Biomedical subjects
Publications and source records attributed to G Ludwig.
The erectile dysfunction (impotence of the man) affects 10% of the male population. It is mostly due to physical problems but also due to mental causes. A hormone deficiency due to age affects only a small percentage of the patients. A differentiated urologic diagnostic is necessary. Therapy includes pharmacological and partly surgical treatment. The different options are demonstrated.
In 1995, the first Venezuelan equine encephalitis (VEE) outbreak in Colombia in 22 years caused an estimated 75,000 human cases, 3000 with neurologic complications and 300 fatal, in La Guajira State. Of the state's estimated 50,000 equines, 8% may have died. An epizootic IC virus, probably introduced from Venezuela, was rapidly amplified among unvaccinated equines. Record high rainfall, producing high densities of vector Aedes taeniorhynchus, led to extensive epidemic transmission (30% attack rate) in the four affected municipalities. Native Wayuu Indians, constituting 24% of the state's population, were at increased risk of infection (risk ratio, 3.3; 95% confidence interval, 2.2-5.3). Epidemiologic studies found no evidence of human-to-human transmission. A higher-than-expected number of abortions during the outbreak confirmed a previously suspected abortifacient role of VEE infection. Pesticide applications and a mass equine vaccination program contributed to preventing the outbreak's spread south of La Guajira.
A bioavailability study of 2 different selegiline preparations were conducted in 20 healthy volunteers to test the bioequivalence. Almost no bioavailability study of selegiline has been published. As plasma levels of selegiline are very low and the elimination half-life is very short being about 9 minutes, therefore, a very sensitive and selective method for determining the 3 main metabolites desmethylselegiline (DMS), methamphetamine (MA) and amphetamine (A) was developed. After application of a single oral dose of 5 mg selegiline the Cmax values of DMS reached 5-6 ng/ml, of MA 6-7 ng/ml and of A about 2 ng/ml. The AUC infinity values were with DMS about 11 ng/ml x h +/- 4.5, with MA about 130 g/ml x h +/- 50 and with A about 50 ng/ml x h +/- 15. The 90% confidence interval was with logarithmic transformed AUC infinity values 92-107% with DMS, 89-107% with MA, and 84-104% with A. The logarithmic transformed Cmax values showed a 90% confidence interval of 92-127% with DMS, 91-101% with MA, and 90-103% with A. All relevant pharmacokinetic parameters showed bioequivalence with all 3 metabolites (DMS, MA, and A).
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A trauma victim with locked-in syndrome demonstrated severely decreased bowel sounds, intact response to suppository, and elevated, but unchanging pulse. Absent cardiac response to tracheal suctioning, high gastric residual volumes, and pulmonary edema in response to a urecholine challenge demonstrated dysfunction in the automatic system. Symptoms persisted for 2 1/2 years until death. At autopsy, asymmetric bilateral involvement of the dorsal motor nucleus of the vagus and of the nerve tract in the medulla were demonstrated. In contrast, a control subject with locked-in syndrome caused by a stroke did not demonstrate these phenomena. In trauma patients with delayed gastric emptying, measurement of the heart rate response to deep suctioning may lead to the diagnosis of this vagus dysfunction syndrome.
Selegiline, used in the treatment of Parkinson's disease, inhibits the intracerebral degradation of dopamine and the uptake of catecholamines. Due to a high volume of distribution and also a high rate of biotransformation the concentrations of selegiline in plasma are rather low. In addition, there are indications that selegiline binds to erythrocytes. An open, randomized, 2-way cross-over study was performed in 24 healthy male volunteers to determine bioavailability and pharmacokinetic parameters of 2 oral selegiline preparations after single dose administration. Statistical tests were applied to the pharmacokinetic parameters AUCinf, AUC0-8, AUCz, Cmax and tmax. The terminal half-lives t1/2 for selegiline with geometric means of 1.69 h (n = 22) and 1.76 h (n = 21) for treatments A and B and for N-desmethyl-selegiline with geometric means of 1.98 h and 1.96 h for treatments A and B agreed very well. AUCinf of selegiline could be compared between treatments for 14 subjects only. The geometric mean ratio was 97.80% with a 90% confidence interval that ranged from 79.58%-120.17% and thus exceeded the (80%, 125%) range by a very small margin. After correction for the actual dose contained in each of the 2 preparations the geometric mean ratio was calculated to 98.39% with a 90% confidence interval that ranged from 80.06%-120.90% and thus was fully contained within the (80%, 125%) acceptance range. Treatments also agreed very well with respect to AUCinf of N-desmethyl-selegiline, the active metabolite of selegiline, with a geometric mean ratio of 96.14% with a 90% confidence interval that ranged from 92.41%-100.01% so that bioequivalence of the 2 treatments could be shown very clearly with respect to this metabolite. The AUC of N-desmethyl-selegiline in serum is about 6-fold higher than that of the parent drug. It is assessed with low variability. Thus, it is reasonable to base the judgement for or against bioequivalence primarily on the data obtained for the metabolite although "a larger acceptance range may be acceptable if inevitable and clinically acceptable" for the parent compound selegiline which certainly can be classified as a "highly variable compound".
