A prospective polysomnographic study on the evolution of complex sleep apnoea.

Complex sleep apnoea (CompSA) may be observed following continuous positive airway pressure (CPAP) treatment. In a prospective study, 675 obstructive sleep apnoea patients (mean age 55.9 yrs; 13.9% female) participated. Full-night polysomnography was performed at diagnosis, during the first night with stable CPAP and after 3 months of CPAP. 12.2% (82 out of 675 patients) had initial CompSA. 28 of those were lost to follow-up. Only 14 out of the remaining 54 patients continued to satisfy criteria for CompSA at follow-up. 16 out of 382 patients not initially diagnosed with CompSA exhibited novel CompSA after 3 months. 30 (6.9%) out of 436 patients had follow-up CompSA. Individuals with CompSA were 5 yrs older and 40% had coronary artery disease. At diagnosis, they had similar sleep quality but more central and mixed apnoeas. On the first CPAP night and at follow-up, sleep quality was impaired (more wakefulness after sleep onset) for patients with CompSA. Sleepiness was improved with CPAP, and was similar for patients with or without CompSA at diagnosis and follow-up. CompSA is not stable over time and is mainly observed in predisposed patients on nights with impaired sleep quality. It remains unclear to what extent sleep impairment is cause or effect of CompSA.

[An assessment tool for analysing the early vocal development of young children with cochlear implant]. / Ein Untersuchungsverfahren zur Analyse der vorsprachlichen Entwicklung bei Kleinkindern mit Cochlea-Implantat.

BACKGROUND: Early vocal development of German-speaking cochlear implant recipients has rarely been assessed so far. There-fore the purpose of this study was to describe the early vocal development following successful implantation. METHODS: A case study was designed to assess the temporal progression of early vocal development in a young cochlear implant recipient who was bilaterally implanted at the age of 8;3 months. Data were collected during one year by recording parent-child interactions on a monthly basis. The first recording was made before the onset of the signal-processors, the 12 following recordings were made during the first year of implant use. The child's vocalizations were classified according to the vocalization categories and developmental levels from the Stark Assessment of Early Vocal Development--Revised (SAEVD-R). This assessment tool was translated into German in this study and used with German-speaking children for the first time. It allows a coding of prelinguistic utterances via auditory perceptual analysis. RESULTS: The results show an overall decrease of early vocalizations and an increase of speech-like vowels and consonants. In the first six months no apparent progress took place; The child produced almost exclusively vocalizations from Levels 1-3. In the second half of the year an increase of canonical utterances (Level 4) and advanced forms (Level 5) was observed. However, vocalizations beyond the canonical babbling phase, especially vocants and closants as well as their combinations, continued to be dominant throughout the first year of implant use. The progress of development of the child investigated in this study is comparable to other children implanted at young age who had also been assessed with the SAEVD-R. In comparison to normal-hearing children, the implanted child's development seemed to progress slightly faster. Interrater- and intrarater-reliability using the SAEVD-R were measured for two independent observers and for a first and second coding procedure and revealed to be acceptable to good. CONCLUSION: The use of SAEVD-R for an implanted German-speaking child allowed the investigation of prelinguistic vocal development before the onset of words. The fact that early vocalizations remain the dominant form throughout the first year of hearing experience emphasizes the importance of documenting and analysing prelinguistic vocal development in order to monitor progression of speech acquisition.

DC-magnetoencephalography and time-resolved near-infrared spectroscopy combined to study neuronal and vascular brain responses.

The temporal relation between vascular and neuronal responses of the brain to external stimuli is not precisely known. For a better understanding of the neuro-vascular coupling changes in cerebral blood volume and oxygenation have to be measured simultaneously with neuronal currents. With this motivation modulation dc-magnetoencephalography was combined with multi-channel time-resolved near-infrared spectroscopy to simultaneously monitor neuronal and vascular parameters on a scale of seconds. Here, the technique is described, how magnetic and optical signals can be measured simultaneously. In a simple motor activation paradigm (alternating 30 s of finger movement with 30 s of rest for 40 min) both signals were recorded non-invasively over the motor cortex of eight subjects. The off-line averaged signals from both modalities showed distinct stimulation related changes. By plotting changes in oxy- or deoxyhaemoglobin as a function of magnetic field a characteristic trajectory was created, which was similar to a hysteresis loop. A parametric analysis allowed quantitative results regarding the timing of coupling: the vascular signal increased significantly slower than the neuronal signal.

