Assessing Alzheimer severity with a global clinical scale.

Diagnosis of dementia needs to be complemented by precise determination of disease severity across the broad spectrum of disease progression. The Mini-Mental State Exam (MMS), the Activities-of-Daily-Living assessment (ADL) and the Clinical Dementia Rating scale (CDR) were modified for direct comparability and administered to 112 outpatients and 45 nursing home residents with a range of dementia severity from mild to profound. The scales showed the highest correlations for the probable Alzheimer's disease patient group (62) (Global Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment; EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86). For these patients, scores on the individual scales tended to be similar. Disparity among the three scores for individual cases was associated with the presence of comorbidities. The high correlations and correspondence among these scales demonstrate their reliability, validity, and utility in the assessment of dementia severity. The use of an average of these measures, with their increased precision, may give a more accurate indication of dementia severity over a broader range of impairment.     

Transfer of DDT used in malaria control to infants via breast milk.

The transfer of p,p'-DDT (1,1,1-tricholoro-2,2-bis(4-chlorophenyl)ethane) and its metabolites to infants via breast-feeding was studied in an area of KwaZulu, South Africa, where DDT is used to interrupt malaria transmission. Samples of whole blood were collected from 23 infants, together with samples of breast milk from their respective mothers. The mean sigma DDT (total DDT) in the whole blood was 127.03 micrograms.l-1 and that in the breast milk, 15.06 mg.kg-1 (milk fat). The % DDT (% DDT of sigma DDT) was significantly higher in the infant blood than in the breast milk (P less than 0.05). A multiplicative regression analysis indicated that sigma DDT increased significantly (P less than 0.01) in infant whole blood with infant age. Multiple regression showed that 70.0% of the variation in sigma DDT was due to the variation in parity of the mother, age of the infant, and the sigma DDT in breast milk. These variables accounted also for 76.3% of the variation in p,p'-DDE but only for 38.2% of that in p,p'-DDT. Organochlorines were therefore largely transferred to the infant from the mother, with DDT in the environment playing a secondary role.     

Early Postnatal Changes in the Somatodendritic Morphology of Ankle Flexor Motoneurons in the Rat

The development of locomotor function in the rat spans the first 3 postnatal weeks. We have studied morphological features of the soma and dendrites of motoneurons innervating the physiological flexor muscles of the ankle, tibialis anterior and extensor digitorum longus, by intracellular injection in vitro between the first and ninth postnatal days. We obtained serial optical sections of 96 adequately filled motoneurons in whole-mounted hemisected spinal cords by confocal microscopy, projected them onto a single plane and analysed them morphometrically. On the day after birth, the somatodendritic surfaces of most such motoneurons were covered in growth-associated spiny, thorny or hair-like appendages. These had disappeared from the soma by the fourth postnatal day and from most proximal dendrites by day 7, but were still common distally on day 9. During this period there was little or no net growth of either the soma (which was still much smaller than in the adult) or the dendritic tree. A dorsal dendritic bias was present and 'sprays' of long, loosely bundled dorsal dendrites were often seen. The mean number of primary dendrites remained constant at about eight, and their combined diameter was already significantly correlated with mean soma diameter, as in the adult cat. Thus, the critical neonatal period during which these ankle flexor motoneurons are known to change their electrophysiological properties and to be particularly sensitive to interference with neuromuscular interaction is characterized by major changes in the neuronal surface, presumably linked to synaptogenesis.     

Posttraumatic cerebral arterial spasm: transcranial Doppler ultrasound, cerebral blood flow, and angiographic findings.

Thirty patients admitted after suffering closed head injuries, with Glasgow Coma Scale scores ranging from 3 to 15, were evaluated with transcranial Doppler ultrasound monitoring. Blood flow velocity was determined in the middle cerebral artery (MCA) and the intracranial portion of the internal carotid artery (ICA) in all patients. Because proximal flow in the extracranial ICA declines in velocity when arterial narrowing becomes hemodynamically significant, the extracranial ICA velocity was concurrently monitored in 19 patients. To assess cerebral perfusion, cerebral blood flow (CBF) measurements obtained with the intravenous 133Xe technique were completed in 16 patients. Vasospasm, designated as MCA velocity exceeding 120 cm/sec, was found in eight patients (26.7%). Severe vasospasm, defined as MCA velocity greater than 200 cm/sec, occurred in three patients, and was confirmed by angiography in all three. Subarachnoid hemorrhage (SAH) was documented by computerized tomography in five (62.5%) of the eight patients with vasospasm. All cases of severe vasospasm were associated with subarachnoid blood. The time course of vasospasm in patients with traumatic SAH was similar to that found in patients with aneurysmal SAH; in contrast, arterial spasm not associated with SAH demonstrated an uncharacteristically short duration (mean 1.25 days), suggesting that this may be a different type of spasm. A significant correlation (p less than 0.05) was identified between the lowest CBF and highest MCA velocity in patients during the period of vasospasm, indicating that arterial narrowing can lead to impaired CBF. Ischemic brain damage was found in one patient who had evidence of cerebral infarction in the territories supplied by the arteries affected by spasm. These findings demonstrate that delayed cerebral arterial spasm is a frequent complication of closed head injury and that the severity of spasm is, in some cases, comparable to that seen in aneurysmal SAH. This experience suggests that vasospasm is an important secondary posttraumatic insult that is potentially treatable.     

Pharmacokinetic aspects of a combination of metoclopramide and paracetamol. Results of a human kinetic study and consequences for migraine patients]

An open trial was carried out in eight healthy male and female volunteers to examine the bioavailability as well as the main kinetic parameters of Migr?nerton (metoclopramide and paracetamol; CAS 364-64-5 and CAS 103-90-2, resp). in comparison with reliable literature data. The results reported here clearly show that the absorption of both active ingredients from the fixed combination is complete and that therapeutically relevant plasma concentrations are achieved within 30 min. Bioavailability as well as tmax, t1/2, and time-lag are comparable with data resulting from reliable and internationally acknowledged kinetic studies. The fixed combination was shown to be kinetically compatible with regard to all parameters determined for metoclopramide and paracetamol.     

Beta-adrenergic blockade following thrombolytic therapy: Is it helpful or harmful?

Beta-adrenergic blockade has been a mainstay in the treatment of patients with acute myocardial infarction for nearly two decades. Clearly, it has withstood the test of time. The emergence of thrombolytic therapy, however, has shifted the medical community's focus, raising questions as to the benefit of beta-adrenergic blockade. Although further investigation is warranted, the available evidence suggests that beta blockers can be given safely to selected patients following coronary thrombolysis, particularly in the absence of moderate to severe left ventricular dysfunction.     

Mesenteriale Ischämie

In the past decade laparoscopic surgery replaced many open operations in general surgery. Apart from therapeutic uses in cholecystectomy, appendectomy, hernia surgery, gastric fundoplication, and increasingly also large intestine surgery, it is indicated diagnostically first of all for unclear abdominal findings and for staging of intra-abdominal malignancies. To date laparoscopy has been used occasionally for diagnosis and therapy of mesenteric ischemia. Patients suffering from mesenteric ischemia are usually old and have comorbid conditions. Quick diagnosis and therapy are necessary due to the pathogenesis of the disease. The low rate of morbidity as well as the easy availability of laparoscopy in principle favor the employment of laparoscopy also for mesenteric ischemia. Against the background of increasing experience in the area of laparoscopic surgery, this study gives an overview of the present value of laparoscopy for mesenteric ischemia.     

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.