Die sekundäre Dekompressionstrepanation bei zunehmendem posttraumatischem Hirnödem nach primärer Entlastungskraniotomie

Zusammenfassung Bei der neurotraumatologischen Versorgung von Patienten mit mäßigem (Glasgow-Coma-Scale- [GCS-]Score 9–12 Punkte) oder schwerem Schädel-Hirn-Trauma (SHT; GCS-Score 8 Punkte) steht neben der Evakuation von epiduralen und subduralen Hämatomen die frühzeitige Entlastungstrepanation mit Duraerweiterungsplastik bei drohender Einklemmung im Vordergrund. Die Frage der Effektivität der sekundären Dekompressionskraniotomie nach primärer Trepanation wird aufgrund des fehlenden Nachweises eines verbesserten Resultats kritisch gesehen. Ziele dieser Analyse an einem konsekutiven Patientenkollektiv waren die Erfassung der Inzidenz eines zunehmenden Hirnödems nach isoliertem SHT und primärer Entlastungskraniotomie, die Identifikation möglicher Entscheidungskriterien für eine sekundäre Dekompressionstrepanation und die neurologische Beurteilung 6 Monate nach Entlassung mit Hilfe des Glasgow-Outcome-Scores (GOS). 58 von insgesamt 131 Patienten (48 Männer, 10 Frauen; medianes Alter 50,9 Jahre) mit isoliertem SHT, die zwischen Januar 1997 und Dezember 2001 primär operativ versorgt werden mussten, wurden in die Analyse eingeschlossen. Bei 11 Patienten (9 m., 2 w.; medianes Alter 40,0 Jahre) war im weiteren Verlauf sekundär entweder eine unilaterale Erweiterungs- oder eine kontralaterale Dekompressionstrepanation nötig. 4 der 11 Patienten (36,4%) überlebten die Verletzung nicht. Sie starben im Median 1 Tag nach der operativen Revision bzw. 6 Tage nach dem SHT. In der Gruppe mit sekundärer Dekompressionstrepanation erfolgte die klinische Aufnahme (80 min nach dem SHT) etwa 35 min später als in der Gruppe mit ausschließlich primärer Entlastungskraniotomie (p=0,009). Eine Blutung aus dem Ohr wurde zudem signifikant häufiger beobachtet (p=0,036). In der univariaten Analyse korrelierten die klinischen Parameter arterielle Hypotonie (p=0,018) und Blutung aus dem Ohr bei Aufnahme (p=0,035), der intrakranielle Druck (ICP; p=0,024) unmittelbar und die Abnahme des maximalen zerebralen Perfusionsdruckes (CPP; p=0,031) unterhalb eines medianen Schwellenwertes von 70 mmHg im Verlauf nach primärer Entlastungskraniotomie mit dem Ereignis einer sekundären Dekompressionstrepanation. In der multivariaten Analyse erwies sich lediglich der niedrigere maximale CPP nach primärer Trepanation als unabhängiger prognostischer Parameter (Score 10,496; df=1; p=0,043) für die sekundäre Dekompressionstrepanation und einen ungünstigen GOS 6 Monate nach Entlassung. Bei Patienten mit isoliertem, mäßigem oder schwerem SHT beeinflussten die präklinische arterielle Hypotonie sowie die Blutung aus dem Ohr bei Aufnahme die Mortalität und Morbidität negativ. Somit ist der frühe Ausgleich einer arteriellen Hypotonie und der rasche Transport in ein neurotraumatologisches Zentrum für das präklinische Management von SHT-Patienten zu fordern. Für die Phase der Überwachung auf der Intensivstation nach der primären Trepanation scheint nur die Abnahme des maximal erreichbaren CPP unterhalb des Schwellenwertes von 70 mmHg trotz Katecholamingabe als unabhängiger Prognoseparameter sowohl auf die Notwendigkeit einer operativen Revision als auch auf einen schlechten neurologischen Verlauf 6 Monate nach Entlassung hinzuweisen.     

