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Biomedical subjects

U Schaad

Publications and source records attributed to U Schaad.

14 recordsLinked to original sources

Immunization of cystic fibrosis patients with a Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine.

Healthy, non-colonized cystic fibrosis (CF) patients (N = 26) were immunized with an octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Vaccination was well tolerated and induced anti-lipopolysaccharide (LPS) antibodies of a high affinity capable of promoting the opsonophagocytic killing of P. aeruginosa by human peripheral lymphocytes. In contrast, anti-LPS antibodies acquired after natural infection possessed a very low affinity and were non-opsonic. To determine if immunization could prevent or delay infections due to P. aeruginosa, the infection rate among immunized patients was compared retrospectively to age and gender-matched controls. After 6 years of clinical follow-up, 15/20 (75%) of control and 8/23 (35%) of immunized subjects were classified as infected (p = 0.022). The persistence of high-affinity antibodies among immunized patients correlated with a significantly lower rate of infection after 4-6 years of observation. Infection of immunized patients was correlated with a dramatic decline in total antibody titer between year 2 and 3 of follow-up. Smooth, typeable strains of P. aeruginosa predominated among immunized patients. In contrast, rough, nontypeable strains were most frequently isolated from nonimmunized patients. Mucoid P. aeruginosa strains were isolated from 6 nonimmunized patients versus only I immunized subject.

ADP Ribose Transferases↗

Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients.

Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.

Adult↗

Pseudomonas aeruginosa cross-colonization and persistence in patients with cystic fibrosis. Use of a DNA probe.

To investigate cross-colonization with and persistence of Pseudomonas aeruginosa in cystic fibrosis (CF), 181 isolates from 76 CF patients were typed using a P. aeruginosa-specific DNA probe. Whereas sibling pairs predominantly harboured genotypically identical P. aeruginosa strains, all of the other patients harboured different strains. Seventy-nine per cent (22/31) of the infected CF patients harboured the same strains at the beginning and the end of a summer camp. A change of strains was seen in 10% (3/31) of the patients at the end of the camp. Forty-six per cent (6/13) of the patients who were apparently initially uninfected, acquired P. aeruginosa by the end of the period. Genotyping proved that strain change or acquisition was due to cross-colonization in four of nine cases. Very little P. aeruginosa was isolated from the inanimate environment. Persistence of P. aeruginosa after a temporary loss due to antibiotic therapy was seen in 12/16 paired patient strains before and after antibiotic therapy. Thus, suppression followed a flare-up seemed to occur in these patients rather than eradication and a new infection. When 35 patients were followed over a period of 6 months, 7 (20%) changed the strain in their sputum. Only one of 43 patients harboured two different P. aeruginosa strains simultaneously over a long period.

Adolescent↗

Susceptibility to infections in children with selective IgA- and IgA-IgG subclass deficiency.

This study included 36 children with IgA-deficiency, increased susceptibility to infections and/or other disorders. Recurrent, usually bacterial infections were noticed in 23 out of 26 patients (88%) with complete and in 7 out of 10 patients (70%) with partial IgA-deficiency. All patients with severe infections had complete IgA-deficiency. Complete IgA-deficiency was also present in the six children who had autoimmune disorders associated with recurrent infections. In 22 out of the 36 patients studied the serum could be analysed for concomitant IgG subclass deficiencies: one patient had marked decrease of IgG2. In a second patient IgG4 was not detectable. Two patients had combined IgG2-IgG4-deficiency. In a girl with severe acute and chronic infections and relapsing idiopathic thrombocytopenic purpura, IgA-IgG2-IgG4-deficiency was found to be the prodromal stage of common variable immunodeficiency with panhypogammaglobulinaemia.

Adolescent↗

Moxalactam therapy for neonatal meningitis due to gram-negative enteric bacilli. A prospective controlled evaluation.

Moxalactam and ampicillin sodium therapy were compared with amikacin sulfate and ampicillin therapy for meningitis due to gram-negative enteric bacilli in 63 infants enrolled in the Third Neonatal Meningitis Cooperative Study. The population characteristics and causative organisms were comparable for the two treatment groups. Cultures of CSF were positive for approximately three days in both study groups. Case-fatality rates were 23% and 15% for moxalactam-treated infants and ampicillin- and amikacin-treated infants, respectively. Developmental or neurological abnormalities were found in about 40% of survivors, and the rates were comparable for both treatment groups. Computed tomograms in 44 infants were interpreted as normal in 13 (30%); hydrocephalus, abscesses, and low-density areas were the most frequent abnormalities. We conclude that moxalactam is a suitable alternative for treatment of meningitis due to gram-negative enteric bacilli.

Amikacin↗

Impaired neutrophil locomotion associated with hyperadhesiveness in a patient with Chédiak-Higashi syndrome.

