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Biomedical subjects

V J Gill

Publications and source records attributed to V J Gill.

At least 19 recordsLinked to original sources

Immune-globulin prophylaxis of respiratory syncytial virus infection in patients undergoing stem-cell transplantation.

Thirty-two patients undergoing allogeneic hematopoietic stem-cell transplantation were given respiratory syncytial virus (RSV) immune globulin (RSVIG) at the time of transplantation and again 3 weeks later. Antibody titers to RSV, human parainfluenza virus 3, measles, and influenza H1N1, H3N2, and B were measured prior to administration of RSVIG and 6 more times over the course of the subsequent 6 weeks. Baseline antiviral titers and increases in antibody after administration of RSVIG were extremely variable for all the viruses. In 18 patients in whom the baseline titers of antibody titers to RSV-F protein were 1:640-1:2048, there was a 7.7-fold initial increase in these titers after the first dose of RSVIG, compared with a 2.1-fold increase in 14 patients with baseline titers of 1:4096-1:20,840; increases in titers of antibody against the other viruses after the first dose of RSVIG reflected similar variability. The subset of patients with the lowest titers appear to receive the greatest benefit from administration of RSVIG.

Antibodies, Viral↗

High-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell transplantation.

We evaluated high-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell transplantation. One hundred and seventy-four consecutive patients who were at risk for CMV infection (either recipient or donor seropositive) and received either intensive chemoradiotherapy and a T cell-depleted stem cell transplant followed by delayed add-back of donor T cells (TCDT: n = 98), or a non-myeloablative preparative regimen followed by an unmanipulated peripheral blood stem cell transplant (NMT: n = 76) from an HLA-identical sibling donor were studied. All received high-dose acyclovir (HDACV) from day - 7 for 3 months post-transplant in conjunction with weekly CMV pp65 antigenemia monitoring and pre-emptive treatment with intravenous immunoglobulin (not CMV-specific) and ganciclovir. The actuarial probabilities of developing pp65 antigenemia were 83 +/- 4% after TCDT and 41 +/- 6% after NMT (P < 0.00001) with reactivation occurring earlier in the TCDT group (the median 36 days vs 55 days). We observed no reactivation of CMV in seronegative recipients with a seropositive donor (n = 23). A total of 11 patients (5 in TCDT, 6 in NMT) developed CMV disease within 400 days after transplantation, and one death was clearly attributable to CMV interstitial pneumonitis (IP). This strategy was associated with effective control of CMV antigenemia in the majority of patients and near-complete eradication of fatal CMV IP.

Acyclovir↗

New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia.

Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.

AIDS-Related Opportunistic Infections↗

The use of oral washes to diagnose Pneumocystis carinii pneumonia: a blinded prospective study using a polymerase chain reaction-based detection system.

Pneumocystis carinii pneumonia (PCP) can be diagnosed by direct microscopic examination of induced sputum or by bronchoalveolar lavage (BAL). However, many institutions have little diagnostic success with induced sputum, and BAL is invasive and expensive. This prospective, blinded study assessed oral washes as a more convenient specimen than either sputum or BAL fluid and used a dissociation-enhanced lanthanide fluoroimmunoassay time-resolved fluorescent hybridization polymerase chain reaction (PCR) detection system that is feasible for clinical laboratories. The study assessed 175 oral washes, each paired with either an induced sputum that was positive for Pneumocystis or a BAL sample. The PCR test based on the Pneumocystis major surface glycoprotein primers had a sensitivity of 91% and a specificity of 94%, compared with a test based on mitochondrial large subunit rRNA primers, which had a sensitivity of 75% and a specificity of 96%. These results suggest that oral washes can provide a useful sample for diagnosis of PCP when a sensitive PCR detection system is used.

Bronchoalveolar Lavage↗

Outbreak of human parainfluenza virus 3 infections in a hematopoietic stem cell transplant population.

Clinical manifestations and epidemiological features are described for a cluster of 12 cases of human parainfluenza virus 3 (HPIV3) infection that occurred among 64 allogeneic hematopoietic stem cell transplant (SCT) recipients in an 11-week period during spring 2000. Upper respiratory symptoms predominated. Pneumonia occurred in 3 patients and was a contributing factor in the death of 1 patient. Exposure histories and molecular analysis of HPIV3 isolates suggested that both community acquired and nosocomially transmitted infections occurred during this outbreak. A chain of transmission within the outpatient clinic appeared to have occurred in 4 outpatients and to have extended to 2 hospitalized patients. Molecular epidemiology was useful in discerning routes of transmission in this outbreak.

