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Biomedical subjects

L Hein

Publications and source records attributed to L Hein.

At least 73 records · Page 4Linked to original sources

Perpetuation of misinterpretations due to lack of methodical insight. A critical re-evaluation of the determination of 45Ca release from intact guinea-pig atria.

1. The evaluation of still more pretentious and complicated methods is accompanied by a decline of methodical knowledge outside of the own technical field. Interpretations or extrapolations are taken as granted without critical examination of the methodical steps applied. An example is given by re-evaluating the 45Ca release from isolated cardiac tissue and the possible interpretations. 2. 45Ca release and tissue Ca content were measured in isolated guinea-pig left atria during Ca equilibrium and under conditions known to induce net Ca movements. 3. At equilibrium condition (1.8 mM Na2+0) 3 exponential phase of 45Ca release from the atria were observed. The compartments contained 61%, 29% and 10% of total 45Ca; the t1/2 were 2, 12 and 90 min, respectively. 4. The release of 45Ca from the slowly exchanging compartment (t1/2 90 min) decreased during incubation in nominal Ca-free solution, although a net loss of tissue Ca occurred. Addition of EGTA (5 x 10(-5) M) to the washout medium abolished this retardation of 45Ca release. 5. At external Na+ concentrations below 40 mM (substituted by sucrose), the 45Ca release from the slowly exchanging compartment decreased. Simultaneously, the tissue Ca content increased massively. The 45Ca release was further reduced in Na-poor, nominal Ca-free solution. Under both conditions, the presence of EGTA in the washout medium normalized the rate of 45Ca release. 6. The results suggest that the apparent decline of 45Ca release from intact atria upon reduction of the external Ca and Na concentration does not reflect a decrease of the cellular efflux rate, but is the consequence of an enhanced re-uptake of 45Ca from the extracellular space into the myocardial cells. The probability for the released 45Ca either to escape into the organ bath or to become reabsorbed depends on the specific radioactivity of 45Ca in the extracellular space during the washout phase. Thus, this experimental procedure is not suited to demonstrate a Na-Ca exchange at the cardiac sarcolemma.

Animals↗

Suppression of cellular immune activity following severe head injury.

Infection is a major cause of morbidity following multiple traumatic and head injury. Although immunosuppression has been demonstrated after multiple traumatic injury, the effects of head injury on immune function have not been thoroughly investigated. In a prospective study of 10 severely head-injured patients, in vitro and in vivo parameters of cellular immune activity were assessed. In vitro measurements of lymphocyte surface antigen expression following mitogen stimulation were made serially over a 3-week period in 10 patients with severe head injury. The control group consisted of 20 healthy subjects. Phenotyping of peripheral blood lymphocytes (PBLs) was performed following incubation with and without mitogens. Phenotypes were determined by flow cytometry using monoclonal antibodies (MABs) to T lymphocyte subsets and the alpha subunit of interleukin 2 (IL-2) receptors. In vivo cellular immune function was determined by measuring patient responses to delayed-type hypersensitivity (DTH) skin testing within 24 h of injury. When head-injured patients were compared to controls, PBLs incubated in the presence of phytohemagglutinin (PHA) demonstrated a decrease in cells marking as T cells (p = 0.005), helper-inducer T cells (p = 0.001), and in the number of IL-2 receptor-bearing cells (p = 0.001). The functional ability of these lymphocyte subpopulations to proliferate in the presence of PHA was significantly suppressed within 24 h of injury and normalized within 3 weeks of injury. DTH skin testing to Candida, mumps, trichophyton, and PPD antigens was performed within 24 h of injury and resulted in anergic responses in all 10 patients when measured at 24, 48, and 72 h following administration. The overall infection rate was 60%, with the majority of infections occurring within the first 4 days following injury. The results of this study indicate that severe head injury results in suppression of cellular immune function with a corresponding high rate of infection. The possible significance of the decrease in the percentage of helper-inducer T cells and in the number of cells bearing IL-2 receptors following mitogen stimulation is discussed.

