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Biomedical subjects

K Sauter

Publications and source records attributed to K Sauter.

At least 19 recordsLinked to original sources

Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA).

The four known members of the KCND/Kv4 channel family encode voltage-gated potassium channels. Recent studies provide evidence that members of the Kv4 channel family are responsible for native, rapidly inactivating (A-type) currents described in heart (I(TO)) and neurons (I(SA)). In this study, we cloned the human KCND1 cDNA, localized the KCND1 gene to chromosome Xp11.23-p11.3, and determined the genomic structure and tissue-specific expression of the KCND1, KCND2, and KCND3 genes, respectively. The open reading frame of Kv4. 1 is 1941 nucleotides long, predicting a protein of 647 amino acids. The deduced protein sequence of Kv4.1 shows an overall identity of 60% with Kv4.2 and Kv4.3L and corresponds to the common structure of voltage-gated potassium channels. KCND1-specific transcripts were detectable in human brain, heart, liver, kidney, thyroid gland, and pancreas, as revealed by Northern blot and RT-PCR experiments. The comparison of the expression patterns of the known Kv4 family members shows subtype specificity with significant overlaps. The KCND gene structures exhibit an evolutionarily conserved exon pattern with a large first exon containing the intracellular N-terminus and the putative membrane-spanning regions S1 to S5, as well as part of the pore region. The KCND3 gene contains an additional exon of 57 bp, which is not present in the other two KCND genes and gives rise to the C-terminal splice KCND3L variant with an insertion of 19 amino acids.

Chromosome Mapping↗

Therapeutic equivalence and acceptability of two multidose powder inhalers in the treatment of asthma.

BACKGROUND: Problems in using conventional inhalation aerosols, in addition to environmental reasons, have driven development of the dry powder inhalers. OBJECTIVE: To compare therapeutic equivalence and acceptability of two dry powder inhalers, Easyhaler (EH) and Diskhaler (DH), in the delivery of beclomethasone dipropionate (BDP) in the treatment of asthma. METHODS: Adult asthmatics (n = 185), previously treated with inhaled steroids, were recruited in this open parallel-group study. After a run-in period of 2 weeks during which the patients inhaled 800 microg/day of BDP via DH, the patients were randomly allocated into three groups: EH 200 group (62 patients) using EH 200 microg/dose inhaler (1 inhalation q.i.d.), EH 400 group (62 patients) using EH 400 microg/dose inhaler (1 inhalation b.i.d.), and DH group (61 patients) using DH 200 microg/dose inhaler (1 inhalation q.i.d.) for 12 weeks. The primary outcome variables were PEF and FEV(1). RESULTS: The 95% CI for treatment difference in morning PEF between the EH 200 and DH groups was -16 to 23 litres/min and between the EH 400 and DH groups -18 to 21 litres/min. There was an increase in the morning PEF of 13 litres/min (p < 0.05) in the EH 200 group, and 9 and 11 litres/min in the DH and EH 400 groups. No differences between the groups were seen in the lung function parameters, in the symptom scores, in the use of rescue medication or in the incidence of adverse events. The treatments had no effects on morning cortisol levels. The patients in the EH groups compared the inhalers by using an 11-item questionnaire. In 8 questions the majority of the patients rated EH superior to DH. CONCLUSION: The tested inhalers were therapeutically equal. However, based on the acceptability data, the EH was better accepted by the patients than DH.

Adult↗

Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group.

OBJECTIVE: Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps. RESEARCH DESIGN AND METHODS: A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire. RESULTS: The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P < 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P < 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro. CONCLUSIONS: Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin.

Adult↗

Cerebrospinal fluid shunt infections in infants and children in Mobile, Alabama.

