RESUMEN
Autosomal dominant early-onset Alzheimer disease (EOAD) is a heterogeneous condition that has been associated with mutations in 3 different genes: the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes. Most cases are due to mutations in the PSEN1 gene, whereas mutations in the APP and PSEN2 genes are rare. Mutation analysis of the APP, PSEN1 and PSEN2 genes was performed. We herein report the case of a German EOAD patient with a family history of dementia and a missense mutation at codon 141 (N141I) of the PSEN2 gene. To our knowledge, this is the first German EOAD patient without a Volga-German ancestry and a positive family history for dementia carries the mutation PSEN-2 N141I. The patient came to our clinic for the first time when she was 47 years old. During the following 3 years, her Mini-Mental State Examination (MMSE) score dropped from 28 to 0. Mild cognitive impairment (MCI) was an early symptom that was already present during the first consultation. The concentration in cerebrospinal fluid (CSF) of tau-protein (1151 pg/ml) was increased, whereas the concentration of beta-amyloid protein (Abeta1-42) was decreased (335 pg/ml). Magnetic resonance imaging (MRI) revealed only slight changes in the early stage of the disease and positron emission tomography with (18F) fluoro-2-deoxy-D-glucose (18F-FDG PET) demonstrated glucose reduction left parietal and in the precuneus region. Follow-up MRI and 18F-FDG PET studies showed progression of atrophy of the left entorhinal cortex with relative sparing of the hippocampus and progressive hypometabolism of both temporoparietal lobes and left frontal lobe.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Mutación Missense , Presenilina-2/genética , Edad de Inicio , Enfermedad de Alzheimer/diagnóstico por imagen , Inhibidores de la Colinesterasa/uso terapéutico , Codón , Donepezilo , Electrofisiología , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Indanos/uso terapéutico , Masculino , Memantina/uso terapéutico , Persona de Mediana Edad , Pruebas Neuropsicológicas , Linaje , Piperidinas/uso terapéutico , Radiografía , Cintigrafía , Radiofármacos , Factores de Tiempo , Resultado del Tratamiento , Proteínas tau/líquido cefalorraquídeoRESUMEN
Alzheimer's disease (AD) is the most common form of dementia. Approximately 0.5 per cent of all AD is caused by single major gene mutations and autosomal dominant inheritance. These familial types with early-onset (EOFAD) usually display dementia before the age of 60. Such mutations have been found in the gene encoding amyloid precursor protein (APP), and in the genes encoding presenilin 1 (PSEN1) or presenilin 2 (PSEN2). We herein report the case of a German patient with a EOFAD and a missense mutation at codon 141 (N141I) of the PSEN2 gene. The patient came to our psychiatric clinic for the first time when she was 49 years old. During the following 3 years, her Mini-Mental-State-Examination (MMSE) score dropped from 14 to 0 points. Positron emission tomography with [18F] Fluorodeoxyglucose (18F-FDG PET) demonstrated glucose reduction left parietal and in the pre-cuneus region. Follow-up 18F-FDG PET studies showed progressive hypometabolism of both temporoparietal lobes and left frontal lobe.
Asunto(s)
Enfermedad de Alzheimer/genética , Mutación Missense/fisiología , Presenilina-2/genética , Adulto , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/psicología , Antidepresivos de Segunda Generación/uso terapéutico , Encéfalo/diagnóstico por imagen , Citalopram/uso terapéutico , Codón/genética , Donepezilo , Electroencefalografía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Indanos/uso terapéutico , Pruebas Neuropsicológicas , Nootrópicos/uso terapéutico , Linaje , Piperidinas/uso terapéutico , Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
Fatty acid ethyl esters (FAEE) are incorporated into hair mainly from sebum. For this reason, the use of their concentration CFAEE as marker of excessive alcohol consumption is complicated by interindividual differences of the activity of the sebum glands and of elimination by hair care and hair cosmetics. Furthermore, an influence of the investigated hair length due to increasing accumulation from proximal to distal was found. Therefore, it was examined whether these sources of error can be avoided if in addition to CFAEE the relative FAEE concentrations CFAEE/CSQ related to squalene SQ as a natural reference compound were used for interpretation. Sebum contains about 10-20% SQ. A sensitive and reliable method for the determination of SQ in addition to FAEE from the same hair extracts by high performance liquid chromatography with photo diode array detector (HPLC-DAD) was developed. The concentrations of ethyl myristate, ethyl palmitate, ethyl oleate, ethyl stearate and squalene were determined and CFAEE/CSQ was calculated for 13 teetotallers, 16 social drinkers, 12 fatalities with excessive alcohol abuse at life time and 9 cases with unclear alcohol anamnesis. CSQ ranged from 0.02 to 1.97 microg/mg (mean 0.67 microg/mg). From the results follows that squalene enables a control of the lipid content of hair and a correction of CFAEE in cases with deviations from the usual lipid content in a similar way as creatinine in urine. Preliminary values of CFAEE/CSQ were suggested for the upper limit for teetotallers (< 0.6 ng/microg) and the lower limit for excessive alcohol abuse (> 1.5 ng/microg). However, the relative concentration CFAEE/CSQ cannot completely replace the absolute concentration CFAEE, and both should regularly be used for an improved interpretation with respect to alcohol abuse.