Intravenous tPA for ischemic stroke team performance over time, safety, and efficacy in a single-center, 2-year experience.

BACKGROUND AND PURPOSE: Safety and efficacy concerns toward thrombolysis for ischemic stroke prevail among many neurologists because of the risks of hemorrhage and the small proportion of suitable patients. We therefore prospectively assessed feasibility, safety, efficacy, and team performance in a single center to prove whether thrombolytic treatment is practical in daily clinical routine. METHODS: Patients were prospectively recruited over a 2-year period. Major inclusion and exclusion criteria from large, randomized controlled trials were combined. Prespecified outcome parameters were the modified Rankin scale (MRS) and the Barthel Index (BI) at 3 months and symptomatic hemorrhagic complications. In addition, certain time intervals during the diagnostic process preceding thrombolysis were prospectively recorded. RESULTS: Within 2 years a total of 75 patients underwent intravenous thrombolysis, corresponding to 9.4% of all admitted patients with stroke and 14.9% of patients with ischemic stroke. Mean+/-SD age was 68+/-13 (range 34 to 90) years; median baseline National Institutes of Health Stroke Scale score was 13+/-6 (range 2 to 34). Thrombolysis was started at an average time of 144 minutes after symptom onset, and 13 patients (17.3%) were treated beyond 3 hours. Two cerebral hemorrhages (2.7%) occurred. Outcome according to the MRS was good (MRS 0 to 1) in 40%, moderate (MRS 2 to 3) in 32%, and poor (MRS 4 to 5) in 13%; the corresponding results, as measured by the BI, were 61% (BI 95 to 100, good), 16% (BI 55 to 90, moderate), and 8% (BI 0 to 50, poor). The mortality rate was 15%. Over 2 years the median door-to-CT time decreased from 30 to 22 minutes (27%), and the door-to-needle time was shortened from 96 to 73 minutes (14%). The mean number of patients treated per month increased from 2 to 4. CONCLUSIONS: Thrombolytic therapy can be performed safely and efficaciously in daily clinical routine. More than a minority of acute stroke patients might be eligible for intravenous thrombolysis. The performance of a stroke team can be improved over time, subsequently increasing the proportion of eligible patients and thereby the efficiency of the method.

Transtentorial herniation after unilateral infarction of the anterior cerebral artery.

BACKGROUND: Fatal cerebral herniation is a common complication of large ("malignant") middle cerebral artery infarcts but has not been reported in unilateral anterior cerebral artery (ACA) infarction. CASE DESCRIPTION: We report a 47-year-old woman who developed an acute left hemiparesis during an attack of migraine. Cranial CT (CCT) was normal but demonstrated narrow external cerebrospinal fluid compartments. Transcranial Doppler sonography was compatible with occlusion of the right ACA. Systemic thrombolytic therapy with tissue plasminogen activator was initiated 105 minutes after symptom onset. Follow-up CCT 24 hours after treatment revealed subtotal ACA infarction with hemorrhagic conversion. Two days later, the patient suddenly deteriorated with clinical signs of cerebral herniation, as confirmed by CCT. An extended right hemicraniectomy was immediately performed. Within 6 months, the patient regained her ability to walk but remained moderately disabled. CONCLUSIONS: This is the first reported case of unilateral ACA infarct leading to almost fatal cerebral herniation. Narrow external cerebrospinal fluid compartments in combination with early reperfusion, hemorrhagic transformation, and additional dysfunction of the blood-brain barrier promoted by tissue plasminogen activator and migraine may have contributed to this unusual course.

Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke: a pilot study.

