Postmortem changes in ear canal resonance and tympanic membrane impedance in the human ear

BACKGROUND: The human temporal bone preparation is a common model for research of physical processes of the ear canal and middle ear. In the past decade only a few reports were published discussing changes of the vibration behaviour of the tympanic membrane, as well as the ear canal resonance, during the time between death and preparation of the temporal bone. The aim of our study is to verify whether measurements at the temporal bone of dead humans can be really applied to the in vivo situation. METHODS: We investigated whether changes of the ear canal resonance and the vibration of the tympanic membrane depend on temperature and time after death. In a female human body we defined the resonance of the outer ear and the impedance of the tympanic membrane using a tympanometer and a real ear measurement system during nine hours post mortem. RESULTS: We were able to prove that before the preparation of the temporal bone none of the parameters changed significantly. CONCLUSIONS: In conclusion, the method of preserving the bone after its preparation is decisive for the validity of measurements at the isolated (post mortem) human temporal bone.     

Postmortem studies in schizophrenia

The past decade has seen renewed interest in the neuropathology of schizophrenia. The advent of new postmortem techniques and functional imaging, along with a greater understanding of the neuropsychology of schizophrenia, have provided many new clues to the nature of the underlying brain dysfunction in this disorder. There has also been a greater understanding of the presence of severe cognitive dysfunction among many elderly persons with schizophrenia. In this article, a series of investigations are described that seek to answer basic questions about the neuropathology of schizophrenia, in particular as it pertains to cognitive impairment. The first study describes neuropathological findings in 100 consecutively autopsied persons with schizophrenia, the majority of whom had had detailed antemortem assessments. Results from this first study prompted the conclusion that schizophrenia is not characterized by classical, histologically identifiable neuropathology. Moreover, most cases of dementia in schizophrenia are probably not the result of neuropathologically identifiable dementing illnesses. The next four studies examined chemical markers that are altered in Alzheimer's disease and some other dementing conditions and have also been suggested to be abnormal in schizophrenia: choline acetyltransferase, catecholamines and indolamines, neuropeptides, and synaptic proteins. Schizophrenia cases as a group did not show a cholinergic deficit; nor did they differ from elderly comparison cases with respect to cortical catecholamines and indolamines. Among the schizophrenia cases, however, cognitive impairment was negatively correlated with choline acetyltransferase activity. Those with cognitive impairment showed evidence of cortical noradrenergic and serotonergic deficits. Neuropeptide deficits were also present in schizophrenia, but their pattern differed from that seen in Alzheimer's disease. Increased synaptic protein activity was found in the cingulate cortex of persons with schizophrenia, and this activity was correlated with schizophrenia symptoms. From this second series of studies, it was concluded that some biological measures in schizophrenia may be related to cognitive impairment (e.g., cortical amines), whereas others may be related to diagnosis (e.g., neuropeptide deficits). In addition, synaptic organization may correlate with schizophrenia symptoms.     

HBs antigen and blood glucose concentration

HBsAg presence was studied by counterelectrophoresis (CEP) in 76 patients with liver cirrhosis and in 431 patients with diabetes mellitus. A striking correlation was found between high blood glucose values and HBsAg absence. Thus, HBsAg-negative cirrhotics (53%) had significantly higher levels of glycemia than the HBsAg-positive patients of the same age group, i.e. 95.75 +/- 6.36 ng/100 ml compared to 78.30 +/- 10.2/100 ml. This absence of HBsAg was also observed in all diabetics but one. As the incidence of HBsAg (CEP) was found to be of 3.63% in 253,460 subjects from different areas of Romania and 6.84% in 14,690 subjects with various non-hepatic diseases included, the chance of finding the 0.2% HBsAg incidence observed in the diabetics would be less than 0.0002 and 0.0001, respectively. The serum HBsAg absence in cirrhotics with high glycemia and in diabetics strongly incriminates the constant high concentrations of blood glucose as the main factor responsible for this negativity. The effect may be direct on virus replication, or indirect, by metabolically-induced hepatic dysfunction interfering with HBsAg secretion or excretion. The presence of high concentrations of glucose in cell culture media might explain the repeated failure of hepatitis B virus serial passage in tissue or organ culture.     

