Showing papers in "The Journal of Infectious Diseases in 1988"

The AIDS Dementia Complex

Abstract: Note from Dr. Merle A. Sande?Progressive dementia has been recognized as a complication of human immunodeficiency virus infection almost since the beginning of the epidemic. To many infectious diseases clinicians, however, the AIDS dementia complex remains ambiguous, and the clinical approach to this problem is less clearly defined than that for other infection-associated syndromes. Dr. Richard W. Price and his colleagues at Memorial Sloan-Kettering Cancer Center have, to a large extent, been responsible for defining this entity. In this AIDS Commentary they present their views of the current state of knowledge regarding the etiology, clinical presentation, and diagnostic and therapeutic approaches to the AIDS dementia complex.

Experimental Campylobacter jejuni Infection in Humans

Abstract: Two strains of Campylobacter jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 10(2) to 2 x 10(9) organisms, caused diarrheal illnesses. Rates of infection increased with dose, but development of illness did not show a clear dose relation. Resulting illnesses with strain A3249 ranged from a few loose stools to dysentery, with an average of five diarrheal stools and a volume of 509 mL. Infection with strain 81-176 was more likely to cause illness, and these illnesses were more severe, with an average of 15 stools and 1484 mL of total stool volume. All patients had fecal leukocytes. The dysenteric nature of the illness indicates that the pathogenesis of C. jejuni infection includes tissue inflammation. Ill volunteers developed a serum antibody response to the C. jejuni group antigen and were protected from subsequent illness but not infection with the same strain.

Correlation of Antimicrobial Pharmacokinetic Parameters with Therapeutic Efficacy in an Animal Model

Abstract: Current antimicrobial dosing regimens are designed to maintain active drug levels for most of the dosing interval and are based on 40-y-old observations. With use of numerous multiple-dosing regimens in an animal model, this study is the first to successfully minimize the interdependence between pharmacokinetic parameters and thereby determine, by stepwise multivariate regression analysis, that the time that serum levels exceeded the minimum inhibitory concentration (MIC) was the most significant parameter determining efficacy for beta-lactams and erythromycin against various pathogens, whereas the log area under the curve was the major parameter for aminoglycosides. Optimal dosing intervals were no greater than the time that serum levels exceeded the MIC plus the duration of the postantibiotic effect. Careful application of these concepts should allow other investigators to use more optimally dosed regimens than those previously used in preclinical trials and to design studies to improve on current dosing regimens for humans.

Fibronectin, Fibrinogen, and Laminin Act as Mediators of Adherence of Clinical Staphylococcal Isolates to Foreign Material

Abstract: Bacterial adherence to polymer surfaces is a required early step in intravenous (iv) device infection. We collected eight strains of Staphylococcus aureus and 19 of coagulase-negative staphylococci from patients with proven iv device bacteremia and studied the role of plasma or connective-tissue proteins in promoting bacterial adherence to polymethylmethacrylate (PMMA) coverslips. Although only a negligible percentage of organisms adhered to albumin-coated PMMA, surface-bound fibronectin significantly promoted adherence of all isolates. Fibrinogen markedly promoted adherence of all S. aureus strains but of only four coagulase-negative strains. Thus, coagulase-negative staphylococci revealed a marked heterogeneity in adherence to fibrinogen-coated surfaces, a result suggesting the existence of heretofore unknown receptors for fibrinogen. Laminin promoted adherence of staphylococci to a much lower extent. Although strain specific, adherence of clinical staphylococcal isolates to foreign surfaces is significantly increased by fibronectin, fibrinogen, and laminin, an observation suggesting the possible contribution of these proteins to the pathogenesis of iv device infection.