Adolescent↗

Human accumulation potential of xenobiotics: potential of catamphiphilic drugs to promote their accumulation via inducing lipidosis or mucopolysaccharidosis.

1. Drug accumulation without a concomitant elevation of blood level may occur if the capacity of the tissue to bind drug increases during chronic treatment. 2. This special type of accumulation is found with cationic-amphiphilic drugs, which induce the formation of lysosomal inclusion bodies containing undergraded lipids or mucopolysaccharides (drug-induced lipidosis or mucopolysaccharidosis, respectively); the stored material provides the additional binding sites for the drug. 3. Factors determining the potential for inducing lipidosis or mucopolysaccharidosis are: (a) affinity of the drugs to phospholipid layers (governed by hydrophobicity) or mucopolysaccharides (drug-induced lipidosis or mucopolysaccharidosis, respectively); the free intra-lysosomal concentration, which is elevated compared with the blood level due to lysosomal trapping (especially with dicationic drugs); (c) the therapeutically required drug concentration in the blood: the therapeutic concentrations are high with drugs that do not act via binding to specific high-affinity receptors.

Glycosaminoglycans↗

The use of magnetic resonance imaging to assess slow fluid flow in a model cerebrospinal fluid shunt system.

Cerebrospinal fluid (CSF) shunt malfunction in patients with hydrocephalus is common and can result in prolonged hospitalisation, operative exploration or progressive neurologic damage. The evaluation of shunt function usually requires invasive techniques that can be inaccurate or cause complications. Magnetic Resonance Imaging (MRI), which has been used to study both intraluminal blood flow and intraventricular CSF flow, may offer an alternative noninvasive test of shunt function. The MR characteristics of flow related enhancement were studied in a model shunt system. A special section of tubing for MRI was inserted into the system proximal to the valve. Flow through the system could be varied from 0 to 20 ml/h. Multiple spin echo images were made (TR2000, TE20) transverse to the specialised tubing. The intensity of the intraluminal MR signal at specific locations along this tubing and from a 'no flow' standard were measured. The signal intensity varied as a linear function of flow rate from 2.5 ml/h to 20 ml/h. These results suggest that MRI has potential for evaluating the slow flow in CSF shunts.

Cerebrospinal Fluid Shunts↗

Mucopolysaccharidosis and lipidosis in rats treated with tilorone analogues.

The experimental immunomodulatory agent tilorone was previously reported to induce generalized mucopolysaccharidosis (lysosomal storage of sulfated glycosaminoglycans) and lipidosis in rats. While lipidosis is a side effect common to many cationic amphiphilic compounds, none of them except tilorone has been known to cause mucopolysaccharidosis in intact animals. The purpose of the present histochemical and ultrastructural study was to examine whether or not mucopolysaccharidosis can be induced by tilorone analogues. Three analogues were selected and administered to rats in short-term and subchronic experiments, and liver, spleen, kidney, and cornea were examined. The analogues caused generalized cellular lesions which had the same histochemical and cytological characteristics and the same distribution as the lesions produced by tilorone. The results show that the ability to induce mucopolysaccharidosis is not a unique property of tilorone; this drug side effect should be taken into account when developing new drugs with molecular structures resembling that of tilorone.

Animals↗

A modification of the Brown-Roberts-Wells stereotactic frame for implantation of ventricular access reservoirs.

A ventricular catheter and connected subcutaneous reservoir (ventricular access reservoir) allows easy, repeated access to the cerebrospinal fluid for a multitude of purposes. In situations in which the ventricles are small or displaced, insertion of a ventricular catheter may be difficult. Multiple passes to cannulate the ventricle may damage the brain and manipulation of the catheter and reservoir may cause migration of the catheter, possibly compromising its function. A stereotactic method for insertion of ventricular access reservoirs using a device that attaches to the Brown-Roberts-Wells stereotactic system has been developed. With this device the catheter and reservoir are guided into place as a single unit, utilizing a guide attached to the Brown-Roberts-Wells frame. This technique has been useful in inserting ventricular access reservoirs into patients with small ventricles or in whom there is some abnormality of the brain or skull that renders classical landmarks for ventricular cannulation useless.