Disease Outbreaks↗

Endocarditis caused by penicillin-resistant viridans streptococci: 2 cases and controversies in therapy.

Although penicillin-resistant viridans streptococci have been isolated from samples from the mouth, blood, and wounds in increasing numbers, viridans streptococci isolated from patients with endocarditis have remained sensitive to penicillin for the past 5 decades. We report the cases of 2 patients with penicillin-resistant viridans streptococcal endocarditis, review 6 other cases from the literature, and summarize 2 studies that used an animal model of penicillin-resistant viridans streptococcal endocarditis.

Aged↗

Dental health and viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.

Viridans streptococci were the most common cause of bacteremia in 61 consecutive myeloablative allogeneic hematopoietic stem cell transplant (HSCT) recipients, occurring in 19 of 31 bacteremic patients (61%) during the period of post-transplant neutropenia. Seven of the 19 had more than one viridans streptococcus in the same blood culture. Twenty isolates from 15 patients were Streptococcus mitis. Most viridans streptococci were resistant to norfloxacin, used routinely for prophylaxis. Comparison of the 19 patients with viridans streptococcal bacteremia with a contemporaneous group of 23 allogeneic HSCT recipients with fever and neutropenia but no identified focus of infection found that patients with viridans streptococcal bacteremia were more likely to have severe intraoral pathology while neutropenic (26% vs 0%) and slightly shorter interval between the last dental procedure and the onset of neutropenia (11 vs 14 days). Poor underlying dental health and the use of norfloxacin thus appear to predispose to viridans streptococcal bacteremia.

Adult↗

Seven cases of surgical native valve endocarditis caused by coagulase-negative staphylococci: An underappreciated disease.

BACKGROUND: Native valve endocarditis caused by coagulase-negative staphylococci is uncommon and the diagnosis is infrequently considered. The disease, however, appears to be increasing in frequency and can pursue an aggressive clinical course. We report the clinical features of 7 cases of coagulase-negative staphylococcal native valve endocarditis (CNS-NVE) seen at 1 institution with a large cardiovascular referral base over a 10-month period. All cases required valve replacement surgery. METHODS: Clinical history, echocardiograms, and microbiologic and histopathologic data were reviewed for 7 patients with surgical CNS-NVE. RESULTS: Four patients had intravenous central catheters, and 1 had recent surgery, whereas the remaining 2 had no identifiable risk factors. Presentations ranged from subacute (4 cases) to acute with complications (3 cases). Complications included congestive heart failure, stroke, and heart block. Echocardiography demonstrated valvular lesions in all 7 cases. Valve pathologic study demonstrated gram-positive cocci in all 7 cases; blood cultures grew coagulase-negative staphylococci in 6 cases and valve cultures grew Staphylococcus epidermidis in 5 cases. CONCLUSIONS: Coagulase-negative staphylococci, including S epidermidis, can cause severe native valve endocarditis requiring valve replacement. The increasing use of intravascular access devices in the community may herald an increase in the incidence of CNS-NVE. A high index of diagnostic suspicion in the appropriate clinical setting is critical for optimal management.

Adult↗

Resistance to multiple fluoroquinolones in a clinical isolate of Streptococcus pyogenes: identification of gyrA and parC and specification of point mutations associated with resistance.

A strain of Streptococcus pyogenes resistant to multiple fluoroquinolones was isolated from the blood of an immunocompromised patient. Resistance to fluoroquinolones in S. pyogenes has not been previously studied. Compared to 10 sensitive strains of S. pyogenes, the fluoroquinolone-resistant clinical isolate of S. pyogenes presented point mutations in gyrA, predicting that serine-81 was changed to phenylalanine and that methionine-99 was changed to leucine, and in parC, predicting that serine-79 was changed to tyrosine. The mechanism of fluoroquinolone resistance in this isolate of S. pyogenes appears to be analogous to previously reported mechanisms for Streptococcus pneumoniae.

