Clinical safety, quality and effect of resin infiltration for proximal caries.

AIM: Resin infiltration of proximal lesions is a new approach to stop caries progression. The aim of this clinical trial was to assess its safety and quality, as well as the therapeutic effect. MATERIALS AND METHODS: In 47 children, adolescents and young adults, ten dentists applied the infiltration material ICON (DMG, Germany) on initial proximal lesions according to the manufacturer's instruction. One lesion with radiographic extension into enamel or the outer third of dentin per participant was allocated for the treatment. The clinical safety and quality of resin infiltration were assessed 1 week, 6 months and 12 months after the treatment and the evaluation of the therapeutic effect was analysed by pair-wise radiographs. RESULTS: The clinical safety and quality of the infiltration were assessed in 45 individuals after 12 months. The test surfaces showed no relevant changes in clinical status, plaque accumulation or gingival status (p > 0.05). A high quality of infiltration was found for the marginal adaptation. In contrast to the improvement of colour at the one-week recall (p = 0.005), the infiltrated surfaces showed a statistically significant increase in the discoloration within the following year (p = 0.014). Out of the 43 lesions which could be assessed radiographically, only two lesions showed progression to a different score (4.7%). CONCLUSION: Resin infiltration can be considered a safe and effective treatment to reduce progression of initial proximal caries.

Sex differences in surgical site infections following coronary artery bypass grafting: a retrospective observational study.

BACKGROUND: Surgical site infection (SSI) following cardiac surgery poses a significant challenge for healthcare providers. Despite advances in surgical techniques and infection control measures, SSI remains a leading cause of morbidity and mortality, in addition to being a significant economic burden on healthcare services. Current literature suggests there is a reproducible difference in the incidence of SSI following cardiac surgery between sexes. We aim to assess the sex-specific predictive risk factors for sternal SSI following coronary artery bypass grafting (CABG) in addition to identifying any differences in the causative organisms between groups. METHODS: Adult patients undergoing isolated CABG between January 2012 and December 2022 in one UK hospital organization were included. In this 10-year, retrospective observational study, a total of 10,208 patients met the inclusion criteria. Pre-operative risk factors were identified using univariate analysis. To assess dependence between sex and organism or Gram stain, a Pearson Chi-squared test with Yates correction for continuity was performed. RESULTS: In total there were 8457 males of which 181 developed a sternal SSI (2.14%) and 1751 females, 128 of whom had a sternal SSI (7.31%). Male patients were found to be significantly more likely to develop an SSI secondary to a Gram-positive organism, whereas female patients were more likely to have a Gram-negative causative organism (P<0.00001). Staphylococcus was statistically more likely to be the causative organism genus in male patients. Pseudomonas aeruginosa was found to be twice as common in the female cohort compared with the male group. CONCLUSION: In our study, we found a statistically significant difference in the causative organisms and Gram stain for post-CABG sternal SSIs between males and females. Male patients predominately have Gram-positive associated SSIs, whereas female SSI pathogens are more likely to be Gram negative. The preoperative risk profiles of both cohorts are similar, including being an insulin-dependent diabetic and triple vessel coronary artery disease. Given these findings, it prompts the question, should we be tailoring our SSI treatment strategies according to sex and associated risk profiles?

A comprehensive qualitative investigation of the factors that affect surgical site infection prevention in cardiac surgery in England using observations and interviews.

