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Biomedical subjects

P Graf

Publications and source records attributed to P Graf.

At least 19 recordsLinked to original sources

A lattice relaxation algorithm for three-dimensional Poisson-Nernst-Planck theory with application to ion transport through the gramicidin A channel.

A lattice relaxation algorithm is developed to solve the Poisson-Nernst-Planck (PNP) equations for ion transport through arbitrary three-dimensional volumes. Calculations of systems characterized by simple parallel plate and cylindrical pore geometries are presented in order to calibrate the accuracy of the method. A study of ion transport through gramicidin A dimer is carried out within this PNP framework. Good agreement with experimental measurements is obtained. Strengths and weaknesses of the PNP approach are discussed.

Algorithms

Treatment of vascular lesions using the VersaPulse variable pulse width frequency doubled neodymium:YAG laser.

BACKGROUND: The flashlamp-pumped dye laser is considered the treatment of choice for vascular lesions including port-wine stains. However, this treatment is associated with an intensive postoperative purpura and considerable pain. OBJECTIVE: We tested a newly developed laser device with a 532-nm neodymium:YAG laser with variable pulse widths between 2 and 10 ms. METHODS: Forty-two consecutive patients from our laser clinics were treated with the new laser system delivering energy through a chilled tip by means of circulating water (cooling temperature was between 4 and 5.5 degreesC). Forty of them had been pre-treated with an argon laser and an argon-pumped dye laser. RESULTS: Out of the 42 patients, 1 patient had a complete clearing, 11 had an excellent result (more than 80% clearing), 21 patients had a good result (51-75% clearing), weak responses were seen in 9 patients. Significant success was already seen after 1 or 2 treatments. Side effects were rare. There was no purpura after treatment. Local anesthesia was only applied in 6 out of 42 patients. CONCLUSION: The variable pulse width frequency doubled neodymium:YAG laser seems to be an alternative to the flashlamp-pumped dye laser and deserves to be investigated in comparative trials.

Adolescent

Standardized tuberculosis treatment outcome monitoring in Europe. Recommendations of a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) for uniform reporting by cohort analysis of treatment outcome in tuberculosis patients.

Consensus-based recommendations have been developed by a Working Group of the World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis (TB) treatment outcome data in countries in Europe. The main purpose of treatment monitoring is to find out how many of the potential infectious TB patients notified were declared cured at the end of treatment. Following the uniform case definitions as defined in 1996, emphasis is placed on cohort analysis of definite cases of pulmonary TB. The Working Group recommends using a minimal set of six mutually exclusive categories of treatment outcome: cure, treatment completed, failure, death, treatment interrupted, and transfer out. More detailed subsets may be chosen. Treatment outcome is expressed as a percentage of the total number of cases notified. Analysis should be separate for new and retreatment cases. Treatment outcome data have to be collected at the local level and passed on to regional and national authorities on an ongoing basis. Evaluation of treatment results becomes, preferably, an inbuilt component of national monitoring of programme performance. Because of the long duration of treatment, it is recommended that analysis is carried out in the first quarter of the calendar year that follows a full year after the last patient was enrolled. Feedback is essential. Treatment outcome results should become an inseparable part of the annual report on tuberculosis.

Cohort Studies

Color-Word Stroop test performance across the adult life span.

In the Color-Word Stroop test (CWST), the basic task is to name the ink color of rows of XXXs, and performance in this condition is compared with performance in naming the ink-color of color words under conditions where word meanings and ink colors mismatch or are incongruent (e.g., the word red printed in green ink). The present study investigated whether Stroop test interference, defined as the cost associated with ink-color naming in the incongruous stimulus condition versus in the basic color-naming condition, provides positive evidence for a kind of processing qualitatively different than that which is required for color naming or for word reading. Does the pattern of age-related differences in Stroop interference force the conclusion that the incongruous condition taps a qualitatively different kind of processing than that required for color naming or for word reading? We gave the CWST to 310 healthy adults. Their performance in each condition of the test replicates and extends previous findings. Structural equation modeling of the data showed a significant, direct link between age and performance in the latent factor associated with the incongruent condition. However, this direct link with age produced a relatively small increase in the model's fit; it amounted to only a .024 increase in the proportion of variance explained in the incongruent condition. In light of this small direct influence due to age, the most parsimonious explanation of our findings is that age effects in Stroop interference are due to age-related slowing (which is also indexed by color naming and by word reading) primarily; the findings do not provide evidence for a qualitatively different kind of processing that declines with age.