Cerebrospinal fluid shunt systems are used to treat hydrocephalus in infants and children; unfortunately, some shunt systems become infected. We sought to define the epidemiology of shunt infections and shunt survival prior to infection at our institution. We identified 268 shunt procedures performed from January 1990 to June 1996 in 145 patients. There were 29 episodes of shunt infection for an incidence of 10.8% per procedure and 13.1% per patient. Staphylococcus epidermidis was the most common isolate recovered. The probability of shunt infection was highest during the first 8 weeks after a shunt procedure and subsequent infection was less likely after 28 weeks.

Adolescent↗

Postoperative magnetic resonance imaging with titanium implants of the thoracic and lumbar spine.

Within recent years, the technologies of radiological imaging and spinal instrumentation have exponentially increased. New methods of preoperative imaging, that is, magnetic resonance imaging (MRI) and computed tomography, have allowed for a better understanding of surgical pathology. Such an understanding is likely to lead to a more successful surgical experience, which certainly is the case with spine surgery with instrumentation. However, after implantation of most instrumentation, imaging is greatly impaired. Metallurgic advancements in titanium were sought to reduce postoperative imaging problems. The purpose of this study is to assess the presence and extent of artifacts seen on postoperative MRI scans in patients with titanium spinal implants. Six patients, four with degenerative spine disease and two with neoplasms, had thoracic and/or lumbar spinal fixation performed with titanium instrumentation. All patients underwent postoperative conventional MRI with the use of T1-weighted, T2-weighted, and gradient-echo sequences. The scans and individual sequences were then analyzed for image quality. A progressive and significant increase in imaging artifact related to the titanium spinal instrumentation was observed on the T1-weighted, T2-weighted, and gradient-echo sequences. Titanium spinal instruments do not allow optimal postoperative imaging on conventional MRI scanners.

Adult↗

Trends of strategic importance for the future information landscape in the hospital.

Hospitals are complex enterprises with, at the time being, evolving organizational structures. In the 80s innovative system concepts for the computer support of such complex organizations were developed, based on a controlled distribution of the components of multi-functional information systems (IS). More recently several R&D initiatives promoted these issues in general and for hospital information and communication systems (HICS) in particular. Three leading strategic ideas have in the meantime attained fundamental importance and will be considered in more detail: distribution, integration, and evolution. Strong interdependencies exist however between those three concepts, mainly expressed by the notions of interoperability and coupling of system components. In the context of a distributed IS, the notion of integration has to be extended since the centralization of all dp resources is replaced by a cooperative system concept with centralized control functions for information of hospital-wide interest, based on global models for data and processes, and distributed dp resources with a powerful central component, which is especially true for most HICS. In view of the broad scope of requirements, it is not feasible to construct these comprehensive multi-functional systems as closed and complete products. Therefore a concept of evolutionary system development is indispensable. Finally, the overall functionality of commercially available software products for integrated HICS is analyzed. With regard to the present German market for HICS of the new generation, the patient administration and hospital management functions of the care system are covered rather well; the medical/clinical functions however are not at all complete.

Germany↗

Treatment of high-dose intrathecal morphine overdose. Case report.

The case is reported of a 45-year-old woman who was being treated for chronic back and right leg pain with intrathecal morphine administered via a subcutaneous continuous-infusion device. She received an accidental 450-mg bolus injection of morphine intrathecally and developed hypertension, status epilepticus, intracerebral hemorrhage, and respiratory failure. Treatment with continuous intravenous naloxone infusion, lumbar catheter drainage of cerebrospinal fluid, and control of hypertension and status epilepticus resulted in an excellent outcome with return to neurological baseline. Care providers who refill pump reservoirs with morphine must be knowledgeable about these devices and the life-threatening consequences associated with errors in refilling them. This case describes the complications and successful treatment of high-dose intrathecal morphine overdose.

Drug Overdose↗

Bioequivalence evaluation of two glyceryl trinitrate patches after 12-h usage in healthy volunteers.