BACKGROUND: Interview and questionnaire studies have identified barriers and challenges to preventing surgical site infections (SSIs) by focusing on compliance with recommendations and care bundles using interviews, questionnaires and expert panels. This study proposes a more comprehensive investigation by using observations of clinical practice plus interviews which will enable a wider focus. AIM: To comprehensively identify the factors which affect SSI prevention using cardiac surgery as an exemplar. METHODS: The study consisted of 130 h of observed clinical practice followed by individual semi-structured interviews with 16 surgeons, anaesthetists, theatre staff, and nurses at four cardiac centres in England. Data were analysed thematically. FINDINGS: The factors were complex and existed at the level of the intervention, the individual, the team, the organization, and even the wider society. Factors included: the attributes of the intervention; the relationship between evidence, personal beliefs, and perceived risk; power and hierarchy; leadership and culture; resources; infrastructure; supplies; organization and planning; patient engagement and power; hospital administration; workforce shortages; COVID-19 pandemic; 'Brexit'; and the war in Ukraine. CONCLUSION: This is one of the first studies to provide a comprehensive overview of the factors affecting SSI prevention. The factors are complex and need to be fully understood when trying to reduce SSIs. A strong evidence base was insufficient to ensure implementation of an intervention.

Renal allograft recipients fail to increase interferon-γ during invasive fungal diseases.

Invasive fungal diseases are a major cause of death in renal allograft recipients. We previously reported that adjunctive recombinant human interferon-γ therapy has clinical utility for invasive fungal diseases after renal transplantation. We have now developed a rapid peripheral blood-based quantitative real-time PCR assay that enables accurate profiling of cytokine imbalances. Our preliminary studies in renal transplant patients with invasive fungal diseases suggest that they fail to mount an adequate interferon-γ response to the fungal infection. In addition, they have reduced IL-10 and increased TNF-α when compared to stable renal transplant patients. These preliminary cytokine profiling-based observations provide a possible explanation for the therapeutic benefit of adjunctive human interferon-γ therapy in renal allograft recipients with invasive fungal diseases.

Prenatal diagnosis for thalassaemia in Egypt: what changed parents' attitude?

OBJECTIVES: To present the current status of the prenatal diagnosis services and results from the largest thalassaemia center in Egypt treating 3000 patients. Traditionally, prenatal diagnosis has not been successful in reducing the births of affected children in Egypt, because the majority of women undergoing prenatal diagnosis continued to have affected pregnancies. METHODS: Seventy-one pregnant mothers at risk for ß-thalassaemia underwent prenatal diagnosis by chorionic villus sampling (n=57) or amniocentesis (n=14) between 11 to 14 weeks of gestation. Molecular characterization of fetal DNA by reverse dot blot hybridization and polymerase chain reaction-amplification refractory mutation system techniques was conducted in all cases. RESULTS: Twenty-four women (33.8%) were found to have affected fetuses; 100% of these women opted to terminate the pregnancy. The change in attitude towards termination of pregnancy was related to in-depth counseling of the religious aspects towards prenatal diagnosis and termination of pregnancy. Forty-eight women (66.2%) with normal or carrier fetuses for ß-thal requested human leukocyte antigen typing of the fetal material to determine if the fetus was a human leukocyte antigen match for their existing thalassaemic siblings. CONCLUSION: This study demonstrates that prenatal diagnosis is feasible and acceptable in Egypt, a Muslim country, provided an in-depth discussion, which also addresses the religious considerations of prevention, is held with the couples.

Exogenous interferon-gamma immunotherapy for invasive fungal infections in kidney transplant patients.

The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon-gamma (IFN-gamma) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN-gamma injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN-gamma immunotherapy was seen and no IFI relapsed during long-term follow-up. Our experience is both uncontrolled and in patients with unpredictable fungal infection-related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN-gamma immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group.

Irrigation of radish (Raphanus sativus L.) with microcystin-enriched water holds low risk for plants and their associated rhizopheric and epiphytic microbiome.

