Zinc and its specific transporters as potential targets in airway disease.

The dietary group IIb metal zinc (Zn) plays essential housekeeping roles in cellular metabolism and gene expression. It regulates a number of cellular processes including mitosis, apoptosis, secretion and signal transduction as well as critical events in physiological processes as diverse as insulin release, T cell cytokine production, wound healing, vision and neurotransmission. Critical to these processes are the mechanisms that regulate Zn homeostasis in cells and tissues. The proteins that control Zn uptake and compartmentalization are rapidly being identified and characterized. Recently, the first images of sub-cellular pools of Zn in airway epithelium have been obtained. This review discusses what we currently know about Zn in the airways, both in the normal and inflamed states, and then considers how we might target Zn metabolism by developing strategies to monitor and manipulate airway Zn levels in airway disease.

Taste in dementing diseases and parkinsonism.

Like with many sensory abilities a reduction of taste and smell occurs during aging. Since there are hints to an additional reduction in dementing diseases, we assessed 52 patients, 26 women and 26 men, who were presented to a memory clinic, using the Sniffin' Sticks, Whole Mouth and Taste Strip Tests. While smoking, alcohol consumption, intake of drugs and sex exerted only minor impact, age and the severity of cognitive impairment were of major importance. There was a moderate but significant correlation between the severity of dementia, taste and smell, even if the age effect was partialled out. Notably, patients with Parkinson syndrome showed worse taste and smell abilities than those without. Here the differences were indeed marked enough to play a possible role in making the diagnosis. This exploratory study confirms a mild reduction of gustatory function in dementing diseases over and beyond that of normal aging which--in addition to a reduction of smell--seems to be especially marked in Parkinson syndromes.

Apnea testing by artificial CO2 augmentation.

We used artificial augmentation of CO2 at a rate of 1 l/min after preoxygenation with 100% O2 to test for apnea in 34 patients with suspected brain death. Observation time was markedly reduced compared with conventional apneic oxygenation, allowing PaCO2 levels > or = 60 mm Hg to be reached within 2 minutes. Properly administered, CO2-supported apnea testing is quick, requires only simple technical equipment, and does not unduly lower PaO2 or pH. It seems to be a useful alternative in cases where reduction of ventilatory volume is not wanted.

Recognition of familiar handwriting in stroke and dementia.

Patients with left stroke (n = 17), right stroke (n = 16), and dementia (n = 17) and healthy controls (n = 15) were asked to recognize familiar handwriting among 10 handwritten texts. All healthy controls and 96% of the left-brain-damaged patients were able to recognize the familiar handwriting, but only 44% of the right-brain-damaged and 41% of the dementia patients (none if Mini-Mental Status Test score was <18, n = 5) were able to do so. The authors conclude that the recognition of handwriting is a special skill that is independent of other verbal and lexical tasks.

Chemosensory event-related potentials in response to trigeminal and olfactory stimulation in idiopathic Parkinson's disease.

Decrease of olfactory function in patients with Parkinson's disease (PD) has been reported by several authors. The current study investigated olfaction in PD patients using olfactory event-related potentials (OERPs) as an electrophysiologic correlate of olfactory function in combination with psychophysical testing. A specific focus was the influence of antiparkinsonian drugs. We investigated PD patients treated with antiparkinsonian drugs (n = 13) and PD patients who received no pharmacologic treatment (n = 18). They were compared to age- and sex-matched control subjects (n = 38). To obtain OERPs, stimulants were chosen to stimulate specifically the olfactory nerve (2.1 ppm vanillin, 0.8 ppm H2S). In addition, chemosomatosensory event-related potentials were recorded after trigeminal stimulation with 52% v/v CO2. Moreover, the subjects' ability to identify and to discriminate odorants was tested by means of a "squeeze bottle" technique. The study yielded the following major results: (1) Odor identification was impaired in PD patients. It was not influenced by treatment with antiparkinsonian drugs. (2) The OERP latencies were prolonged in both PD patients taking and not taking antiparkinsonian drugs; however, this effect was more pronounced in PD patients taking antiparkinsonian drugs. (3) The intranasal chemosensory trigeminal system seemingly was neither affected by the neuronal degeneration seen in PD nor by treatment with antiparkinsonian drugs.

Longitudinal study of neurotoxicity with occupational exposure to aluminum dust.

Two cross-sectional studies were conducted at a German aluminum (Al) powder plant to evaluate possible nervous system effects from occupational Al exposure. The investigation included biological monitoring, a neuropsychological test battery, and event-related P300 potentials. Neurophysiologic findings in workers chronically exposed to Al dust did not differ from non-Al-exposed controls from the same plant. The authors suggest that chronic exposure to Al dust, at the levels documented in this study, does not induce measurable cognitive decline.