Cysteine protease activity is up-regulated in inflamed ankle joints of rats with adjuvant-induced arthritis and decreases with in vivo administration of a vinyl sulfone cysteine protease inhibitor

OBJECTIVE: Cysteine proteases are postulated to play a role in tissue destruction in the joints of animals with arthritis. The purpose of the present study was to confirm the concept that cysteine proteases are enzymes involved in the pathology of rheumatoid arthritis (RA). METHODS: Arthritis was induced in Lewis rats by adjuvant injection (adjuvant-induced arthritis [AIA] model) and scored for inflammation. At necropsy, the rear paws were either fixed in formalin and assigned a histologic score (based on synovial cell proliferation, cartilage erosion, bone erosion, and fibroproliferative pannus) or frozen, cryosectioned, and assayed for enzyme activity either by in situ cytochemical staining with a post-azo-coupling method using a chromogenic substrate (Z-arg-arg-MNA) or by a novel assay placing the tissue section directly in a cuvette using the fluorogenic substrate Z-arg-arg-AMC. RESULTS: Enzymatic activity, measured either in frozen sections in situ or in the cuvette assay, was positively correlated with joint destruction (r = 0.7) and inflammation (r = 0.8). Activity was not inhibited significantly by Pefabloc (a serine protease inhibitor), EDTA (a metalloprotease inhibitor), or pepstatin A (an aspartyl protease inhibitor) but was inhibited by E-64 and vinyl sulfone irreversible inhibitors of cysteine proteases. The effect of one of the vinyl sulfone cysteine protease inhibitors, Mu-Leu-HomoPhe-vinylsulfone, was tested in vivo by dietary administration at 2.2 mg/kg/day in the AIA model; this resulted in a significant decrease in inflammation and in the amount of cysteine protease activity measured in the joint tissue. CONCLUSION: Cysteine protease activity levels increase in the diseased state and may be an important target for designing small molecule inhibitors to reduce the inflammation and tissue destruction associated with RA.     

Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies

Context  Dietary factors modifying type 1 diabetes mellitus (DM) risk have been proposed, but little is known if they trigger the islet autoimmunity that precedes clinical disease. Objective  To determine whether breastfeeding duration, food supplementation, or age at introduction of gluten-containing foods influences the risk of developing islet autoantibodies. Design and Setting  Prospective natural history cohort study conducted from 1989 to 2003 in inpatient/outpatient clinics in Germany. Participants  The BABYDIAB study follows newborn children of parents with type 1 DM. Eligibility requirements were met in 1610 children. Blood samples were obtained at birth, age 9 months, 2, 5, and 8 years. Dropout rate was 14.4% by age 5 years. Breastfeeding data were obtained by prospective questionnaires (91% complete), and food supplementation data were obtained by family interview (72% for food supplementation and 80% for age of gluten introduction). Main Outcome Measure  Development of islet autoantibodies (insulin, glutamic acid decarboxylase, or IA-2 antibodies) in 2 consecutive blood samples. Results  Life-table islet autoantibody frequency was 5.8% (SE, 0.6%) by age 5 years. Reduced total or exclusive breastfeeding duration did not significantly increase the risk of developing islet autoantibodies. Food supplementation with gluten-containing foods before age 3 months, however, was associated with significantly increased islet autoantibody risk (adjusted hazard ratio, 4.0; 95% confidence interval, 1.4-11.5; P = .01 vs children who received only breast milk until age 3 months). Four of 17 children who received gluten foods before age 3 months developed islet autoantibodies (life-table 5-year risk, 24%; SE, 10%). All 4 children had the high-risk DRB1*03/04,DQB1*0302 genotype. Early exposure to gluten did not significantly increase the risk of developing celiac disease–associated autoantibodies. Children who first received gluten foods after age 6 months did not have increased risks for islet or celiac disease autoantibodies. Conclusion  Ensuring compliance to infant feeding guidelines is a possible way to reduce the risk of development of type 1 DM autoantibodies.      

Olfactory changes at threshold and suprathreshold levels following septoplasty with partial inferior turbinectomy

Partial inferior turbinectomy with septoplasty is routinely carried out for airway obstruction. However, its effects on the sense of smell have not been systematically evaluated. The aim of this prospective study was to evaluate the influence of septoplasty with partial inferior turbinectomy on threshold and suprathreshold olfactory acuity. The subjects were 30 patients undergoing septoplasty including partial inferior turbinectomy. Olfactory function was determined by the "Sniffin' Sticks," which allow the assessment of odor thresholds, odor discrimination, and odor identification. The patients rated both olfactory function and nasal airflow using visual analog scales. Nasal airflow was measured by anterior rhinomanometry. Multivariate analyses of variance for repeated measures were used to analyze the results before and after surgery (mean interval, 9.1 weeks). After operation, 87% of the patients had increased airflow, 80% had improved olfactory function in terms of odor identification, and in 70% odor discrimination was found to be improved - but only 54% had improved olfactory function in terms of odor thresholds. Surgery increased ratings of nasal airflow in 93%, and those of olfactory function in 77% (p < .001). Similarly, bilateral inspiratory nasal flow increased (p < .001) and olfactory function was improved (p < .001) after surgical treatment. However, this increase was most pronounced for suprathreshold tests, while it was moderate for odor thresholds (interaction "surgery" x "olfactory test," p = .001). The present investigation suggests that septoplasty in combination with inferior turbinectomy has a beneficial effect on olfaction, mainly on suprathreshold olfactory functions. This effect may be partly due to interactions between the increased perception of nasal airflow and cognitive factors involved in olfactory sensitivity. According to the present results and data from the literature, a moderate decrease of olfactory function appears to occur in as many as 20% of patients. However, anosmia seems to be an extremely rare complication of septoplasty and partial turbinectomy.     