Fever is associated with poor outcome in acute stroke. Forty-two consecutive, normothermic patients with acute ischemic stroke were, within 24 hours from symptom onset, randomized to either receive 4 g acetaminophen daily (n = 20) or matched placebo (n = 22). Fever of greater than 37.5 degrees C occurred in 36.4% of patients in the placebo group, compared with 5.0% in the acetaminophen group (Fisher's exact test, p = 0.014). Prophylactic antipyretic treatment with acetaminophen may be effective in the prevention of fever after acute ischemic stroke.

A simplified procedure for the isolation of immunoglobulins from human serum using a novel type of thiophilic gel at low salt concentration.

By coupling 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)dione (MECH) to divinyl sulfone activated agarose, a novel thiophilic matrix was obtained which allows the binding of immunoglobulins from different sources. In contrast to other thiophilic gels, antibodies are bound at low ionic strength and can easily be desorbed in intact form by elution with dilute alkali. The potential of using the MECH-gel was demonstrated by the purification of antibodies from human and animal (goat, rabbit, mouse) sera. The functional integrity of the purified antibodies was established with cytoplasmic islet cell antibodies from the sera of patients with type I diabetes and autoantibodies against thyroid peroxidase from patients with Graves' and Hashimoto's disease.

Unique frequency of known mutations in Brazilian MPS I patients.

The frequency of 10 known mutations in the IDUA gene-Q70X, A75T, H82P, R89Q, 678-7 g-->a, L218P, A327P, R383H, W402X, and P533R-was estimated in a group of 24 index cases with mucopolysaccharidosis type I. Three affected relatives were also analysed. Six of the 10 mutations screened were present in our patients (Q70X, R89Q, A327P, R383H, W402X, and P533R). These mutations account for 54% of the alleles; 37% of the genotypes were defined. Frequencies of these mutations are markedly different from those in the literature. A novel combination Q70X/A327P is described. This was the first time Brazilian MPS I patients were analysed with molecular techniques. The low frequency of common mutations indicates that a more comprehensive analysis of the IDUA gene should be done to delineate the mutation profile of MPS I better in our population.

Molecular analysis of the Pi*Z allele in patients with liver disease.

Alpha1-antitrypsin (AAT) is the main protease inhibitor in human plasma. There are more than 75 variants of this protein that differ from each other by their isoelectric point. Most of these alleles cause a reduction in AAT levels; the most common allele is Pi*Z. The main complications related to the Pi*Z allele are obstructive pulmonary disease and liver disease. Some Pi*Z allele carriers present cholestatic jaundice and cirrhosis. The Z type is associated with a secretion defect, which leads to deficiency of AAT and to the formation of intrahepatocytic inclusions in affected subjects. The diagnosis of AAT deficiency can be made by different techniques, including molecular analysis, although the final diagnosis should be done in conjunction with demonstration of the periodic acid-Schiff-positive globules on liver biopsy. In this study, specimens of 29 patients with cryptogenic cirrhosis between age 1 month and 18 years, and of 100 controls were submitted to polymerase chain reaction followed by digestion with TaqI enzyme. Five of the 29 patients had undergone liver transplantation. Three patients were heterozygous for the Pi*Z allele, and two were homozygous (allele frequency = 12.07%; 7/58). Among the controls, who represented the population of Porto Alegre, 1 in 100 individuals was heterozygous for the Pi*Z allele, resulting in an allele frequency of 0.5% (1/200). The high frequency of Pi*Z alleles among the patients indicates the usefulness of AAT molecular testing in children with cholestatic jaundice and cirrhosis.

Non-invasive single-trial monitoring of human movement-related brain activation based on DC-magnetoencephalography.