Catheterization↗

Evaluation of recombinant tissue plasminogen activator in embolic stroke.

In an effort to determine the value of tissue-type plasminogen activator (TPA) in the treatment of embolic stroke, 17 rabbits were subjected to a model of embolic stroke in which 2-hour-old, tin-impregnated, autologous clots were embolized to the bifurcation of the internal carotid artery at the circle of Willis via retrograde injection into the cannulated external carotid artery. High-resolution digital subtraction radiography was used to localize clots intracranially at the carotid bifurcation. Circulation through the internal carotid artery and intracranial vessels was monitored with serial digital subtraction angiography before and after embolization and during treatment. Disappearance of the tin marker on the digital subtraction radiograph indicated dissolution of clot and was associated with reestablishment of circulation on the digital subtraction angiogram. Experimental animals were treated with human-specific recombinant TPA 30 minutes, 2 hours, or 4 hours after clot embolization. TPA was administered as an intravenous bolus of 0.5 mg/kg followed by an infusion of 1 mg/kg/h for 2 hours. Digital subtraction angiograms were performed every 30 minutes. All clots dissolved, and cerebral circulation was reestablished within 120 minutes of treatment. In control animals treated with saline, embolized clots were stable, and the internal carotid artery remained occluded. At the completion of each study, the animal was perfused with freshly prepared, buffered 2,3,5-triphenyltetrazolium chloride (TTC) for demarcation of cerebral infarction. Control animals demonstrated infarction of 50 +/- 3.6% of the ipsilateral cerebral hemisphere, with an infarct weight of 2.1 +/- 0.2 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Solubilization and partial characterization of phospholipase A from rat heart sarcoplasmic reticulum.

Phospholipase A has been solubilized from the sarcoplasmic reticulum of rat heart by treatment with Tris buffer, potassium chloride, taurodeoxycholate or octyl glucoside. On HPLC gel permeation, two phospholipases were identified at the void volume of a TSK 3000 column and at an apparent molecular mass of 60 kDa. The two activity peaks exhibited a predominance of phospholipase A1 activity (83-91%) and a lesser phospholipase C activity (4-9%) using sonicated 1-palmitoyl-2[1-14C]oleoylphosphatidylcholine liposomes as substrate. The voiding phospholipase A peak, which represented the bulk of the recovered activity, exhibited a requirement for calcium ions in the 0.3-3 microM range. The heat stability and response to mercuric ions was studied and some similarities were noted between the solubilized sarcoplasmic reticulum phospholipases A and the cytosolic phospholipases A of rat heart. It is speculated that the cytosolic phospholipase A which we reported earlier may represent in part phospholipase A released from sarcoplasmic reticulum during isolation of the subcellular membrane fractions.

Animals↗

[Physical treatment of herpetic diseases. Report of a pilot study with low-frequency electrotherapy].

Standard methods employed in physiotherapy are seldom applied to florid herpes zoster since they bring little benefit. Initial experience with electrotherapy for herpes is reported. Pulsed galvanic current at a frequency of 30 hertz was applied to the region of the affected segmental nerve. In two centres (Vienna and Maribor) treatment was carried out on 32 patients with herpes zoster (recovery in Vienna after a mean duration of treatment of 6.3 days; in Maribor recovery after 20 days of treatment) and 18 patients with herpes simplex (recovery after 5 or 6.5 days respectively) were treated. Follow up of all patients treated in Vienna showed that only one patient out of the zoster group developed post-herpetic neuralgia. Three patients with herpes simplex had a relapse of the disease, but it was less severe than before treatment. The better results in Vienna were explained by the use of strictly monopolar wave forms and the fact that treatment was applied every day, while in Maribor patients received no treatment over a weekend.

Electric Stimulation Therapy↗

Videodensitometric estimation of the protective effect of hyperbaric oxygen in the ischemic gerbil brain.