Therapy of olfactory loss

BACKGROUND: Apart from olfactory loss due to sino-nasal disease therapy of olfactory dysfunction is a difficult task. METHODS: Own investigations were carried out using alpha-lipoic acid (Hummel et al. 2002) and caroverine (Quint et al. 2002) in both patients with posttraumatic olfactory dysfunction and patients with olfactory loss following viral infections. Both studies were designed as unblinded trials; the study using caroverine contained an arm where patients received zinc. RESULTS: While data from these investigations are preliminary both studies indicated a beneficial effect of the medication on olfactory loss. Therapeutic principles may involve the release of nerve growth factors through alpha-lipoic acid and the NMDA-antagonistic action of caroverine which might act at higher order centers of olfactory processing. CONCLUSIONS: These studies and other work indicate that olfactory loss may be treated through different pharmacological approaches. However, only double-blind, randomized, controlled trials will tell whether these effects are due to the potential pharmacological activity of these drugs, or, whether they merely reflect spontaneous recovery as it is seen in a relatively large percentage of patients suffering from olfactory dysfunction.     

Decreased trigeminal sensitivity in anosmia

The present study aimed to investigate intranasal trigeminal sensitivity in a large sample of patients with anosmia due to different etiologies. We investigated the trigeminal detection threshold for formic acid in healthy controls (n = 96) and patients with anosmia due to head trauma (n = 18) or sinonasal disease (n = 54). Anosmics exhibited higher thresholds compared with normosmics (p < 0.001). In addition, thresholds were found to be higher in patients with posttraumatic anosmia compared to anosmics with sinonasal disease (p < 0.001). The data indicate that (1) loss of olfactory sensitivity in humans may be associated with a decreased sensitivity towards trigeminal stimuli and (2) alteration of intranasal trigeminal function is stronger in patients with posttraumatic anosmia compared to patients with sinonasal disease. This may have implications for the medicolegal investigation of anosmic patients where trigeminal stimuli are frequently used to assess the patient's response bias.     

The enjoyment of red wine is influenced by the shape of the wine glass

BACKGROUND: It is frequently claimed that the glass shape has a direct impact on wine aroma. METHODS, PATIENTS: Healthy volunteers (43 m, 46 f, age 19-60 years) tried 3 glasses. Three glasses of different shape but of the same height and of comparable opening diameter were used. Glasses were of "tulip"-like, "beaker"-like, and "egg"-like shapes. Intensity, hedonic tone, and quality of a red wine were rated before and after drinking. RESULTS: Both intensity and hedonic ratings of wines from different glasses were influenced by glass shape. Glass shape also influenced the complexity of wine odors. This appeared not to be related to the esthetic impression the glasses made. CONCLUSIONS: The present data indicate that egg-shaped glasses, compared to "tulip" or "beaker" glasses, appear to produce higher intensity and higher complexity of wine odors. This may relate to the trapping of odors in egg-shaped glasses.     

Medical technology assessment: the use of the analytic hierarchy process as a tool for multidisciplinary evaluation of medical devices

Most types of medical technology assessment are performed only after the technology has been developed. Consequently, they have only minor effects on changes in clinical practice. Our study introduces a new method of constructive medical technology assessment that can change the development and diffusion of a medical device to improve its later clinical effectiveness. The method, based on Saaty's Analytic Hierarchy Process, quantitatively supports discussions between various parties involved in technological development and diffusion. We applied this method in comparing a new blood pump with two competitors based on technical, medical and social requirements. These discussions changed the evaluators' perspectives, reduced diasagreements, and ended in a reliable evaluation of the pump's performance. On the basis of these results, adaptations were derived which improved the design and diffusion of the blood pump. This application shows the adequate potential of our method to steer technological development and diffusion of artificial organs.