Neuroimaging techniques, such as fMRI, PET and near-infrared spectroscopy, monitor task-related neuronal activations in the brain indirectly through the associated neurovascular/metabolic responses. To assess the primary neuronal activations directly, magnetoencephalography was combined here with a mechanical modulation of the head-to-sensor position and signal separation via independent component analysis. In all of five subjects this approach allowed to monitor the time evolution of DC fields (<0.1 Hz) over the left hemisphere related to complex finger movements of the right hand alternating with rest periods (30 s each). Throughout the recording period of 30 min, stable task-related DC fields were recordable in a single-trial mode, i.e. without any averaging. DC-MEG opens up the possibility of analysing non-invasively cortical DC-activity also in stroke, migraine or epilepsy patients.

Thiyl radical-induced cis/trans-isomerization of methyl linoleate in methanol and of linoleic acid residues in liposomes.

PURPOSE: To investigate the role of a thiol-containing biologically active compound in lipid peroxidation of membranes. MATERIALS AND METHODS: Thiyl radicals were generated from 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)-dione (MECH) using pulse radiolysis and gamma-radiolysis in aqueous and alcoholic solutions saturated with N2O. The products were analysed by 1H NMR and by HPLC. RESULTS: THE thiyl radicals abstract bisallylic hydrogens from [cis-9, cis-12]-methyl linoleate, yielding a pentadienyl radical. In the absence of oxygen, a thiyl radical-induced cis/trans-isomerization leads to linoleic-type isomers. These chain-type isomerization reactions can occur with the long living pentadienyl radical, followed by a 'repair' reaction of the attached thiol, and with the thiyl radical adduct with a double bond of the fatty acid residue. CONCLUSIONS: The results show that the mechanism of cis/trans-isomerization is an integral part of the thiyl radical attack on polyunsaturated fatty acids in homogeneous solutions and in bilayers.

[Synthesis of 4-methyl-6-phenyl-thieno(2,3-d)pyrimidines with a formamidino- or oxalamidocarbonic acid residue with antianaphylactic activity]. / Synthese von 4-Methyl-6-phenyl-thieno[2,3-d]pyrimidinen mit Formamidin- bzw. Oxalsäureamidrest mit antianaphylaktischer Wirkung.

3-Amino-4-methyl-6-phenyl-thieno[2,3-d]pyrimidine-2-carbonic acid alkylesters 1a, b were hydrolyzed to the potassium salt of the carbonic acid 2. Cyclization of 2 with acetanhydride yielded the tricyclic 1,3-oxazinone derivative 4. This compound reacted with pyrrolidine by different conditions of reaction to give the bisamide 7, the acetamidino carbonic acid 5 and their decarboxylated product 6. Compound 1a yielded with Vilsmeier reagents the formamidino compound 3. 3-Amino-thieno[2,3-d]pyrimidin-2-carbonitrile gave under different conditions of reaction with oxalic acid diethylester or with oxalic acid ethylester chloride the tetracyclic 4-methoxy-9-methyl-7-phenyl-thieno[2,3-d:4,5-d']dipyrimidine-2-car bonic acid methylester 10 or the N-(2-cyano-4-methyl-6-phenyl-thieno[2,3-d]pyrimid-3-yl)oxalamid ic ethylester 12. These compounds were hydrolyzed to give the carbonic acids 11 and 13. Some of the synthesized substances showed an antianaphylactic activity.

[Synthesis of N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)amidines by means of reaction of 4-oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazines with primary aliphatic amines]. / Synthese von N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)amidinen durch Reaktion von 4-Oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazinen mit primären aliphatischen Aminen.

The title compounds were synthesized by the reaction of tricyclic compounds of structure B with primary aliphatic amines under different conditions and useful isolation methods in good yields. These compounds showed an acceptable antianaphylactic activity.

[Synthesis of 11-aryl-7,8,9,10-tetrahydro-1,2,3-triazino-(4',5':4,5)-thienol- -(2,3-b)-quinolines with antianaphylactic action]. / Synthese von 11-Acyl-7,8,9,10-tetrahydro-1,2,3-triazino[4',5':4,5]- thienol[2,3-b]chinolinen mit antianaphylaktischer Wirkung.

