PubMed HealthSearch

Biomedical subjects

D L Palmer

Publications and source records attributed to D L Palmer.

At least 19 recordsLinked to original sources

Inorganic pyrophosphate generation from adenosine triphosphate by cell-free human synovial fluid.

OBJECTIVE: To quantify inorganic pyrophosphate (PPi) production from extracellular adenosine triphosphate (ATP) by human synovial fluids (SF). METHODS: Serial measurements of ATP hydrolysis rate (t1/2) were performed by the luciferase method from a starting concentration of 500 nM in 21 pathologic and one normal cell-free SF samples incubated under physiologic conditions. ATP was then pumped into a sample of each fluid, using the rate constant derived from the t1/2 of that fluid, to provide steady state levels simulating those reported in SF. Trace [32P] gamma ATP was added at the start of the infusion; conversion to [32P] Pi and to [32P] PPi was determined by precipitation of Pi as reduced phosphomolybdate before and after treatment with yeast inorganic pyrophosphatase. Finally, the pumping experiment was repeated and PPi production was calculated from direct measurement of PPi at time zero and at 60 min. PPi hydrolysis was measured in each fluid by [32P] Pi precipitation from [32P] PPi tracer added at time zero. RESULTS: ATP was hydrolyzed by all SF. The mean t1/2 (seconds) in 8 osteoarthritis (OA) samples was 72 s, in 5 calcium pyrophosphate dihydrate (CPPD) 30 s (p < 0.02), in 3 rheumatoid arthritis (RA) 1160 s, in normal 86 s, in 3 olecranon bursal (OB) 54 s, and in 2 total knee replacement fluid samples 17 and 121 s. The major product of ATP hydrolysis was PPi in all but 2 fluids (1 RA, 1 OB), even at lower than steady state levels. At simulated in vivo steady state ATP levels, mean conversion of APT to PPi was stoichiometric in OA and CPPD fluids. PPi hydrolysis was < 4% in all noninflammatory fluids. CONCLUSION: PPi is the major product of extracellular ATP catabolism in most SF. Hydrolysis rates were significantly faster in SF containing CPPD crystals. Mean PPi production by these fluids at simulated in vivo steady state levels was 6-fold that of OA SF (p < 0.01). Hydrolysis of extracellular ATP by ectonucleotide pyrophosphohydrolases can account for all PPi produced by joint issues previously estimated from [32P] PPi pool and turnover studies in human knee joints.

Adenosine Triphosphate

Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics.

Broad-spectrum versus narrow-spectrum antibiotic prophylaxis for patients who undergo cardiac operations is variously advocated to reduce the incidence of all infections or, conversely, to prevent resistant superinfections. Previous studies of prophylaxis have shown a reduction in the incidence of staphylococcal infections with some increased resistance. We studied preoperative and postoperative wound colonization as a surrogate for infection. Among 78 patients undergoing cardiac procedures, the type of prophylaxis was allocated as follows: narrow-spectrum (nafcillin), 24 patients; midspectrum (cephapirin), 26 patients; and broad-spectrum (ceftriaxone), 28 patients. Seventeen patients who underwent other procedures received no antibiotics and served as controls. Cultures of the operative site were done preoperatively, and 3 and 6 days postoperatively. The incidence of preoperative skin colonization with staphylococci was identical (95%) in all groups. Postoperatively, more patients receiving nafcillin (48%) were culture-negative for all organisms than were either of the other groups receiving antibiotics (27% and 22%) (p < 0.05). Gram-negative bacilli were infrequent colonizers and neither did the incidence of infection with these organisms increase nor did resistance develop in any group. The infection rates were not different among the treatment groups. Thus, a narrow-spectrum antistaphylococcal penicillin may offer an advantage in terms of both prophylaxis for cardiac operations and hospital costs.

Bacteria

HIV-1 infection despite immediate combination antiviral therapy after infusion of contaminated white cells.

