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Biomedical subjects

H Jakobsen

Publications and source records attributed to H Jakobsen.

At least 19 recordsLinked to original sources

Mucosal vaccination against encapsulated respiratory bacteria--new potentials for conjugate vaccines?

Polysaccharide (PS)-encapsulated bacteria such as Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococcus), Neisseria meningitides (meningococcus) and group B streptococcus (GBS), cause a major proportion of disease in early childhood. Native PS vaccines are immunogenic and provide protection against disease in healthy adults but do not induce immunological memory. PSs are T-cell-independent antigens and do not elicit antibodies in infants and young children, but by conjugating PS to proteins they become T-cell dependent and immunogenic at an early age. Despite excellent efficacy of PS-protein conjugate vaccines against invasive disease, protection against mucosal infections such as pneumococcal otitis media has been less efficacious. Circulating PS-specific antibodies may protect against infections at mucosal sites, but mucosal immunoglobulin A antibodies may also contribute significantly to protection against mucosal infections. Mucosal immunization of experimental animals with conjugate vaccines against Hib, pneumococcus, meningococcus and GBS induces systemic and mucosal immune responses, which provide protection against carriage, otitis media and invasive disease in a variety of challenge models, providing new means for protection against encapsulated bacteria. In addition, mucosal immunization of neonatal mice with a pneumococcal conjugate and the nontoxic adjuvant LT-K63 has been superior to parenteral immunization in eliciting protective antibodies and PS-specific memory, and thus circumventing the limitations of antibody responses to PS that are responsible for enhanced susceptibility of neonates and infants to infections caused by encapsulated bacteria. Through T-cell dependent enhanced immunogenicity of PS-protein conjugate vaccines, mucosal immunization could be an attractive approach for early life immunization against encapsulated bacteria.

Adult↗

Amyloidosis of the seminal vesicle--a case report and review of the literature.

The finding of amyloid deposits in the seminal vesicles has been known for many years. The deposits are usually localized and asymptomatic. In recent years seminal vesicle amyloidosis has been reported to simulate prostate and bladder cancer invasion on MRI. We therefore feel that knowledge of the entity is important and present herein a typical case confirming the previous findings that amyloidosis of the seminal vesicles is a unique form of amyloidosis, a relatively common incidental finding and one that may be related to prostate cancer.

Amyloidosis↗

Urinary bladder volume measurements: comparison of three ultrasound calculation methods.

OBJECTIVE: To assess the precision of three different automatic calculation methods in real-time bladder volume measurement. MATERIAL AND METHODS: Bladders from 34 medical staff volunteers were examined. Two examinations of each subject were performed independently by 2 examiners using 2 identical ultrasound scanners with no delay between the examinations. Three different automatic calculation algorithms, available as software in the ultrasound scanner, were applied on the frozen ultrasound pictures. After registration of the voided volume with an uroflowmeter, the subjects were scanned again in order to assure complete emptying. RESULTS: Voided volumes ranged from 45 ml to 508 ml. The precision of each method was equal but the LWH method measured significantly lower values than the ELLIPSOID and AREA method. Errors in the range of -56.1% to +58.8% for all volumes and methods were found. Data for voided volumes greater than 150 ml (n = 29) were investigated separately, but no significant improvement in accuracy for any of the methods was found. CONCLUSIONS: Ultrasound bladder volume calculation is an easy method for estimation of bladder volume. The prolate ellipsoid method (LWH) is recommended as the standard calculation method because it is fast and easy. Unacceptable large measure errors are found and too rigid conclusions based on ultrasound measurements of bladder volume should be avoided.

Adult↗

Characterization of the antibody response to pneumococcal glycoconjugates and the effect of heat-labile enterotoxin on IGg subclasses after intranasal immunization.

The antibody response to pneumococcal glycoconjugate (Pnc) was characterized by analyzing pneumococcal polysaccharide (PPS)-- and protein carrier-specific IgG subclass profiles and their relationship. Mice were immunized intranasally (inl) or subcutaneously (sc) with Pnc with mutants of Escherichia coli heat-labile enterotoxin, LT-R72 and LT-K63, as mucosal adjuvants. Subcutaneous immunization with Pnc alone induced predominantly IgG1, whereas native PPS administered sc induced very low IgG titers that were exclusively of the IgG3 subclass. Compared with sc immunization with Pnc alone, inl immunization with Pnc and LT mutants induced significantly higher systemic IgG2a, IgG3, and IgA antibodies to both PPS and the carrier, whereas the IgG1 titers were comparable. There also was a significant correlation between PPS- and protein carrier--specific antibody responses for all IgG subclasses. This demonstrates that LT mutants can be used to both enhance and modulate the antibody response to the PS moiety of glycoconjugate vaccines.

