Drug-resistant pneumococcal pneumonia: clinical relevance and approach to management.

Community-acquired pneumonia is the most common infectious disease that causes death, with Streptococcus pneumoniae remaining the leading causative pathogen. The worldwide incidence of infections caused by pneumococci resistant to penicillin, macrolides, and other antimicrobial agents has increased at an alarming rate during the past 2 decades. Yet, these agents are still used as first-line empirical therapy in the outpatient setting. There are several reasons for this, including the infrequency of making a pathogen-specific diagnosis, the failure of studies to demonstrate the relevance of resistance, and the infrequency with which clinicians recognize clinical failures. Despite this, there is mounting evidence that supports the practice of using high doses of some antimicrobial agents, a more active antimicrobial agent within a class, or switching to another class of antimicrobial agents when a patient is identified as being at an increased risk of infection with a resistant pneumococcus. There is now information that will allow the physician to identify not only the patient at risk for infection with a resistant pneumococcus but also the antimicrobial class and, in some cases, the agent within the class to which the organism is more likely to be resistant. This will allow clinicians to better define optimal therapy for patients with community-acquired pneumonia.

Patterns of polymorphism detected in the chloroplast and nuclear genomes of barley landraces sampled from Syria and Jordan.

In order to examine how molecular polymorphism in barley landraces, sampled from five different ecogeographical regions of Syria and Jordan, is organised and partitioned, genetic variability at 21 nuclear and 10 chloroplast microsatellite loci were examined. Chloroplast polymorphism was detected, with most variation being ascribed to differences between the five regions (Fst 0.45) and to within sites within each region (Fst 0.44). Moreover, the distribution of chloroplast polymorphism is structured and not distributed randomly across the barley landraces sampled. From a total of 125 landrace accessions (five lines from each of five sites from each of five regions) genotyped with 21 SSRs a total of 244 alleles were detected, of which 38 were common to the five regions sampled. Most nuclear variation was detected within sites. Significant differentiation between sites (Fst 0.29) was detected with nuclear SSRs and this partially mirrored polymorphism in the chloroplast genome. Strong statistical associations/interaction was also detected between the chloroplast and nuclear SSRs, together with non-random association (linkage disequilibrium) of alleles at both linked and unlinked SSR loci. These results are discussed in the context of adaptation of landraces to the extreme environment, the concept of 'adapted gene complexes' and the exploitation of landraces in breeding programmes.

Alternative splicing of U12-dependent introns in vivo responds to purine-rich enhancers.

Alternative splicing increases the coding capacity of genes through the production of multiple protein isoforms by the conditional use of splice sites and exons. Many alternative splice sites are regulated by the presence of purine-rich splicing enhancer elements (ESEs) located in the downstream exon. Although the role of ESEs in alternative splicing of the major class U2-dependent introns is well established, no alternatively spliced minor class U12-dependent introns have so far been described. Although in vitro studies have shown that ESEs can stimulate splicing of individual U12-dependent introns, there is no direct evidence that the U12-dependent splicing system can respond to ESEs in vivo. To investigate the ability of U12-dependent introns to use alternative splice sites and to respond to ESEs in an in vivo context, we have constructed two sets of artificial minigenes with alternative splicing pathways and evaluated the effects of ESEs on their alternative splicing patterns. In minigenes with alternative U12-dependent 3' splice sites, a purine-rich ESE promotes splicing to the immediately upstream 3' splice site. As a control, a mutant ESE has no stimulatory effect. In minigene constructs with two adjacent U12-dependent introns, the predominant in vivo splicing pattern results in the skipping of the internal exon. Insertion of a purine-rich ESE into the internal exon promotes the inclusion of the internal exon. These results show that U12-dependent introns can participate in alternative splicing pathways and that U12-dependent splice sites can respond to enhancer elements in vivo.

Streptococcus iniae virulence is associated with a distinct genetic profile.