We present a sixth human case in which primary human immunodeficiency virus (HIV-1) infection occurred, despite antiretroviral prophylaxis, after accidental inoculation of infected blood. In the prior five instances, variables such as large virus dose, late administration of antivirals, viral resistance to zidovudine, and pre-existent immunosuppression, may have played a role in the treatment failure. In this case, high-dosage oral zidovudine was given within minutes of the accident and replaced 2 1/2 days later with interferon alpha and dideoxyinosine (ddl). Despite aggressive treatment, HIV-1 infection was demonstrated in blood, spleen, and brain tissue at autopsy 16 days later. Of the tissues studied, detection of HIV-1 was most prominent in the spleen. Double-label immunocytochemistry confirmed the morphologic impression that while some of the infected spleen cells were CD3-positive T cells, the majority were macrophages. Thus, current single or dual (zidovudine, ddl-interferon) therapies for accidental HIV-1 inoculation may not be effective in preventing early infection. Further trials in animals appear warranted to evaluate protection by other strategies, such as passive immunity or combinations of agents that penetrate the brain and attack HIV-1 viral replication at differing sites.

Aged

Early viral brain invasion in iatrogenic human immunodeficiency virus infection.

We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.

Aged

Seroprevalence of HIV-1 and hepatitis B and C in prostitutes in Albuquerque, New Mexico.

A survey of persons soliciting sex in an area known to be frequented by prostitutes in Albuquerque, NM, included 43 females and 66 males. Seroprevalence rates found in this population-based study were as follows: human immunodeficiency virus type 1 (HIV-1), 3%; hepatitis B, 39%; hepatitis C, 45%. Increased age, intravenous drug use, and condom use were independent risk factors for hepatitis B. Female gender and intravenous drug use were independent risk factors for hepatitis C. Neither sharing injection equipment nor engaging in receptive anal intercourse was independently associated with hepatitis B or C.

Adult

Melioidosis. Forgotten, but not gone!

Melioidosis, infection by the soil bacterium Pseudomonas pseudomallei, has the potential for prolonged latency with recrudescence into an acute, often fulminating, and fatal infection. Although the organism is never found in North America, infection is endemic in areas of southeast Asia, and populations of service personnel exposed during the Vietnam war and southeast Asian immigrants are at risk of severe recrudescent disease. Diagnosis, however, has been missed or delayed because of lack of familiarity with this disease. We present a case of recrudescent melioidosis that illustrates the difficulties encountered in diagnosis and treatment. This case involves a 76-year-old Vietnam veteran who presented with melioidosis of the bone 18 years after exposure to the organism and 10 years after a missed diagnosis of latent pulmonary disease. This case illustrates the protean nature of latent infection and the difficulty of selecting successful antibiotic therapy.

Aged

Surgical therapy for rectovaginal fistulas in ulcerative colitis.

During a 9-year period, six women with ulcerative colitis (UC) and rectovaginal fistulas were surgically treated. Three underwent ileoanal pull-through procedures with simultaneous repair of the rectovaginal fistulas. Two patients had Kock pouches, and one had a Brooke ileostomy because extensive destruction of the rectal sphincter prohibited ileoanal procedures. The three patients who had ileoanal procedures all had excellent functional results. There has been no evidence of Crohn's disease or fistula recurrence. We believe that rectovaginal fistulas occur more frequently in UC than is generally accepted, and they can be safely managed with current reconstructive techniques.

Adult

Septic necrosis of the midline wound in postoperative peritonitis. Successful management by debridement, myocutaneous advancement, and primary skin closure.

Wound management following laparotomy for postoperative peritonitis and varying degrees of parietal necrosis remains a challenging and controversial problem. Because maintained peritoneal integrity and primary wound closure offer the best opportunity for survival, an original technique involving bilateral incisions to relax skin and rectus fascia is proposed. This technique permits medial myocutaneous advancement and primary tension-free skin closure of midline laparotomy incisions. Sixty-nine patients with severe postoperative peritonitis were treated according from 1980 through 1985. Nine of these patients died of advanced multiple organ failure soon after referral, and eight more died after prolonged treatment. Fourteen patients had one or more reoperations for complications. Only nine wound failures resulted, including five eviscerations and four wound infections followed by progressive dehiscence. The bilateral relaxing incisions healed secondarily without complication. Survivors developed midline wound hernia; ten of the 52 surviving patients have had these repaired. This method of primary closure is safe when performed in conjunction with rigorous surgical care of intraperitoneal infection and may enhance survival. We recommend the technique to surgeons who treat severe postoperative peritonitis and septic necrosis of midline laparotomy wounds.