Adolescent

Rhinitis medicamentosa: aspects of pathophysiology and treatment.

With modern vasoconstrictors, such as oxy- and xylometazoline, the risk of developing rhinitis medicamentosa (RM) has been considered to be small or even nonexistent. However, recent studies have shown that overuse of these drugs may result in rebound congestion, nasal hyperreactivity, tolerance, and histologic changes of the nasal mucosa. Using rhinostereometry, it has also been shown that the long-term use of the preservative benzalkonium chloride (BKC) in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers. A nasal decongestant spray composed of a combination of vasoactive substances and BKC has a long-term adverse effect on the nasal mucosa. BKC alone induces mucosal swelling after 30 days use of the nasal spray in healthy subjects, unlike placebo. According to the author, rhinitis medicamentosa can be defined as a condition of nasal hyperreactivity, mucosal swelling, and tolerance that is induced, or aggravated, by the overuse of topical vasoconstrictors with or without a preservative. An adequate treatment of these patients consists of a combination of vasoconstrictor withdrawal and a topical corticosteroid to alleviate the withdrawal process. The underlying nasal disorder must then be treated. Patients with rhinitis medicamentosa who overuse topical decongestants and are able to stop using such drugs should be careful about taking these drugs again, even for a few days. They must be informed about the rapid onset of rebound congestion upon repeated use in order to avoid the return of the vicious circle of nose-drop abuse.

Benzalkonium Compounds

Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa.

BACKGROUND: Controversy still exists about the treatment of rhinitis medicamentosa and treatment has never been objectively evaluated. OBJECTIVE: To study the effect of fluticasone propionate aqueous nasal spray compared to placebo nasal spray in the treatment of rhinitis medicamentosa. METHODS: A parallel randomized, double-blind study was conducted to evaluate the treatment of rhinitis medicamentosa. Two groups containing 10 patients with rhinitis medicamentosa in each group stopped their overuse of nasal vasoconstrictor spray immediately and were treated with either fluticasone propionate nasal spray once daily 200 micrograms, or placebo nasal spray for 14 days. The nasal mucosal swelling was recorded with rhinostereometry, acoustic rhinometry and a peak inspiratory flow meter. Nasal stuffiness was estimated on a visual analogue scale in the morning and in the evening of each day. RESULTS: The mucosal swelling decreased after 7 and 14 days of treatment with fluticasone propionate as well as placebo, but the reduction was significantly greater after treatment with fluticasone propionate. The symptom scores for nasal stuffiness showed a marked reduction during the treatment period in both groups, but there was a faster onset of symptom reduction after treatment with fluticasone propionate. CONCLUSION: Fluticasone propionate is more effective and has a faster onset of action than placebo in the treatment of rhinitis medicamentosa. An adequate treatment of these patients consists of a combination of vasoconstrictor withdrawal and a topical corticosteroid to alleviate the withdrawal process.

Administration, Intranasal

[Neovascularization of pre-formed tissue flaps in relation to arteriovenous blood flow of the implanted vascular pedicle. Experimental study in the rabbit].

In 45 Chinchilla-Bastard rabbits, a skeletonised arterio-venous pedicle was implanted on the subsurface of a 15 x 8 cm abdominal skinflap to create a neovascularised axial prefabricated flap. In order to evaluate the potency of neovascularisation in relation to the blood flow of the pedicle, we compared minimal blood flow by distal ligation (model 1) with maximal blood flow by distal microvascular arteriovenous shunt anastomoses (model 2) of the implanted vascular pedicle. The results show that 8 and 12 days after pedicle implantation, tissue flap perfusion in model 2 is significantly earlier and better in comparison to model 1.

Anastomosis, Surgical

Temporary ectopic implantation for salvage of amputated digits.

