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PubMed1989

Nucleic acid probes in infectious diseases.

Few of the probes described here are available as practical assays for clinical laboratories, and some have argued that currently available kits have not lived up to their promise to provide increased sensitivity, specificity, and speed of identification and detection at a reasonable cost. While these sentiments are true to some extent now, the rapid advance of techniques to enhance the rate of hybridization, to amplify the target sequences, and to label and detect hybrids nonradioactively will have a substantial impact on the availability of hybridization kits for the clinical laboratory. It is conceivable that probe technology will be simplified to the extent that it can be adapted to small laboratories, clinics, and field sites. Not only can we expect probes to speed detection and identification of established pathogens, we also look forward to perhaps the most exciting future aspect of this technology, the discovery of new agents and new infectious disease syndromes that will be brought about through its application.

Animals↗
PubMed1989

A peptidoglycan protein complex purified from M. leprae cell walls contains most or all immunodominant M. leprae T-cell antigens.

The outcome of an infection with Mycobacterium leprae is correlated with the T-cell-mediated immune response developed against this pathogenic agent. The identification of M. leprae antigens that are recognized by T cells is therefore of great importance. In this paper we present the results of in vitro lymphoproliferation assays in which T-cell reactivity was measured against a peptidoglycan-protein complex (PPC) which was purified from the cell wall of M. leprae. Twelve M. leprae-reactive T-cell clones with different antigen specificities from a tuberculoid (TT) leprosy patient showed proliferative responses, but only when PPC was presented by HLA-DR-matched antigen-presenting cells (APCs). Four of these clones were known to react with the recombinant mycobacterial 65-kDa protein. A tetanus-toxoid-reactive T-cell line from a healthy control was not stimulated by this complex, supporting the idea that the stimulation by PPC was antigen specific. Both PPD-reactive and M. leprae-reactive T-cell lines from healthy individuals were stimulated by PPC. However, when this complex was presented to PPD-reactive T-cell lines derived from two lepromatous (LL) leprosy patients, we did not observe any proliferative responses. From these results we conclude that PPC contains most or all of the antigens which stimulate M. leprae-reactive T cells in association with relevant HLA class II molecules, including the 65-kDa protein or at least some immunogenic parts of it.

Antigens, Bacterial↗
PubMed1989

Antimicrobial therapy: past, present, and future.

Antimicrobial chemotherapy is a growth industry in the rapidly changing world of health care. The identification of new pathogens, new treatment modalities, and new issues related to our patterns of antimicrobial use ensure that the practise of Infectious Diseases in 1994 will be markedly different than it has been in 1988. Ongoing adaptation and radical change will both be required of each one of us as we modify our treatment guidelines to ensure that our patients receive optimal antimicrobial therapy for maintaining or regaining their health.

4-Quinolones↗
PubMed1977

[Increasing importance of Haemophilus influenzae in nose, ear and throat infections].

After the review of the morphology, the identification and the pathogenic properties of H. influenzae, its occurrence in the different ENT infections is discussed. H. influenzae is found in chronic tonsillitis in 64% of the cases, in the deeper tissue of the tonsils, while its occurrence in the throat swabs is rare. In acute otitis media H. Influenzae is present in 10 to 150% of the cases, while in rhinitis and sinusitis its increasing occurrence until 1974 is noted (28% of all sinusitis cases showed H. Influenzae in that year); since 1974 its occurrence is somewhat decreasing: 18% in 1976. Susceptibility testing for antibiotics with the disc-method is unreliable; we have to use the tube or plate-dilution methods. The increasing occurrence of ampicilline resistant strains of H. influenzae is discussed.

Acute Disease↗
PubMed1988

Medical management of osteomyelitis: considerations for home antibiotic chemotherapy.

