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Biomedical subjects

H Stephensen

Publications and source records attributed to H Stephensen.

At least 19 recordsLinked to original sources

Objective B wave analysis in 55 patients with non-communicating and communicating hydrocephalus.

BACKGROUND: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH). OBJECT: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves. METHODS: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs. RESULTS: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients. CONCLUSIONS: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

Adult↗

Mental development after modified pi procedure: dynamic cranioplasty for sagittal synostosis.

A prospective developmental assessment was performed on 26 patients operated on with dynamic cranioplasty for sagittal synostosis. Because this technique entails the application of compressive force, it was of great concern to assess the effect of surgery on development and mental status. The surgical technique used was a modified pi procedure. Perioperative variables were recorded. Six patients underwent preoperative intracranial pressure (ICP) measurements. To evaluate objectively the developmental outcome, the Griffiths' Mental Development Scales was used for analysis before and after surgery. A parental questionnaire was used for subjective outcome measurement. Preoperative ICP recordings during sleep ranged from 12.8 to 22.8 mmHg (mean, 16.1 mmHg). The mean age at the time for surgery was 6.9 months (range, 4-16 months; standard deviation [SD], 2.32 months). The surgical technique included shortening of the anteroposterior diameter of the skull by a mean of 16.6 mm. The mean global development quotient (GDQ) preoperatively was 104.5 (range, 82-144; SD, 12.4) and the mean GDQ postoperatively was 101.4 (range, 62-129; SD, 13.6). Mean age at follow-up was 16.3 months (range, 9-40 months; SD, 4.04 months). There was no significant correlation between the amount of intraoperative shortening and mental development. In comparison of means, the GDQ preoperatively did not differ significantly from the GDQ postoperatively. The modified pi procedure is safe and efficient. When surgery was performed before 1 year of age, no significant (p = 0.33) effect on mental development-either detrimental or beneficial-was demonstrated.

Child Development↗

How effective is endoscopic third ventriculostomy in treating adult hydrocephalus caused by primary aqueductal stenosis?

OBJECTIVE: To evaluate the long-term efficacy of third ventriculostomies for adult patients with hydrocephalus caused by primary aqueductal stenosis. METHODS: Eighteen of 64 patients who underwent endoscopic third ventriculostomies (ETVs) between June 1991 and July 1995 were treated because of primary aqueductal stenosis. All of these patients accepted follow-up investigations, which were performed 3 months to 5 years after surgery. If hydrocephalic symptoms persisted, the patency of the ventriculostomy was investigated; in cases of open ventriculostomies, the patients were offered shunt surgery. The effects of the shunt surgery were evaluated after 3 months. RESULTS: After ETV, nine of the patients exhibited excellent improvements, two exhibited slight improvements, one displayed no change, and six demonstrated temporary improvements. The ventriculostomies were patent in all nine patients who experienced less than excellent results. Subsequent ventriculoperitoneal shunt placement produced improvements for all seven patients who accepted the surgery. CONCLUSION: In our experience, the long-term effectiveness of ETVs for adult patients with noncommunicating hydrocephalus was sufficient in only 50% of the cases. One-third of the patients exhibited temporary improvements, lasting 1 to 12 months (average duration, 5 mo) after the ETVs, and then demonstrated deterioration to even worse clinical conditions, despite patent ventriculostomies. All patients who did not exhibit permanent improvements after the ETVs benefited from shunt surgery. Efforts should be made to establish methods for the selection of patients for ETV or ventriculoperitoneal shunt surgery.

Adolescent↗

Sequential Nucleophilic Substitution: A Powerful Strategy for the Solid-Phase Production of Diverse Compound Libraries.

Polyfunctionalized, unprotected reagents (e.g. amines and thiols) can be used in the production of highly diverse compound libraries by performing sequential nucleophilic substitutions on support-bound polyelectrophiles (see scheme). The procedure reported here enables the efficient preparation of new beta-alanine derivatives which are suitable for lead discovery. E*=polyelectrophile, *=solid support.

Journal Article↗

Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents.

(3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid 1 (tiagabine, Gabitril) is a potent and selective gamma-aminobutyric acid (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans. This drug, which has a unique mechanism of action among marketed anticonvulsant agents, has been launched for add-on treatment of partial seizures with or without secondary generalization in patients >12 years of age. Using this new agent as a benchmark, we have designed two series of novel GABA uptake inhibitors of remarkable potency, using a putative new model of ligand interaction at the GABA transporter type 1 (GAT-1) uptake site. This model involves the postulated interaction of an electronegative region in the GABA uptake inhibitor with a positively charged domain in the protein structure of the GAT-1 site. These two novel series of anticonvulsant agents contain diaryloxime or diarylvinyl ether functionalities linked to cyclic amino acid moieties and were derived utilizing the new model, via a series of design steps from the known 4,4-diarylbutenyl GABA uptake inhibitors. The new compounds are potent inhibitors of [(3)H]-GABA uptake in rat brain synaptosomes in vitro, and their antiepileptic potential was demonstrated in vivo by their ability to protect against seizures induced by the benzodiazepine receptor inverse agonist methyl 4-ethyl-6,7-dimethoxy-beta-carboline-3-carboxylate (DMCM) in mice. From structure-activity studies of these new GABA uptake inhibitors, we have shown that insertion of an ether oxygen in conjugation with the double bond in tiagabine (K(i) = 67 nM) improves in vitro potency by 5-fold to 14 nM.