Streptococcus iniae causes meningoencephalitis and death in commercial fish species and has recently been identified as an emerging human pathogen producing fulminant soft tissue infection. As identified by pulsed-field gel electrophoresis (PFGE), strains causing disease in either fish or humans belong to a single clone, whereas isolates from nondiseased fish are genetically diverse. In this study, we used in vivo and in vitro models to examine the pathogenicity of disease-associated isolates. Strains with the clonal (disease-associated) PFGE profile were found to cause significant weight loss and bacteremia in a mouse model of subcutaneous infection. As little as 10(2) CFU of a disease-associated strain was sufficient to establish bacteremia, with higher inocula (10(7)) resulting in increased mortality. In contrast, non-disease-associated (commensal) strains failed to cause bacteremia and weight loss, even at inocula of 10(8) CFU. In addition, disease-associated strains were more resistant to phagocytic clearance in a human whole blood killing assay compared to commensal strains, which were almost entirely eradicated. Disease-associated strains were also cytotoxic to human endothelial cells as measured by lactate dehydrogenase release from host cells. However, both disease-associated and commensal strains adhered to and invaded cultured human epithelial and endothelial cells equally well. While cellular invasion may still contribute to the pathogenesis of invasive S. iniae disease, resistance to phagocytic clearance and direct cytotoxicity appear to be discriminating virulence attributes of the disease-associated clone.

Communication and decision-making in seriously ill patients: findings of the SUPPORT project. The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

OBJECTIVES: The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) represents one of the largest and most comprehensive efforts to describe patient preferences in seriously ill patients, and to evaluate how effectively patient preferences are communicated. Our objective was to review findings from SUPPORT describing the communication of seriously ill patients' preferences for end-of-life care. METHODS: We identified published reports from SUPPORT describing patient preferences and the communication of those preferences. We abstracted findings that addressed each of the following questions: What patient characteristics predict patient preferences for end of life care? How well do physicians, nurses, and surrogates understand their patients' preferences, and what variables are correlated with this understanding? Does increasing the documentation of existing advance directives result in care more consistent with patients' preferences? RESULTS: Patients who are older, have cancer, are women, believe their prognoses are poor, and are more dependent in ADL function are less likely to want CPR. However, there is considerable variability and geographic variation in these preferences. Physician, nurse, and surrogate understanding of their patient's preferences is only moderately better than chance. Most patients do not discuss their preferences with their physicians, and only about half of patients who do not wish to receive CPR receive DNR orders. Factors other than the patients' preferences and prognoses, including the patient's age, the physician's specialty, and the geographic site of care were strong determinants of whether DNR orders were written. In SUPPORT patients, there was no evidence that increasing the rates of documentation of advance directives results in care that is more consistent with patients' preferences. CONCLUSIONS: SUPPORT documents that physicians and surrogates are often unaware of seriously ill patients' preferences. The care provided to patients is often not consistent with their preferences and is often associated with factors other than preferences or prognoses. Improving these deficiencies in end-of-life care may require systematic change rather than simple interventions.

Intracranial mass lesions: sequential thallium and gallium scintigraphy in patients with AIDS.

PURPOSE: To determine the efficacy of sequential thallium and gallium scintigraphy to differentiate intracranial neoplasms (lymphoma and glioma) from other nonmalignant intracranial mass lesions among patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: The authors reviewed the cases of 40 patients with human immunodeficiency virus (HIV) who underwent thallium and gallium scanning to evaluate intracranial mass lesions from October 1991 through November 1997. There was a definitive final diagnosis of the nature of the mass lesions in 21 of these cases. In these 21 cases, the scintigraphic patterns were reviewed and were compared with the final diagnosis. RESULTS: On the basis of results at thallium and gallium scanning, the patients were divided into three groups. Group A included 13 patients (11 with brain tumors [lymphomas and gliomas] and two with progressive multifocal leukoencephalopathy [PML]) with thallium-positive, gallium-positive scans. Group B included five patients with intracranial infections (tuberculosis, Cryptococcus, bacteria) with thallium-negative, gallium-positive scans. Group C included three patients (one with PML and two with infarcts) with thallium-negative, gallium-negative scans. All patients with lymphomas were in group A. The sensitivity and specificity of the thallium-positive, gallium-positive pattern for intracranial malignancy were 100% and 80%, respectively. CONCLUSION: Sequential thallium and gallium scanning helped differentiate tumors from nonmalignant intracranial mass lesions and may help differentiate infections from PML or infarcts.

Influenza vaccination of human immunodeficiency virus (HIV)-infected adults: impact on plasma levels of HIV type 1 RNA and determinants of antibody response.