Osteomyelitis can result from hematogenous seeding or contiguous infection, especially in association with impaired vascularity. Appropriate antibiotic therapy requires identification of the pathogen or pathogens and confirmation that the pathogens are susceptible to the antibiotic selected. Because of the long duration of parenteral antibiotic therapy required, treatment of osteomyelitis is expensive when patients are kept in the hospital for this reason alone. The development of long-half-life antibiotics that can be administered intramuscularly once a day and that are well tolerated has made outpatient parenteral therapy possible for many such patients. Cefonicid is a long-acting second-generation cephalosporin with activity against many of the microorganisms involved in osteomyelitis. Clinical studies have shown that cefonicid is effective and safe when used in an outpatient treatment program. Such programs have realized considerable savings over the cost of inpatient therapy.

Ambulatory Care↗
PubMed1986

[Sensitivity of 858 strains of staphylococci to 27 antibiotics].

Susceptibility to 27 antimicrobial agents of 858 strains of staphylococci was determined. Tested strains belonged to the following species: S. epidermidis, S. saprophyticus, S. haemolyticus, S. hominis, S. simulans, S. warneri, S. cohnii, S. xylosus and S. intermedius. The antibiotics were: penicillin G, amoxycillin, augmentin, oxacillin, streptomycin, kanamycin, tobramycin, dibekacin, amikacin, gentamicin, sisomycin, netilmicin, doxycycline, minocycline, chloramphenicol, erythromycin, josamycin, clindamycin, pristinamycin, rifampin, fusidic acid, fosfomycin, trimethoprim, sulfamethoxazole, cotrimoxazole, and vancomycin. The ATB system was used, with the criteria for categorization recommended by the Antibiotic Sensitivity Testing Committee. Penicillin-resistance, that was found in all species, was high for hospital-acquired strains (67 to 75%) but also for some other strains (32% for S. simulans). Oxacillin-resistance varied across species (0% for the least prevalent hospital strains, 6% for S. epidermidis and 28% for S. haemolyticus). All strains were susceptible to vancomycin. For some drugs, resistance was a characteristic of the species: resistance to fosfomycin was often found for S. saprophyticus, S. haemolyticus, S. warneri, S. cohnii, and S. capitis; resistance to trimethoprim was common for S. simulans, and S. haemolyticus. S. haemolyticus was the most resistant species, a fact that justifies routine identification of this pathogen in clinical specimens.

Anti-Bacterial Agents↗
PubMed1978

[Bacteriological aspects in the diagnosis and treatment of endocarditis (author's transl)].

The role of the laboratory is capital in ensuring the diagnosis of bacterial endocarditis. At the present time, the circumstance surrounding the onset of endocarditis have become broadened. The bacteria responsible may belong to various species, certain requiring the use of special techniques in their culture. If blood cultures are performed under suitable conditions, they should lead to isolation of the organism in more than 90 per cent of cases of endocarditis. Precise identification of the pathogenic organism forms the basis for rational antibiotic therapy. The bactericidal activity of treatment must nevertheless be confirmed in vitro, firstly by study of the reaction of the strain to antibiotics, and secondly by study of the bactericidal activity of the serum.

Anti-Bacterial Agents↗
PubMed1985

[Intracranial late abscesses following injuries caused by grenade splinters].

On the basis of 6 cases of late cerebral abscesses after lesions caused by shell-splinters treated by us, clinic, diagnostics and therapy of this complication are discussed in detail. In 3 patients there were no direct relations between the splinters and the abscesses so that further factors (age, vascular wall changes, and the like) must play a role in the formation of the abscesses; such vascular wall fibroses were found histologically in 3 of the examined abscess capsules. In 3 cases the bacteriological identification of the pathogens was possible. The treatment was carried out by employing puncture or extirpation or the combination of the two methods.

Aged↗
PubMed1986

[Prospective evaluation of coagglutination and latex agglutination in the diagnosis of bacterial meningitis in childhood].

