Results of continuous long-term intravenous application of octreotide via an implantable pump system in acromegaly resistant to operative and X-ray therapy.

Long term results after surgery for growth hormone (GH)-secreting adenomas indicate only a limited cure rate, particularly in patients with tumours invading the dural boundaries of the sella with suprasellar extension. Since octreotide had become a treatment option, it was used i.v. via an implantable pump system in five patients (age range 24-46 yr) showing symptoms of uncontrolled acromegaly, in spite of previous surgery and X-ray therapy. The octreotide doses used permanently for a cumulative treatment period of 8.8 yr ranged between 300 and 1000 micrograms/24 h. Serial evaluations of clinical findings, 24-h GH and insulin profiles, insulin growth factor-1 (IGF-1), oral glucose tolerance test and pituitary function revealed sustained GH suppression, without interim escape, below 2 ng/ml in two and below 5 ng/ml in three patients, IGF-1 decrease in all with normalization in two patients and no clinically relevant disturbances of carbohydrate tolerance or thyroid-stimulating hormone secretion. In one case of previous unresponsiveness to dopamine agonists i.v. octreotide application for 29 months facilitated later disease control by bromocriptine only. In two patients octreotide was terminated after 15 and 30 months of i.v. administration, respectively, because the effects of irradiation had occurred. For a subgroup of patients with resistant acromegaly continuous i.v. octreotide can be considered as a safe and effective alternative, which increases patients' independency from the inconvenience of daily repeated s.c. injections.


Gangliosides in meningiomas: correlation of Glac2 to intermediary filament.

Human meninges and 29 meningiomas were analyzed as to their glycosphingolipid composition. In the neutral fraction GSL, a mostly even distribution of mono-, di-, tri-and tetrahexoside was demonstrated. In the group of the gangliosides, Glac1 in one broad band in chromatograms occurred in almost all meningiomas; Glac2 was present in 84% of tumours. Members of the Gtn-family were only found in a small minority of tumours while various Gtet-gangliosides were detectable in nearly half of them. No constant pattern or patterns emerged and no correlation to either morphological subtype or malignancy grade could be established. Immunohistochemistry revealed focal presence of Glac2 in a pattern similar to that of vimentin expression. Semiquantitative evaluation showed good correlation between both parameters.


Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas.

The aim of this study was to determine possible relationships between Ki-67 labelling index (Ki-67 LI), amplification of the epidermal growth factor receptor (EGFR) gene, and prognosis in human glioblastomas. Ki-67 LI was determined on cryosections of biopsy specimens of 20 human glioblastomas with a mouse anti-human Ki-67 monoclonal antibody. Amplification of the EGFR gene was determined by slot blot and Southern blot analyses of DNA extracted from the tumour biopsies. The Ki-67 LI was higher in the glioblastoma group with EGFR gene amplification (8 tumours, median value of Ki-67 LI 4.2, range 0.4-24.6) than in those without EGFR gene amplification (12 tumours, median value of Ki-67 LI 0.8, range 0.2-11.8) (0.05 p less than 0.1). The glioblastoma patients with Ki-67 LI greater than 1.5 (10 tumours) had a statistically significant shorter survival than those with Ki-67 LI less than 1.5 (10 tumours) (p less than 0.05). The glioblastoma patients with EGFR gene amplification lived shorter time than those without EGFR gene amplification (p greater than 0.05).


Malignancy and viability of intraparenchymal brain tumours: correlation between Gd-DTPA contrast MR images and proliferative potentials.