Adjuvants, Immunologic↗

Serum samples from infants vaccinated with a pneumococcal conjugate vaccine, PncT, protect mice against invasive infection caused by Streptococcus pneumoniae serotypes 6A and 6B.

Streptococcus pneumoniae serogroup 6 is an important cause of respiratory tract disease worldwide. Vaccination with 6B polysaccharide induces antibody response to the cross-reacting serotype 6A, but the protective capacity of 6A antibodies induced in infants remains unknown. In this study, passive immunization with serum samples obtained from infants vaccinated with an octavalent polysaccharide protein conjugate vaccine, PncT, protected mice against bacteremia and/or lung infection caused by intranasal challenge with serotypes 6B and 6A. Protective infant serum samples had significantly higher serotype-specific IgG levels and opsonic activity than did nonprotective serum samples. The protective level to either serotype was approximately 1 microg of specific IgG antibodies injected per mouse (corresponding to approximately 0.3 microg/mL). The protection was strongly related to opsonophagocytic antibody levels measured in vitro. These results demonstrate that PncT induces antibodies in infants that protect mice against invasive disease caused by the homologous serotype and by the cross-reacting serotype 6A.

Animals↗

The porcine bronchial artery. Anastomoses with oesophageal, coronary and intercostal arteries.

Information about the existence and anatomy of arterial anastomoses with the porcine bronchial artery is lacking in the literature. Prior to basic physiological investigations in a porcine model related to lung transplantation with bronchial artery revascularisation, this study was designed to examine the anatomy of systemic arterial anastomoses with the bronchial artery system. Twenty pigs were studied in 3 groups. In 2 groups the heart-lung block was removed with all mediastinal structures. One group served for investigation of coronary-bronchial artery anastomoses and one for investigation of oesophageal-bronchial artery anastomoses. The systemic arteries to be examined were cannulated. The inflated heart-lung block was examined macroscopically with Evans blue, and radiographically after contrast injection. In the 3rd group intercostobronchial artery anastomoses were studied radiographically with the heart-lung block in situ. Coronary-bronchial artery anastomoses were demonstrated in 3 of the 5 pigs with an aortic 'pouch' technique, but contrast was very limited in 2 of these 3. Oesophageal arterial anastomoses with bronchial arterial branches and/or the pulmonary veins were demonstrated in 6 of the 7 pigs and more markedly than the coronary-bronchial anastomoses. Intercostobronchial artery anastomoses could not be demonstrated angiographically. It was concluded that the existence of coronary-bronchial and oesophageal-bronchial artery anastomoses in the pig appear to establish an arterial net between the base of the heart and the distal oesophagus. The resemblance to human oesophageal-bronchial artery anastomoses supports use of a porcine model for experimental studies.

Animals↗

Effect of a full bladder on urine production in humans.

OBJECTIVE: To demonstrate the reduction in urine production in healthy humans upon bladder distension and to identify the factors responsible for this reduction. MATERIALS AND METHODS: Twelve healthy females were investigated twice in a cross-over designed experiment: once with the urinary bladder empty at the start and once pre-filled to 60% of the maximum bladder capacity. Glomerular filtration rate, effective renal plasma flow, urine content of catecholamines, blood pressure, pulse rate, plasma arginine vasopressin (AVP) and plasma concentration of renine and electrolytes were analysed together with serum osmolality. RESULTS: Three subjects failed to reach maximum bladder capacity during the "full bladder" test and were excluded. The urine production in the "full-bladder" test was significantly lower than the "empty-bladder" test (p = 0.024). In the "full-bladder" test a significant increase in mean blood pressure was found (p=0.01). No further significant changes were demonstrated. CONCLUSIONS: Acute bladder distension causes a reduction in urine production or a "pooling of urine" in the upper urinary tract in healthy humans. The mechanism is unknown.

Adult↗

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.

Adjuvants, Immunologic↗

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i. n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections.

Administration, Intranasal↗

Pressure-flow studies: an evaluation of within-testing reproducibility--validity of the measured parameters.