The acute effects of amitriptyline, iprindole and trazodone on blood pressure and heart rate in rats

The cardiovascular effects of the tricyclic anti-depressant amitriptyline, a monoamine uptake inhibitor, and iprindole and trazodone, two novel anti-depressants of unknown mechanism, were monitored in urethane anesthetized rats following intravenous (IV) or intracerebroventricular (IVT) injection. Amitriptyline (2 mg IV or 0.25 mg IVT) produced hypotension that might reflect an action of norepinephrine on the anterior hypothalamus. Iprindole (2 mg IV) produced hypertension and (0.25 mg IVT) tachycardia that is consistent with a partial beta-agonist mechanism. Trazodone (1 mg IV or 0.25 mg IVT) produced hypotension and bradycardia that is consistent with the activation of noradrenergic neurons in the anterior hypothalamus perhaps as a result of trazodone acting on presynaptic alpha 2 receptors or on presynaptic serotonin receptors to increase the release of norepinephrine. All three of these anti-depressants have the potential to precipitate cardiovascular complications, particularly in patients with pre-existing cardiovascular abnormalities.     

CNS regulation of blood lactate concentration in anesthetized rats

This study evaluated the effect of stimulating the central nervous system (CNS) with neostigmine, an inhibitor of acetylcholinesterase, on the blood lactate concentration in fed rats and in rats fasted for 48 hours. After the rat was anesthetized with pentobarbital, neostigmine was stereotaxically injected into the third cerebral ventricle. In fed rats, the central injection of neostigmine significantly increased the blood lactate level, while concomitantly increasing plasma glucagon, epinephrine and norepinephrine concentrations. Constant infusion of somatostatin throughout the experiments, to inhibit glucagon secretion from the pancreas, did not affect alterations in blood lactate by central injection of neostigmine. In adreno-medullated rats, CNS-stimulation by neostigmine still increased plasma norepinephrine significantly, however, the alteration in blood lactate was only one-third of that in intact rats. Intraperitoneal propranolol, but not phentolamine, prevented the rise in lactate. Neostigmine increased lactate in fasted rats as well as in fed rats. We conclude that in anesthetized rats, stimulation of the CNS by neostigmine increases blood lactate mainly through circulating epinephrine and partially through circulating norepinephrine or direct sympathetic nervous stimulation; glucagon does not appear to be involved in the increase in blood lactate.     

Safe levels of hemoglobin concentration in autologous blood transfusion

It has been generally accepted that an adequate oxygen-carrying capacity can be achieved with a hemoglobin concentration of 7 g/dl, as far as the patient's intravascular volume is sufficient to allow tissue perfusion. To guarantee patient's safety in the operating theater, patient's oxygenation, ventilation, circulation and temperature, which enable oxygen utilization in tissues, should be monitored vigilantly and ensured strictly. This is also true when taking care of anemic patients outside the operating theater, because failure of these functions in anemic patients leads directly to tissue hypoxia. Besides the standard monitoring, measuring oxygen carrying capacity/consumption parameters and gastric/sigmoidal intramucosal pH have been shown to be helpful to estimate tissue oxygenation. Therefore, safe levels of hemoglobin concentration should be determined according to the ability of doctors and nursing staffs to evaluate and to maintain patient's systemic and tissue oxygenation as well as to the patient's pathophysiological conditions.     

Cerebral blood flow changes in cluster headache

Serial cerebral blood flow studies performed by the intra-carotid 133Xenon method were fortuitously determined during the course of a cluster headache in a 32 year old man. The initial study was performed about 10 min after the headache began and showed values at the upper limit of normal. Twenty min after the headache started a second procedure showed that the autoregulatory response on hyperventilation was normal. Ergotamine tartrate was given intra-muscularly 23 min after the headache began and there was partial relief. A third cerebral blood flow estimation showed abnormally high values. The probable reasons for this are discussed.     

Postmortem diagnosis of leukodystrophies

Leukodystrophies are progressive disorders involving the development and maintenance of myelin in the central and peripheral nervous systems. Although relatively uncommon, leukodystrophic disorders may be undiagnosed or misdiagnosed during life, and may appear as "sudden death." In such instances, these victims may be referred to a forensic pathologist. In general, leukodystrophies are inherited in an autosomal recessive manner so that proper postmortem diagnosis by the forensic pathologist is extremely important to the decendant's family for future family planning.     