Title compounds of structure B with an oxo function in position 4 of the triazine ring were synthesized by reaction of the aminocarboxamides A with sodium nitrite in acetic acid. Aminocarbonitriles of structure H yielded with sodium nitrite in acetic acid and hydrochloric acid the 4-chloro derivatives I. These compounds gave with N-nucleophiles, methoxide or thiourea the substances J. Tetracyclic compounds with a hydroxyethyl or a piperidinoethyl residue in position 3 in the triazine ring (E, G) were also prepared. Some of the investigated compounds showed an antianaphylactic activity.

[Bis((2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl)alkyl)disulfane and 3-(mercaptoalkyl)quinazolin-2,4(1H,3H)-dione: synthesis by ring transformation and antiviral activity. 42. Heterocyclic azines with heteroatoms in the 1- and 3- positions]. / Bis[(2,4-dioxo-1,2,3,4-tetrahydrochinazolin-3-yl)alkyl]disulfane and 3-(Mercaptoalkyl)chinazolin02,4,(1H,3H)-dione: Synthese durch Ringtransformation and antivirale Aktivität. 42. Mitteilung: Mehrcyclische Azine mit Heteroatomen in 1- and 3-Stellung.

Reaction of N-(sulfonyloxy)phtalimide derivatives 1, 2, with cystamine and homocystamine, respectively, affords bis[2,4-dioxol-1,2,3,4-tetra-hydroquinazolin-3-yl)alkyl] disulfanes [sequence: see text] 3, which could be reduced to 3-(mercaptoalkyl)quinazoline-2,4(1H,3H)-diones. 5. (3-(2-Mercaptoethyl)quinazoline-2,4(1H,3H)-dione (5a) was also obtained in a one-pot reaction from 1 or 2 and cysteamine. 2-Ethoxy-4H-3,1-benzoxazin-4-ones 4a-c were converted with cysteamine to 3-(mercaptoethyl)quinazoline-2,4-diones 5a-c by a new ringtransformation reaction. 3-(2-Mercaptoethyl)quinazoline-2,4(1H,3H)dione (5a) and the corresponding disulfane 3a were evaluated for antiviral activity in vitro. Compounds 3a and 5a showed significant antiviral activity against some DNA- and RNA-viruses (vaccinia-, herpes simplex virus type 1; influenza A virus) at concentrations that were nontoxic to the host cell cultures.

[Synthesis of N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)-formamidines corresponding alkyl esters with antianaphylactic activity]. / Synthese von N-(2-Carboxy-thieno[2,3-b]pyridin-3-yl)-formamidinen und entsprechender Alkylester mit antianaphylaktischer Wirkung.

A lot of N-(2-carboxy-thieno[2,3-b]pyridin-3-yl)formamidines especially in form of their amine salts--were synthesized by reaction of 3-amino-thieno[2,3-b]pyridine-2-carboxylic acids with dimethylformamide/phosphoroxide chloride or by reaction of 4-oxo-4H-pyrido[3',2':4,5]thieno[3,2-d]1,3- oxazines with amines. Carboxylic acid alkylesters of this structure were yielded from 3-amino-thieno[2,3-b]pyridine-2-carbonic acid alkylesters by reaction with dimethylformamide/phosphoroxide chloride or with N-formyl-piperidine or N-formyl-morpholine and phosphoroxide chloride. The compounds showed antianaphylactic activity.

[Reactions of 4-oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazines with amines]. / Reaktion von 4-Oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)1,3-oxazinen mit Aminen.

The reaction of the title compounds with amines gave in dependence of the reaction conditions and the structure of the title compounds and the amine 3-acylamino-thieno[2,3-b]pyridine-2-carbonamides (B), 4-oxo-4 H-pyrido[3',2':4,5]thieno[3,2-d]pyrimidines (D),N-(2-carboxy-thieno[2,3-b]pyridine-3-yl)amidines (C) and N-(thieno[2,3-b]pyridin-3-yl)amidines (E). Substances of structure C and E seem to be of biological interest, especially for their antianaphylactic reactions.