Neutrophils from a patient with Chédiak-Higashi (CH) syndrome exhibited defective directional locomotion in a gradient of activated plasma. Further analysis of the nature of this defect showed that CH neutrophils could respond normally to stimulation with f-Met-Leu-Phe, by increasing both their motility and polarization, provided the cells were kept in suspension. Contact with the substratum resulted in the loss of both motility and polarity in the majority of cells. CH neutrophils, in contrast to normal cells, did not respond chemokinetically to f-Met-Leu-Phe. Unstimulated random locomotion of CH neutrophils was also depressed, and this correlated with increased spreading on the substratum. Our results indicate that motility, locomotion and polarisation of CH neutrophils on the substratum are depressed because of excessive adhesion.

Cell Adhesion↗

Hypodipsia-hypernatremia syndrome.

The pathogenesis of the rare hypernatremia, usually described in the literature as "neurogenic" or "essential" hypernatremia, consists of defective thirst mechanism either alone or in combination with impaired osmoregulation of ADH release. As etiology, disturbances of the neoplastic, vascular and degenerative type and malformations in the hypothalamic area are known. In patients with the hypodipsia-hypernatremia syndrome, dysfunction of the anterior pituitary lobe, obesity, abnormal regulation of body temperature, psychomotor retardation and episodic muscular weakness are frequently encountered as additional abnormalities. A 6-year-old patient is described with hypodipsia-hypernatremia syndrome manifest for 3 years. Besides hypernatremia, hypodipsia and the relative insensitivity of the osmoreceptors regulating ADH release, elevated body temperature, polyphagia and obesity, partial hypothalamic-hypophyseal dysfunction, lethargy and psychomotor retardation are the principal findings. An inflammatory lesion or one occupying an intracranial space was not demonstrable until now. Under forced water intake and hypocaloric diet the patient has progressed well with nearly complete normalization of the hypernatremia, body temperature and obesity.

Child↗

Value of 1-hour blood-xylose test in diagnosis of childhood coeliac disease.

In a series of 46 children with untreated coeliac disease and in 102 controls with normal mucosa the 1-hour blood-xylose test was, in view of its simplicity, of much value in the diagnosis of childhood coeliac disease. Only one blood-xylose result was falsely normal in the 46 coeliac patients. It is concluded that a normal blood-xylose value does not exclude coeliac disease and should not prevent peroral biopsy in the presence of strong clinical suspicion. On the other hand, patients who have repeatedly abnormal blood-xylose values merit an intestinal biopsy even in the absence of suggestive clinical symptoms.

Adolescent↗

One-hour blood-xylose in cystic fibrosis.

One-hour blood-xylose concentrations after an oral xylose load were measured in children with cystic fibrosis (CF) and healthy controls. The mean of the 1-hour blood-xylose values was significantly increased in the group with CF. The finding confirms an earlier observation by Rolles et al. (1973). Its significance is not at present understood but it suggests that small intestinal function should be further investigated in CF.

Adolescent↗

Protein-losing enteropathy due to segmental erosive and ulcerative intestinal disease cured by limited resection of the bowel.

Two children suffering from extensive intestinal protein loss due to subacute and chronic segmental small bowel disease are presented. In the first case a tentative diagnosis of chronic erosive and ulcerative non-granulomatous jejunitis as described in adults was made. The second child suffered from subacute erosive and ulcerative segmental transmural ileitis following mechanical ileus. In both instances resection of the involved segments of small intestine promptly cured the enteric protein loss. It is suggested that excessive protein loss due to subacute or chronic segmental erosive and ulcerative intestinal disease may be cured definitively by surgical resection. An explorative laparotomy should be performed if broad internistic investigations do not provide an explanation for the severe and prolonged enteric protein loss.

Adolescent↗

[The blood-xylose test in childhood: correlation between 1 hour blood-xylose levels and numbers of intraepithelial lymphocytes in intestinal mucosa in celiac disease].

In 59 children who underwent diagnostic small-intestinal biopsies the correlation between the intraepithelial lymphocyte infilration of the distal duodenal mucosa and the blood-xylose concentration 1 h after ingestion of 5 g D-xylose was investigated. 16 patients with active coeliac disease had blood-xylose values below 20 mg%, and the correlation between blood-xylose levels and the numbers of intraepithelial lymphocytes in this same group of patients was found to be highly significant. Provided that the methodology is meticulously followed, it is our experience that the one-hour blood-xylose test, in addition to the clinical investigation, facilitates the decision whether or not to perform a small-intestinal biopsy in the diagnosis and follow-up of coeliac disease in childhood. The test however cannot replace the intestinal biopsy which remains the only acceptable criterion for the diagnosis of this disease.

Adolescent↗