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Our practice is to defer donors with blood platelet (PLT) counts of < 180 x 10(9)/L because PLT yields are low, when compared to PLT units collected from donors with higher counts. In an attempt to minimize deferral, we determined whether 33 donors, who repeatedly demonstrated low-normal PLT counts (150-180 x 10(9)/L) on multiple occasions during the prestudy period. might safely donate satisfactory apheresis PLT units simply by extending the apheresis collection time by 20 min (men) and 40 min (women). Repeat plateletpheresis procedures were scheduled at > or = 28-day intervals. The mean PLT yield (N = 92) was 5.8 x 10(11) with 97% of units containing > or = 4.0 x 10(11) PLTs. Although donors entered the study only after they had repeatedly exhibited predonation PLT counts of < 180 x 10(9)/L, PLT counts were not always below this level at the time of study collections. However, analyzing only donations with true predonation PLT counts of < 180 x 10(9)/L (N = 35), the mean PLT yield was excellent-5.4 x 10(11) with 97% of units containing > or = 4.0 x 10(11) PLTs. The average fall in donor blood PLT counts (pre-vs. postdonation) was 36%, with only ten of 99 postdonation counts being < 100 x 10(9)/L; the lowest was 69 x 10(9)/L. Thus, extending the apheresis collection time permitted donors who in the past were routinely deferred because of low PLT counts to safely donate satisfactory PLT units.
Venezuelan equine encephalomyelitis (VEE) virus is a mosquito-borne arbovirus of major human health significance in the New World. Currently two forms of VEE virus are used for immunization of humans and horses, i.e. a live attenuated and a formalin-inactivated vaccine. Clinical evidence suggests that these vaccines are not fully efficacious and may produce certain undesirable side-effects. In the present study, microspheres composed of biocompatible and biodegradable poly (DL-lactide-co-glycolide) (DL-PLG) were evaluated for their effectiveness as a delivery system of whole, inactivated VEE virus vaccine for the induction of protective immune responses. Mice receiving 50 micrograms VEE virus in microspheres composed of an equimolar ratio of DL-lactide and glycolide (50:50 DL-PLG) exhibited a primary circulating IgG antibody response which was approximately 32-times higher than the response induced with the same dose of unencapsulated (free) virus. A similar difference in responses was seen with antigen doses ranging from 3.1 to 50 micrograms. A rapid increase in antibody activity was seen after the secondary immunization (day 50). Formalin fixation of inactivated VEE virus was important for immunogenicity since the circulating anti-VEE virus antibody response induced with microencapsulated nonformalin-fixed virus vaccine was lower than that induced with microencapsulated formalin-fixed virus vaccine. Furthermore, at low antigen concentrations, DL-PLG microsphere vaccines prepared with the solvent methylene chloride induced higher antibody responses than those prepared using ethyl acetate as the solvent. Microencapsulated vaccine also induced higher VEE virus neutralization titers than did free virus vaccine. Finally, the microencapsulated virus was more effective than the free virus in inducing immune responses protective against systemic challenge with virulent VEE virus. These results demonstrate that DL-PLG microspheres containing formalin-fixed, inactivated VEE virus were effective in augmenting circulating IgG antibody levels and neutralization titers to the VEE virus following systemic immunization and in affording enhanced protection against systemic challenge with virulent VEE virus. The effects of antigen form and the microsphere processing solvent on the immunogenicity of the vaccine are discussed.
BACKGROUND: We describe a recently observed set of autosomal dominant GEMSS (glaucoma, lens ectopia, microspherophakia, stiffness of the joints, and shortness) syndrome in a 47-year-old woman and her 23-year-old son. In addition, sclerosis of the skin, from which both patients suffered, is investigated in detail. OBSERVATIONS: The histologic examination of skin biopsy specimens obtained from the upper aspects of the backs of both patients revealed a markedly thickened dermis. Immunohistochemical examination of the dermal collagen bundles showed a collagen pattern similar to systemic sclerosis and normal control skin. In situ hybridization showed a markedly enhanced gene expression of transforming growth factor beta 1. CONCLUSION: The sclerotic skin changes in GEMSS syndrome are the result of an abnormally increased production of normal collagen that might be attributable to the enhanced in situ production of transforming growth factor beta 1.
The gene encoding a novel DnaJ-like protein, termed Xdj1, has been identified by amplification of Saccharomyces cerevisiae genomic DNA. An open reading frame of 1380 bp was detected. Disruption of XDJ1 did not yield any detectable new phenotype. A double-deletion strain containing a disruption of both XDJ1 and YDJ1, another gene coding for a DnaJ-like protein, was still viable. Under a variety of growth conditions, no XDJ1 transcripts could be detected by Northern blot analysis and no translation product was found by immunoblotting with antibody against Xdj1 produced in Escherichia coli. Thus, XDJ1 is either expressed only under very specific conditions or represents a silent gene.
