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Biomedical subjects

R L Penn

Publications and source records attributed to R L Penn.

At least 19 recordsLinked to original sources

Possible clinically significant interaction of itraconazole plus rifampin.

We report two patients treated with the combination of itraconazole plus rifampin for more than 4 months. While on itraconazole plus rifampin, patient 1 lost weight at a rate of 30 g/d. After stopping rifampin, he gained 14 g/d. While on itraconazole plus rifampin, patient 2 lost 41 grams/day. After stopping rifampin, he gained 33 g/d. Weight loss while taking the combination of itraconazole plus rifampin, followed by weight gain after stopping rifampin, suggests the possibility of a clinically significant drug interaction between itraconazole and rifampin.

AIDS-Related Opportunistic Infections↗

Aggregation-based crystal growth and microstructure development in natural iron oxyhydroxide biomineralization products.

Crystals are generally considered to grow by attachment of ions to inorganic surfaces or organic templates. High-resolution transmission electron microscopy of biomineralization products of iron-oxidizing bacteria revealed an alternative coarsening mechanism in which adjacent 2- to 3-nanometer particles aggregate and rotate so their structures adopt parallel orientations in three dimensions. Crystal growth is accomplished by eliminating water molecules at interfaces and forming iron-oxygen bonds. Self-assembly occurs at multiple sites, leading to a coarser, polycrystalline material. Point defects (from surface-adsorbed impurities), dislocations, and slabs of structurally distinct material are created as a consequence of this growth mechanism and can dramatically impact subsequent reactivity.

Betaproteobacteria↗

Trimethoprim-sulfamethoxazole prophylaxis in granulocytopenic patients with acute leukemia: evaluation of serum antibiotic levels in a randomized, double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study.

Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (< 100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purported activity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.

Acute Disease↗

Interleukin-2 enhances the translocation of Escherichia coli from the intestines to other organs.

To determine if interleukin-2 (IL-2) would inhibit gastrointestinal bacterial translocation, mice were gut-decontaminated and recolonized with Escherichia coli C25; some groups were pretreated with 200 mg/kg cyclophosphamide. IL-2 (1.68 mg/kg) or sterile diluent was injected twice daily for 3 or 5 days, and mice were sacrificed the next day. High cecal levels of E. coli C25 were present in all mice. The overall incidence of E. coli C25 translocation to mesenteric lymph nodes was not reduced by IL-2. The median numbers of translocated E. coli C25/g of mesenteric lymph node were significantly (P less than .005) higher after both 3 days (659 vs. 117) and 5 days (550 vs. 50) of treatment with IL-2 with cyclophosphamide and after 5 days (1784 vs. 225) of IL-2 without cyclophosphamide. IL-2 prevented neutropenia and exacerbated lymphopenia caused by cyclophosphamide. The in vitro growth of E. coli C25 was not affected by up to 10(5) units/ml IL-2. Ileal and cecal structures assessed by light and electron microscopy were not altered by IL-2. Thus, IL-2 unexpectedly enhanced the translocation of E. coli C25 from the gastrointestinal tracts of both cyclophosphamide-pretreated and normal mice.

Animals↗

Factitious meningitis: a recurring problem.

Although gram-negative meningitis is rare in our hospital, between July, 1982 and July, 1983 clusters of cerebrospinal fluid (CSF) smears were reported positive for gram-negative bacilli. Fourteen specimens were obtained by diagnostic lumbar punctures, and one was obtained during a myelogram. No CSF cultures were positive, and a diagnosis of factitious meningitis was eventually established for each patient. Nonviable gram-negative bacilli were found in 6.7% of manometers, and 23.3% to 90% of the specimen tubes tested from the same lots of commercial lumbar puncture trays. It was estimated that there were between 44 and 333 organisms per specimen tube. Two lots of the commercial myelogram trays yielded nonviable gram-negative bacilli from 50% of the specimen tubes and 33.3% of the manometers tested. Retrospective review of laboratory records for 1982 and 1983 revealed 23 total CSF smears positive for gram-negative bacilli. No CSF grew gram-negative bacilli, and chart reviews confirmed a diagnosis of factitious meningitis in each case. In addition to the clusters of false-positive smears, this had occurred sporadically in both years. The problem did not recur after separate sterile tubes were provided for CSF collection. Physicians and laboratories should be aware that nonviable contaminants in commercial products may be a source of false-positive CSF gram-stained smears.