Asunto(s)
Alcoholismo/diagnóstico , Ácidos Grasos/análisis , Cabello/química , Escualeno/análisis , Detección de Abuso de Sustancias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas , Biomarcadores/análisis , Niño , Cromatografía Líquida de Alta Presión , Femenino , Medicina Legal/métodos , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lípidos/análisis , Masculino , Persona de Mediana Edad , Estructura Molecular , Escualeno/químicaRESUMEN
Fatty acid ethyl esters (FAEE) are known to be formed in blood and almost all human tissues after alcohol consumption and to be incorporated from sebum into hair where they can be used as long-term markers for excessive alcohol consumption. In order to examine whether skin surface lipids which consist mainly of sebum are an equally useful matrix for measurement of FAEE as alcohol abuse markers, samples were collected by a wipe-test from the forehead of 13 teetotallers, 16 social drinkers, 10 death cases with known recent alcohol misuse and five death cases without indications of alcohol misuse. The samples were analysed by headspace solid-phase microextraction and gas chromatography-mass spectrometry for ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate and by high performance liquid chromatography with photodiode array detector for squalene, (SQ), as a natural reference substance which the FAEE concentrations were related to. The ratio mFAEE/mSQ ranged between 0.16 and 1.12 ng/microg (mean 0.34 ng/microg) for the teetotallers and between 0.08 and 0.94 ng/microg (mean 0.37 ng/microg) for the social drinkers with no significant difference between both groups. For the alcoholics 2.4-24.2 ng/microg (mean 13.1 ng/microg) were found. For two volunteers the course of mFAEE/mSQ 2 weeks before and 3 weeks after a single high alcohol dose was pursued by daily wipe tests. A strong increase of mFAEE/mSQ occurred between 7 and 12 days after the drinking event. This delay can be explained by the transition time of about 8 days between sebum production and its appearance on the skin surface known from literature. For seven social drinkers skin surface lipid samples were also collected using drug of abuse patches of the firm PharmCheck. The ratios mFAEE/mSQ in these samples were in the same range as from the wipe-test. The comparison with the self-reported ethanol amounts consumed the week before and during the test gave no good correlation (R2 = 0.42). It can be concluded from the results that FAEE in skin surface lipids can be used for medium-term retrospective detection of heavy drinking.
Asunto(s)
Alcoholismo/metabolismo , Ácidos Grasos/metabolismo , Metabolismo de los Lípidos , Piel/metabolismo , Escualeno/metabolismo , Detección de Abuso de Sustancias/métodos , Adulto , Anciano , Consumo de Bebidas Alcohólicas/metabolismo , Biomarcadores/análisis , Niño , Cromatografía Líquida de Alta Presión , Ácidos Grasos/análisis , Femenino , Medicina Legal/métodos , Cromatografía de Gases y Espectrometría de Masas , Cabello/química , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The POEMS syndrome is a multisystem disorder characterised by polyneuropathy, organomegaly, endocrinopathy, plasma cell dyscrasia and skin changes. A coincidence with angiofollicular lymphoid hyperplasia (Castleman's disease) exists in about 60% of all cases. The POEMS syndrome may be associated with macroangiopathy and acute vascular obliterations. Most case reports refer to involvement of the coronary and lower limb arteries. There are only few reports dealing with cerebral strokes and POEMS syndrome. We report on a 32-year-old female with an incomplete form of POEMS syndrome with Castleman's disease and associated cerebral vasculitis. After sufficient treatment of the plasma cell dyscrasia, recurrent cerebral ischemias occurred. A stable state was finally reached after primary treatment of the vasculitis with cyclophosphamide.
