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Biomedical subjects

D Schmidt

Publications and source records attributed to D Schmidt.

At least 127 records · Page 7Linked to original sources

[Drug therapy before and after surgery for epilepsy. Critical review and recommendations].

As a result of a critical review of the literature and a survey at German epilepsy centers of usual pre- and postoperative drug treatment, the following strategy is recommended: 1. Patients under consideration for surgery should be referred to specialists. Experience has shown that surgery is reasonable for only about a third of all patients with refractory epilepsies. The patient should first have been treated for at least 3 years with at least two first-line drugs in monotherapy and subsequent combined therapy. This applies only to medial temporal lobe epilepsies with very good postoperative prognoses. All other surgically removable epilepsy syndromes with less positive prognosis should be treated with additional antiepileptic drugs before any surgery. 2. There is no exception to the continuation of drug treatment after epilepsy surgery. If the patient remains free of seizures for at least 2 years, discontinuing the drug treatment can be discussed, just as with patients who are free of seizures due to drug treatment alone. In general, the less successful the operative therapy, the longer and more intensive the drug treatment.

Adult↗

[Oxcarbazepine (Trileptal). An effective and well tolerated new drug as first choice in treatment of focal seizures].

Oxcarbazepin (OXC; 10,11-dihydro-10-oxo-5H-dibenz-[b,f]azepin-5-carboxamid, trade name Trileptal) is a new antiepileptic drug for treatment of mono- and adjunctive therapy of partial seizures with or without secondary generalization for adults and children above 6 years of age. It was developed through structural variation of carbamazepine. Extensive postmarketing use includes more than 200,000 patient years. The mechanism of action mainly involves blockage of sodium currents. The recommended daily starting dose of oxcarbazepin for both mono- and adjunctive treatment is 8-10 mg/kg (600 mg/day for adults) in two doses and can be titrated according to clinical benefit up to 2400 mg/day. Oxcarbazepin undergoes reductive metabolism at its keto moiety to form MHD, which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes. Thus, OXC has limited drug interactions and does not require slow titration, allowing for better tolerability. Oxcarbazepin compares favorably to presently available new anticonvulsants of the second generation for two reasons: it is available immediately for both mono- and adjunctive therapy in adults and children, and extensive postmarketing experience from many countries is already available. In addition, OXC has been thoroughly tested in an unusually large clinical development program and been shown to be similarly effective as standard antiepileptic drugs.

Adult↗

The effect of the enantiomers of formoterol on inherent and induced tone in guinea-pig trachea and human bronchus.

The long-acting beta2-adrenoceptor agonist formoterol is, like all other members of this class of drugs, used as a racemate in the clinic. While the effects of the individual enantiomers have been studied on airway smooth muscle from guinea pig, comparable data on human bronchial smooth muscle are scanty or absent. Therefore, we compared the effects of the enantiomers of formoterol on inherent and induced tone in isolated human bronchi with that on guinea-pig trachea in vitro. The human bronchi either were studied under resting tension conditions or were precontracted with 10 microM carbachol or 0.1 mM histamine. The guinea-pig trachea was precontracted with 0.01, 0.1 or 1 microM carbachol. The racemate and (R,R)-formoterol caused a concentration-dependent relaxation of all preparations with an EC50 of about 1 nM. In the guinea-pig trachea, the concentration-effect curve for formoterol was moved to the right in response to an increased concentration of carbachol. In both human bronchus and guinea-pig trachea, (S,S)-formoterol was more than 1,000 times less potent than (R,R)-formoterol. Thus the relaxing effect of formoterol in human airways as well as in guinea-pig trachea was shown to lie with the (R,R)-enantiomer. Notably, (S,S)-formoterol did not exert any contractile effects within the tested concentration range in either airway preparation. Therefore, we conclude that with regard to relaxant effects the pure (R,R)-enantiomer of formoterol does not offer a benefit over the racemate.

Adrenergic beta-Agonists↗

Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI.

We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated amino-acid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[123I]iodo-alpha-methyl-L-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures.

Aphasia↗

[Reading speed in movement in the peripheral visual field].