Continuous figure recognition in dementia and unilateral cerebral damage.

By means of continuous figure recognition (CFR) using visual pictorial, geometric and nonsense material demented patients could easily be distinguished from vascular controls without dementia and healthy subjects. In cases of infarction in the territory of the middle cerebral artery the hemisphere affected was only a minor determinant of overall scores. Within aphasics there was a tendency for the CFR results to reflect the severity of aphasia being most severely impaired in global aphasics. When aphasics and other cerebrally impaired patients, judged clinically to suffer from memory impairment, were considered as a group, CFR performance was lower than in those without apparent memory problems for the pictures only. It is concluded that CFR is a sensitive indicator of defective memory and/or gross brain lesions and that it is relatively independent of linguistic mediation.

Blood pressure and heart rate changes during apnoea testing with or without CO2 insufflation.

OBJECTIVE: To determine changes of blood pressure and heart rate during apnoea testing for brain death without (A) and with (B) artificial CO2 augmentation. DESIGN: Prospective, consecutive study. SETTING: 12 intensive care units in six towns in Northern Bavaria. PATIENTS AND PARTICIPANTS: A total of 55 apnoea tests were performed on 55 consecutive patients as part of the determination of brain death, 27 without and 28 with CO2 augmentation. INTERVENTIONS: Apnoea tests following oxygenation with 100% O2 either after reduction of ventilatory volume (A) or after insufflation of CO2 during normoventilation (B). In each case, an arterial partial CO2 pressure of at least 8 kPa was documented. RESULTS: All apnoea tests were without serious adverse effects (hypoxia, newly induced cardiac arrhythmia, cardiac asystole). An increased dopamine infusion rate was deemed necessary in only one case of group (A) because of marked systolic hypotension (< 8 kPa). Individual variation of systolic and diastolic blood pressure (BP) did not exceed + 62 to -46% and + 49 to -52% respectively, in group (A) and + 35 to -57% and + 40 to -48% respectively, in group (B). Variation of heart rate (HR) remained within the range + 24 to -31% in group (A) and + 37 to -22% in group (B). CONCLUSIONS: HR varied less than BP. The possibility of a marked relative rise of fall of BP in group (A) was equal; in group (B) there was a lower change of rising BP. The chances for a rise or fall in HR were equal for the two groups. There was a tendency for less variation of cardiovascular parameters in group (B).

Creutzfeldt-Jakob disease via dural and corneal transplants.

A review of all published cases of iatrogenic Creutzfeldt-Jakob disease (CJD) via dural (N=71) and corneal (N=4) transplants is given. All but three of the dural cases were obviously due to a commercial product recalled in 1996. Two of the corneal grafts were taken from patients who had died of sporadic CJD. These cases differed from CJD due to human growth hormone injections and the new variant. Instead. they were akin to sporadic cases, but memory loss, disorders of higher cerebral functions and extrapyramidal signs were fewer, while cerebellar abnormalities were more frequent. Progressive dysarthria and gait disorder/gait ataxia were prominent signs during the early stages, myocloni the most salient feature later. A nonperiodic EEG did not contradict the diagnosis. Using current diagnostic criteria the disease was underdiagnosed ante mortem. Utmost care is needed in selecting, harvesting and handling dural and corneal grafts to avoid inadvertent transmission of CJD.

Visually guided exploration in Huntington disease.

We compared 24 patients in various stages of Huntington disease (HD) with 26 control patients free from cerebral disorders using a simple visual saccadic tracking test. The two groups were well matched in regard to age, sex, verbal IQ and years of schooling. Test results differed widely. On a time versus error plot, sensitivity (96%) and specificity (100%) were high and the results did not depend on age, education, or disease duration, although an influence of disease stage could be observed. This study shows that a simple saccadic tracking task may be useful in detecting visuomotor disturbances in HD.

The use of neuroimaging techniques for clinical detection of neurotoxicity: a review.

Although toxins exert their impact on a molecular level, they may yield molar effects by affecting areas large enough to be visualized by neuroimaging techniques. Therefore, neuroimaging of the brain may be used to render the macroscopic sequelae of neurotoxins visible. Toxic agents may induce brain edema or atrophy, demyelination, infarctions, calcifications, hemorrhages, or changes of perfusion, metabolism or receptor density. Although they do not readily disclose their nature, clues as to the offending agent may in some instances be gleaned from the pattern, distribution, and appearance of the cerebral changes. Intoxication, however, has always to be proved or substantiated independently by appropriate means. This paper deals with the extent and certainty to which conclusions as to some of the most common offending substances may be drawn from pictures of the brain.

Recall and recognition in Huntington's disease.