We assessed the effect of influenza vaccination on plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and the impact of age, plasma HIV-1 RNA level, CD4 cell count, and anti-HIV therapy on immune response. Forty-nine adults (mean age, 38.7 years; mean CD4 cell count +/- SD, 190 +/- 169/mL; mean plasma HIV-1 RNA level +/- SD, 154,616 +/- 317,192 copies/mL) were immunized. Elevations of > or = 0.48 log in plasma HIV-1 RNA levels occurred in two (4%) of 49 subjects within 4 weeks of vaccination. A fourfold or greater increase in antibody titer occurred in 13 (45%) of 29 subjects, correlating directly with CD4 cell count (P = .002) and inversely with plasma HIV-1 RNA level (P = .034). By multivariate analysis, CD4 cell count was a stronger predictor of antibody response than was plasma HIV-1 RNA level. We conclude that increases in plasma HIV-1 RNA levels following influenza vaccination are rare and transient and that antibody response is impaired with CD4 cell counts of < 100/mL and plasma HIV-1 RNA levels of > 100,000 copies/mL. Prospective trials are needed to evaluate the impact of highly active therapy on immune response after vaccination.

Development of specific nested oligonucleotide PCR primers for the Streptococcus iniae 16S-23S ribosomal DNA intergenic spacer.

Streptococcus iniae is a cause of septicemia, meningoencephalitis, and death in farmed fish and of cellulitis in human beings. A set of nested oligonucleotide PCR primers that specifically amplified a 373-bp subunit from a variety of clinical isolates from farmed fish and human patients were constructed from a 524-bp consensus sequence of the S. iniae 16S-23S ribosomal DNA intergenic spacer.

Pulmonary mycobacterial infections in AIDS: characteristic pattern of thallium and gallium scan mismatch.

PURPOSE: To evaluate the diagnostic specificity of thallium and gallium scan mismatch as a sign of mycobacterial infection in immunodeficient patients. MATERIALS AND METHODS: Thallium and gallium scans obtained in 56 immunodeficient patients between January 1989 and March 1994 were retrospectively reviewed, with special attention to the final diagnoses in all patients with thallium-gallium scan mismatch compared with those whose scans showed other scintigraphic patterns. RESULTS: Fourteen patients had focal gallium uptake, but no thallium uptake, in the mediastinum and hilar nodes (thallium-gallium mismatch). Twelve of the 14 had culture-proved mycobacterial infections; one had cryptococcal infection; and in one, the diagnosis was not established. Thirty-seven of the remaining 42 patients who had different scintigraphic patterns on thallium-gallium scans had other complications of acquired immunodeficiency syndrome such as Kaposi sarcoma, non-Hodgkin lymphoma, and bacterial pneumonia. The diagnosis in five of the 42 patients was not known because follow-up data were incomplete. CONCLUSION: The thallium-gallium mismatch pattern in immunodeficient patients is specific for mycobacterial infection.

Intensity of treatment in malnutrition. The ethical considerations.

Decisions about initiation and withdrawal of life-sustaining artificial nutrition and hydration are complex and sometimes are agonizing to make. Artificial feeding is considered by most medical ethicists to be a medical intervention about which decisions should be made based on the benefits, risks, and burdens of the treatment. State law varies, particularly with regard to the inclusion of artificial feeding in advance directives and in laws about its discontinuance. Conditions in which it is common for patients or families to consider refusal of artificial feeding include terminal cancer, advanced dementia, and persistent vegetative state. Alternative approaches to nutrition, such as offering favorite foods or treating underlying depression, may obviate the need for tube feeding. Competent patients may refuse any medical treatment, including life-sustaining treatment. An appropriate proxy decision maker may also refuse treatment on behalf of a mentally incapacitated patient.

Pulmonary Kaposi sarcoma in patients with AIDS: scintigraphic diagnosis with sequential thallium and gallium scanning.

Pulmonary Kaposi sarcoma associated with acquired immunodeficiency syndrome (AIDS) is difficult to diagnose because the clinical presentations and radiographic findings are nonspecific. The authors report three proved cases of AIDS-associated pulmonary Kaposi sarcoma diagnosed with sequential thallium and gallium scans. These scans demonstrated abnormal increase of pulmonary thallium uptake, whereas the gallium uptake was negative. In the authors' experience and in reports in the radiology literature, infected areas of the chest are generally thallium-negative on the delayed (3-hour) scans but are gallium-avid, whereas lymphomas are both thallium- and gallium-avid. The authors conclude that sequential thallium and gallium scans can be used to help diagnose pulmonary Kaposi sarcoma and distinguish it from other common AIDS-associated chest complications such as lymphoma and infections.

Respiratory arrest and prolonged respiratory depression after one low, subcutaneous dose of alphaprodine for obstetric analgesia. A case report.

Alphaprodine hydrochloride is an analgesic used commonly in the obstetric suite. A case of prolonged respiratory depression occurred after the administration of low-dose alphaprodine. Other cases of serious sequelae associated with the use of this drug have been reported on.