BACKGROUND: Moving and distracting stimuli often occur in the peripheral visual field during visual tasks in daily life. Do they influence reading performance? METHOD: In 30 normal subjects with a normal visual acuity we investigated eye movements by electronystagmography (ENG) during silent reading of a standardized text. The 17 degrees-wide text was presented at a distance of 1 m, ENG was recorded bitemporally. Blinks were monitored via vertical ENG electrodes. For surrounding stimulation we presented a bar stimulus moving at 30 degrees/s. Three experimental conditions were compared: [1] no peripheral motion, [2] peripheral motion to the right, and [3] peripheral motion to the left. We quantitatively analyzed reading speed and blink frequency. RESULTS: Reading speed and blink frequency was nearly identical in the three experimental conditions, they differed by 1-8%. CONCLUSIONS: Although the full periphery was stimulated, and the moving stimulus was noticed by our subjects, reading was not affected by surrounding optokinetic stimulation. Attentive reading does not appear to be affected by visual motion in the periphery.

Adult↗

[Classical brain stem syndrome. Definitions and history].

BACKGROUND: Inaccurate definitions of brain stem syndromes in the literature. METHOD: The original publications of the authors during the last century and the early years of this one were studied in relation to the neuro-ophthalmological diagnosis and neuroanatomy. It is the goal of this medico-historical investigation to compare the knowledge available at this time when the first descriptions were made with the clinical experience and understanding of today. RESULTS: The following classical brain stem syndromes are important for an ophthalmologist: diseases with III-paresis: Weber's syndrome (1863, ipsilateral oculomotor paralysis with alternating hemiplegia), Benedikt's syndrome (1889, oculomotor paralysis and crossed hemiparesis with tremor), Nothnagel Claude's syndrome (III-Paresis with alternating ataxia); diseases with VII-paresis: Millard Gubler's syndrome (1856, nuclear 7th nerve palsy with crossed hemiparesis), Foville's syndrome (1858, conjugate lateral gaze paralysis, ipsilateral nuclear palsy of the 7th nerve, crossed hemiparesis); diseases with VI-paresis: Raymond Cestan's syndrome (1895, abducent nerve paralysis with contralateral hemiparesis). Brain stem lesions are also found in Wallenberg's syndrome (1895, Horner's syndrome, absent corneal reflex, lateropulsion of saccadic eye movements, nystagmus, ataxia, dysphagia, hoarseness, sensory loss over the facial region, contralateral dissociated diminished sensibility (hemiparesis), etc.). The following two syndromes do not belong to the above-mentioned classical examples, because lesions of the long tracts of the brain stem are absent. However, since these two syndromes are accompanied by both ocular and neurological signs which indicate typical lesions of the brain stem, they are also mentioned here: Parinaud's syndrome (1883, paralysis of conjugate vertical gaze and paresis of convergence together with additional neuro-ophthalmological signs) and the Koerber Salus Elschnig's syndrome (1903, 1910, 1913, nystagmus retractorius, vertical gaze palsy, pupillary disturbances, and signs of midbrain disease). CONCLUSIONS: The first descriptions of these syndromes, together with the figures illustrating the neuroanatomical findings in these lesions, are helpful for assessing the clinical picture. Some named syndromes which are used today in clinical diagnosis (e.g. Parinaud's syndrome) do not exactly correspond to the first descriptions in the last century.

Brain Stem Infarctions↗

The endometrium in breast cancer patients on tamoxifen.

We restudied histologically and immunohistochemically 17 endometrial carcinomas, 2 malignant mixed tumors and 180 endometria with benign changes during or after tamoxifen therapy. The carcinomas were subtyped according to the 1994 WHO-classification. Endometrial biopsies were taken only if the endometrial thickness was > 8 mm sonographically, when a polyp was seen, or for postmenopausal bleeding. About half of the endometrial specimens showed simple or cystic atrophy, 55-76% had cystic-atrophic polyps or regressive hyperplasia. Depending upon the dose of tamoxifen, 7-19% (30 mg) to 27-36% (20 mg) showed moderate glandular proliferation. 20-33% had foci of mucinous, clear cell or serous-papillary metaplasia. 68-70% revealed diffuse extensive fibrosis of the endometrial stroma. None of 11 patients biopsied before starting tamoxifen therapy had advanced endometrial glandular proliferation in the second endometrial biopsy after tamoxifen treatment. None of the 19 endometrial neoplasms after tamoxifen therapy was of the endometrioid type: 11 were mucinous adenocarcinomas, 4 clear cell carcinomas, 2 serous-papillary carcinomas, one carcinosarcoma and one malignant Mullerian mixed tumor. The reasons for discrepancies between suspicious sonograms and endometrial atrophy are discussed.