Cerebrospinal Fluid↗

Multiple myeloma: infectious complications.

We review a ten-year experience in treating 60 patients with multiple myeloma. Infectious episodes occurred in 33 patients. Urinary tract infections caused by gram-negative organisms were the most frequent infections, and most of these were the result of catheterization. Pneumonia due to Streptococcus pneumoniae was encountered infrequently. This series confirms the emergence of gram-negative bacilli as the predominant pathogens in patients with multiple myeloma, and emphasizes the risk of instrumentation in these patients.

Adult↗

Pneumococcosuria in adults.

Pneumococcal bacteriuria is usually felt to indicate systemic pneumococcal infection, especially in children. To determine the frequency and significance of pneumococcosuria in adults, we reviewed the Shreveport Veterans Administration Medical Center microbiology laboratory log books for 1982 through 1985. During these 4 years, more patients had pneumococcal bacteriuria than bacteremia (38 versus 33), but only 2 patients had both. The medical records from 31 bacteriuric patients with 35 positive urine specimens were available for review. The collection technique was reliable for 23 (66%) urine specimens; the type of collection technique used was unknown for 12 (34%). The urine pH was less than or equal to 6 in 24 (68%) specimens, and the specific gravity was greater than 1.020 in 12 specimens (34%). A total of 24 specimens grew only Streptococcus pneumoniae, and 11 yielded mixed growth. All 31 patients were men, 25 (81%) were 60 years or older, and 13 (42%) had underlying genitourinary disorders. A total of 7 patients had genitourinary symptoms, 7 had fever, 5 had leukocytosis, and 12 had pyuria; however, these symptoms and signs were frequently accounted for by factors other than pneumococcosuria. Pneumococcosuria was an unexpected finding in all but two (6%) bacteremic patients. These were the only patients with systemic pneumococcal infections, and both died despite appropriate antibiotics. Among the 20 surviving patients with follow-up urine samples, pneumococcosuria resolved whether or not they had received antibiotics. Thus, pneumococcosuria in our patient population was frequently not accompanied by systemic pneumococcal infection and by itself did not require antibiotic therapy.

Adult↗

Candida krusei infectious arthritis. A rare complication of neutropenia.

Candida krusei infections are increasing in neutropenic patients. This is the first report of a case of C. krusei arthritis in a neutropenic leukemic patient. The organism colonized the patient's respiratory tract and most likely seeded the right knee by hematogenous spread. Knee swelling and tenderness were minimal. Joint fluid Gram stain and fungal smears did not show the organism despite positive results on cultures. With therapy, the joint fluid converted from neutrophilic predominance to lymphocytic predominance. Despite sterilization of knee fluid, clinical relapse occurred after therapy with 256 mg of systemic amphotericin B; the infection was cured after a total dose of 456 mg.

Adult↗

Clinical differentiation of abscess from neoplasm in newly diagnosed space-occupying lesions of the liver.

The clinical presentations of liver abscess, hepatoma, and metastatic tumor to the liver may be quite similar, and procedures such as computerized tomography, radionuclide scanning, and ultrasonography of the liver cannot make a specific diagnosis. Therefore, we compared the clinical presentations of 38 patients seen during the last five years with liver abscess (13 patients), hepatoma (eight patients), and undifferentiated carcinoma metastatic to the liver (17 patients). Patients with liver abscess were distinguished from the other two groups by a significantly shorter prodrome, a history of known risk factors for liver abscess, fever, leukocytosis, and a normal-sized liver (P values all less than .1). A finding of three or more of these criteria correctly identified all cases of liver abscess. Only one of the 25 patients with neoplasms had three of the criteria. The presence of multiple or single lesions, abdominal pain, weight loss, or liver function abnormalities did not differ significantly among the three groups. Thus patients with liver abscess can be reliably differentiated from patients with hepatic neoplasms by clinical criteria alone, and appropriate empiric antibiotic therapy can be started while the diagnosis is being confirmed.