Microcystins (MCs) are toxins produced during cyanobacterial blooms. They reach soil and translocated to plants through irrigation of agricultural land with water from MC-impacted freshwater systems. To date we have good understanding of MC effects on plants, but not for their effects on plant-associated microbiota. We tested the hypothesis that MC-LR, either alone or with other stressors present in the water of the Karla reservoir (a low ecological quality and MC-impacted freshwater system), would affect radish plants and their rhizospheric and phyllospheric microbiome. In this context a pot experiment was employed where radish plants were irrigated with tap water without MC-LR (control) or with 2 or 12 µg L-1 of pure MC-LR (MC2 and MC12), or water from the Karla reservoir amended (12 µg L-1) or not with MC-LR. We measured MC levels in plants and rhizospheric soil and we determined effects on (i) plant growth and physiology (ii) the nitrifying microorganisms via q-PCR, (ii) the diversity of bacterial and fungal rhizospheric and epiphytic communities via amplicon sequencing. MC-LR and/or Karla water treatments resulted in the accumulation of MC in taproot at levels (480-700 ng g-1) entailing possible health risks. MC did not affect plant growth or physiology and it did not impose a consistent inhibitory effect on soil nitrifiers. Karla water rather than MC-LR was the stronger determinant of the rhizospheric and epiphytic microbial communities, suggesting the presence of biotic or abiotic stressors, other than MC-LR, in the water of the Karla reservoir which affect microorganisms with a potential role (i.e. pathogens inhibition, methylotrophy) in the homeostasis of the plant-soil system. Overall, our findings suggest that MC-LR, when applied at environmentally relevant concentrations, is not expected to adversely affect the radish-microbiota system but might still pose risk for consumers' health.

Fourier-transform Raman spectroscopic study of a Neolithic waterlogged wood assemblage.

The use of Fourier-transform Raman spectroscopy for characterising lignocellulosics has increased significantly over the last twenty years. Here, an FT-Raman spectroscopic study of changes in the chemistry of waterlogged archaeological wood of Pinus sp. and Quercus sp. from a prehistoric assemblage recovered from northern Greece is presented. FT-Raman spectral features of biodeteriorated wood were associated with the depletion of lignin and/or carbohydrate polymers at various stages of deterioration. Spectra from the archaeological wood are presented alongside spectra of sound wood of the same taxa. A comparison of the relative changes in intensities of spectral bands associated with lignin and carbohydrates resulting from decay clearly indicated extensive deterioration of both the softwood and hardwood samples and the carbohydrates appear to be more deteriorated than the lignin. The biodeterioration of the archaeological timbers followed a pattern of initial preferential loss of carbohydrates causing significant loss of cellulose and hemicellulose, followed by the degradation of lignin.

Heart transplantation for homozygous familial transthyretin (TTR) V122I cardiac amyloidosis.

Heart failure is the usual cause of death in patients with amyloid cardiomyopathy. The commonest form of hereditary cardiac amyloidosis is associated with the Val122Ile variant of transthyretin (TTR), which is carried by 3-4% of the African American population. Here, we report the outcome of the first cardiac transplantation in a patient with TTR V122I. A 59-year-old Caribbean man presented with biventricular failure. Other than previous bilateral carpel tunnel syndrome, he had been well and had no evidence of extracardiac amyloidosis. An endomyocardial biopsy demonstrated amyloid of TTR type. Sequencing of TTR gene indicated homozygosity for V122I. He underwent cardiac transplantation and 3 years later, remains well with no evidence of allograft or systemic amyloid deposition.

Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide.

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations.

Intracranial infections: clinical and imaging characteristics.

The radiologist plays a crucial role in identifying and narrowing the differential diagnosis of intracranial infections. A thorough understanding of the intracranial compartment anatomy and characteristic imaging findings of specific pathogens, as well incorporation of the clinical information, is essential to establish correct diagnosis. Specific types of infections have certain propensities for different anatomical regions within the brain. In addition, the imaging findings must be placed in the context of the clinical setting, particularly in immunocompromised and human immunodeficiency virus (HIV)-positive patients. This paper describes and depicts infections within the different compartments of the brain. Pathology-proven infectious cases are presented in both immunocompetent and immunocompromised patients, with a discussion of the characteristic findings of each pathogen. Magnetic resonance spectroscopy (MRS) characteristics for several infections are also discussed.

Diabetes, Gray Matter Loss, and Cognition in the Setting of Parkinson Disease.