The within-examination variation in selected test parameters in repeated pressure-flow studies was determined in a retrospective study of consecutive pressure-flow examinations in 105 patients. It was further evaluated to see whether there was a systematic change in the measured parameters during retesting. To see if variation and reproducibility were influenced by the procedure of investigation, i.e., transurethral or suprapubic, patients were grouped according to the method employed. Finally, the effect of detrusor instability on the measurements was evaluated. Using the Abrams-Griffiths nomogram, patients were classified as obstructed, equivocal, or unobstructed. The test-retest variations in classification were evaluated. We found a systematic variation in Pdet.Qmax' Pdet.Open' and Qmax during testing, indicating a physiological effect of repeated pressure-flow studies resulting in a less obstructed second voiding. Accordingly, 69% of the patients who shifted group of classification during retesting shifted to a group of lesser obstruction at the second voiding. Still, 88% of patients remained in the same group of classification of bladder outlet obstruction. Within- and between-patient variations and reproducibility of the test results were not influenced by the procedure of investigation, i.e., the transurethral or suprapubic method. However, we found variations suggesting a decrease in urethral resistance and bladder contractility from test to test in the transurethral group, whereas variations suggesting an isolated decrease in bladder contractility were seen in the suprapubic group. Detrusor instability per se does not seem to cause any systematic changes during repeated testing.

Adult↗

Prostatic specific antigen and benign prostatic hyperplasia.

The aim of this study on patients (n = 51) with urodynamically proven obstruction was to search for correlations between serological levels of prostatic specific antigen (PSA) and age of patients, volume of prostate and prostatic morphology as evaluated on transurethral resection specimens. No correlations could be found between PSA levels and morphological parameters such as degree of inflammation and relative degree of stromal or epithelial hyperplasia. Significant correlations were demonstrated between PSA levels and age of patients and prostatic volume.

Age Factors↗

Benign prostatic hyperplasia. Does a correlation exist between prostatic morphology and irritative symptoms?

Fifty-two consecutive patients with prostatism who underwent a prostatectomy were investigated with regard to irritative symptom score, age, prostate volume, urine culture results, degree of detrusor instability, inflammation in the prostate, and stromal, glandular or mixed prostatic histopathology. We did not find any statistical correlations between irritative symptom score and the mentioned parameters. This indicates that irritative symptoms should rather be attributed to extraprostatic factors such as e.g. bladder reaction.

Age Factors↗

Five-year follow up of patients with cervical intra-epithelial neoplasia in the cone margins after conization.

Three hundred eighty-five women treated with conization due to repeated CIN I, CIN II or CIN III of the cervix uteri have been followed up for 5 years. All cones were classified according to diagnosis and status of the resection margins. A significantly greater recurrence rate of 16.2% was found in the group with neoplasia in the resection margins, in contrast to 3.9% in the group with normal resection margins. However, 83.8% (75.4-92.2%) of patients with neoplasia in the resection margins can be expected to be free of recurrence after a 5-year postoperative follow-up period. Whether the non-free resection margins were endocervical, ectocervical or both, did not influence the recurrence rate. While the prevalence of non-free resection margins increased significantly with increasing dysplasia, this could not be found with increasing age. The risk of recurrence could not be correlated with the grade of dysplasia. We conclude that neoplasia in the resection margins of the cone represents an increased risk of recurrence. Therefore, we changed the normal smear check-up with a cotton-swab to smear with cyto-brush, supplemented with colposcopy in the non-free resection margin group, but it remains to be proven that this procedure is safer.

Carcinoma in Situ↗

Pad weighing tests with 50% or 75% bladder filling. Does it matter?

In order to evaluate the influence of bladder filling at the beginning of a 40 minutes pad test, 71 women completed this study. Thirty-six patients were randomized to pretest filling of the bladder to 50% of the bladder capacity, and 35 patients to 75% pretest filling. In all patients, a retest was performed approximately fourteen days later. The leakage in the two groups was equal. Median leakage during the first test was 3 g in both groups (p = 0.97). The leakage was numerically larger during the second test, median 6.5 g and median 13 g, respectively (p = 0.69). The test-retest variation was calculated in both groups. In patients with 50% bladder filling test-retest variation (mean +/- 2 S.D.) was -28.4% +/- 206.8%. In patients with 75% bladder filling mean variation was -58.0% +/- 203.0%. The difference in test-retest variation between groups was not statistically significant (p = 0.17). Only the subjective evaluation by the patients revealed a preference in favor of the test with 50% bladder filling. Significantly more patients in the 50% group reported that the results of the first test and the retest corresponded well with the daily urinary leakage (p = 0.04). The most striking finding of this study was that, despite filling to either 50% or 75% of the bladder capacity at the beginning of the test, the fluid load during the test, i.e. the initial volume instilled into the bladder plus the diuresis during the test, was equal in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Induction of intracellular and plasma 2',5'-oligoadenylate synthetase by pentostatin.