Detection of Cytomegalovirus in Urine from Newborns by Using Polymerase Chain Reaction DNA Amplification

Abstract: Polymerase chain reaction (PCR) amplification was used to detect cytomegalovirus (CMV) in tissue culture and in urine specimens from newborns. Synthetic oligonucleotide primer pairs were used to amplify DNA from the major immediate-early and the late antigen genes of CMV. Amplified products were detected by gel electrophoresis and by dot-blot hybridization with oligonucleotide probes. Using one or both of the primer pairs and associated probes, we found 46 different tissue culture isolates of CMV that were positive; no reaction products were detected when the same primers and probes were used to amplify other herpes family viruses or human genomic DNA. Urine samples from 44 congenitally infected infants were positive when tested with one or both primer pairs and probes. When compared with tissue culture, detection by gel electrophoresis provided a sensitivity of 93%, a specificity of 100%, and a predictive value of a positive result of 100%. Dot-blot analysis raised the sensitivity to 100%. We conclude that PCR amplification may be a valuable tool for diagnosing congenital CMV infection.

A Broad-Spectrum Probe for Molecular Epidemiology of Bacteria: Ribosomal RNA

Abstract: We investigated the use of ribosomal RNA (rRNA) as a probe for molecular epidemiology of bacterial pathogens. The chromosomal DNA of Escherichia coli, Pseudomonas cepacia, and nontypable Haemophilus influenzae was digested with EcoRI. Agarose gel electrophoresis, Southern blotting, and hybridization by 32P-labeled rRNA revealed eight to 13 bands. The P. cepacia and H. influenzae banding patterns, observed by using an E. coli rRNA probe, were identical to those produced with homologous rRNA probes. Polymorphism of several hybridization bands distinguished all E. coli isolates, nine of 10 H. influenzae isolates, and seven of eight P. cepacia isolates. Two to four bands were common to all P. cepacia and E. coli isolates. The banding patterns of H. influenzae isolates cultured from the trachea and blood of an infant and from the mother's cervix were identical. These data demonstrate that this method is a widely applicable system for determining the molecular epidemiology of genetically diverse gram-negative organisms.

The Eagle Effect Revisited: Efficacy of Clindamycin, Erythromycin, and Penicillin in the Treatment of Streptococcal Myositis

Abstract: We investigated the relative efficacies of penicillin, clindamycin, and erythromycin in a mouse model of myositis due to Streptococcus pyogenes Penicillin was ineffective unless given at the time of bacterial injection, and treatment delays of 2 h reduced its efficacy such that survival was no better than that of untreated control animals (P less than 05) Survival of erythromycin-treated mice was greater than that of both penicillin-treated mice and untreated controls, but only if treatment was begun within 2 h Mice receiving clindamycin, however, had survival rates of 100%, 100%, 80%, and 70% even if treatment was delayed 0, 2, 6, and 165 h, respectively Thus, clindamycin demonstrated superior efficacy to penicillin among all the various treatment groups (P less than 05) Our results corroborate the failure of penicillin in this model of streptococcal infection and suggest that, unlike penicillin, the efficacy of clindamycin is not adversely altered by the "Eagle effect"

Cryptococcal Meningitis in Patients with AIDS

Abstract: The Cryptococcus has become a major cause of meningitis in patients infected with the human immunodeficiency virus (HIV), and the expression of cryptococcal infection in this population of patients is quite unique. Often the infection is devoid of inflammatory response and is associated with very high antigen and fungal titers. Response to amphotericin therapy is erratic, and relapse is common. We have asked Dr. William E. Dismukes, principal investigator of the NIAID Mycoses Study Group, to discuss the following clinical questions: When and how does cryptococcal infection in HIV-infected patients present? How does it differ in HIV-infected and non-HIV-infected individuals? How is the diagnosis established? What is the sensitivity of the CSF cryptococcal antigen test? Is the serum antigen test of any value? What is the best way to treat patients--the recommended drugs, dosages, and duration of therapy? Is maintenance therapy necessary, and finally, what drugs are available for it? [Please note that an AIDS training program is now available for members of the Infectious Diseases Society of America and that details of this program appear in the Notices section of this Journal issue (pages 859-60).]