Temporary ectopic implantation for salvage of amputated parts is a fascinating idea. The first successful case, to our knowledge, of preserving digits by means of temporary ectopic implantation to the contralateral forearm is presented and this treatment concept is discussed. The indication for temporary ectopic implantation is an amputation injury with associated extensive soft tissue damage in which immediate replantation with either adequate shortening or preservation of length does not seem feasible, although the amputated part itself is uninjured and should therefore be salvaged. The groin, axilla and lower arm are compared as possible recipient sites for ectopic implantation. Early replantation of the ectopic implanted parts will provide superior functional results although replantation may be technically more demanding. The function of a replanted extremity after ectopic implantation will probably always be inferior to a comparable, immediately replanted extremity.

Adult

Variations in congestion of the nasal mucosa in man.

Congestion of one side of the nose is accompanied by decongestion of the other side. This is called the nasal cycle. The nasal cycle does not seem to be present in all subjects and it has not been shown with rhinostereometry. There are very few studies showing whether there are spontaneous day-to-day variations in nasal mucosal congestion and no studies showing differences in nasal mucosal congestion between morning and afternoon. This, however, may be very important in studies covering a longer period. In the present study, data from four healthy volunteers were recorded 18 or 19 times in the mornings and afternoons on different days. Measurements were made with rhinostereometry, a peak flow meter (PNIF) and by symptom scores. A nasal cycle was found in some subjects. There was no difference in total nasal mucosal swelling in the mornings and in the afternoons and no day-to-day variation in the total nasal mucosal swelling.

Activity Cycles

An epidemiological study of tuberculosis and HIV infection in Tanzania, 1991-1993.

OBJECTIVE: In Tanzania during the past 6 years reported tuberculosis (TB) cases have nearly doubled, with proportionately much greater increases in smear-negative and extrapulmonary cases compared with smear-positive cases. At the same time, HIV infection has become widespread throughout the country. This survey was undertaken in order to study the association of TB and HIV and to determine the impact of HIV on present and future TB cases in Tanzania. METHODS: The survey design provided for HIV testing of a representative country-wide sample of approximately one-sixth of all new and relapse cases registered between January 1991 and December 1993, with linkage to demographic, clinical and bacteriological data for these cases. HIV surveillance data were used for comparison purposes. RESULTS: A total of 6928 TB cases from all of the country's 20 mainland regions were tested. The overall HIV seroprevalence was 32%. Both crude and adjusted odds ratios (OR) for HIV infection were higher in women, those aged 25-44 years, urban residents, cases of smear-negative and extrapulmonary disease, and persons with a bacille Calmette-Guérin (BCG) vaccination scar. The age-and sex-adjusted relative risk for HIV infection in TB patients compared to blood donors in the same regions was 7.1 (95% confidence interval, 6.6-7.5), and was significantly higher among those aged 25-34 years. Of 3360 patients with bacteriological culture results 46% were culture-positive for Mycobacterium tuberculosis. Drug susceptibility tests were performed on 1164 isolates with the overall rate of drug resistance of 6.2%. Rates of initial resistance were low in both HIV-positive (4%) and HIV-negative (5.8%) patients. Rates of acquired resistance were higher (19% overall) and did not vary significantly by HIV serostatus. Initial combined resistance to both isoniazid and rifampicin was uncommon (0.4%) as was monoresistance to rifampicin (0.3%). CONCLUSIONS: The higher OR for women and young adults reflect the higher rates of HIV infection in those populations. The finding that smear-positive relapse cases were no more likely to have HIV infection than new smear-positive cases suggests that the treatment regimen for new cases is effective in HIV-associated TB. The low rates of both initial and acquired drug resistance in HIV-positive patients is further evidence of adequacy of treatment. The higher relative risk for HIV infection among patients aged 25-34 years suggests increased HIV-related TB transmission. Finally, it is estimated that approximately two-thirds of the increase in the rate of smear-positive tuberculosis in the country can be directly attributed to HIV infection.

Adult

Effect on the nasal mucosa of long-term treatment with oxymetazoline, benzalkonium chloride, and placebo nasal sprays.