Carcinoma, Hepatocellular↗

Acid-fast staining of urine and gastric contents is an excellent indicator of mycobacterial disease.

It is a commonly held opinion that acid-fast staining of urine or gastric aspirates is not a reliable indicator of mycobacterial disease because of the presence of saprophytic mycobacteria. In order to determine the clinical usefulness of acid-fast staining of these body fluids, we reviewed our 10-yr experience with acid-fast stains. Forty-seven of 5,829 urine specimens (0.8%) and 39 of 309 gastric aspirates (12.6%) yielded mycobacteria on culture. Twenty-three urine specimens and 12 gastric aspirates had positive acid-fast stains. Of these, only one possible false positive acid-fast stain of urine (less than 1%) was found and none was found in gastric aspirates. Thus, acid-fast stains of urine and gastric aspirates are, when positive, reliable indicators of true mycobacterial disease.

Bacteriological Techniques↗

Factors associated with a poor outcome in tularemia.

To identify the factors associated with a poor outcome, we reviewed the records of 28 patients with tularemia diagnosed between 1974 and 1984. Most of the patients were men between the ages of 35 and 45 years, who presented with ulceroglandular tularemia. Twelve patients had the anticipated rapid response to therapy, with resolution of their presenting symptoms within one week (group A). Surprisingly, the majority (16 [58%] of 28) had a more prolonged or fatal illness (group B). Group B patients more often had a serious underlying medical disorder, and waited longer before seeking medical attention. Only patients in group B presented with electrolyte or renal function abnormalities (31%), pneumonia and pleural effusions (25%), elevated serum creatine phosphokinase levels (25%), and Francisella tularensis bacteremia (12.5%). Sterile pyuria, however, was an unexpectedly frequent finding in both groups. Group B patients more often experienced a prolonged delay from the time of physician contact to therapy, and were not treated with an aminoglycoside; relapse (12.5%) and death (6.2%) occurred only in group B. Thus, earlier and more appropriate intervention by the physician may have prevented some of the increased morbidity in our patients. These findings suggest that rapid presumptive aminoglycoside therapy (gentamicin sulfate or streptomycin sulfate) should be considered soon after tularemia is suspected, especially for patients with serious underlying medical disorders.

Adult↗

Isolation of Francisella tularensis from blood.

The isolation of Francisella tularensis from blood culture is extremely rare; a review of the literature produced only five documented cases. However, over a recent 17-month period we saw four cases of tularemia in which the organism was isolated in blood culture. The clinical presentations of our patients and those reported previously were very similar. Most of the patients had a significant underlying disease and presented with the typhoidal form of tularemia. Furthermore, all our patients had sepsis, pleuropulmonary disease, and rhabdomyolysis. Tularemia agglutinins were not performed on admission serum specimens or were nondiagnostic. All the F. tularensis isolates from blood culture in our series and most of the recent documented cases were obtained in radiometric blood culture systems, which may be more sensitive than conventional systems for detecting this fastidious microorganism.

Aged↗

Antigen detection in the diagnosis of fungal respiratory infections.

The diagnosis of fungal infections of the respiratory tract is often difficult and may require invasive diagnostic procedures. The detection of soluble fungal antigens in bodily fluids such as serum, pleural fluid, and bronchoalveolar lavage fluid may substantially improve the ability to diagnose fungal respiratory diseases. For instance, uncommon presentations of diseases with the pathogenic fungi, such as chronic cavitary histoplasmosis, coccidioidal empyema, and cryptococcal pneumonia are often difficult to diagnose with present techniques, and the detection of fungal antigens may prove to be more sensitive. There is an especially urgent need for sensitive, reliable, commercially available tests for the diagnosis of opportunistic fungal pneumonias that occur in immunocompromised hosts. Preliminary data holds promise for the noninvasive diagnosis of deep-seated candidiasis (including pneumonia) and pulmonary aspergillosis by the detection of fungal antigens in serum and bronchoalveolar lavage fluid. We review current techniques used for the detection of fungal antigens, including their sensitivity and specificity, and their use in diagnosing human infections.