Adenocarcinoma, Clear Cell↗

Identification of rare Candida species and other yeasts by polymerase chain reaction and slot blot hybridization.

Invasive candidiasis has become a major cause of morbidity and mortality in immunocompromised hosts. Here we describe a fast and reliable DNA extraction and PCR amplification method in combination with a slot blot hybridization assay. A genus-specific probe was designed that allowed to detect DNA from a broad range of Candida species and 3 other yeasts. In addition, species-specific oligonucleotides for emerging Candida and other yeast species allowed to identify DNA extracted from Candida lusitaniae, Candida humicola, Candida kefyr, Candida inconspicua, Candida solani, Malassezia furfur and Trichosporon cutaneum. A sensitivity of at least 10(1) CFU, corresponding to 100 fg of fungal DNA, was documented for all species-specific probes and the common Candida probe. In addition, the 18S rRNA genes of 7 yeast species (C. humicola, C. kefyr, C. solani, C. inconspicua, C. norvegensis, C. utilis and M. furfur) were completely sequenced. The sequencing primers described bind to highly conserved primer binding sites. Therefore, these primers would allow rapid cycle sequence of additional ribosomal genes throughout the whole kingdom of fungi.

Candida↗

Tiagabine in the treatment of epilepsy--a clinical review with a guide for the prescribing physician.

Tiagabine is currently recommended mainly as add-on therapy in adults and children above 12 years with partial epilepsy not satisfactorily controlled with other antiepileptic drugs. Based on available evidence and our clinical experience, tiagabine should be used preferably in patients sharing one or more of the following additional features, (i) a history of drug-induced cutaneous adverse events; (ii) mild to moderate epilepsy allowing for a slow titration and gradual onset of anticonvulsant action over a few weeks; (iii) patients for whom it is particularly important to avoid a deterioration in cognitive performance; and, (iv) patients who failed to respond to previous treatment with sodium channel blocker agents as they may particularly benefit from the introduction of tiagabine, due to its GABAergic mechanism of action. Tiagabine can also be used successfully in other patients with refractory partial epilepsy. Tiagabine is not indicated for patients with generalized or unclassified epilepsies and for patients with severely impaired liver function.

Adult↗

p53 immunoreactivity in biopsy specimens of T1G3 transitional cell carcinoma of the bladder--a helpful parameter in guiding the decision for or against cystectomy?

The aim of this study was to determine whether p53 is helpful in making the decision to undergo cystectomy in T1, G3 transitional cell carcinoma (TCC) of the bladder, by prospectively comparing the p53 status of bladder biopsies with the histology and p53 status of the corresponding cystectomy specimens. From January 1996 to August 1997, 38 consecutive patients with T1G3 TCC at 6 different centres were enrolled into the study. Bladder biopsies and cystectomy specimens were examined with three different antibodies against p53. The p53 status of each bladder biopsy was compared with p53 status, tumour stage and grade of the cystectomy specimen. An independent evaluation of the histology and immunohistochemistry was carried out by two pathologists. 15 of 38 patients (39%) were found to have a higher tumour stage in the cystectomy specimen compared with the staging by transurethral resection of the bladder tumour (TUR-B). 3 patients did not show residual tumour in the cystectomy specimen. No differences in p53 positivity were noted between the different antibodies. 14 of 31 evaluable tumours (45%) were p53 positive at the time of the TUR-B. p53 staining of the TUR-B specimen did not correctly predict the residual tumour in the cystectomy specimen. We, therefore, concluded that compared with standard histopathology, the p53 status of the TUR-B specimen does not provide additional relevant information with regard to local tumour staging and, thus, is not helpful in making the decision for or against a cystectomy.