RATIONALE AND OBJECTIVES: Parkinson disease (PD) is a progressive neurodegenerative disorder affecting motor and cognitive functions. Prior studies showed that patients with PD and diabetes (DM) demonstrate worse clinical outcomes compared to nondiabetic subjects with PD. Our study aimed at defining the relationship between DM, gray matter volume, and cognition in patients with PD. MATERIALS AND METHODS: This study included 36 subjects with PD (12 with DM, 24 without DM, mean age = 66). Subjects underwent high-resolution T1-weighted brain magnetic resonance imaging, [(11)C]dihydrotetrabenazine positron emission tomography imaging to quantify nigrostriatal dopaminergic denervation, clinical, and cognitive assessments. Magnetic resonance images were postprocessed to determine total and lobar cortical gray matter volumes. Cognitive testing scores were converted to z-scores for specific cognitive domains and a composite global cognitive z-score based on normative data computed. Analysis of covariance, accounting for effects of age, gender, intracranial volume, and striatal [(11)C]dihydrotetrabenazine binding, was used to test the relationship between DM and gray matter volumes. RESULTS: Impact of DM on total gray matter volume was significant (P = 0.02). Post hoc analyses of lobar cortical gray matter volumes revealed that DM was more selectively associated with lower gray matter volumes in the frontal regions (P = 0.01). Cognitive post hoc analyses showed that interaction of total gray matter volume and DM status was significantly associated with composite (P = 0.007), executive (P = 0.02), and visuospatial domain cognitive z-scores (P = 0.005). These associations were also significant for the frontal cortical gray matter. CONCLUSION: DM may exacerbate brain atrophy and cognitive functions in PD with greater vulnerability in the frontal lobes. Given the high prevalence of DM in the elderly, delineating its effects on patient outcomes in the PD population is of importance.

Comparative study of the biomechanical performance of trained and untrained skeletal muscle.

UNLABELLED: Changes in contraction and relaxation parameters during chronic electrical stimulation can exert profound effects on diastolic augmentation during skeletal muscle assistance (SMA) of the circulation, in both short and long term. The physiological properties of latissimus dorsi muscle (LD) performance in a system that mimics the clinical setting has not been adequately studied. OBJECTIVE: To quantify changes in the biomechanical performance of trained and untrained skeletal muscle in relation to circulatory assistance using an ex-vivo Windkessel mock circulation. METHODS: Twelve Welsh Mountain sheep were divided into 2 groups: Group A (n = 6) underwent implantation of intramuscular electrodes into the left LD connected to a myostimulator (Telectronics Pacing Systems, Inc., Colorado) and progressively trained by burst stimulation over a 12-week period using standard stimulation parameters (2.5-5 V, 35 Hz, 6 pulses per burst, 240 microseconds per pulse); Group B (n = 6) were the untrained controls. At the end of 12 weeks, the LD was mobilised on its neurovascular pedicle and wrapped around a latex rubber aorta connected to two Windkessel chambers pressurised to 70 mmHg and stimulated to contract 40 times per minute continuously for 60 min. Pressure change per contraction (augmentation, delta P), volume displacement, contraction (Ct) and relaxation to 90% (Rt90) times, and the standardised rate of change of pressure generation (+dP/dt: delta P) and decay (-dP/dt: delta P) were determined and assessed for potential clinical efficacy. RESULTS: In Group A, the LD was fatigue-resistant in all 6 animals with a mean pressure augmentation of 13.7 (s.e.m. 1.3) mmHg and mean stroke volume of 12.5 (s.e.m. 1.0) ml. These muscles were slow with a mean Ct and +dP/dt: delta max of 243.2 (s.e.m. 6.1) ms and + 6.5s-1, respectively, and Rt90 and -dP/dt: delta max of 261.0 (s.e.m. 4.8) ms and -7.8s-1, respectively. In contrast, the LD in Group B was fatiguable with a mean pressure augmentation and stroke volume of 24.6 (s.e.m. 0.9) mmHg and 21.1 (s.e.m. 0.7) ml at 1 min and only 5.4 (s.e.m. 0.3) mmHg and 5.2 (s.e.m. 0.3) ml, respectively, at 30 min (P < 0.001). These muscles were faster at all time points compared to group A (P < 0.02). Acute diminution of power output per contraction in Group B coincided with a prolongation in the Rt90 by 101% compared to the Ct which decreased by less than 5% (P < 0.001). The Ct/Rt90 ratio did not significantly change during performance testing in Group A (fatigue-resistant animals) (P > 0.1). CONCLUSIONS: Using a mock circulation system, we have identified significant differences in biomechanical properties of trained and untrained skeletal muscle. Optimisation of these parameters during and after electrical training may alter the clinical efficacy of SMA.