Animals↗

Subarachnoid blood infusion versus raised intracranial pressure: effects on the amino acid pattern in the extracellular fluid of the rabbit hippocampus.

In order to evaluate the role of a hemorrhage versus that of a transient increase in intracranial pressure in subarachnoid hemorrhage, the two components were induced separately in rabbits. Extracellular glutamate, sampled from the hippocampus with microdialysis, was used to evaluate the degree of CNS tissue damage. In four rabbits, autologous arterial blood was infused in the cisterna magna in a volume that would not affect the intracranial pressure. The other group of animals was infused with saline to elevate the intracranial pressure from 10 to > 100 mmHg. The increase of intracranial pressure per se did not induce significant changes in extracellular glutamate. However, 20-60 min after infusion of blood, a significant glutamate increase was recorded. Furthermore, aspartate, alanine, glycine and serine were also raised. The results indicate that blood in the subarachnoid space damages the brain primarily by inducing ischemia. Furthermore, the parameters employed gave no indication that an increase in intracranial pressure had a deleterious effect on CNS tissue.

Amino Acids↗

Adult patients with "asymptomatic" and "compensated" hydrocephalus benefit from surgery.

OBJECTIVES: There exists no consensus regarding the appropriate treatment of the group of adult hydrocephalus patients often denoted as "arrested"/ "compensated", "asymptomatic" or "symptomatic congenital". Our case series describes the results of CSF diversion in these patients. MATERIAL AND METHODS: During the period of 1984 to 1994, 23 consecutive adult patients with "asymptomatic" (n = 10), "compensated" (n = 7) and "symptomatic congenital" (n = 6) hydrocephalus were prospectively evaluated. All patients showed signs of motor or psychometric impairment, had indications of an infantile or childhood debut, and had previously been ignored. In 15 patients the ventricular enlargement was a coincidental finding. Seventeen patients underwent shunt surgery or endoscopic third ventriculostomy. RESULTS: All but one operated upon improved. Six patients declined surgery, but have been followed with 1 showing deterioration, the remaining being unchanged. CONCLUSION: In addition to patients with "symptomatic congenital" most adult "asymptomatic" and "arrested"/"compensated" hydrocephalus patients can benefit from surgery despite a considerable duration of disease.

Adult↗

A standardized neurosurgical neurointensive therapy directed toward vasogenic edema after severe traumatic brain injury: clinical results.

OBJECTIVE: Analysis of a standardized therapy focusing on prevention and treatment of vasogenic edema in patients suffering severe traumatic brain injury (TBI). DESIGN: A retrospective analysis. SETTING: Neurointensive care unit at Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS: 38 patients with severe TBI were included. The median Glasgow Coma Score was 5 (range 3-8) and median age 27 years (range 5-70 years). INTERVENTIONS: Measurement of intracranial pressure (ICP). Surgical evacuation of hematomas and contusions. Volume expansion aiming at normovolemia. Sedation with continuous intravenous infusion of low-dose thiopentone and reduction of stress response by clonidine. Normalization of capillary hydrostatic pressure by metoprolol and clonidine. If ICP and cerebral perfusion pressure (CPP) were not stabilized (ICP < 20 mmHg and CPP > 60 mm Hg), a continuous infusion of dihydroergotamine was added. In 4 patients a craniectomy was performed. RESULTS: Of the 38 patients, 27 (71%) survived with good recovery or moderate disability, 5 (13%) survived with severe disability, 1 (3%) remained in a vegetative state, and 5 (13%) died. The mortality due to intracranial hypertension was 11% (4 patients). CONCLUSION: A therapy focusing on treatment of the assumed vasogenic edema in combination with aggressive neurosurgery resulted in an outcome as good as the best previously reported.

Acute Disease↗

Gait abnormality is not the only motor disturbance in normal pressure hydrocephalus.

Thirteen different motor and balance functions were examined in 76 patients age 65 +/- 13 (mean +/- SD) years with normal pressure hydrocephalus (NPH) before and 3 months after a ventriculoperitoneal shunt operation. Preoperatively, the tests were performed before and after lumbar tap of 50 cc cerebrospinal fluid. The patients showed significant improvement in all thirteen functions at the 3-month examination. The improvement was approximately 25% in all the motor functions, except for balance, in which the improvement was even more striking. Different etiological subgroups of NPH patients, including the idiopathic form, exhibited the same degree of improvement. The improvement after the lumbar tap was significant in all functions except one-legged stance, and amounted to approximately 30% of the improvement seen after the shunt operation. Our results clearly show that the impairment in motor functions in NHP patients is general, involving many motor activities performed in daily life, and is not restricted solely to the gait.