The chronic mononucleosis syndrome.

Abstract: In January 1985, two reports captured the attention of the lay and medical communities by suggesting that a chronic illness characterized by fatigue is associated with unusual serological responses to Epstein-Barr virus (EBV) antigens [1, 2]. Those reports unleashed countless demands for serological testing and consultations by infectious disease specialists. In the ensuing three years the merits and deficiencies of the hypothesis that EBV infection is associated with chronic fatigue have been further explored. I have been charged with placing the existing data into a more manageable perspective. To do so I address a series of issues: whether chronic EBV infection exists; what EBV and a recently described human herpesvirus may have to do with chronic fatigue; the diagnostic value of EBV serological testing; and the utility of acyclovir therapy for treating patients with chronic fatigue. In addition, I reflect on the "outbreak" of chronic fatigue reported in Lake Tahoe in 1985 [3, 4].

Cross-Protection by B Subunit-Whole Cell Cholera Vaccine Against Diarrhea Associated with Heat-Labile Toxin-Producing Enterotoxigenic Escherichia coli: Results of a Large-Scale Field Trial

Abstract: The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24 770 persons who ingested two or more doses of BS-WC vaccine were compared with 24 842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P < .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86^0; P < .05).

Characterization of enteroadherent-aggregative Escherichia coli, a putative agent of diarrheal disease.

Abstract: Escherichia coli that exhibit the aggregative pattern of adherence to HEp-2 cells (enteroadherent-aggregative E. coli [EA-AggEC]) have been epidemiologically incriminated as a cause of diarrhea. We undertook a preliminary microbiological and pathogenetic characterization of 42 isolates of this putative pathogen. The strains were negative by tests with DNA probes for enteropathogenic, enterotoxigenic, enteroinvasive, and enterohemorrhagic E. coli and, by serotype, did not fit these categories. Thirty-nine of 42 strains had a 55-65-megadalton plasmid; many shared DNA homology. With one representative strain, plasmid transfer was accompanied by transfer of smooth lipopolysaccharide, fimbriae expression, and the aggregative property. EA-AggEC caused characteristic lesions in rabbit and rat ileal loops. The intestinal lesions and (Shiga-like) limb paralysis and death in rabbits inoculated with live organisms suggest toxin involvement; assays for Shiga-like toxins were negative. These preliminary results support the contention that EA-AggEC may represent a distinct category of diarrheagenic E. coli.

Cytomegalovirus infection in patients with AIDS.

Abstract: Advances in the field of antiviral therapy are now occurring with increasing frequency and rapidity and often generate varying degrees of confusion among those of us whose practices are focused primarily on therapy with antibacterial agents. How to treat cytomegalovirus infections in patients infected with the human immunodeficiency virus constitutes one of the best examples of the quandaries engendered by these advances, and the topic is reviewed in this first AIDS Commentary update. Given the U.S. Food and Drug Administration's recent approval of foscarnet, this discussion is very timely; it is particularly relevant for clinicians to be made aware of current lines of thought regarding induction versus maintenance therapy, the benefits of efficacy versus adverse effects of drug-related toxicity, and the interactions between antiretroviral drugs and ganciclovir or foscarnet. Dr. W. Lawrence Drew's career in this area has been long-standing and productive, and he is one of the leading experts in the field. In this update he addresses these perplexing issues.