Clenbuterol induces cardiac hypertrophy with normal functional, morphological and molecular features.

OBJECTIVE: Several pharmacological agents have been shown to produce 'physiological' or 'pathological' hypertrophy based on their functional characteristics. The aim of this study was to examine the features of cardiac hypertrophy induced by the selective beta 2-adrenergic agonist, clenbuterol. METHODS: Cardiac hypertrophy was induced in 7-week-old Sprague-Dawley rats by daily injections of clenbuterol for 3 weeks. Thyroxine and isoproterenol were also used to produce cardiac hypertrophy to serve as positive controls for physiological and pathological hypertrophy, respectively. Left ventricular function was determined using an isolated rat heart preparation. Ventricular samples were used for morphological examination while interstitial collagen was measured using high-pressure liquid chromatography. Expression of sarcoplasmic reticulum Ca(2+)-ATPase2a (SERCA2a) and phospholamban (PLB) were measured by dot blot analysis. RESULTS: Clenbuterol treatment induced 26% left ventricular hypertrophy. These hearts demonstrated normal systolic isovolumic parameters and diastolic (active relaxation and passive stiffness) function. In addition, left ventricular concentration of collagen and morphology was normal as were the expression of SERCA2a and PLB mRNA. CONCLUSION: These results suggest that clenbuterol-induced hypertrophy is 'physiological' in terms of its function, extracellular structure and gene expression.

Severity of MIH findings at tooth surface level among German school children.

AIM: This study was to investigate the distribution and clinical characteristics of teeth diagnosed with MIH at surface and defect type level in a cohort of German children. METHODS: The study cohort included 242 children diagnosed with MIH which had been recorded during the compulsory dental school examinations of 20 German primary schools. The subjects had been enrolled by cluster sampling. All children attended the second to fourth grade (age 7-10 years, mean 8.1 ± 0.8). The children were examined by five calibrated examiners (kappa = 0.9) after tooth brushing. The recording comprised teeth, surfaces, type and severity of MIH defects and was conducted using a portable light, mirrors and cotton rolls. MIH was registered according to the EAPD criteria. Defects <1 mm were not recorded. Statistical analysis included descriptive statistics and Spearman's correlation. RESULTS: Most affected teeth were first permanent molars (71.4 %) followed by the maxillary central incisors (15.6 %). The most common defects were demarcated opacities (82.2 %), while the remaining 17.8 % of the affected teeth exhibited severe enamel defects. The most frequently affected surface in molars was the occlusal surface (72.4 %); in incisors, it was the buccal surface (73.5 %). There were no atypical restorations in the affected incisors. Different types of MIH defects at various surfaces of the same tooth were common. The number of affected tooth surfaces was positively correlated with the severity of MIH at child (p < 0.001). CONCLUSIONS: The study demonstrates severe enamel defects involving in almost one-fifth of all MIH teeth. The knowledge of the intra-oral distribution and severity of MIH findings at the enamel surface level is important for assessing the treatment needs.

Excitatory transmitter amino acid-containing neurons in the rat visual cortex: a light and electron microscopic immunocytochemical study.

