meningitis

Drug-resistant tuberculosis, including drug-resistant tuberculous meningitis, is an emerging health problem in many countries. An association with Beijing strains and drug resistance-related mutations, such as mutations in katG and rpoB genes, has been found. The pathology, clinical features and neuroimaging characteristics of drug-resistant tuberculous meningitis are similar to drug-responsive tuberculous meningitis. Detection of mycobacteria in cerebrospinal fluid (CSF) by conventional methods (smear examination or culture) is often difficult. Nucleic acid amplification assays are better methods owing to their rapidity and high sensitivity. The Xpert^® MTB/RIF assay (Cepheid, CA, USA) is a fully-automated test that has also been found to be effective for CSF samples. Treatment of multidrug-resistant tuberculous meningitis depends on the drug susceptibility pattern of the isolate and/or the previous treatment history of the patient. Second-line drugs with good penetration of the CSF should be preferred. Isoniazid monoresistant disease requires addition of another drug with better CSF penetration. Drug-resistant tuberculous meningitis is associated with a high mortality. HIV infected patients with drug-resistant tuberculous meningitis have severe clinical manifestations with exceptionally high mortality. Prevention of tuberculosis is the key to reduce drug-resistant tuberculous meningitis.     

Comparison of scanning acoustic microscopy and histology images in characterizing surface irregularities among engineered human oral mucosal tissues

Acoustic microscopy was used to monitor an ex vivo produced oral mucosal equivalent (EVPOME) developed on acellular cadaveric dermis (AlloDerm^®). As seeded cells adhered and grew, they filled in and smoothed out the surface irregularities, followed by the production of a keratinized protective outermost layer. If noninvasive in vitro ultrasonic monitoring of these cellular changes could be developed, then tissue cultivation could be adjusted in-process to account for biologic variations in the development of these stratified cell layers. Cultured keratinocytes (from freshly obtained oral mucosa) were harvested and seeded onto AlloDerm^® coated with human type IV collagen and cultured 11 days. EVPOMEs were imaged on the 11th day post-seeding using a scanning acoustic microscope (SAM) that consists of a single-element transducer: 61 MHz center frequency, 32 MHz bandwidth, 1.52 f-number. The specimen surface was determined by thresholding the magnitude of the signal at the first axial incidence of a value safely above noise: 20–40 dB above the signal for the water and 2-dimensional (2-D) ultrasonic images were created using confocal image reconstruction. A known area from each micrograph was divided into 12–40 even segments and examined for surface irregularities. These irregularities were quantified and one-way analysis of variance (ANOVA) and linear regression analysis were performed to correlate the surface profiles for both the AlloDerm^® and EVPOME specimens imaged by SAM. Histology micrographs of the AlloDerm^® and EVPOME specimens were also prepared and examined for surface irregularities. Unseeded AlloDerm^® averaged seven to nine surface changes per 400 μm. The number of changes in surface irregularities decreased to two to three per 400 μm on the mature EVPOMEs. The numbers of surface irregularities between the unseeded AlloDerm^® vs. developing EVPOME are similar for both histology and SAM 2-D B-scan images. For the EVPOME 2-D B-scan micrographs produced by SAM, the decrease in surface irregularities is indicative of the stratified epithelium formed by seeded oral keratinocytes; verified in the histology images between the AlloDerm^® and EVPOME. A near 1:1 linear correlation shows the similarities between the two imaging modalities. SAM demonstrates its ability to discern the cell development and differentiation occurring on the EVPOME devices. Unlike histology, SAM measurements are noninvasive and can be used to monitor tissue graft development without damaging any cells/tissues.     

Malassezia furfur-related colonization and infection of central venous catheters

Objective To determine the incidence ofMalassezia furfur-related colonization and infection of central venous catheters.Design Prospective clinical study.Setting A paediatric intensive care unit at a University Hospital.Patients 66 newborns with central venous catheters for parenteral nutrition including lipid emulsions (Intralipid^®).Methods When a central venous catheter was removed, it was rinsed with 1 ml of physiological saline, transported at ambient temperature to the clinical laboratory and cultured on Dixon's medium. The tip of the central venous catheter was used for a bacteriological study using Maki's technique. In case of suspected sepsis, blood cultures were obtained using an Isolator^® tube.Results 74 central venous catheters were included: mean duration of use of a central venous catheters and infusions of lipid emulsion (Intralipid^®) were 19.3±10 days and 8.6±8 days respectively. Only 2 central venous catheters (2.7%) were colonized byMalassezia furfur: (Mf) one in an asymptomatic newborn, and the other in an infected newborn with signs of sepsis, who most probably died at 4 months of age from refractory hypoxia due to pulmonary hypoplasia, but not from Mf sepsis.Conclusions The incidence ofMalassezia furfur-related colonization of central venous catheters appears to be low but not negligible, which warrants the use of specific culture techniques.This study was partially supported by a clinical research pilot study grant from INSERM France (91CN52)     