Isolation and Characterization of a Capsular Polysaccharide Adhesin from Staphylococcus epidermidis

Abstract: We isolated a polysaccharide adhesin from Staphylococcus epidermidis strain RP-62A. The adhesin was composed of a complex mix of monosaccharides (with galactose and glucosamine predominating), bound well to silastic catheter tubing, inhibited adherence of strain RP-62A to catheters, and elicited antibodies that both blocked adherence and stabilized an extracellular structure (visualized by transmission electron microscopy) that appeared to be a capsule. Two of three heterologous, highly adherent strains of coagulase-negative staphylococci also produced this adhesin, and their adherence to catheters was inhibited by both purified adhesin and antibody to adhesin. In contrast, the adherence of one highly adherent and two poorly adherent heterologous strains was unaffected by the RP-62A purified adhesin or antibody, a result suggesting the expression of alternate adhesins by these strains. We conclude that the capsular polysaccharide of some strains of coagulase-negative staphylococci is an important factor in adherence to catheter tubing.

Comparison of Immunoblotting and Indirect Enzyme-Linked Immunosorbent Assay Using Different Antigen Preparations for Diagnosing Early Lyme Disease

Abstract: We compared immunoblotting and indirect enzyme-linked immunosorbent assay (ELISA) using different antigen preparations to test for antibody to Borrelia burgdorferi in patients with early Lyme disease. With immunoblotting, 16 (53%) of 30 patients had positive tests in acute-phase sera and 25 (83%) had them in convalescent-phase sera. Among 64 controls, false-positive results were obtained in only three individuals with syphilis and in one hospitalized patient with renal allograft rejection. Among the patients with Lyme disease, both IgM and IgG antibodies most commonly bound to the 41-kilodalton (kDa) flagellar antigen, but many patients had binding to other components, particularly those of 25, 55, 58, or 66 kDa, and the order of their appearance was variable. Compared with indirect ELISA (using sonicated whole spirochetes or a flagellin-enriched fraction as the antigen preparation), more patients with Lyme disease had positive tests by immunoblotting, and fewer control subjects had false-positive results. Our results indicate that immunoblotting is superior to indirect ELISA for diagnosing early Lyme disease.

Detection of cytomegalovirus DNA in peripheral blood of patients infected with human immunodeficiency virus.

Abstract: Detection of cytomegalovirus (CMV) DNA can be facilitated by the polymerase chain reaction (PCR), an in vitro gene amplification technique. Twenty-eight CMV tissue culture isolates were examined by amplification of two separate CMV genes. All were found to contain CMV, although two of the isolates were positive for only one of the two genes. No detectable amplification occurred with human genomic or other viral DNA controls. The amplification products from as few as one CMV plaque-forming unit could be detected after the PCR. CMV DNA was detected in the blood of 14 of 27 patients with AIDS and one of six patients who were infected with human immunodeficiency virus but who did not have AIDS. Normal CMV-seropositive or -seronegative individuals did not have CMV DNA detected in their blood. The CMV PCR was more sensitive than the standard culture assay, can be completed in one to two days, uses only 20 microL of blood, and may be useful for rapidly detecting CMV in clinical specimens.

Changing Presentation of Herpes Simplex Virus Infection in Neonates

Abstract: We compared the clinical presentation of 95 newborns with herpes simplex virus (HSV) infection from 1973 through 1981 (first period) with data from 196 newborns evaluated from 1982 through 1987 (second period). There was a significant change in the presentation of infection in these infants. From the first to the second period, the frequency of disseminated disease decreased from 50.5% to 22.9%, whereas the frequency of skin, eye, and mouth (SEM) diseases increased from 17.9% to 43.4% (P less than .001). The frequency of infants with central nervous system (CNS) disease remained relatively unchanged--31.6% versus 33.7%. We also compared the demographic and clinical characteristics of the infants and their mothers. For neonates with CNS or disseminated infection, disease duration and frequency of prematurity were significantly decreased in the second period, as was the frequency of skin vesicles for newborns with SEM or disseminated infection. These changes are most likely the consequence of recognizing and treating SEM infection before its progression to more-severe disease.