Aged↗

Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects.

Relative regional cerebral blood flow (rrCBF) was measured by single-photon emission tomography (SPET), using technetium-99m-d,l-hexamethylpropylene amine oxime (HMPAO) as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq 99mTc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3-12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of pathophysiological and prognostic importance in NPH.

Adult↗

Quantitative SPECT cisternography in normal pressure hydrocephalus.

Twenty-one patients with normal pressure hydrocephalus (NPH), 8 patients with various brain diseases with an element of hydrocephalus, and 7 patients with miscellaneous dementia disorders were investigated with quantitative radionuclide cisternography (RC) using single photon emission computerized tomography (SPECT). The total intracranial counts as well as the counts in the lateral and third ventricles were measured. All 15 NPH patients accessible for postoperative examination were improved after shunt surgery. In all groups the ventricular and total intracranial counts level increased during the measurement period but remained constant in distribution in each group. The NPH patients had a higher relative count value in the lateral and third ventricles compared to the patients with miscellaneous dementia disorders. The relative values in the third and lateral ventricles were predictive for the outcome of shunt surgery. Quantitative SPECT RC appears to be a useful diagnostic procedure in NPH investigations.

Adult↗

Temporal heterogeneity of the blood flow velocity at the middle cerebral artery in the normal human characterized by fractal analysis.

The objective of this study is to characterize the temporal fluctuation of the axial blood flow velocity (BFV) at the middle cerebral artery (MCA). Biological observables such as BFV present complex oscillations. The irregularity of physiological systems may be assessed by fractal analysis by computing the fractal dimension (D gamma) and the corresponding temporal correlation (r gamma). The BFV at the MCA was registered with transcranial Doppler ultrasonography (TCD) in four adult volunteers. As fractal processes are assumed to have no absolute time scale, two time scales were compared. The digitized signal was averaged respectively at 1-s intervals and for each heart beat. D gamma and r gamma were determined using relative dispersion analysis. The results were D gamma = 1.24 +/- 0.09 and r gamma = 0.45 +/- 0.19 (mean +/- SD) for the 1-s based time scale and D(r) = 1.17 +/- 0.09 and r gamma = 0.57 +/- 0.20 for the heart-beat scale. We conclude that the temporal heterogeneity of the BFV at the MCA in the normal human has fractal properties. Fractal analysis of TCD data may become useful in clinical diagnosis because loss of complexity in physiological systems has been linked to senescence or disease conditions. Wide variations of the so called normal values of BFV measured by TCD have been reported. The physiological BFV fluctuations may explain, in part, the variability of values recorded during routine TCD diagnostic examinations. Our observations may also be of value for understanding the interaction of the vascular endothelium and the blood flow stream (shear stress).

Adult↗

The transoccipital approach for transcranial Doppler ultrasonography of the vertebrobasilar circulation.

With the transoccipital paramedian approach for transcranial Doppler examination of the vertebrobasilar circulation, a complete examination of the intracranial vertebral arteries and basilar artery is possible without moving the patient from the supine position; this may be of value in intensive care conditions. Blood flow velocity and flow direction in these vessels are registered through the occipital bone at relatively more superficial levels, and identification of right and left vertebral arteries usually represents no problem.

Adult↗

Management of a giant intracranial aneurysm using surface-heparinized extracorporeal circulation and controlled deep hypothermic low flow perfusion. A case report.

Extracorporeal circulation with controlled hypothermic low flow perfusion was introduced during the surgical treatment of a patient with a giant intracranial aneurysm of the anterior communicating artery. Heparin-coated equipment (Carmeda Bio-Active Surface; CBAS) was utilized, thus reducing the need for systemic heparinization. Direct cannulation of the right atrium and aorta was established through thoracotomy. Blood flow through the circuit was kept at 4.5 l/min during normothermia. Core cooling, in combination with external surface cooling, was performed for 30 min to a temperature of 18 degrees C (nasopharynx). During a period of 25 min, the time for surgical repair of the aneurysm, blood flow was minimized to 0.4 l.min-1, equilibrating central and peripheral blood pressures to approximately 5-10 mmHg (0.65-1.3 kPa). Reperfusion was started immediately after the low flow period concomitantly with rewarming, aiming at a temperature of 36 degrees C following 150 min. The patient could be weaned off the extracorporeal circulation with minimal inotropic support. The postoperative course was uneventful apart from a left-sided hemiparesis, probably due to an infarction in the area of the right pericallosal artery (A2). The patient was weaned off the ventilator after 6 days. He recovered and the hemiparesis regressed slowly.

Aged↗