Debridement

Diagnosis of pneumococcal pneumonia.

Pneumococcal pneumonia presents peculiar problems to the diagnostician. It is at once the most common form of community-acquired bacterial pneumonia and simultaneously the most difficult to document microbiologically. Bacteremia, empyema, meningitis, or septic arthritis due to S pneumoniae unmistakably verifies this bacterium as the cause of a coexistent pneumonia; this coexistence fortunately occurs infrequently. The diagnostic dilemma arises in the less sick patient. While recognizing the common presence of pneumococci in the oropharynx of healthy individuals, we give undue credence to S pneumoniae cultured from sputum obtained by expectoration. At the same time, pneumococci are frequently not found in cultures of sputum obtained from patients with confirmed bacteremic disease. More invasive techniques (transtracheal aspiration, protected bronchoscopic catheter, lung needle aspiration) are too complex, dangerous, or both for routine use. Attempts to detect pneumococcal antigen in blood, sputum, or urine by modern immunologic techniques give promise of avoiding the problems of either contamination or lack of bacteriologic growth. However, they have not yet been evaluated in sufficiently large groups with pneumonia of independently determined bacterial etiology to calculate test sensitivity and specificity. At the present time then, the careful clinician will use all the epidemiologic and clinical evidence at hand, including a careful Gram's stain and culturing of sputum, blood, and other sources, to arrive at the most likely etiology. The probabilities must be weighed in light of the imprecision of current laboratory confirmation and modified by clinical course. Choice of antimicrobial therapy still favor penicillin for patients with community pneumonia severe enough to warrant hospitalization, despite ominous trends in multiple resistance of S pneumoniae.

Anti-Bacterial Agents

Cellular immune competence and diarrheal morbidity in malnourished Bangladeshi children: a prospective field study.

A year-long prospective study of 152 Bangladeshi children with mild to moderate protein-calorie malnutrition related nutritional status and cellular immune defects to morbidity due to diarrheal, respiratory, and febrile diseases. In children older than 36 mo, wasting correlated with skin test anergy to three recall antigens and with inability to initiate hypersensitivity to dinitrochlorobenzene. In this older age group, anergy was associated with a 58% increased attack rate and an 83% increased duration of diarrheal diseases but not with febrile or respiratory infections. In stepwise regression analysis, this anergy effect was independent of the small negative impact of poorer nutritional status on morbidity. Ninety-three percent of diarrheal illnesses lasting at least 14 d were among anergic children. Cellular immune incompetence, indicated by anergy of unknown etiology, is associated with increased diarrheal morbidity and may promote the vicious cycle of repeated infections and deteriorating nutritional status.

Bangladesh

Pneumonia treated with imipenem/cilastatin.

In an open, prospective, multicenter trial the efficacy and tolerance of imipenem/cilastatin for the treatment of bacterial pneumonia was investigated. Forty-three adults were studied: 29 with nosocomial and 14 with community-acquired infections. Significant underlying disease was present in 91 percent of patients. Nosocomial infection was frequently associated with endotracheal intubation (48 percent), prior antibiotic therapy (48 percent), and recent surgery (31 percent). Most frequent sputum isolates included Pseudomonas aeruginosa (10, all nosocomial), Hemophilus influenzae (10), Escherichia coli (eight), Staphylococcus aureus (seven), and Streptococcus pneumoniae (six). Treatment with imipenem/cilastatin was associated with clinical cure in 93 percent of patients. Two of three failures and one superinfection occurred in association with isolates of Pseudomonas aeruginosa resistant to imipenem. Overall, six of 10 strains of Pseudomonas aeruginosa isolated prior to therapy developed resistance to imipenem after an average of 10 days of therapy. Adverse effects occurred in nine patients (21 percent) and included one case of pseudomembranous colitis. Monotherapy with imipenem/cilastatin of serious lower respiratory tract infections was relatively safe and highly effective with the exception of disease associated with P. aeruginosa.