Asunto(s)
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiología , Enfermedad de Castleman/complicaciones , Enfermedad de Castleman/diagnóstico , Síndrome POEMS/diagnóstico , Vasculitis del Sistema Nervioso Central/complicaciones , Vasculitis del Sistema Nervioso Central/diagnóstico , Adulto , Isquemia Encefálica/tratamiento farmacológico , Enfermedad de Castleman/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Síndrome POEMS/tratamiento farmacológico , Prevención Secundaria , Resultado del Tratamiento , Vasculitis del Sistema Nervioso Central/tratamiento farmacológicoRESUMEN
In the present randomized, comparative, double-blind, 3-way crossover study, possible effects of 3 antivertiginous medications on vigilance were investigated. 30 healthy volunteers received single doses of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevert, ARL), dimenhydrinate 50 mg, or betahistine dimesylate 12 mg, in randomized order at 1-week intervals. Spontaneous brain electrical activity (EEG), acoustic late evoked potentials (ALEP) with P300, and reaction time were measured before and 90 (t90) and 180 minutes (t180) after drug intake. All 3 medications led to a delay of P300 (primary criterion) and a decrease of its amplitude. The maximum delay at t180 was found for dimenhydrinate (16.42 ms) and the lowest for betahistine (6.33 ms). Differences ARL vs dimenhydrinate and ARL vs betahistine were not statistically significant (p > 0.05). Spectral analysis of spontaneous EEG showed slight and similar decreases in the power in the a-band under dimenhydrinate and ARL (p = 0.07 and p = 0.03 with respect to baseline, respectively), but basically no change under betahistine. There was no effect on reaction time by either medication. None of the subjects reported drowsiness or any other adverse event. The findings confirm the reported suitability of P300 latency for measurement of drug effects on brain activity, but provide no indication of concomitant impairment of performance capacity by the tested drugs. Global assessment of the results suggests that the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg exerts only a minor effect on vigilance, not significantly different from betahistine, which is commonly regarded as a non-sedating antivertiginous drug
Asunto(s)
Betahistina/uso terapéutico , Cinarizina/uso terapéutico , Dimenhidrinato/uso terapéutico , Agonistas de los Receptores Histamínicos/uso terapéutico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Adolescente , Adulto , Betahistina/administración & dosificación , Betahistina/efectos adversos , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Cinarizina/administración & dosificación , Cinarizina/efectos adversos , Estudios Cruzados , Dimenhidrinato/administración & dosificación , Dimenhidrinato/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Electroencefalografía/efectos de los fármacos , Potenciales Relacionados con Evento P300/efectos de los fármacos , Potenciales Evocados Auditivos/efectos de los fármacos , Femenino , Agonistas de los Receptores Histamínicos/administración & dosificación , Agonistas de los Receptores Histamínicos/efectos adversos , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/efectos de los fármacos , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the utility of the iSTAT blood analyzer, a bedside device for hematocrit, sodium, potassium, and glucose measurement during cardiopulmonary bypass (CPB). METHODS: Forty patients scheduled for elective CPB were evaluated prospectively. In addition to using the iSTAT analyzer, blood samples were analyzed at four time points: following induction of anesthetic, 10 min. after initiation of CPB, 60 min. after initiation of CPB, and following heparin neutralization by protamine. Blood glucose concentration was measured by the hospital laboratory using a Kodak Analyzer and by a glucose meter, electrolytes were evaluated by the Kodak Analyzer and BGE (a device which is commonly used for "satellite laboratory" determinations of electrolyte and blood gas results), and hematocrit samples were measured by the hospital laboratory using an NE 8,000 and a centrifuge. The means and standard deviations of the differences between the methods were calculated. RESULTS: The hematocrit values determined by the iSTAT machine, when adjusted for the level of total protein (according to manufacturer's directions), differed from the laboratory values by 0.53 +/- 1.46 percentage points. An alternative to measuring total protein and making the adjustment is simply adding 1% to the hematocrit in the pre-CPB period and 3% on-CPB or post-CPB, which we found to yield values that differed from the laboratory by 0.52 +/- 1.42 percentage points. For all four tests (hematocrit, sodium, potassium, and glucose) the iSTAT had a similar relationship to the laboratory values as did the other commonly used means (centrifuge, BGE, and glucose meter) of clinical evaluation. CONCLUSION: In summary, we found that in patients undergoing CPB, the iSTAT values agreed sufficiently well with standard laboratory values and that the iSTAT instrument can be relied upon for bedside measurements.
Asunto(s)
Análisis Químico de la Sangre/instrumentación , Puente Cardiopulmonar , Hematócrito , Pruebas Hematológicas/instrumentación , Glucemia/análisis , Proteínas Sanguíneas/análisis , Hemodilución , Humanos , Persona de Mediana Edad , Sistemas de Atención de Punto , Potasio/sangre , Estudios Prospectivos , Sodio/sangreRESUMEN
We reviewed the records of 66 patients who underwent cardiopulmonary bypass; half of these patients received the plasmin inhibitor, tranexamic acid. The demographics were not different between the group who received tranexamic acid and the group who did not (control group). There was no difference in the heparin or protamine requirements between the two groups. There was a significantly greater amount of 12-hr chest tube bleeding in the control group (495 +/- 484 vs. 863 +/- 655 in the control and tranexamic acid groups, respectively; p < .02). There was no difference between the groups in either the post-operative hematocrit, platelet count or the number of patients requiring transfusion. Although tranexamic acid decreased the amount of chest tube output, there was no demonstrable patient benefit derived from its use.