Antigens, Fungal↗

Increased translocation of bacteria from the gastrointestinal tracts of tumor-bearing mice.

Aerobic gram-negative bacilli and other indigenous gastrointestinal (GI) bacteria are important opportunistic pathogens in immunosuppressed cancer patients. These same bacteria frequently translocate from the GI tracts of mice immunosuppressed by single injections of certain anticancer drugs or by T-lymphocyte impairments. Since similar cellular and humoral immune deficiencies may be present in the tumor-bearing host, we sought to determine if progressive growth of a tumor alone would be sufficient to enhance the translocation of indigenous bacteria from the murine GI tract. Pathogen-free DBA/2 mice were injected intraperitoneally with 10(6) viable sarcoma 180 (S-180) cells or 0.5 ml of sterile buffer. Mesenteric lymph nodes, livers, spleens, and kidneys were tested for the presence of translocated aerobic GI bacteria on various days after tumor injection. Immunity was assessed by measuring footpad delayed-type hypersensitivity and serum hemagglutinins to sheep erythrocytes. Overall, translocated aerobic GI bacteria infected 33 of 92 S-180-bearing mice (36%) and only 9 of 99 control mice (9%) (P less than 10(-6)). Cumulatively, 50 of 460 sites (10.9%) in S-180-bearing mice were infected with translocated GI bacteria as opposed to only 9 of 485 sites (1.9%) in control animals (P less than 10(-7)). GI bacteria often translocated to infect more than one site in tumor-bearing mice, but not in controls. Aerobic gram-negative bacilli translocated 11 times in tumor-bearing mice, but only once in controls, even though the mean cecal population levels of these bacteria were relatively low (range, 4.33 to 5.28 log10 bacteria per g). The population levels of cecal aerobic bacteria were similar in S-180 and control mice throughout the period of observation. S-180 mice had significantly suppressed (P less than 0.04) delayed-type hypersensitivity and serum hemagglutinin responses when sensitized 4 or 8 days after S-180 injection. S-180 growth was associated with a neutrophilic leukocytosis and a slight drop in platelet counts; no bleeding was detected. Thus, the translocation of gram-negative bacilli and other indigenous aerobic bacteria from the GI tract to the mesenteric lymph nodes and other organs was increased in immunosuppressed S-180-bearing mice, and this increase was not caused by bacterial overgrowth in the intestines or by neutropenia.

Animals↗

Mycobacterial, fungal, actinomycotic, and nocardial infections of the pleura.

Granulomatous pleuritis is relatively common, comprising about 10 per cent of all pleural effusions. A search for the etiologic agent is important since mycobacteria, fungi, and the higher bacteria Actinomyces and Nocardia produce similar clinical, radiographic, and pleural fluid findings. The appropriate use of diagnostic tests including pleural biopsy and serologic techniques is discussed, as are current approaches to the management of these infections.

Actinomycosis↗

Activity of ceftizoxime combined with gentamicin against 100 clinical isolates of Pseudomonas aeruginosa.

The effects of ceftizoxime and gentamicin alone and in combination were determined against 100 Pseudomonas aeruginosa strains. Concentrations of 32 micrograms of ceftizoxime and 8 micrograms of gentamicin per ml inhibited 22 and 43% of the strains, respectively. At concentrations of ceftizoxime and gentamicin that are readily achievable in serum, 15 strains were affected synergistically and 17 strains were affected antagonistically. Gentamicin accounted for most of the anti-P. aeruginosa activity of ceftizoxime-gentamicin combinations.

Cefotaxime↗