UNLABELLED: Two simple and low-priced kits to detect bacterial antigens in cerebrospinal fluid (CSF) specimens from patients with suspected meningitis have recently become available. Methods employed by these kits are staphylococcal coagglutination (COA) and latex agglutination (LA). The COA "Phadebact CSF-kit" (Pharmacia) detects Haemophilus influenzae type b (HIb), Neisseria meningitidis (NM) groups A, B, C, Y and W 135 and Streptococcus pneumoniae (SP), whereas the LA "Slidex Méningite-kit" (BioMérieux) includes HIb, NM A, NM C and SP. These two diagnostic tests were compared with the standard methods for analyzing CSF specimens from children with suspected meningitis. A total of 336 CSF specimens were tested. Forty-three were from children with bacterial meningitis due to HIb, NM or SP obtained before antimicrobial therapy. Thirty-four of them (79%) were correctly detected by COA, 23 (54%) by LA, and 42 (97%) by microscopic analysis of stained smears. There were 65 CSF samples of such meningitis cases obtained after initiation of antimicrobial therapy: COA detected 26 (40%), LA 17 (26%) and staining 26 (40%). With culture-positive CSF specimens from patients before therapy, the best sensitivities were obtained with LA for SP (100%) and COA for HIb (87%), whereas the results for NM antigen detection were only 43% with COA and 0% with LA (no reagent against NM B). Cross-reactions with other bacterial antigens were frequent with COA (26%) and rare with LA (2%), resulting in false-positive findings in 6 of the 66 positive tests with COA (9%) but in none of the 40 positive tests with LA (0%). One of the 48 specimens from aseptic meningitis cases was false-positive for HIb by COA, whereas all 172 normal specimens were negative with both methods. With 5 culture-negative CSF specimens from patients with unequivocal purulent meningitis COA detected bacterial antigen in 5 and LA in 2. CONCLUSIONS: The two kits evaluated cannot replace standard methods for analyzing CSF specimens, in view of insufficient sensitivity (mainly LA) or frequent cross-reactions and false-positive values (COA). However, due to their simplicity, rapidity, and possible identification of bacterial pathogens after initiation of antimicrobial therapy, these kits are recommended as an useful addition to standard methods.

Adolescent↗
PubMed1985

[Penetration of aztreonam and ampicillin to cerebrospinal fluid in the concomitant administration to rabbits with Staphylococcus aureus meningitis].

Aztreonam (AZT) and ampicillin (ABPC) were independently administered to 6 and 7 rabbits respectively, with S. aureus meningitis. Additionally, AZT and ABPC were concomitantly given to 6 rabbits with S. aureus meningitis. Concentrations of AZT and ABPC in cerebrospinal fluid (CSF) and serum were determined by HPLC method, and the results in concomitant treatment were compared with those for single treatment of each agent. Results were as follows: Maximum serum concentrations of AZT in concomitant treatment of AZT and ABPC were higher than those in single treatment of AZT. However, there was no significant difference between the 2 treatment groups with regard to maximum CSF concentration, percentage of AUC of CSF to serum, and T1/2 of the CSF and serum concentrations of AZT. ABPC in the concomitant treatment did not influence the CSF concentration of AZT. There was no significant difference in serum concentration of ABPC between concomitant treatment and the single one. However, the values of maximum CSF concentration, percentage of maximum CSF to serum concentration and percentage of AUC of CSF to serum in the concomitant treatment were lower than those in the single treatment of ABPC. With regard to T1/2 of CSF concentration of ABPC, there was no remarkable difference between the 2 treatment groups. The above results suggest that the distribution of ABPC into CSF is suppressed in the concomitant treatment of AZT and ABPC. AZT has no antimicrobial activity against Gram-positive bacteria. The CSF concentration of ABPC is suppressed in the concomitant treatment. Those facts suggest that AZT should be administered for meningitis cases after the identification of causative pathogens.

Ampicillin↗
PubMed1984

Renal osteodystrophy.