The feasibility of diagnosing the malignancy and viability of intraparenchymal brain tumours using Gd-DTPA, enhanced and unenhanced T1-weighted MRIs was investigated. The relationship between the Gd-DTPA enhancement pattern, the growth fraction (GF) determined by using the anti-bromide-oxyuridine (BrdU) monoclonal antibody, the clinical condition, the proliferative potential and the change of Gd-DTPA enhancement over time was studied. Forty-five patients with intracranial tumours were studied with the static method of Gd-DTPA MRI. The enhanced effect in Gd-DTPA MRIs was dependent on tumour-cell density, vascularization, necrosis, and dilatation of vascular lumen. Tumour-cells were observed in eighty-seven of eighty-nine specimens taken from areas with Gd-DTPA enhanced MRIs. Seventy-four percent of these specimens (64 of 87) showed a malignancy of more than 5% growth fraction. On the other hand, tumour cells were observed in twenty-seven of fifty-six specimens taken from areas with Gd-DTPA unenhanced MRIs. Eighty-five percent of these specimens (23 of 27) showed a malignancy value of less than 5% GF. However, fifteen percent of these specimen showed values between 5 and 15% GF. In the kinetic study of Gd-MRIs five patients who were in a clinically stable condition and one patient who had radionecrosis showed a constant pattern of enhancement or slightly increased enhancement 30 min after injection compared to 4 min after injection. Therefore, GD-DTPA MRI can be used effectively in the diagnosis of tumour viability and malignancy after treatment.


Osseous metastases from a benign intraventricular meningioma. Case report.

The authors report a case of a 6 month-old male presenting with increasing head circumference and a large benign intraventricular meningioma which was grossly removed at the initial surgery. Twenty-four months later, the patient returned with subcutaneous and osseous metastatic lesions at the site of the previous craniotomy, revealing the same histology as the original tumour. The presentation, pathology and management of this unique case are discussed.


Experimental study on the indications for barbiturate therapy. Change in haemodynamics and the influence of dopamine.

The effect of barbiturates on the cerebral haemodynamics and the influence of dopamine on barbiturates were investigated using 20 cats, and clinical indication of barbiturate therapy is discussed. Cerebral blood flow, oxygen extraction fraction, and cerebro-vascular resistance as well as physiological variables were evaluated at various concentrations of barbiturates in the blood. Thiamylal caused simultaneous reduction of mean arterial blood pressure and cerebral blood flow. As the disruption of autoregulation proceeded, cerebro-vascular resistance and oxygen extraction fraction increased till the barbiturate-induced coma stage. Furthermore, cerebro-vascular resistance increased much more markedly by the combined use of dopamine. Clinically, our results indicate barbiturates would increase cerebral circulatory disturbances caused by vasospasm following subarachnoid haemorrhage because barbiturates further increase cerebro-vascular resistance. Then again, the combined use of dopamine is not preferable because of deterioration in vasospasm.


Changes in mechanical responsiveness of the rat aorta after cervical spinal cord stimulation.

The effect of cervical spinal cord stimulation on the mechanical vascular responsiveness of rat aortic artery rings was studied "in vitro". Arteries with and without endothelium from sham and stimulated male Wistar rats were placed in an organ bath studying the contractile response induced by noradrenaline, prostaglandin F2 alpha and serotonin. For spinal cord stimulation two electrodes were placed in the cervical epidural space using microsurgical technique. The parameters of stimulation were: monophasic waveform current, pulse width of 0.1 ms, frequency of 120 cps, and intensity one third of the threshold which produced motor responses (between 0.3 and 0.5 v). The total period of stimulation was 120 minutes. The potency of each vaso-active agent was calculated in the organ bath for each experimental group. There were differences only when arteries with endothelium from sham (7.2587 +/- 0.2308) and stimulated (8.0720 +/- 0.3723) rats were tested with noradrenaline (p less than 0.01). Our results suggest that cervical spinal cord stimulation induces changes in the vascular wall that might explain the effects of spinal cord stimulation on vasomotor control.


The use of coaxially aligned freeze-thawed skeletal muscle autografts in the repair of the cauda equina--in the sheep.

The aim was to develop a model for study of nerve regeneration in nerve roots above the level of the dorsal root ganglion and to investigate the use of freeze-thawed muscle autografts for repair of nerve roots at this level. Four adult sheep were used for the experiment. A laminectomy was performed at the lumbosacral junction and the S2 root identified. Both the dorsal and ventral S2 roots were divided unilaterally within the dura and a freeze-thawed muscle graft was inserted into the nerve gap. When assessed at 6 months an action potential was recordable from the ventral root in one sheep. Histological examination of the nerve roots showed evidence of regeneration across the graft in the ventral roots of all the sheep and the dorsal roots of some. This preliminary work indicates a capacity for regeneration of the cauda equina and that freeze-thawed muscle can support this. It provides a useful model for further study of nerve root repair.


Jugulare foramen paragangliomas.