Asunto(s)
Antifibrinolíticos/uso terapéutico , Puente Cardiopulmonar , Fibrinolisina/antagonistas & inhibidores , Ácido Tranexámico/uso terapéutico , Pérdida de Sangre Quirúrgica , Transfusión de Sangre Autóloga , Heparina/administración & dosificación , Humanos , Recuento de Plaquetas , Protaminas/administración & dosificación , Estudios RetrospectivosRESUMEN
A total of 1566 patients with fractures of the pelvis were treated at the Department of Traumatology at the Hannover Medical School between 1972 and 1990. Of these, 1350 patients had fractures of the pelvic ring, 216 isolated acetabulum fractures, and 398 combinations of pelvic ring fractures and acetabular involvement. Of these patients, 718 were admitted with severe polytrauma. For 1254 patients complete files were available for clinical and radiological evaluation of fracture distribution, classification (Tile and anatomical location) and concomitant injuries. A significant increase in the severity of trauma, the severity of the pelvic fractures and the rate of internal stabilization, especially of the posterior pelvic ring, was observed during the observation period. The overall mortality after pelvic fracture was 18.1%. This mortality was correlated to the Hannover Polytrauma Score (PTS) and the associated extrapelvic blunt trauma. Internal fixation of pelvic fractures was performed in 195 patients. Our experience led to standardized procedures for the different fracture locations. In fractures type Tile B, an anterior procedure led in all cases to anatomic or near anatomic healing. In unstable pelvic ring fractures (Tile C), external fixation led to a significantly higher rate of posterior dislocations (over 1 cm) than did internal fixation. In these situations a combined posterior and anterior internal fixation procedure improved the result compared to posterior internal stabilizations alone. As a result, internal stabilization using a standardized technique for every fracture location is recommended for all unstable pelvic ring fractures.
Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Huesos Pélvicos/lesiones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Niño , Preescolar , Femenino , Curación de Fractura/fisiología , Fracturas Óseas/clasificación , Fracturas Óseas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/clasificación , Traumatismo Múltiple/mortalidad , Traumatismo Múltiple/cirugía , Huesos Pélvicos/cirugía , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/cirugía , ReoperaciónRESUMEN
1566 patients with fractures of the pelvis were treated at the Department of Traumatology of the Hannover Medical School between 1972 and 1990: 1350 patients had fractures of the pelvic ring, 216 isolated acetabulum fractures, 398 combinations of pelvic ring fractures and acetabular involvement; 718 of these patients were admitted with severe polytrauma. For 1254 patients a complete file was available for clinical and radiological evaluation of fracture distribution, classification (Tile and anatomical location) and concomitant injuries. During the observation period, significant increase in the severity of the trauma, the severity of the pelvic fractures and the rate of internal stabilization, especially of the posterior pelvic ring was observed. The overall mortality after pelvic fractures was 18.1%. This mortality depended significantly on the Hannover Polytrauma Score (PTS) and the associated pelvic and extrapelvic blunt trauma. Internal fixation of pelvic fractures was performed in 195 patients. This experience has now led to standardized procedures for the different fracture locations. With the task of minimizing soft tissue trauma and reducing the implant size, more differentiated treatment of sacral fractures is now applied. Adapted small fragment implants ("local osteosyntheses") can be applied, with an unilateral longitudinal dorsal incision providing an excellent overview over the fracture line. For internal fixation of sacral fractures, involvement (penetration by screws, transfixation) of the sacroiliac joint is avoided whenever possible. In our experience early open reduction and internal fixation of pelvic fractures facilitates the management of these severely injured patients.
Asunto(s)
Fijación Interna de Fracturas/métodos , Traumatismo Múltiple/cirugía , Huesos Pélvicos/lesiones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Placas Óseas , Tornillos Óseos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/clasificación , Traumatismo Múltiple/mortalidad , Complicaciones Posoperatorias/mortalidadRESUMEN
Freshly isolated rabbit lenses were cultured in isosmolar TC-199 medium or hyperosmolar medium containing 180 mM sorbitol or mannitol. These experiments were performed to investigate the probable effects of hyperosmolar media on lens clarity and the ability of lens fiber cells to synthesize membrane intrinsic protein, MP-26. The data from these experiments show that incubation in hyperosmolar medium causes depressed MP-26 synthesis, whereas the presence of sugar alcohols in the culture medium induced anterior and posterior subcapsular opacities. The cation levels of lenses incubated in iso- and hyperosmolar medium were also measured. Data from these experiments revealed that although the experimental lenses display prominent opacities, their cation levels are generally similar to those of control lenses. It is proposed that the observed lens opacities are due to the presence of sugar alcohols in the culture medium and not to hyperosmolar shock.