As is apparent from the preceding discussion, renal osteodystrophy is a complex entity with multiple causes and many manifestations. Significant problems have included the identification and management of the various forms of bone disease seen in uremia. The prevention and therapy of osteitis fibrosa and secondary hyperparathyroidism have been significantly improved as a result of adequate phosphate restriction and the use of active forms of vitamin D (primarily calcitriol in the U.S., dihydrotachysterol and 1 alpha-hydroxyvitamin D in Europe). Recently, a major problem has been the recognition of bone disease due to aluminum accumulation. The therapy of this bone disease was generally unsuccessful until recent preliminary data suggested that deferoxamine therapy may be useful in these patients. The study of renal osteodystrophy has certainly advanced our knowledge of mineral metabolism, with clarification of the metabolism and action of PTH and vitamin D metabolism and identification of the pathogenic role for aluminum. In the future, most manifestations of renal osteodystrophy may be preventable or adequately treated.

Alkaline Phosphatase↗
PubMed1983

[Antibiotic therapy in severe infections].

The problems of selecting antibiotics for hospital use from the broad variety offered, and the problems of what is often necessarily a non-specific initial therapy, are discussed. A review is given of groups of antibiotics which are important for hospital therapy such as penicillins, aminoglycosides, metronidazole and cephalosporins. Firstly the range of effects of the individual groups of antibiotics is summarized in a simplified form from which the indications are then derived. In discussing the clinical use of antibiotics special importance is attached to initial therapy prior to or in the absence of identification of the pathogens in fatal infectious diseases. From this aspect the therapy for pneumonia, peritonitis, sepsis and urosepsis as well as meningitis is discussed. The small number of indications for the prophylactic use of antibiotics is briefly dealt with. Finally a selection of antibiotics necessary for hospital therapy is presented.

Aminoglycosides↗
PubMed1981

The value of cuticular fine structure in identification of juvenile anisakine nematodes.

Juveniles of the ascarid nematodes Anisakis sp. and Phocanema sp. from marine teleosts, have been implicated as major causative agents of human anisakiasis. Whereas juveniles of the related genus Thynnascaris sp. have not been reported from humans, this nematode may occur in fish concurrently with the aforementioned species. The juvenile anisakine nematodes are not readily identified, and reliable morphological markers would provide a valuable aid in identification of potentially pathogenic individuals. In this study of cuticular fine structure, the following characteristic difference appeared to be most significant: a wide electron lucent area containing partitions and previously unreported electron dense rods occurred in the basal layer of the Phocanema sp. cuticle, but not in that of Anisakis sp. or of Thynnascaris sp. Juveniles of Thynnascaris sp. possessed a cuticle that was structurally similar to that of Anisakis sp., but only about one-half as thick. Comparatively, the third stage Ascaris lumbricoides cuticle was poorly developed, and less definitively layered than those of the anisakines.

Animals↗
PubMed1994

Direct sequence identification and kinetic analysis of an MHC class I-restricted Listeria monocytogenes CTL epitope.

Murine infection with the intracellular bacterium Listeria monocytogenes elicits MHC class I-restricted CTL with specificity for multiple bacterial peptides. The variety and relative abundance of self-peptides bound by MHC molecules make identification of pathogen-derived peptides difficult. In this report, the sequence of a pathogen-derived CTL epitope is determined by direct analysis of peptides extracted from MHC class I molecules. The epitope, p60 217-225, is presented to L. monocytogenes-specific CTL by the H-2Kd MHC class I molecule and is derived from p60, a secreted invasion-associated protein. Quantitation of p60 217-225 in infected cells shows that this epitope is detectable within 2 h of infection and, after a 9-h infection, there are over 3000 epitopes per infected cell. This contrasts with listeriolysin 91-99, the other major L. monocytogenes epitope, which is present in quantities below 200 epitopes per cell until 5 h of infection and reaches 800 epitopes per cell 9 h after infection. This report shows that identifying new T lymphocyte epitopes by direct sequence analysis of peptides isolated from MHC molecules is feasible. Furthermore, kinetic and quantitative analysis of T cell epitopes in infected cells is a useful approach to investigate the multispecific CTL response to complex intracellular pathogens.