The Pharmacokinetics,Efficacy, Safety,and Ease of Use of a Novel Portable Metered-Dose Cannabis Inhaler in Patients With Chronic Neuropathic Pain: A Phase 1a Study

ABSTRACT

Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a “main stream” pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ⁹-tetrahydrocannabinol (THC) and 11-hydroxy-Δ⁹-THC were taken at baseline and up to 120 minutes. Pain intensity (0–10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ⁹-THC plasma C_max ± SD was 38 ± 10 ng/mL, T_max ± SD was 3 ± 1 minutes, AUC_0→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma C_max increase per mg Δ⁹-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of C_max (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15–30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ⁹-THC pharmacokinetic profile with low interindividual variation of C_max, achieving pharmaceutical standards for inhaled drugs.     

Totally implanted catheters to reduce catheter-related infections in patients receiving interleukin-2: a 2-year experience

A high incidence of bacterial infections has been previously reported during interleukin-2 (IL-2) treatment, mainly due to catheter-related infections. Antibiotic prophylaxis has been successfully used to decrease such infections. The goal of this study was to evaluate an alternative way to reduce catheter-related infections in IL-2-treated patients by the use of totally implanted catheters. A total of 74 patients with metastatic renal cell carcinoma, referred to our institution to receive IL-2 from March 1989 to July 1991, were included in this prospective study. IL-2 was given on a 2-days-a-week schedule (24x10⁶ IU m^-2 day^-1) either alone (41 patients) or in association with interferon (33 patients). All these patients were prospectively evaluated for fever, bacteremia and line-site infection. Seven patients (9.5%) had one (2 patients) or more (5 patients) positive blood cultures with Staphylococcus aureus. Antibiotics were used only in 5 patients, and the catheter had to be removed in only 2 of these patients. In the other patients, no further infection developed despite the lack of antibiotics. Moreover, 9 patients had positive blood cultures with Staphylococcus epidermidis (1.9% of total number of blood cultures). In conclusion, a totally implanted catheter appears to reduce the incidence of infections in IL-2-treated patients, at least on a 2-days-a-week schedule.     

Elite control of HIV infection: implications for vaccine design

Background: ‘Elite controllers’ are rare HIV-infected individuals who are able to spontaneously control HIV replication without medication, maintaining viral loads that are consistently below the limits of detection by currently available commercial assays. Objective: To examine studies of elite controllers that may elucidate mechanisms of HIV immune control useful in designing a vaccine. Methods: Recent literature on HIV controllers and studies that have evaluated aspects of viral and host immunology that correlate with viral control are examined. Results/conclusions: Although many elements of innate and adaptive immunity are associated with control of HIV infection, the specific mechanism(s) by which elite controllers achieve control remain undefined. Ongoing studies of elite controllers, including those examining host genetic polymorphisms, should facilitate the definition of an effective HIV-specific immune response and guide vaccine design.     

Effect of surfactant replacement onPneumocystis carinii pneumonia in rats

The effect of intratracheal surfactant instillation on pulmonary function in rats withPneumocystis carinii pneumonia (PCP) was investigated. In those animals which developed PCP with severe respiratory failure after administration of cortisone acetate s. c. over 8–12 weeks, pulmonary function was improved by surfactant instillation. PaO₂ values 30 min after surfactant instillation were significantly higher compared to pretreatment values and also compared to PaO₂ values of rats 30 min after receiving saline (482.9 mmHg±44.7, 170.7 mmHg ±39.3 and 67.2 mmHg±17.4, respectively). Histological examination showed that alveoli of rats with PCP which received no exogenous surfactant are filled with foamy edema, whereas after exogenous surfactant alveoli are stabilized and well-aerated. These results indicate that exogenous surfactant may help patients with severe PCP to overcome an acute stage of respiratory distress.This work was financially supported, in part, by The Dutch Foundation for Medical Research (SFMO)