Anti-Infective Agents↗

Development of a PCR assay for diagnosis of Pneumocystis carinii pneumonia based on amplification of the multicopy major surface glycoprotein gene family.

We have evaluated a PCR technique using primers based on Pneumocystis carinii major surface glycoprotein (MSG) genes, a multicopy gene family, for utility in detection of P. carinii in BAL and oropharyngeal samples obtained from immunosuppressed patients. These primers were able to detect P. carinii DNA in as little as 16 fg of genomic DNA. PCR using MSG primers detected P. carinii DNA in 7 smear-positive BAL samples (100% sensitivity), and found no P. carinii DNA in 12 smear-negative BAL samples (100% specificity). Mitochondrial ribosomal RNA (mrRNA) primers, commonly used in PCR studies of PCP, detected P. carinii in six of seven positive samples (85.7% sensitivity) and none of 12 were negative samples (100% specificity). Diagnosis of PCP by amplification of 81 oropharyngeal samples using MSG primers had a 50% sensitivity (4/8) and 96% specificity (70/73). PCR with mrRNA primers was 37.5% sensitive (3/8) and 100% specific (73/73). All three false-positive MSG results showed a very low intensity on Southern hybridization. PCR using MSG gene primers should prove valuable in the diagnosis of PCP.

Fungal Proteins↗

Optimal activation of isopsoralen to prevent amplicon carryover.

We compared the efficiencies of activation of the photochemical isopsoralen compound 10 and its resulting amplicon neutralizations under conditions with a UV transilluminator box at room temperature (RT) and a HRI-300 UV photothermal reaction chamber at RT and at 5 degrees C. Our data suggest that use of the HRI-300 reaction chamber at 5 degrees C results in a statistically significantly higher degree of amplicon neutralization.

DNA Primers↗

Recurrent bacteremia caused by a "Flexispira"-like organism in a patient with X-linked (Bruton's) agammaglobulinemia.

Helicobacter spp., except for Helicobacter cinaedi, have only rarely been reported in cases of septicemia. A patient with X-linked (Bruton's) agammaglobulinemia was found to have persistent sepsis with a Helicobacter-like organism despite multiple courses of antibiotics. His periods of sepsis were associated with leg swelling thought to be consistent with cellulitis. The organism was fastidious and required a microaerophilic environment containing H(2) for growth. Optimal growth was observed at 35 to 37 degrees C on sheep blood, CDC anaerobe, and Bordet-Gengou agars. Serial subcultures every 4 to 5 days were required to maintain viability. The organism was strongly urease positive and showed highest relatedness to Helicobacter-like organisms with the vernacular name "Flexispira rappini" by 16S rRNA gene sequence analysis. Genomic DNA hybridization studies, however, found 24 to 37% relatedness to "F. rappini" and even less to other Helicobacter spp. Although the organism phenotypically resembles "Flexispira" and Helicobacter, it is thought to represent a new taxon. The patient's infection was eventually cleared with a prolonged (5-month) course of intravenous imipenem and gentamicin.

Adult↗

An uncommon Helicobacter isolate from blood: evidence of a group of Helicobacter spp. pathogenic in AIDS patients.

An unusual Helicobacter sp. was isolated from the blood of a human immunodeficiency virus (HIV)-infected patient. This organism had spiral morphology, with single amphitrichous flagella, and was negative for hippurate hydrolysis, production of urease, and reduction of nitrate. 16S rRNA gene sequence analysis verified that the isolate was a species of Helicobacter, most closely related to an undescribed Helicobacter-like isolate from Vancouver, British Columbia, Canada, and to Helicobacter westmeadii, a recently described species from Australia. Both organisms had also been isolated from the blood of HIV-infected patients. These blood isolates, along with Helicobacter cinaedi, form a cluster of closely related Helicobacter spp. that may represent an emerging group of pathogens in immunocompromised patients.

AIDS-Related Opportunistic Infections↗

Burkholderia pseudomallei infection in a Puerto Rican patient with chronic granulomatous disease: case report and review of occurrences in the Americas.