Adult↗

Serum immunoglobulin E levels predict human airway reactivity in vitro.

BACKGROUND: Airway hyperresponsiveness to non-specific stimuli is one characteristic feature of airway diseases such as bronchial asthma and chronic bronchitis. Until now, studies aiming to demonstrate a relationship between in vivo conditions associated with airway hyperreactivity and in vitro airway responsiveness have been inconclusive. OBJECTIVE: Since serum immunoglobulin (Ig) E is believed to be one determinant of airway reactivity in vivo, we studied whether in vitro airway reactivity in lung resection material from patients with elevated levels of serum IgE was increased as compared with patients with undetectable IgE. By this approach, we aimed to elucidate the role of circulating IgE for bronchial smooth muscle reactivity in vitro. METHODS: Bronchial rings from nine patients with total serum IgE levels above 200 U/mL and 10 patients with total serum IgE levels below 10 U/mL were passively sensitized, i.e. incubated overnight with buffer or sensitizing serum containing high levels of total IgE (> 250 U/mL). Afterwards, contractile responses to histamine were assessed in the organ bath. RESULTS: Histamine responsiveness was significantly increased in airways obtained from patients with IgE levels above 200 U/mL as compared with airways from patients with IgE levels below 10 U/mL (P < 0.05). Passive sensitization of bronchi from patients with low IgE significantly increased histamine responsiveness, as compared with non-sensitized controls from the same patients (P < 0.05). In contrast, passive sensitization of airways from patients with elevated IgE did not further increase responsiveness. There was no difference in histamine reactivity between non-passively sensitized and passively sensitized tissue preparations from patients with IgE above 200 U/mL and passively sensitized tissues from patients with IgE below 10 U/mL. CONCLUSION: Our findings reveal that elevated levels of serum IgE predict airway hyperresponsiveness to histamine in vitro. At the same time, they indicate that the in vitro model of passive sensitization, in addition to its ability to induce allergen responses, also mimics conditions of non-specific airway hyperreactivity, which are relevant under in vivo conditions.

Aged↗

Immune mechanisms of smooth muscle hyperreactivity in asthma.

Asthma is characterized by bronchial hyperresponsiveness to a variety of bronchospasmogenic stimuli. To study the pathophysiologic mechanisms underlying the increased sensitivity and degree of maximal airway narrowing, various in vivo and in vitro models have been developed with methods of active and passive sensitization. These studies indicated a major role for alterations in the smooth muscle itself rather than neural dysfunction or airway inflammation as the underlying cause for the development of bronchial hyperresponsiveness. During the last years smooth muscle cells were found to exhibit not only the "classical" contractile phenotype but also a proliferative-synthetic phenotype, which is capable of producing proinflammatory cytokines, chemotaxins, and growth factors. Allergic sensitization can alter both contractile and secretory functions, thereby indicating that the smooth muscle cell could contribute directly to the persistence of airway inflammation in asthma. A better understanding of the changes within the smooth muscle cells and of the mechanisms that lead to their induction could contribute to the development of novel therapeutic approaches for the treatment of asthma.

Asthma↗

Quantification of fungal DNA by using fluorescence resonance energy transfer and the light cycler system.

The Light Cycler technique combines rapid in vitro amplification of DNA in glass capillaries with real-time species determination and quantification of DNA load. We have established a quantitative PCR protocol for two clinically important pathogens, Candida albicans and Aspergillus fumigatus. The sensitivity of the assay was comparable to those of previously described PCR protocols (5 CFU/ml). Specific detection of C. albicans and A. fumigatus could be achieved. The assay showed a high reproducibility of 96 to 99%. The assay was linear in a range between 10(1) and 10(4) Aspergillus conidia. As capillaries do not have to be reopened for post-PCR analysis, the risk of carryover contaminations could be minimized. The Light Cycler allowed quantification of the fungal loads in a limited number of clinical specimens from patients with hematological malignancies and histologically proven invasive fungal infections. Five of nine positive samples had fungal loads between 5 and 10 CFU/ml of blood, two of nine positive samples had fungal loads between 10 and 100 CFU/ml of blood, and two of nine samples had fungal loads of more than 100 CFU/ml of blood. All samples were also found to be PCR positive by PCR-enzyme-linked immunosorbent assay analysis.