A survey is given of the clinical picture, diagnosis and management of foramen jugulare paragangliomas (JFP), based on reports of 175 cases from the literature and personal experience of 26 cases. Special emphasis is given to the operative techniques. Improvements of diagnostic possibilities as well as operative techniques, including the pre-operative occlusion of tumour-feeding arteries by endovascular methods have markedly reduced the operative mortality to a rate between 0 and 5 percent. The rate of incomplete removal of C and D tumours dropped to about 15%. But very large and extensive tumours remain a real challenge. Teamwork between neuroradiologists, ENT-surgeons and neurosurgeons is mandatory.


Experience with 36 surgical cases of petroclival meningiomas.

Thirty-six patients with petroclival meningiomas underwent surgery between 1978 and 1990. The tumours accounted for 13% of a total of 284 skull base meningiomas operated upon during the same time period. The most frequent neurological signs related to cranial nerve deficits, mainly of the 8th, 5th, and 7th nerves respectively. The approaches to the petroclival region were: retromastoid, pterional, subtemporal, and combined retromastoid-subtemporal. In 12 patients we used a modification of the retromastoid-subtemporal approach with preservation of the sigmoid and transverse sinus (presigmoid approach). "Total" tumour removal was achieved in 27 cases (75%). There was no postoperative death, and in 83% of cases no severe morbidity. With careful pre-operative evaluation, improved operative approaches and microsurgical techniques the treatment of petroclival meningiomas has been considerably improved.


Surgical treatment of anterior third ventricle tumours.

A review is given on the operative management of anterior third ventricle tumours, with special emphasis on the selection of the approach, the postoperative results and complications. The review is based on our own experiences with 337 cases and 340 operations, among them 198 craniopharyngiomas, 80 gliomas, 23 colloid cysts, 11 ependymomas, and 25 others. The tumours can be approached through the lamina terminals or transcallosally or using a combination of both of these approaches. The approach through the lamina terminalis is useful only in rather small tumours, because it does not allow a sufficient revision of the upper and posterior third ventricle compartments. For larger tumours the transcallosal approach is preferable. We have abandoned the approach through the anterior horn of the lateral ventricle, because it does not allow an equally good vision of both sides of the third ventricle. In some of the craniopharyngioma cases it was necessary to combine the transcallosal and subfrontal approaches in order to achieve total or subtotal tumour resection. In craniopharyngiomas total or subtotal tumour removal was possible in 66% of the children and 59% of the adult patients, with a mortality higher in adults (30%) than in children (18.5%). The main causes of complications in craniopharyngiomas were acute disturbances of hypothalamic circulation and function, with water-electrolyte imbalance and other signs of diencephalic insufficiency. In glioma cases an additional important cause of complications has been haemorrhage into the remaining tumour parts. Colloid cysts could be exstirpated without mortality, using the transcallosal approach.(ABSTRACT TRUNCATED AT 250 WORDS)


Tumours of the limbic and paralimbic systems.

Clinical manifestations, findings, management and outcome of a series of 177 cases with tumours of the limbic and paralimbic systems are presented. There was no operative mortality. Postoperatively 95% of them had no or only minor neurological deficits. Most of them were able to resume work. Pre-operatively 77% of the patients had epilepsy, but 84% became seizure-free after tumour removal. All 77 cases with malignant tumours died within 1-5 years. In the past many neurosurgeons were reluctant to attempt complete tumour removal in these areas. This series demonstrates the efficacy of highly skilled microneurosurgery.


Surgical experiences with giant intracranial aneurysms.

The common method of presentation of intracranial aneurysms is at the time of their rupture (with subarachnoid haemorrhage) or on the occasion of their compression of neighbouring structures. While giant aneurysms may occasionally present with subarachnoid haemorrhage, their more common methods of presentation are due to their space occupying and neighbourhood effects. Giant aneurysms are commonly defined as those with a diameter larger than 2.5 cm. Previously this diameter was assessed either by arteriography, so that size meant internal diameter, or by the displacement of surrounding structures, as for example, small perforating vessels, which could be attributed positively to the presence of a larger mass. Before CT scanning however, the factor of a very considerable larger aneurysm, partly occluded by clot could occasionally cause unexpected operative difficulty. The advent of CT scan and now especially MR imaging has made the prediction of the size of the aneurysm much easier and the extent of the intra-aneurysmal clot also clearly definable. This paper describes one surgeon's experience with 64 giant cerebral aneurysms operated on in the last 10 years (Table 1). It has emerged from this experience that the most satisfactory method of handling the lesion is to remove the intra-aneurysmal clot and clip the neck of the aneurysm, and the steps necessary to secure this laudable design from the burden of the paper.