To verify its protective effect on the ischemic mammalian brain, hyperbaric oxygen was administered to six groups of carotid-ligated gerbils. The outcome was evaluated clinically and by a colorimetric videodensitometry technique by comparing differences in the interhemispheric color density through the translucent intact cranium. It was found that there was a graded decrease in interhemispheric differences with increasing exposure to hyperbaric oxygen (the appearance of the ischemic hemisphere increasingly approached that of normal brain). This correlated with the incidence of ischemia in each group.

Animals↗

Life events and prisoners.

This study explores retrospectively the relationship of the accumulation of life events as it relates to prison incarceration and extends further the concept that coping with increasing environmental changes results in a variety of overt behaviors. The prison sample comprised 176 male inmates of a federal prison (McNeil Island, Washington) and a state penitentiary (Walla Walla, Washington). Life change scores were derived from the Schedule of Recent Experience (SRE). There was an escalation of annual life change scores of prisoners, indicating the mounting frequency of occurrence of life events prior to incarceration. The SRE may have value in the prediction of socially deviant behavior as with health changes. Variables seen as influencing life change scores were race, age, and education. Analyses of life event frequencies as compared to a normative group indicated that prisoners have evolved a coping life-style that reflects antisocial and criminal behavior.

Adult↗

2',3'=Carbonates in the synthesis of uridine 5'-deoxy and 2',5'-dideoxy derivatives.

Detritylation of 2',3'-O-carbonyl-5'-O-trityluridine (Ia) with ethereal hydrogen chloride affords 2',3'-O-carbonyluridine (Ib; 83%) which is converted by mesylation to the 5'-mesylcarbonate Ic (75%). Reaction of compound, Ic with tetrabutylammonium bromide in DMF affords the 5'-bromo carbonate Id (77%) which is reduced with tributyltin hydride to the 5'-deoxyuridine 2',3'-cyclic carbonate Ie (70%). When heated with imidazole, compound Ie affords the 2,2'-anhydro derivative IIa (76%) which is converted to the 2'-chloro derivative IIIa (88%) on heating with HC1/DMF. The tributyltin hydride reduction of compound IIIa gives 2',5'-dideoxyuridine (IIIb; 68%). When heated with NaHCO3 in DMF, the 5'-bromo carbonate Id affords the anhydro bromo derivative IIb (50%) which is converted to the 2',5'-dichloro derivative IIIc (86%) on heating with HC1/DMF. The tributyltin hydride reduction of compound IIIc affords the 2',5'-dideoxy derivative IIIb (59%). Alkaline hydrolysis of the 2,2'-anhydro derivative IIa affords the arabinosyl derivative IVa which is converted to the diacetyl derivative IVb (34%) by acetylation. When refluxed in water, the 2',3'-cyclic carbonates Ib, Id, and Ie are hydrolysed to the parent nucleosides, namely, uridine (Va; 81%), 5'-bromo-5'-deoxyuridine (Vb; 78%), and 5'-deoxyuridine (Vc; 83%). Hydrolysis of carbonates Ib and Ie is accompanied by the formation of the 2,2'-anhydro derivatives IIc (10%) and IIa (5%) as by-products.

Carbonates↗

Synthesis of substituted 5-fluoro-5,6-dihydropyrimidines.

The reaction of 5-substituted uracils with fluorine in acetic acid and other solvents and the following treatment with different alcohols yielded the corresponding 5-fluoro-5,6-substituted-5,6-dihydropyrimidines. Thymine gave 5-fluoro-5-methyl-6-alkoxy-5,6-dihydropyrimidines. 5-Halogeno uracils and 5-nitrol uracil were converted into 5-fluoro-5-halogeno-6-hydroxy-5,6-dihydropyramidines and the 5-nitroanalogue, respectively. The structures of the compounds were confirmed by mass spectrometry.

Fluorine↗

Teleform: a blessing or burden?

Burgeoning technology has created numerous alternatives for even the most mundane aspect of research, that is, data entry. Our research team is conducting a large NIH NINR clinical trial, and data entry and management are important aspects of this study. Our research team needed to decide whether to use manual data entry or a scannable form of data entry. This article describes some of the advantages and disadvantages related to our decision to use scannable data entry Teleformtrade mark.

Clinical Trials as Topic↗