A parallel, randomized, double-blind study was performed in 30 healthy subjects to investigate the effects on the nasal mucosa of a 1-month treatment with nasal sprays. Ten subjects received oxymetazoline nasal spray; 10 subjects used a nasal spray containing the preservative benzalkonium chloride, and the others were treated with a placebo nasal spray. The three variables that were studied --nasal mucosal swelling, symptom scores, and nasal reactivity-- were estimated by histamine challenge before and after 28 days of treatment. Rhinostereometry was used to measure nasal mucosal swelling and nasal reactivity. After 28 days of use, benzalkonium chloride spray alone induced an increase in nasal mucosal swelling. At the end of the month, the score for nasal stuffiness was significantly higher for the group treated with oxymetazoline than for those treated with benzalkonium chloride. Oxymetazoline nasal spray induced a pronounced increase in nasal reactivity, which was significantly greater than that induced in the placebo group. Long-term use of placebo and benzalkonium chloride nasal sprays also caused an increase in nasal reactivity, but not to the same extent as with the nasal sprays containing oxymetazoline. The authors concluded that long-term use of oxymetazoline induces a sensation of nasal stuffiness, which may be due to unconscious exaggeration of the degree of nasal stuffiness, induced nasal hyperreactivity, or a combination of both. These factors are probably the main reasons for the prolonged use of nasal decongestive sprays and the development of rhinitis medicamentosa. Benzalkonium chloride induces mucosal swelling, which explains why the presence of this preservative in a decongestant spray aggravates rhinitis medicamentosa.

Administration, Intranasal

Immunoassays in monitoring biotechnological drugs.

For the evaluation and interpretation of pharmacokinetic data reliable quantitative determinations are a requirement that can only be met by well-characterized and fully validated analytical methods. To cope with these requirements a method is being established that is based on an integrated and automated fiber-optic biospecific interaction analysis system (FOBIA) for immunoassays. Performance characteristics of this system used in monitoring of recombinant hirudin (CGP 39 393) are presented. Recombinant hirudin is a highly potent and selective inhibitor of human thrombin. Owing to its size and charge, recombinant hirudin is mainly eliminated by glomerular filtration. But only a fraction of the hirudin dose seems to be reabsorbed at the proximal tubule by luminal endocytosis and hydrolyzed by lysosomal enzymes, leaving approximately 50% of the dose to be extracted in the urine. Thus, renal clearance of recombinant hirudin in the absence of renal insufficiency appears to depend primarily on the glomerular filtration rate. During a 3-month i.v. tolerability study in dogs, some of the dogs developed antibodies against recombinant hirudin. The hirudin-antibody complex accumulated in plasma and apparent hirudin plasma concentrations were therefore much higher than expected from single-dose kinetics. Hirudin captured by antibodies showed an extended half-life and the hirudin-antibody complex is still pharmacologically active, as demonstrated by the observed increase in thrombin time. In conclusion, only appropriate analytical methods allow adequate monitoring and pharmacokinetic characterization of biotechnology drugs in biological materials.

Animals

Clinical and rhinostereometric assessment of nasal mucosal swelling during histamine challenge.

The correlation between the subjective sensation of nasal stuffiness and nasal mucosal swelling measured with rhinostereometry during histamine challenge was studied in 13 healthy subjects. To permit a study of the entire range from decongestion to maximal congestion, the mucosa was pre-treated with a local vasoconstrictor 1 h before it was challenged with eight doses of increasing concentrations of histamine applied to one side of the nose. Ten minutes after each application, the subject estimated stuffiness on the challenged side, using a 100 mm visual analogue scale. The amount of mucosal swelling was measured with rhinostereometry. In 12 of 13 individuals and in the group as a whole, there was a strong positive correlation between a feeling of nasal stuffiness and the degree of mucosal swelling with this nasal provocation model (R = 0.59; P < 0.001).

Adolescent

Long-term use of oxy- and xylometazoline nasal sprays induces rebound swelling, tolerance, and nasal hyperreactivity.

It has been suggested but never confirmed, that the severity of the rebound swelling and rhinitis medicamentosa are directly proportional to the period during which the drug is used, to the frequency of its use, and to the amount of drug administered. However, no studies have been performed to evaluate the effects of various amounts of the vasoconstrictors on the development of rhinitis medicamentosa. Moreover, no in vivo studies have yet been performed to investigate whether benzalkonium chloride in nasal decongestant solutions affects the development of rhinitis medicamentosa. This study shows that rhinitis medicamentosa is a condition of nasal hyperreactivity, mucosal swelling and tolerance induced, or aggravated, by the overuse of topical vasoconstrictors with or without a preservative.

Administration, Intranasal