Aspergillosis↗

Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnoea: response to CPAP therapy.

BACKGROUND: Reduced endothelium dependent vasodilation has been reported in patients with obstructive sleep apnoea (OSA) but direct measurements of the most potent naturally occurring vasodilator, nitric oxide (NO) or its derivatives (nitrate and nitrite, NO(x)), have not yet been performed in these patients. METHODS: In 21 patients with OSA of mean (SE) age 54 (2) years, body mass index (BMI) 30.9 (1.1) kg/m(2), and apnoea-hypopnoea index (AHI) 37 (4)/h, NO(x) levels were measured in peripheral venous blood samples by chemiluminescence. Blood samples were obtained before and after two nights of continuous positive airway pressure (CPAP) and after 5.5 (1.5) months of follow up. Thirteen age matched, healthy volunteers and 18 patients without OSA but with a similar spectrum of comorbidity served as controls (control groups 1 and 2). RESULTS: Before CPAP NO(x) levels were 21.7 (1.5) microM in patients with OSA compared with 42.6 (2.2) microM and 36.7 (1.7) microM in control groups 1 and 2, respectively (p<0.01 for each comparison). NO(x) concentrations increased to 32.1 (2.7) microM after two nights of CPAP and remained constant at 32.9 (2.3) microM at follow up (p<0.01 compared with levels before CPAP). CONCLUSIONS: Plasma NO(x) levels are reduced in OSA and can be increased by short and long term CPAP therapy. Although the precise mechanism underlying this observation remains to be clarified, it may have important implications for the development of cardiovascular disease in patients with OSA and for the life saving effect of CPAP.

Case-Control Studies↗

Use of water jet resection in renal surgery: early clinical experiences.

OBJECTIVE: Various surgical techniques have been developed to reduce the risk of bleeding during dissection of renal tissue. Water jet technology has been designed for a gentle transection of parenchymal organs. We report about first experiences with a new water jet resection device in kidney surgery. METHODS: 7 patients underwent open surgery because of renal cell carcinoma or nephrolithiasis. In tumor patients a partial nephrectomy, in 1 stone patient a nephrolithotomy, and in the other 1 a lower pole resection were performed. RESULTS: By means of water jet resection tissue was dissected effectively avoiding damage to the vascular structures, which were then ligated selectively. Resection time was between 14 and 30 min with a minimal intraoperative blood loss. No significant problem was seen postoperatively. CONCLUSIONS: The results demonstrate that water jet technology is an applicable tool for transection of renal parenchyma. It has been shown to reduce the risk of blood loss significantly compared to other techniques.

Carcinoma, Renal Cell↗

The role of leukotrienes in the regulation of tone and responsiveness in isolated human airways.

Cysteinyl-leukotrienes and histamine are the major determinants of inherent tone in isolated human bronchi, which is mainly the result of a balance of continual production and release of contractile mediator, in particular cysteinyl-leukotrienes and to a lesser extent histamine, and on the other side bronchodilating prostanoids. Cysteinyl-leukotrienes are also powerful constrictors of isolated human airways through direct interaction with Cys-LT1 receptors on airway smooth muscle, and with a potency 1,000-fold higher than histamine. On stimulation inflammatory cells such as eosinophils and mst cells produce and release significantly increased amounts of leukotrienes leading to smooth muscle contration in vitro. In isolated human airways, leukotrienes are the most important mediators of allergen and adenosine-induced contractile responses. The induction of allergen responses in passively sensitized airways is not only related to an increased release of leukotrienes and histamines, but also to an enhanced responsiveness of the airway smooth muscle, particularly to LTC4. Studies in isolated human airways in vitro have demonstrated that understanding the regulation of human airway tone and airway reactivity are closely linked to the understanding of baseline and stimulated production of and smooth muscle responsiveness to leukotrienes in vitro and in vivo.

Airway Resistance↗

Factors influencing T-cell turnover in HIV-1-seropositive patients.

HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.

CD4-Positive T-Lymphocytes↗