The study objective was to determine the bioavailability and main pharmacokinetic parameters of glyceryl trinitrate (GTN, CAS 55-63-0) following cutaneous application of two different glyceryl trinitrate patches using a randomized cross-over design. The two patches investigated were Deponit 5 (a newly developed test patch) and an already marketed reference patch. Thirty-seven healthy male volunteers were included in this study; 36 of them completed the investigation. Blood samples were withdrawn up to 15 h after start of patch application and plasma concentrations of glyceryl trinitrate were quantified by a GC/MS method. For the areas under the curve from time 0 to the last quantifiable sample, AUC(O-Tlast), mean values of 1545 (test patch, n = 35) and 1686 h.pg/ml (reference patch, n = 35) were found. The corresponding peak glyceryl trinitrate plasma levels were 253 and 263 pg/ml, respectively; they were reached after 6.58 h (test patch) and 7.72 h (reference patch). The statistical comparison (ANOVA, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both patches. Typical side-effects known and described under glyceryl trinitrate therapy were also observed in this study.

Administration, Cutaneous↗

Bioequivalence evaluation of the metabolites 1,2 and 1,3-glyceryl dinitrate of two different glyceryl trinitrate patches after 12-h usage in healthy volunteers.

In the course of this study both the bioavailability and main pharmacokinetic parameters of the glyceryl trinitrate (GTN, CAS 55-63-0) metabolites 1,2 and 1,3-glyceryl dinitrate (1,2-GDN and 1,3-GDN) were to be determined following transdermal application of a glyceryl trinitrate test patch (Deponit 5) and an already marketed reference patch. For this purpose, both patches were examined in healthy volunteers according to a randomized two-way cross-over design, blood samples were withdrawn up to 15 h after start of patch application and the plasma concentrations of both metabolites were quantified using a GC/MS method. The investigation showed the following results: Metabolite 1,2-glyceryl dinitrate: For the area under the curve from time 0 to the last quantifiable sample (AUC(0-Tlast) arithmetic mean values of 23.77 h.ng/ml (test patch) and 27.83 h.ng/ml (reference patch) were found. The corresponding peak plasma levels were 2.45 ng/ml and 2.93 ng/ml, respectively; they were reached after 6.4 h (test patch) and 8.31 h (reference patch). Metabolite 1,3-glyceryl dinitrate: The arithmetic mean values for AUC(0-Tlast) were 3.32 h.ng/ml (test patch) and 3.81 h.ng/ml (reference patch). The maximum plasma levels were 0.35 ng/ml and 0.41 ng/ml for the test and reference preparation, reached after 6.4 h and after 7.86 h, respectively. The statistical comparison (ANOVA, confidence intervals) showed bioequivalence between both patches concerning the metabolites investigated. The typical side effects known after nitrate therapy also occurred in the course of this study.

Administration, Cutaneous↗

Localized hypertrophic mononeuropathy involving spinal roots and associated with sacral meningocele. Case report.

Hypertrophic nerve lesions displaying onion-bulb cellular formations are quite rare in the absence of a generalized hypertrophic neuropathy. The isolated peripheral nerve lesion has been termed "localized hypertrophic mononeuropathy" (LHN), and fewer than 30 cases of this condition have been reported. Very little is known regarding the etiology and the natural course of this rare disorder. A unique case of LHN afflicting spinal roots in association with a sacral meningocele is reported with a brief review of the relevant literature. The unique features of this case not only reveal a variable clinical presentation of the disease but also support the theory that LHN may be a localized reaction to nerve trauma or entrapment.

Adult↗

Clinical comparison of systemic methylprednisolone acetate versus topical budesonide in patients with seasonal allergic rhinitis.