We assessed 19 patients with Huntington's disease (HD) at early to moderately advanced stages of their disease using memory tests that investigated verbal and visual recall and recognition. In those tests where identical material was subject to recall and recognition the standardized results (z scores) were lower for recognition. Performance was better with pictorial than with verbal material. While recognition bias and savings scores did not differ significantly from controls, all other recognition parameters did so. This is in contrast to the claim that defective retrieval in HD is greatly enhanced by multiple choice recognition. One major reason for maintaining this assumption was apparently the disregard of false-positive responses. Our results indicate that verbal and visual recognition are impaired in HD, and the notion of a salient deficit of free recall is not supported.

Palmar (displaced) fracture of the proximal index metacarpal.

A patient sustained a fracture of the ulnar side of the proximal end of the second metacarpal. The fragment was completely displaced into the palmar soft tissues. Open reduction was necessary.

Transcutaneous and intra-arterial blood gas monitoring--a comparison during apnoea testing for the determination of brain death.

Intra-arterial (i.a.) and transcutaneous (t.c.) blood gas monitoring were compared with in vitro blood gas analysis (abg) during apnoea testing for the determination of brain death in a prospective observational study. All three methods were used simultaneously in 19 patients in whom brain death was suspected. Brain death was confirmed in each case adhering to the recommendations of the Scientific Advisory Board of the German Federal Chamber of Physicians which demand a PCO2 of at least 60 mmHg. In vitro parameters ranged from 23.2 to 80.4 mmHg (PCO2), 52.7 to 509.9 mmHg (PO2), and 7.072 to 7.591 (pH). The intra-individual correlations between both monitoring methods (rPCO2=0.958, rPO2=0.859) and between each of them and abg (r>0.960) were high. Absolute deviations from abg for the corrected as well as uncorrected measurements were similar for both methods, except with regard to group bias where an advantage for the i.a. values emerged. Since many of the i.a. measurements failed and the disposable i.a. probes cost much more than the t.c. electrodes, the i.a. technique at present holds no advantage over t.c. measurements in testing for apnoea in suspected brain death except where simultaneous monitoring of pH and temperature are desired.

[Cerebrovascular circulation from a clinical view. Historical review, physiology, pathophysiology, diagnostic and therapeutic aspects]. / Die Hirndurchblutung aus klinischer Sicht. Historischer Uberblick, Physiologie, Pathophysiologie, diagnostische und therapeutische Aspekte.

Strokes have been known since ancient times. Today, stroke is the second most frequent cause of death and the most frequent cause of invalidity. In about 80% of cases, stroke is caused by cerebral ischemia and in about 20% by intracerebral hemorrhage, subarachnoidal hemorrhage, venous thrombosis and other cerebrovascular diseases. The brain is one of the most richly perfused tissues and depends fundamentally on the supply of oxygen and glucose. In order to assure adequate cerebral blood flow, the brain is capable of autoregulation through the interaction of diverse autoregulatory mechanisms (myogenic, neurogenic and metabolic factors, blood viscosity, renin-angiotensin-system and endothelium). Reduction of cerebral blood flow below the threshold of about 25 ml/100 g x min leads to an impairment of the functional metabolism and later to impairment of the structural metabolism. Pathophysiologically, a large number of isolated pathobiochemical processes (loss of energy, lactate acidosis, excitating amino acid release, ion balance disorders, calcium overload, free radical release, etc.) start to interfere with each other. Delayed edema and inflammation lead to secondary brain damage. Apoptosis is probably induced by ischemia and can cause secondary deterioration. The basic principles in the treatment of ischemia are firstly the rapid restoration of cerebral blood flow (lysis, carotid endarterectomy) and secondly--following infarction--a limitation of brain damage (preservation of ischemic but not necrotic brain tissue, prevention of secondary complications). Stroke treatment requires profound diagnostic and therapeutic expertise and interdisciplinary cooperation of neuroradiologists, neurosurgeons, vascular surgeons and cardiologists. Stroke can best be managed in special "stroke units", which have now been established in nearly all parts of Germany. Beside acute management of stroke and neurological rehabilitative treatment, emphasis has to be laid on primary (public information, education, treatment of risk factors) and secondary prophylaxis (treatment with antiaggregants, anticoagulants, a. o.).

[Why patients with simple cervical vertebral sprains may develop persistent neurological symptoms]. / Warum Patienten mit einfacher Halswirbelsäulendistorsion persistierende Beschwerden auf neurologischem Gebiet entwickeln können.

Possible causative mechanisms and sequelae of neck strain, the so-called whiplash injury, are reviewed critically and evaluated regarding their influence on the persistence of symptoms in the neurological field. In the light of contemporary knowledge monistic or dualistic models have proven inefficient to come up for the multifaceted aspects of this complex problem. We propose a multidimensional biopsychosocial model whose impact on an adequate understanding as well as a better and more efficient therapy of these patients is elaborated.