Kinins are Generated During Experimental Rhinovirus Colds

Abstract: We investigated the pathophysiology of rhinovirus colds by challenging volunteers with either of two strains of rhinovirus or with placebo. Nasal lavages were done before challenge and every 4 h for five days after challenge. We measured the levels of histamine, kinins, [3H]-N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity, and albumin and counted the number of neutrophils in the recovered lavage fluid. Subjects who became both infected and symptomatic showed increases in levels of kinins (P less than .03), TAME-esterase activity (P less than .04), and albumin (P less than .05), as well as in the number of neutrophils (P less than .01). The total number of symptoms reported correlated significantly with the net increase in the concentration of kinins (r = .549; P less than .01), albumin (r = .674; P less than .001), TAME-esterase activity (r = .563; P less than .005), and neutrophils (r = .605; P less than .005). Levels of histamine did not change during the course of infection. During symptomatic rhinovirus infections (1) kinins are generated, (2) vascular permeability increases, (3) basophils and mast cells do not participate, and (4) neutrophils enter nasal secretions.

Bidirectional interactions between human immunodeficiency virus type 1 and cytomegalovirus.

Abstract: Interactions between human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS, and human cytomegalovirus (CMV), a frequent opportunistic agent in AIDS, were studied in vitro. Coinfection of H9 cells with HIV-1 enhances productive CMV infection, as measured by immunofluorescence using monoclonal antibodies to late CMV proteins, slot-blot hybridization for CMV DNA, and cytopathic effects of CMV on human embryonic lung cells. Experiments using vaccinia virus recombinants and Jurkat cells transfected with the transactivating (tat) gene of HIV-1 suggest that this enhancement is not mediated primarily by the tat protein. In addition, coinfection of H9 cells or a monocyte cell line with CMV and HIV-1 results in enhanced HIV-1 replication, as measured in a virus-yield assay or by radioimmunoassay for the p24 antigen of HIV-1. The interactions between HIV-1 and CMV are thus bidirectional.

Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies.

Abstract: Infections with cytomegalovirus (CMV) and other herpesviruses are a major source of morbidity and mortality after organ transplantation [1]. Of all the herpesviruses, CMV is the agent most often associated with severe disease or death [2]. A number of factors contribute to the severity of CMV infection in transplant recipients. Primary infection as opposed to reactivation infection with the virus [2, 3] and the use of immunosuppressive regimens containing anti-thymocyte globulin (ATG) appear to be associated with more-severe CMV disease [4, 5]. In addition, the type of transplant operation is an important determinant of the morbidity due to CMV. For instance, both bone marrow and heart-lung transplant recipients have higher rates of CMV pneumonia than do kidney recipients [1, 6, 7]. Our earlier studies of infections in kidney, heart, heart-lung, and liver transplant recipients in Pittsburgh showed that CMV and other herpesviruses were a significant problem in liver transplant recipients receiving cyclosporine [8]. A study of viral infections, incuding herpesvirus infections, in pediatric transplant recipients, most of whom were liver recipients, has recently appeared [9], but there still has been no comprehensive study of herpesvirus infections in adult liver transplant recipients, particularly since the initiation of routine cyclosporine monitoring in 1983. Therefore, we studied 121 consecutive adult liver transplant recipients at our institution to analyze the incidence, timing, risk factors, and clinical outcome associated with herpesviruses infections. We hoped to determine whether the hepatic allograft was a significant source of CMV infection and whether the use of newer immunosuppressive measures, such as OKT3 monoclonal antibody (Ortho Pharmaceutical, Raritan, NJ) introduced for treating liver rejection, had a measurable impact on CMV or herpes simplex virus (HSV) infection.

Field trial of oral cholera vaccines in Bangladesh

Abstract: The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2-15 years and women aged over 15 years. Each received three doses of BS-WC, WC, or placebo in a randomised, double-blinded fashion. Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group (protective efficacy 85%; p less than 0.0001), and 11 cases in the WC group (protective efficacy 58%; p less than 0.01). For each vaccine protective efficacy was consistent in different age-groups (2-10 years versus greater than 10 years) and for different severities of cholera.