Thirty patients with seasonal allergic rhinitis entered a double blind study comparing budesonide (nasal spray, 400 micrograms/d) and i.m. injection of 80 mg methylprednisolone acetate. Symptoms were assessed over a "run in" period of 3-7 days followed by a treatment period of 3 weeks. Pollen counts were evaluated daily. Both the systemic and topical corticosteroid treatment resulted in a significant improvement of nasal and ocular symptoms and were accompanied by reduced antihistamine intake. A comparison of the two treatments in relation to the pollen count yielded statistically significantly fewer nasal symptoms, such as itching, secretion, and sneezing in the budesonide-treated group. Nasal blockage and ocular symptoms remained unchanged, but the use of eyedrops was significantly reduced in the methylprednisolone-treated group. Side effects of both treatments were mild and the incidence negligible. Methylprednisolone-treated patients had a significantly lower cortisol value after 7 days but still had a normal response to ACTH-stimulation. We conclude that the acute symptoms of allergic rhinitis are at least as well ameliorated by regular topical application of budesonide as by a single injection of methylprednisolone acetate. The accompanying allergic conjunctivitis may require additional treatment.

Administration, Intranasal↗

Severe adult hypersomnia--sleep apnea syndrome in craniofacial dysostosis.

Polysomnography and blood gas measurements during sleep in a young man with craniofacial dysostosis, who presented with an extremely severe sleep apnea syndrome, are reported. Tracheostomy relieved all his complaints permanently, namely hypersomnia, deteriorated intellectual performance, automatic behaviour with hypnagogic hallucinations and snoring. Laboratory results also returned to normal. The polygraphic data of night sleep (and daytime naps) before and after surgery suggest that hypersomnia was primarily caused by severe nighttime oxygen desaturations and that the hypnagogic hallucinations were caused by apnea-induced chronic REM sleep deprivation. Furthermore, the periodic variation of central respiratory drive, which was also abolished after surgery, is interpreted as the cause of apnea-induced fluctuations between sleep stages in this case.

Adult↗

[How useful is the ultrastructural study of the cilia of the respiratory tract in the diagnosis of an immotile cilia syndrome?].

The immotile cilia syndrome (ICS) comprises a range of congenital defects of the ciliary apparatus most probably transmitted by autosomal recessive inheritance. Because cilia occur mainly in the respiratory and genital tract, the clinical symptoms of ICS are most commonly chronic sinusitis, bronchitis, bronchiectasis and male sterility. The syndrome can be associated with a situs inversus and is then called Kartagener's syndrome. We studied the ciliary ultrastructure in airway biopsies of 5 patients suffering from chronic upper and lower respiratory tract infections. With the single exception of one female patient with confirmed ICS diagnosis (Kartagener's syndrome) the etiology of the recurrent infections was unknown. The following ciliary defects were observed: missing dynein arms, radial spoke defects, missing nexin links, microtubular transpositions, compound cilia, supernumerary, absent, or incomplete microtubules, lack of ciliary orientation and various abnormal patterns of microtubular arrangement. In no instance did a patient show only a single anomaly; defects were always combined. Missing dynein arms, radial spoke defects and microtubular transpositions have frequently been described as lesions specific for ICS. Whenever these lesions were found simultaneously in both the respiratory and genital tracts, their genetic origin cannot be doubted. In our confirmed ICS patient the outer dynein arms were not missing but were reduced in number and length in a large number of cilia. The biopsy was, however, obtained from the heavily infected maxillary sinus and it is known that inflammation can lead to a loss of dynein arms. In the light of our investigations and of a review of the published cases of ciliary anomalies, it is concluded that none of the above defects in itself is specific for ICS. They may all occur as secondary lesions or sporadically as varieties in otherwise healthy subjects. It therefore appears questionable whether ICS can be diagnosed from the ciliary ultrastructure of a single airway biopsy. Assessment of ICS cannot be based simply on the ultrastructural demonstration of a particular ciliary defect, but necessitates additional considerations particularly regarding the origin of the biopsy, the sampling procedures and quantitation of defects. It appears necessary to investigate samples from different parts of the airways and quantitatively analyze the prominent lesions.

Abnormalities, Multiple↗