Burkholderia species, notably Burkholderia cepacia and Burkholderia gladioli, are important pathogens in patients with chronic granulomatous disease (CGD). Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in Southeast Asia and northern Australia but is a rare pathogen in other parts of the world. We describe the occurrence of B. pseudomallei infection in a Puerto Rican patient with CGD. This is one of only a small number of documented cases of melioidosis autochthonous to the Americas and is the first reported case of B. pseudomallei infection in a CGD patient from the Americas. We conclude that B. pseudomallei, like B. cepacia and B. gladioli, should be considered a potential pathogen in patients with CGD and that melioidosis should be considered in the differential diagnosis for ill residents of or travelers to Puerto Rico.

Americas↗

Detection of Legionella by PCR in respiratory specimens using a commercially available kit.

Using polymerase chain reaction (PCR) for the detection of pathogens that are difficult to grow, such as Legionella species, may reduce difficulties encountered with culture and immunofluorescent staining. We evaluated a commercial PCR and hybridization kit, designed for environmental samples, for the detection of Legionella in respiratory specimens. Sixteen Legionella species cultures tested positive with the Perkin Elmer Legionella EnviroAmp Amplification and Detection kits (Perkin Elmer, Foster City, Calif). The assay detected as few as 100 colony-forming units per milliliter of spiked bronchoalveolar lavage (BAL) fluid, and no false-negative results were obtained. PCR inhibition by blood in the specimens was removed by washing pelleted specimens in sterile distilled water. Of 126 specimens screened with the kit, 1 induced sputum and 3 BAL specimens were positive by PCR. All 4 were validated as true-positive results by culture or serologic testing. The entire PCR and hybridization assay can be completed in less than 6 hours, whereas isolation and identification by culture requires up to 12 days, and serologic conversion may not be demonstrated for weeks. Molecular techniques based on direct extraction and amplification of DNA from respiratory specimens nay be useful for the timely diagnosis of legionellosis.

Bronchoalveolar Lavage Fluid↗

Infections with Roseomonas gilardii and review of characteristics used for biochemical identification and molecular typing.

Roseomonas is a recently described genus of gram-negative coccobacilli formerly designated as "pink-coccoid" groups I through IV by the Centers for Disease Control and Prevention (Atlanta, Ga) because of the organism's characteristic pink colonies. Since 1991 we have isolated Roseomonas from eight patients; in seven from blood cultures and in one from a skin lesion. The seven blood isolates were from patients with clinically significant underlying diseases who had central venous catheters in place; the majority were associated with polymicrobial catheter infections. Additional characteristics of their infections are described. The eight isolates had originally been identified by us as Centers for Disease Control (CDC) pink-coccoid group III. These organisms were re-identified using the criteria of Rihs et al, and all isolates fit most closely with Roseomonas gilardii. Antibiotic profiles were fairly homogeneous showing susceptibility to many antibiotics, but uniform resistance to cefoxitin, ceftazidime, and piperacillin. Attempts to determine whether the isolates were the same strain by pulsed-field gel electrophoresis suggested that 3 of the isolates were similar. Random amplified polymorphic DNA analysis, however, demonstrated that each of the eight isolates was a unique strain.

Adult↗

Cytomegalovirus infection in children with human immunodeficiency virus infection.

OBJECTIVES: To determine retrospectively the prevalence of positive cytomegalovirus (CMV) cultures in pediatric patients with human immunodeficiency virus infection. METHODS: We reviewed the records of 273 children with human immunodeficiency virus infection referred to the Pediatric Branch of the National Cancer Institute for whom CMV cultures were performed between January, 1991, and October, 1994. RESULTS: Of this group 189 patients (69%) had negative CMV cultures and 84 (31%) had positive cultures. The prevalence of CMV-related disease was 9% for the entire group, including 4 (2.1%) patients with negative CMV cultures. Among the 84 patients with positive CMV cultures, 21 (25%) had evidence of CMV disease. Patients with positive CMV cultures had a statistically significant decrease in survival in the presence of severe immunocompromise defined as an age-corrected CD4 count of < 21%. Nine of 35 (26%) autopsies performed demonstrated evidence of CMV disease, including 7 patients with disseminated CMV disease. CONCLUSIONS: Although CMV disease appears to be less frequent in children than adults, CMV infection still contributes significantly to morbidity and mortality in this population, especially when combined with severe immunosuppression.

AIDS-Related Opportunistic Infections↗