Postprandial blood pressure changes in the elderly

Postprandial blood pressure reductions have been observed in frail elderly individuals. This study evaluated blood pressure and heart rate changes in 10 healthy elderly subjects at intervals before and after a morning meal. Subjects did not exhibit significant reductions in systolic blood pressure or increases in heart rate over time, rather, such changes were due to variation within subjects. They did not exhibit significant changes in diastolic blood pressure. Age, health, and meal choice may have influenced results. Further research will determine which groups of elderly are most at risk for postprandial blood pressure reductions and consequently at risk for injury from falls due to dizziness and syncope.     

Age-related ocular blood flow changes

PURPOSE: Pulsatile ocular blood flow (POBF is influenced by well-known parameters, such as intraocular pressure (IOP), heart rate, scleral rigidity, blood pressure, and posture. Age is also likely to influence POBF strongly. The purpose of this study was to evaluate POBF in relation to age in normal subjects. METHODS: Relevant data were collected from a sample of 105 normal subjects, ranging in age from 10 to 80 years. To measure the effect of age on POBF, the subjects were divided into seven groups of 15 subjects each; the age range of each group spanned one decade, beginning with age 10. POBF and pulse amplitude (PA) were measured in sitting and supine positions and after suction cup application. RESULTS: Using linear regression analysis, there was a significant correlation between PA and age in the supine position (P = 0.012) and after suction cup application (P = 0.002); in the sitting position, there was a borderline level of statistical significance (P = 0.053). In the sitting position, POBF was 819 +/- 212 microliters/minute in the second decade and 630 +/- 194 microliters/minute in the eighth decade. In the sitting position and after suction cup application, but not in the supine position, a statistically significant correlation between POBF decrease and age was found with linear regression analysis (P < 0.001 and P = 0.004, respectively). Using multiple regression analysis, POBF values revealed a significant correlation with age (P < 0.001), but not with systolic and diastolic brachial pressure. Considering all the subjects, analysis of variance for repeated measures highlighted a significant decrease of POBF from the sitting to the supine position and associated with an IOP increase (P < 0.001) without significant changes of PA. After suction cup application, there was a significant reduction of both PA and POBF (P < 0.001). CONCLUSIONS: The data revealed that as age increased, PA decreased in all three series of measurements. POBF decreased with age, and in subjects older than 50 years, the decrease was more evident. These findings are especially noticeable after IOP increase with suction cup. It must be considered that the age-related value of POBF is a fundamental parameter to evaluate correctly the hemodynamic aspects of the pathologies affecting the eye.     

Cardiovascular effects of amitriptyline in anaesthetized dogs

1. The effect of amitriptyline on cardiovascular variables has been studied in anaesthetized dogs. 2. In small doses (0.25 mg/dg) amitryptyline caused small increases in heart rates, contractility, blood pressure, coronary blood flow and aortic flow. 3. Large doses produced initial depressant effects on myocardial reflex rises in these and rate and blood pressure, which were followed by secondary reflex rises in these measurements. 4. The depressant effects were dose-related and were accompanied by marked increases in coronary flow and smaller increases in ortic flow. 5. The secondary reflex rises in cardiac parameters were abolished by propranolol and that of the blood pressure was much reduced.     

Pharmacokinetics of amitriptyline infused intravenously in man

Amitriptyline was given to four male volunteers by constant rate intravenous infusion. Blood samples were collected before, during and at various times after the infusion for estimation of the serum concentrations of amitriptyline. The level of nortriptyline never reached a detectable level. A two compartment open model was shown to be applicable to the data obtained. The meaning of the parameters obtained by a non-linear, least squares curve fitting procedure is discussed and the values are compared to those recently published for nortriptyline. The calculated biological half-life of amitriptyline was about 17 hours, a figure which differs considerably from previously calculated values for volunteers, but is in accordance with some newer results from patients.     

Electrocardiographic findings in patients undergoing amitriptyline treatment

Fifteen depressed patients were treated with amitriptyline in a dosage ranging from 75 mg to 200 mg/day for a minimum of three weeks, two of which were at a fixed dosage. Plasma samples were drawn 12 to 16 hours after the bedtime dose of medication for determination of amitriptyline and its metabolite nortriptyline. Electrocardiograms were taken prior to treatment and after three weeks of drug treatment. The only abnormality noted prior to treatment was bradycardia in one patient. After treatment, two patients exhibited nonspecific T-wave abnormalities. Otherwise, the electrocardiograms were unremarkable. A significant increase in heart rate (p less than 0.001) was noted. The mean increase in rate was sixteen beats per minute. Those patients having a rate change greater than sixteen beats per minute had significantly higher amitriptyline levels (p less than 0.05), and total tricyclic antidepressant levels (p less than 0.05), than those patients having a mean rate increase less than sixteen. While tricyclic antidepressants can produce multiple cardiac effects, the risk of cardiac morbidity and mortality is relatively low in patients undergoing tricyclic antidepressant treatment with moderate dosages.     