Adult

Enterobacter mediastinitis following cardiac surgery.

Eight cases of sternal/mediastinal infection due to Enterobacter species were seen in postoperative cardiac patients during 1980 to 1981. The attack rate was 14.5% (8/55), compared to 3.7% (2/54) for an identical period in 1979 to 1980 (p less than 0.05). Cases varied in severity from fulminant, acute bacteremic infections (one death) to less severe wound infection. Late complications or recurrences were not seen. There was a hospital-wide increase, relative to all other gram-negative bacillary isolates, in Enterobacter laboratory isolations, but no increased rate of infection in any other specific surgical condition. No personnel, materials, or techniques were associated with the outbreak, and all but two environmental cultures were negative. Case-control analysis suggested that surgical complications and prophylactic cephalosporins were associated with infection. Prospectively, an additional 85 cardiac surgery patients had increased Enterobacter skin/wound colonization following perioperative prophylaxis with cephalosporin antibiotics. After introduction of barrier isolation and restriction of contacts no further mediastinitis occurred in 100 subsequent cardiac surgery patients. This study indicates that Enterobacter may be major pathogens causing post-cardiac-surgery infection not prevented by cephalosporin prophylaxis.

Cardiac Surgical Procedures

Microbiology of pneumonia in the patient at risk.

Microorganisms causing pulmonary infections in high risk patients vary considerably with the predisposing illness (immunosuppression, alcoholism, or diabetes), the setting (nosocomial or community-acquired), and previous therapy (antibiotics, surgery, and inhalation therapy). Even in the immunocompromised patient, conventional bacteria are the most prevalent opportunistic pathogens, and gram-positive cocci such as staphylococci and gram-negative bacilli such as Escherichia coli cause most pneumonias. Fungi, viruses, and protozoa also cause pulmonary infections, but they vary in frequency from one institution to another. Diagnostic proof of the etiology of pulmonary infection is often difficult to obtain. The microbial flora of sputum is not definitive and must be confirmed by blood or pleural fluid culture, antigen or serologic response in body fluids, or morphologic presence in lung tissue. Resistance to antimicrobial therapy is increasing, especially among nosocomially acquired gram-negative bacilli and methicillin-resistant staphylococci. A potential for increased resistance exists in pneumococcal, viral, and fungal infection but is not yet apparent in pulmonary infections due to protozoal pathogens. Tests to predict antibiotic response such as serum bactericidal assay, repeated cultures, and serologic studies are helpful but correlate imperfectly with clinical outcome.

Cross Infection

Multidrug-resistant Serratia marcescens bacteriuria related to urologic instrumentation.

An outbreak of urinary tract infections caused by multidrug-resistant Serratia marcescens lasted for 12 months and was found to be related to urologic instrumentation. Thirty-four patients had primary infections; four had cross-infections. Only six patients had indwelling bladder catheters. The median interval between instrumentation and initial isolation of Serratia was six days. Seventy-three percent of patients were symptomatic, two were bacteremic. No common instruments, personnel, or wards were identified, and environmental cultures failed to reveal the epidemic strain of Serratia. The outbreak ended when the instrument disinfectant was changed. Serotyping was identical in nine of ten isolates. Intraspecies conjugation demonstrated resistance transfer of gentamicin, tobramycin, carbenicillin, chloramphenicol, and co-trimoxazole. The enzyme 6'-N-acetyl transferase was responsible for gentamicin-inactivation in patient isolates and a transconjugate. Although no significant spread of this multidrug-resistance plasmid to other Enterobacteriaceae occurred in the hospital, two instances of apparent in vivo transfer to other bladder organisms occurred.

Adult