This paper examines the factors governing the frequency response of ultrasonic polyvinylidene fluoride (PVDF) polymer needle-type hydrophones, in particular the sensitivity variations in the lower frequency range of 1-6 MHz. A theoretical model was used to analyze the influence of the hydrophone's diameter, the metal electrodes, thickness, PVDF material properties, the adhesive layer acoustical characteristics and the backing material, on the frequency response of the hydrophone. The results of the theoretical modelling differ by less than +/- 0.5 dB from those obtained experimentally from the reciprocity calibration in the frequency range 1-20 MHz. It is shown that the needle hydrophone's diameter and backing material are the main reasons for the sensitivity variations observed in the frequency range below 6 MHz.
The influence of spatial polarization distribution on spot poled PVDF membrane hydrophone performance was calculated and then experimentally verified using a one-dimensional model based on acoustic wave propagation through a layered medium. It is shown that the sensitivity of the hydrophone is markedly dependent on the spatial polarization distribution. It is also shown that there can be a significant difference between the voltage sensitivities measured in the same hydrophone probe depending on which electrode is actually facing the acoustic source. The measurements carried out in the frequency range 1-20 MHz indicate that this difference, while negligible below 2 MHz, may exceed 1.6 dB at higher frequencies. The model developed can also be used to determine the "effective" piezoelectric constant d33 of the PVDF material as a continuous function of frequency. Moreover, the model predicts the existence of a negative slope in the frequency response of the spot poled membrane hydrophone. The experimental confirmation of this prediction underscores the importance of using swept frequency methods during calibration measurements.
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Conservative approaches to the treatment of Peyronie's disease are limited. Irradiation is of no value because the efficacy has not been proven and it may cause tissue damage requiring or hampering subsequent surgery. Vitamin-E therapy is ineffective and is also not recommended. p-Aminobenzoate treatment has to be discontinued because of intolerance in one third of the cases, and the response rate is not superior to that of a placebo. Local infiltration of the plaques with orgotein (Peroxinorm) results in a marked improvement in just under 50% of cases and is therefore a justified approach in the early stages of the disease. It is, however, unclear how great the placebo effect and the spontaneous remission rate are. Surgery suited to the individual case must be considered in patients with severe angulation of the penis rendering introitus impossible, calcium deposits, or worsening of the condition despite injections of Peroxinorm.
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Testosterone, a steroid hormone which increases blood pressure by hitherto unknown mechanisms, is known to induce renin synthesis in the submandibular gland (SMG) of mice. Since renin as well as all other components of the renin-angiotensin system are present in organs important for cardiovascular control, e.g. the kidney, heart, adrenal gland and brain, it is of interest to study the effect of testosterone on renin gene expression in these organs. Renin messenger (m) RNA concentrations were measured by a solution hybridization assay using a 32P-labeled mouse SMG renin complementary (c) RNA as a radioactive probe (detection limit: 1 pg renin mRNA). Measurements were performed after 2 h and after 2, 7, 14 and 21 days of dihydrotestosterone (DHT) treatment in female NMRI mice. Renin mRNA concentration (values are expressed as pg renin mRNA/ micrograms total RNA) in the SMG was significantly increased after 7 days (108 +/- 22 in controls versus 630 +/- 101 in DHT-treated mice), after 14 days (83 +/- 15 in controls versus 743 +/- 83 in DHT-treated mice) and after 21 days (107 +/- 30 in controls versus 579 +/- 76 in DHT-treated mice), but did not reach levels found in untreated male NMRI mice (1021 +/- 84). In the kidney, a decrease was observed within 21 days, from 43 +/- 4 and 40 +/- 4 to 29 +/- 2 and 22 +/- 1.7 pg/micrograms in controls and DHT-treated groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Imaging methods are essential in the diagnosis of erectile dysfunction. With sonography the penile cavernous tissue and the deep arteries can be shown. This visualization is optimized by high-resolution ultrasonography with pulsed Doppler spectrum analysis or angiodynography. Pharmacocavernosonography combined with pharmacocavernosometry is the method of choice to verify pathologic venous leakage from the penis. Phalloarteriography is absolutely necessary before surgery for revascularization of the penis. In investigations of fertility sonography of the scrotum only plays a subordinate role, as an occlusion of the epididymis cannot be diagnosed in this way. In contrast, good visualization of any small intraparenchymous tumor of the testicle is possible. Transrectal sonography allows the best assessment of the vesicular glands. A persisting varicocele is visualized by retrograde phlebography of the internal spermatic vein. Antegrade phlebography of the spermatic vein with Valsalva maneuver is used by some workers in preference to the above-mentioned method, but has not yet been fully evaluated. Scrotal thermography can visualize a varicocele in a satisfactory manner. Obstacles to ejaculation can sometimes be visualized with retrograde urethrography and/or voiding urethrography. Focused x-rays of the sella turcica are necessary if there is any suspicion of a prolactinoma. Mammography will help to differentiate between gynecomasty and alimentary pseudo-gynecomasty. CT and NMR are used to diagnose tumors of the adrenal and pituitary glands; these methods are rarely used to diagnose abdominal cryptorchidism. Radiologic representation of the ductus deferens with contrast medium (vasography) now has to be rejected as harmful and obsolete.