Amino Acid Sequence↗
PubMed1995

[A very up-to-date stage in the fate of infectious diseases: parasitic and fungal opportunistic infections].

Opportunistic parasitosis and mycosis are becoming ever more widespread, mainly under the influence of major immunodeficiencies, either acquired (AIDS) or therapeutic. In this general overview, their main aspects, both clinical and epidemiological, are underlined. In terms of epidemiology, three types of phenomena have been observed: 1) emergence of human parasitosis unknown before (microsporidiosis due to Enterocytozoon bieneusi, Encephalitozoom hellem or Septata intestinalis); 2) among the human parasites already known, identification of very pathogenic strains (Toxoplasma gondii, Aspergillus fumigatus, Cryptococcus neoformans); 3) origin probably or certainly nosocomial of certain infections (pneumocystosis; toxoplasmosis and visceral leishmaniasis transmitted during bone-marrow or organ transplantations). The development of deep mycosis (invasive aspergillosis) is particularly promoted by granulopenia and alterations in the phagocytosis. On the other hand, opportunistic protozoosis (toxoplasmosis and leishmaniasis) and helminthiasis (strongyloidosis due to Strongyloides stercolaris) are related, above all, to disorders in cellular immunity (deficit of CD4+, mainly). Finally, several of these infections may be characterised by a variety of clinical pictures and outcome, depending on the contributory factors (immunodeficit or not) which led to the development of the infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Characterization of microflora in pyo-destructive lung diseases].

The microflora pattern of the endobronchial secretion was investigated in 74 patients with purulent destructive diseases of the lungs. Specimens of the endobronchial secretion were collected by transtracheal aspiration and bronchoalveolar lavage. The anaerobic isolates were cultivated in anaerostats (OXOID, England) with the use of GasPacks. Bacteriological identification of the pathogens was carried out with respect to 67 patients (90.5 per cent). Non-sporulating anaerobic microflora was isolated from 51 patients (76.1 per cent). Anaerobic causative agents in the patients with complicated pulmonary destructions were detected in 54.3 per cent of the cases. Mono-infection represented by one species of the anaerobes was stated in 23 patients (34.4 per cent). Associations of aerobes and anaerobes were isolated from 28 patients (41.7 per cent). Associations of one strain of the anaerobic causative agents and aerobic microflora were detected in 17 patients (60.7 per cent). In 11 patients the microflora pattern was polymicrobial (89.3 per cent). A total of 66 strains of non-sporulating anaerobic pathogens were isolated. Gram-negative bacilli represented by Prevotella spp., Porphiromonas asaccharolitica and Bacteroides spp. were the most frequent isolates.

Adult↗
PubMed1994

Unravelling the conundrums of the diabetic heart diagnosed in 1876: prelude to genetics.

During the past two decades epidemiological, clinical and laboratory studies have confirmed the existence of the diabetic heart in some patients with diabetes mellitus. The diagnosis was made in patients in whom other known etiological factors, such as coronary artery disease, alcoholism or hypertensive cardiovascular disease, were ruled out. The newer concept of the diabetic hypertensive heart is clinically based on a higher incidence of congestive heart failure caused by extensive myocardial involvement. In patients with hypertension and hypertension associated with diabetes, the intramyocardial arterioles present medial hypertrophy and a diminished lumen, increased periarteriolar fibrosis, accumulation of fibrillar collagen and patent extramural coronary arteries. Such confirmatory findings have been previously seen in experimental animals and in patients with diabetes and no hypertension. In the genetically diabetic rat, diabetes may be prevented by neonatal thymectomy, suggesting the existence of an autoimmune deficiency syndrome. Furthermore, conversion of Ala 776 into Thr 776 on the polyprotein by a point mutation results in loss of diabetogenicity. Abnormalities in systole and diastole related to lowering of CK-M and CK-B mRNA levels are normalized following insulin therapy. Identification of the genetic factors in the diabetic heart may lead to the identification of its pathogenic mechanisms.

Animals↗