The distribution and morphology of neurons labelled with antisera to glutamate or aspartate were examined, at the light and electron microscope levels, in the rat visual cortex. Using widely accepted light microscopic features as well as well-established nuclear, cytoplasmic, and synaptic criteria, we noted that glutamate-immunoreactive neurons were pyramidal cells distributed in layers II-VI, with an increased concentration in layers II and III. Aspartate immunoreactivity was localized chiefly to pyramidal neurons in layers II-VI. However, approximately 10% of immunolabeled cells were nonpyramidal neurons scattered throughout the cortex. Cell-body measurements revealed that, for both groups of neurons, layer V contained the largest labelled neurons, whereas layers IV and VI contained the smallest. Furthermore, in every layer, aspartate-stained neurons were larger than glutamate-positive cells. Finally, glutamate- and aspartate-labelled axon terminals formed asymmetrical synapses, which are presumably excitatory in nature, primarily with dendritic spines. These findings, together with recent detailed studies of the projections of glutamate- and aspartate-labelled cortical neurons, may provide essential background information for studies aimed to elucidate the function(s) of excitatory amino acids in the cortex and their role in pathological conditions.

Influence of clenbuterol treatment during six weeks of chronic right ventricular pressure overload as studied with pressure-volume analysis.

OBJECTIVES: Chronic pressure overload cardiac hypertrophy produces ventricular dysfunction. There is evidence that clenbuterol, a beta(2)-adrenoceptor agonist, produces cardiac hypertrophy with preserved function in rodents. We sought to determine the cardiac hypertrophic effects of clenbuterol on the thin-walled ventricles of large animals undergoing chronic pressure overload by means of pulmonary artery banding. METHODS: Right ventricular pressure-volume loops were obtained in open-chest sheep before and after 6-1/2 weeks of pulmonary artery banding by using micromanometer conductance catheters. Animals were randomly assigned to treatment with either saline solution (n = 7) or clenbuterol (n = 8). Treatment was started immediately after pulmonary artery banding. RESULTS: Acute pulmonary artery banding increased the right ventricular systolic pressure equally in both groups (saline group, 23.9 +/- 3.3 to 48.1 +/- 9.7 mm Hg; clenbuterol group, 24.3 +/- 2.8 to 48.6 +/- 10.7 mm Hg [mean +/- standard deviation]). Six weeks of treatment produced no significant differences in the body weight, heart weight, heart/body weight ratio, right ventricular wall thickness, heart rate, and stroke volume between the groups. However, the slope of the end-systolic pressure-volume relation and the slope of the first derivative of the right ventricular developed pressure/end-diastolic volume relation were significantly increased when compared with baseline values in clenbuterol-treated animals but not in saline-treated animals. CONCLUSION: Clenbuterol treatment during pulmonary artery banding improves systolic function of the chronically pressure-overloaded right ventricle. This has important implications for the use of pharmacologic agents in modulating cardiac adaptation.

The use of unstented homograft valves for aortic valve reoperations. Review of a twenty-three-year experience.

Unstented homograft valves offer several theoretical advantages when used for patients who have had previous operations on the aortic valve. Between January 1970 and February 1993, 177 patients received unstented homograft valves after previous aortic valve operations. One hundred thirty-four patients had previous aortic valve replacement in the form of homografts (101 patients), mechanical prostheses (24 patients), and bioprostheses (9 patients), and 43 had previous valve repair. The indication for reoperation was deterioration of a noninfected valve (124 patients), infective endocarditis (40 patients), and failure of a noninfected mechanical valve (12 patients). Fresh homograft valves were implanted in 60 patients, homografts preserved in antibiotics were used in 111 patients, and 6 patients received cryopreserved valves. Aortic valve and root replacement was performed in 60 patients, and in 117 the homograft was inserted freehand in the subcoronary position. The early mortality was 5.1%. The actuarial survival at 10 years was 71%. Multivariate analysis demonstrated that patients with previous homograft replacement have a better long-term survival than patients who had previous mechanical valves (p = 0.017). The freedom from valve-related death and reoperation was 70% at 10 years. Fresh homografts faired better than antibiotic-sterilized homografts (p = 0.007). None of the patients had recurrence of endocarditis at 6 months, although 1 patient died of uncontrolled infection despite valve replacement. The freedom from recurrent endocarditis was 88% at 10 years. We conclude that unstented aortic homografts provide good early and long-term results for aortic valve reoperations, particularly in patients with previous homograft replacement. Recurrent endocarditis is uncommon even in patients operated on for prosthetic valve infections.