Similar to interferon alpha, pentostatin is highly effective in hairy cell leukemia and moderately active in other chronic lymphoid malignancies. In ten patients with hairy cell leukemia (HCL) and seven patients with other B-cell chronic leukemias (BCL), we have studied the intracellular 2',5'-oligoadenylate synthetase (2,5OAS) activity of the mononuclear cells before, 4 h, 24 h, and 48 h after pentostatin administration. In patients with HCL the median level of intracellular 2,5OAS increased 4.6-fold at 4 h and 11.5-fold at 24 h compared to the pretreatment value. Among the other seven patients, the median intracellular 2,5OAS remained unchanged in three patients and rose slightly by 2 to 14 times in four patients. Eleven patients (eight with HCL and two with BCL) responded to pentostatin. The median increase in 2,5OAS among the responders was 13.0-fold (range 4.8-30.0) whereas that among non-responders was 2.2-fold (range 0.2-6.3). The difference was highly significant (p less than 0.0001). In five of the total seventeen patients, the plasma levels of 2,5OAS activity were also determined and changes in plasma levels paralleled those measured intracellularly. To determine if the elevation of 2,5OAS is mediated by induction of interferon alpha, the expressions of mRNA for interferon alpha and beta were investigated by means of reverse transcription and polymerase chain reaction using the corresponding sense primers. In none of the five patients thus studied could we find an induction of mRNA for interferon alpha or beta in the leukemic cells during treatment with pentostatin. Thus, response to pentostatin correlates with induction of 2,5OAS directly and the 2',5'-oligoadenylate system seems to be involved in cytotoxicity.

2',5'-Oligoadenylate Synthetase↗

[The intraurethral plug. A new alternative in the treatment of women with stress incontinence].

The intraurethral plug has been developed for treatment of women with stress-incontinence. The plug is made of thermoplastic-elastomeric material and consists of a meatus plate, a soft stalk and one or two beads along the stalk. The individual plug is constructed on the basis of the result of the urethral pressure profile. The plug is removed manually prior to micturition and after micturition a new plug is introduced by the patient. A plug with two beads was employed in period 1 (seven days) and a plug with one bead for period 2 (seven days). Twenty-two patients completed period 1. Eight of these patients did not complete period 2, mainly on account of unchanged incontinence during period 1 or repeated loss of the plug with one bead. In periods 1 and 2, 73% and 79% of the patients, respectively, were both subjectively and objectively continent or considerably improved. This preliminary investigation demonstrates that the intraurethral plug may be an alternative form of treatment of women with stress incontinence.

Adult↗

Lack of effect of cholinergic blocking and alpha-adrenergic stimulation on nocturnal incontinence after ileocaecal bladder replacement. A controlled randomised study.

A controlled randomised trial was carried out in 9 patients to examine the possibility of achieving nocturnal continence after ileocaecal bladder replacement by reducing the amplitude of the peristaltic contractions and by increasing the maximum urethral pressure pharmacologically. The trial consisted of 4 treatment periods, each of 2 weeks' duration: a single-blind placebo period was followed by 3 double-blind periods with phenylpropanolamine hydrochloride 50 mg bd (Kontexin), oxybutynin chloride 5 mg tid (Ditropan), and combined treatment. Each patient completed a frequency/volume chart before the trial and for the last 7 days of each treatment period. Filling and storage urethrocystometry was performed before treatment and at the end of each treatment period. Treatment with phenylpropanolamine and oxybutynin failed to reduce the nocturnal urine leak of about 600 ml. Treatment did not influence the maximum urethral closure pressure, which remained unchanged at about 16 cm of water with the bladder substitute at rest and filled to its maximum cystometric capacity. At storage urethrocystometry, the treatment resulted in a decrease in the amplitude of the peristaltic contractions of about 10 cm of water to approximately 45 cm of water. Accordingly, the effect of alpha-adrenergic stimulation and anticholinergic suppression was found to be insufficient to achieve nocturnal continence in patients with ileocaecal bladder replacement.

Aged↗