[One-step synthesis of 2-aminothieno [2,3-d]thiazen-4-ones in some cases 5,6-anellated from ethyl 2-benzoylthioureidothiophen-3-carboxylates and evaluation of their anti-allergy activity]. / Einstufige Darstellung von zum Teil anellierten 2-Amino-thieno[2,3-d][1,3]thiazin-4-onen aus 2-Benzoylthioureido-thiophen-3-carbonsäureethylestern und deren Prüfung auf antiallergische Wirksamkeit.

The cyclization of ethyl 2-benzoylthioureidothiophen-3-carboxylates under basic conditions is known to give 2-thioxothieno[2,3-d]pyrimidin-4(1H, 3H)-ones. On the other hand, we have found that ethyl 2-benzoylthioureidothiophen-3-carboxylates 10-16 on treatment with concentrated sulphuric acid or polyphosphoric acid/ethanol undergo cyclization to give the new 2-aminothieno[2,3-d][1,3]thiazin-4-ones 17-23, in some cases 5,6-anellated. Reaction of 10-16, which are readily available from ethyl 2-aminothiophen-3-carboxylates 3-9 and benzoyl isothiocyante affords the title compounds 17-23 in good yields. Mass spectral fragmentation of 17-23 is discussed. A series of 2-aminothieno[2,3-d][1,3]thiazin-4-ones, which contain a free or substituted amino group was evaluated in the rat active cutaneous anaphylaxis test for anti-allergy activity. One compound, 23 had weak activity in the range of theophylline. Only high concentrations of this compound inhibited weakly the histamine release from rat peritoneal mast cells activated by protamine sulfate.

[Synthesis of thieno(2,3-b)pyridines with oxalamidic acid or an oxalamidic alkylester residues and of 4-alkoxy-pyrido(3',2':4,5)thieno(3,2-d)pyridine-2-carboxylic acid derivates]. / Synthese von Thieno(2,3-)pyridinen mit Oxalamidsäure- bzw. Oxalamidsäurealkylester-Rest und von 4-Alkoxy-pyrido(3',2':4,5)thieno(3,2-d)pyrimidin-2-carbons]aure-Derivat en

N-(2-Alkoxycarbonyl-thieno[2,3-b]pyrid-3-yl)oxalamide acid alkylester B were synthesized by the reaction of 3-amino-2-carboxylic esters A with oxalic acid diethylester in presence of sodium alkoxides. The 3-amino-2-cyano-thieno[2,3-b]pyridines C yielded under the same conditions via the N-(2-cyano-thieno[2,3-b]pyrid-3-yl)oxalamidic acid alkylesters D/1-D/4 the 4-alkoxy-pyrido[3',2':4,5]thieno[3,2-d]pyrimidine-2-carboxylic acid alkylesters E/1-E/8. The compounds D/1, D/2 and E/1-E/5 were hydrolyzed to give the corresponding carboxylic acids. The 3-amino-furo[2,3-b]pyridine-2-carboxylic acid ethylester H reacted with oxalic ethylester chloride to give the oxalamide ethylester I. The synthesized substances showed an antinaphylactic activity.

[Synthesis of new pyrido-(3',2':4,5)-thieno-(3,2-d)-1,2,3-triazine derivatives as antianaphylactics]. / Synthese neuer Pyrido[3',2':4,5]thieno[3,2-d]1,2,3-triazin-Derivate als Antianaphylaktika.

Some new pyrido[3',2':4,5]thieno[3,2-d]1,2,3-triazine-4(3H)-ones (C) were synthesized from 2-thioxo-1,2-dihydro-3-carbonitriles (A) via the 3-amino-thieno[2,3-b]pyridine-2-carboxamides (B). Substances of structure A were converted to 3-amino-thieno[2,3-b]pyridine-2-carbonitriles (G) which yielded the desired 4-amino substituted compounds I via the tricyclic 4-chloro-pyrido[3',2':4:5]thieno[3,2-d]1,2,3-triazines (H) by the reaction with N-nucleophiles. Some of the investigated compounds showed a respectable antianaphylactic activity.