In Vivo Postantibiotic Effect in a Thigh Infection in Neutropenic Mice

Abstract: The postantibiotic effect (PAE) is the suppression of bacterial growth that persists after limited exposure of organisms to antimicrobial agents. We demonstrated and standardized the in vivo PAE in a thigh infection model in neutropenic mice. Inhibitors of protein and nucleic acid synthesis induced PAEs of 1.4-7.5 h against aerobic gram-negative bacilli, whereas beta-lactam antibiotics did not induce significant PAEs. Against aerobic gram-positive cocci, cell wall-active agents and inhibitors of protein and nucleic acid synthesis induced PAEs of 1.2-7.1 h, except for penicillins, which did not induce PAEs against streptococci. With few exceptions the in vivo PAE correlated well with the PAE reported in prior in vitro studies. Residual drug in thigh tissue did not cause the PAE. Theoretically, the presence of a PAE may allow antimicrobial agents to be given more intermittently without organism regrowth after drug levels fall below the minimal inhibitory concentration.

In Vivo Behavior of Genetically Engineered Herpes Simplex Viruses R7017 and R7020: Construction and Evaluation in Rodents

Abstract: The herpes simplex virus (HSV) recombinant R7017 was constructed from HSV-1 (strain F) by deleting a portion of the thymidine kinase (tk) gene and by replacing the sequences representing the internal inverted repeats and adjacent genes in the L component with a fragment of the HSV-2 genome encoding the glycoproteins G, D, I, and a portion of E In addition, the R7020 recombinant contains an HSV-1 DNA fragment encoding the tk gene fused to the alpha 4 gene promoter The results of studies in mice, guinea pigs, and rabbits were as follows: Both recombinants remained unchanged after nine serial, intracerebral passages in mice; the recombinants could not be differentiated with respect to attenuation in mice injected intracerebrally, in vaginally infected guinea pigs, and in rabbits inoculated on the scarified cornea Given intradermally or intramuscularly, the recombinants prevented severe infections by virulent challenge viruses, and R7020 established latent infections (at a low frequency) in all species tested, whereas latent R7017 virus was detected in rabbits only

Treatment of Gram-Negative Septic Shock with Human IgG Antibody to Escherichia coli J5: A Prospective, Double-Blind, Randomized Trial

Abstract: In a randomized, double-blind, multicenter trial we compared the efficacy of a preparation of human IgG antibody to Escherichia coli J5 (J5-IVIG) with that of a standard IgG preparation (IVIG) for the treatment of gram-negative septic shock. At study entry, patients received a single intravenous dose of 200 mg/kg of body weight (maximal dose, 12 g) of either J5-IVIG or IVIG. Of the 100 patients randomized, 71 (30 receiving J5IVIG and 41 receiving IVIG) had a documented gram-negative infection. Mortality from gram-negative septic shock was 50% (15 of 30) in J5-IVIG recipients and 49% (20 of 41) in IVIG recipients. In addition, treatment with J5-IVIG did not reduce the number of systemic complications of shock and did not delay the occurrence of death due to septic shock. Thus we conclude that J5-IVIG was not superior to IVIG in reducing mortality or in reversing gram-negative septic shock.

Impaired Neutrophil Function in Patients With AIDS or AIDS-Related Complex: A Comprehensive Evaluation

Abstract: We measured the neutrophil function of 6 patients with AIDS and Kaposi's sarcoma (KS); 22 patients with AIDS-related complex (ARC); and 28 healthy, heterosexual controls. Neutrophils from patients with ARC showed significantly less chemotaxis (P less than or equal to .025) than did those from patients with AIDS and KS or from controls. Serum from patients with AIDS and KS or with ARC significantly (P less than or equal to .05) inhibited chemotaxis of neutrophils from controls; heat treatment of the serum abolished this inhibitory effect. Bacterial killing by neutrophils from patients with AIDS and KS or with ARC was also significantly (P less than or equal to .05) less than for neutrophils from controls, as was neutrophil phagocytosis binding of Candida albicans (P less than or equal to .05). Expression of OKM1 antigen was increased in the patients studied. Enzyme degranulation, adherence, and aggregation were also examined. The defects found in neutrophil function are selective and may be important in the increased susceptibility of patients with human immunodeficiency virus infection to bacterial and fungal infections.

Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predominantly serotype 1 rotavirus season.

Abstract: We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P less than .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of the WC3-vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.

Enzymatic Gene Amplification: Qualitative and Quantitative Methods for Detecting Proviral DNA Amplified in Vitro

Abstract: We evaluated various detection methods to identify amplified human retroviral sequences after Thermus aquaticus-directed polymerase chain reaction (PCR) A combination of hybridization formats and direct incorporation assays provided the most information This multiphasic approach enabled us to detect specific human T cell leukemia virus type I (HTLV-I)-homologous regions in several HTLV-I-seronegative patients with T cell lymphoma, as well as variants of HTLV-I and human immunodeficiency virus type 1 in patients with prototype disease In all diagnostic assays designed to detect a particular retrovirus, it was necessary to include a hybridization step, because sequences (endogenous or exogenous) homologous to certain primers were present in most human DNA preparations and yielded discrete products, sometimes of the predicted molecular weight, after amplification These products could be discriminated by hybridization from amplified prototype proviral sequences The intensity of the signal generated after hybridization was proportional to input target DNA, an observation making it feasible to quantitatively measure the proviral load in a DNA sample

Comparison of Translocation Rates of Various Indigenous Bacteria from the Gastrointestinal Tract to the Mesenteric Lymph Node

Abstract: Bacterial translocation is defined as the passage of indigenous bacteria from the gastrointestinal (GI) tract through the lamina propria to the mesenteric lymph nodes (MLN) and other organs. We compared the relative abilities of various aerobic, facultatively anaerobic, and obligately anaerobic bacteria to translocate from the GI tract to the MLN in gnotobiotic mice colonized with single strains of bacteria. Indigenous gram-negative enteric bacilli translocated in large numbers to the MLN, whereas gram-positive bacteria translocated at intermediate levels and obligately anaerobic bacteria at only very low levels. Our results suggest that enteric bacilli such as Escherichia coli, Proteus, and Enterobacter are associated with a higher incidence of bacteremia in debilitated patients, because these bacteria translocate more efficiently from the GI tract than do other bacteria, especially obligate anaerobes.

Guidelines for improving the use of antimicrobial agents in hospitals: a statement by the Infectious Diseases Society of America.

Abstract: This is the first in a series of reports being prepared by the Infectious Diseases Society of America (IDSA) that will deal with issues in antimicrobial therapy. Antimicrobial agents are often used inappropriately [1-19]. This may be attributed to their success in the treatment and prevention of serious infections, the complexity of the decision-making process in patients with infectious diseases, the desire of physicians to use the very best drugs available, and the promotional efforts of pharmaceutical manufacturers. The reasons for concern about excessive use of antibiotics are the burden of resistant organisms, adverse reactions to these drugs, and excessive costs. The issue of cost containment has become increasingly important as government and third-party payers seek to control expenditures in the health care system. The members and fellows of the IDSA were polled to obtain their views on the issues of optimum usage of antibiotics in hospitals. They registered concern about excessive and often inappropriate use of antibiotics in hospitals [20]. Effective antimicrobial agents are an essential part of patients' care. Intensive use of antimicrobial agents is associated with development of resistant strains [21-33], and excessive use increases costs unnecessarily [34-46]. Nevertheless, new agents are welcome that fill important therapeutic needs and overcome problems of resistance. To help hospitals provide the very best agents for care of patients by their staff, assure quality of care, and decrease the problems of emergence of resistant strains, the IDSA has prepared a series of general guidelines for evaluating and con-