Age-related changes in brain T1 are correlated with iron concentration

Age-related changes in brain T1 from 115 healthy subjects (range, 4.5-71.9 yr) were analyzed in relation to published regional brain iron concentration in cortex, caudate, putamen, and frontal white matter. The relaxation rate in these structures was linear with respect to iron concentration (P < 0.001). The iron relaxivity, k1 (s(-1)/mg iron/g wet weight), was much higher in cortex (5.5) and white matter (6.1) than in caudate (1.7) and putamen (1.0). These results are consistent with evidence that iron is an important factor in determining the relaxation properties of brain tissue. Iron relaxivity may reflect regional differences in the physical state of brain iron or in the interaction of brain iron with tissue water.     

Early changes in iris blood vessels in exfoliation syndrome

PURPOSE: To look for possible changes in iris blood vessels that might precede the formation of true exfoliation material, and to correlate these changes, if present, to aging of the iris. METHODS: Iris blood vessels of 10 clinically normal irises from 10 eyes (ages: 1 day-80 years), 4 irises with exfoliation (ages: 64-80 years) and 3 irises from primary open-angle glaucoma (POAG) (ages: 27-65 years) were examined with an electron microscope. RESULTS: Pronounced multilayering of the basal lamina around the vessels, abnormal excessive formation of microfibrils, presence of atrophic invaginations in the outer cell membranes of endothelial cells containing interlacing basal lamina, and an apparent decrease in the perivascular collagen fibers were evident in exfoliative iris vessels devoid of true exfoliation material. Similar, but much milder, changes were evident in normal aged and POAG irises. CONCLUSIONS: Abnormal elastic tissue and/or basal lamina production plays a role early in the formation of exfoliation material around iris blood vessels.     

Nonmonotonous changes in erythrocyte sedimentation rate in whole blood

Scaphoid nonunion with avascular necrosis of the proximal pole remains a difficult problem. We have endeavoured to heal the fracture, restore scaphoid height and revascularize the proximal pole of the scaphoid by means of a vascularized dorsal interposition graft from the distal radius. The procedure has resulted in union of six of ten fractures. Fractures that healed had not been treated by a previous bone grafting procedure. Dissatisfaction was due to loss of motion in patients who had healed fractures, and pain in those patients with persistent non-unions.     

A physiologic assessment of intrathecal amitriptyline in sheep

BACKGROUND: Intrathecal injection of amitriptyline enhances antinociception from intravenous morphine and reduces neuropathic pain behavior in animals. This study represents part of a preclinical assessment of intrathecal amitriptyline to determine its safety for use in humans. METHODS: Low thoracic intrathecal, femoral, and pulmonary arterial catheters were inserted in 18 adult ewes, followed 96 h later by intrathecal injection of saline or 5 mg amitriptyline and by determination of spinal cord blood flow, hemodynamic variables, behavioral changes, cerebrospinal fluid concentrations of catecholamines and amitriptyline, and spinal tissue concentrations of amitriptyline. In six other ewes, low thoracic intrathecal and femoral arterial catheters were inserted and blood pressure and heart rate were measured after intrathecal injection of saline or 0.25, 1, or 5 mg amitriptyline. Four other ewes received cervical intrathecal injection of 5 and 10 mg amitriptyline, and antinociception was determined. RESULTS: Thoracic intrathecal injection of amitriptyline produced dose-dependent sedation but did not significantly affect spinal cord blood flow or hemodynamic variables. Spinal cord tissue concentrations of amitriptyline were 100 times greater in tissue near the tip of the thoracic intrathecal catheter compared with cervical cord tissue. Cerebrospinal fluid concentrations of catecholamines did not significantly change after amitriptyline was administered. Cervical intrathecal injection of 5 mg amitriptyline produced mild antinociception, whereas 10 mg produced intense sedation and, in one sheep, seizures and death. CONCLUSIONS: Although other preclinical toxicity studies are necessary before introducing intrathecal amitriptyline for use in humans, this study did not reveal dangerous changes in blood pressure or spinal cord blood flow from this agent.