Management of pulmonary aspergillosis in AIDS: an emerging clinical problem.

AIMS: To review the clinical, radiographic, and therapeutic features of 11 cases of respiratory Aspergillus infection in patients with AIDS. METHODS: All induced sputum and bronchoalveolar lavage samples obtained from HIV seropositive patients between January 1985 and March 1993 were analysed for Aspergillus species. Additionally, where appropriate, bronchial or renal biopsy specimens, or both, were taken before treatment had started. RESULTS: In 11 patients Aspergillus fumigatus was identified in alveolar samples obtained by sputum induction. This was confirmed by bronchoalveolar lavage in eight. Three patients had Aspergillus plaques in the trachea and bronchus, while a fourth patient had an aspergilloma. Risk factors for Aspergillus infection were present in all patients, including corticosteroid treatment in three cases and neutropenia in four, three of whom had received chemotherapy for Kaposi's sarcoma. Four patients had concomitant cytomegalovirus infection. Ten patients had a CD4 count of less than 50 cells/mm3 while one patient had a disseminated T cell lymphoma with a CD4 count of 242 cells/mm3. Of the three patients with samples obtained by sputum induction who did not undergo bronchoscopy, two had a normal chest x ray picture and the third had a right lobar pneumonia complicating an aggressive lymphoma. All three were treated with itraconazole 200 mg twice a day without further investigation. Survival from the time of diagnosis of Aspergillus infection was short: seven patients died within six weeks, although only one death was directly attributed to pulmonary aspergillosis. At six monthly follow up, one patient, who initially had a positive Aspergillus culture from bronchial washings and a normal chest radiograph, developed a renal aspergilloma despite the disappearance of Aspergillus sp from the sputum. CONCLUSION: Pulmonary aspergillosis is an important clinical problem in patients with AIDS with a CD4 count of less than 50 cells/mm. Furthermore, patients with Aspergillus sp in sputum induction or bronchial washings may develop disseminated disease despite adequate treatment of the primary infection.

A global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion. Global Antifungal Surveillance Group.

An improved fluconazole 25-mg disk diffusion method was used to test the susceptibility of 20,900 consecutively isolated clinical strains of Candida species from 40 hospital laboratories in 26 countries. The procedure is similar to the National Committee for Clinical Laboratory Standards (NCCLS) M2-A6 method for testing bacteria, except Mueller-Hinton agar is supplemented with 2% glucose and 0.5 mcg/mL methylene blue. Plates were incubated at 35 degrees C and read after 18 to 24h. Tentative zone interpretive criteria were based on the correlation by regression analysis with the NCCLS M27-A Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: > =19mm Susceptible, < = 12mm Resistant, and 13-18 mm Susceptible-Dose Dependent. Of 14,368 isolates of Candida albicans, 2,073 C. glabrata, 869 C. tropicalis, 752 C. parapsilosis, and 351 C. krusei, 99%, 67%, 90%, 94%, and 26%, respectively, were susceptible in vitro to fluconazole. All study sites used the BIOMIC System to electronically read zones on plates, interpret, record test results and verify quality control data. This is the largest study to date that evaluated a broad range of sequentially collected yeasts from various infections and different types of hospitals. The modified disk testing procedure is facile and economical to perform and offers a reproducible and accurate means to assess the in vitro susceptibility of Candida species to fluconazole.