Multiple intracranial aneurysms: a high risk condition.

There is still a relative silence in the literature on what policy should be followed in treating multiple aneurysms. The main risks are: bleeding of a formerly asymptomatic aneurysm during the haemodynamic tides of the peri-operative period; aneurysm(s) can be hidden on angiograms and tend to be overlooked easier in case of an already revealed aneurysm; misjudgement of the ruptured one as a silent additional aneurysm, therefore left for second stage surgery. This paper, based on a material of 330 operations for multiple aneurysms, focuses on these problems. It advocates the one stage complete repair of all lesions using both options of bilateral pterional craniotomies or the contralateral approach. But it also describes those silent aneurysms which safely could be clipped later. Hazards and disadvantages concerning the more aggressive surgery proved to be less significant than the natural history of multiple aneurysms represents.


Interventional neuroradiology for the treatment of inaccessible arterio-venous malformations.

Embolization of cerebral arterio-venous malformations (AVM) has been performed at the Department of Neuroradiology of Verona in 136 patients with a total of 310 procedures. The complication rate was 16%. In most of the cases embolization was followed by either operative removal of the AVM or by radiosurgery. In a group of 38 embolized patients, who refused operation or radiosurgery, rebleeding occurred 7 times (18%), but only in patients who already had bleedings before embolization. Indications and techniques of embolization are described and discussed.


Evaluation of intracranial pressure gradients by means of transcranial Doppler sonography.

The authors investigated the effects of intracranial pressure gradients generated by a unilateral intracranial mass on transcranial Doppler (TCD) readings. Eleven patients harbouring a symptomatic chronic or subacute subdural haematoma underwent pre- and post-operative TCD examinations of the intracranial internal carotid and middle cerebral arteries. Mean values of velocity and pulsatility index (PI) were compared to the contra-lateral counterpart. The haematomas were evacuated by means of burr hole drainage under local anaesthesia. Symptomatic subdural haematomas lowered the ipsilateral blood velocity in the internal carotid and middle cerebral arteries by a mean side-to-side difference of 15.64 +/- 3.01 m.sec-1. The ipsilateral PI was higher than the contralateral values by an average of 0.23 +/- 0.04. Low mean velocity and high PI values were associated with high subdural pressure. Abnormal pre-operative ipsilateral TCD readings returned to normal following haematoma drainage. We postulate that intracranial pressure gradients generated by the subdural mass lesion are responsible for the asymmetry of TCD readings. These differences should be considered in the interpretation of post-subarachnoid haemorrhage vasospasm, as it is frequently associated with lateral clots. Our findings also provide a useful method for non-invasive monitoring of intracranial pressure gradients.


HM-PAO spect in head trauma.

Single Photon Emission Computed Tomography (SPECT) after intravenous administration of Technetium-99m hexamethylpropylene-amine oxime (Tc-99m HM-PAO) makes possible the evaluation of cerebral perfusion. We have been assessing the diagnostic accuracy of SPECT in some groups of head trauma patients: the preliminary results of this study are presented. Fourteen patients have been selected, all of them showing some kind of focal neurological deficit; the Computed Tomography (CT) and Nuclear Magnetic Resonance (NMR) were normal, or showed lesions that could not be responsible for the neurological deficits. In all of the patients Tc-99m HM-PAO SPECT has been performed, showing changes in cerebral perfusion in areas correlated with the abnormalities elicited on clinical examination. These results show that Tc-99m HM-PAO SPECT is a better technique than CT or NMR in demonstrating the organic basis of some neurological deficits observed after head trauma.


Early post-traumatic cerebral blood flow mapping: correlation with structural damage after focal injury.

Focal post traumatic mass lesions such as contusions and intracerebral haematomas are common, and often difficult for neurosurgeons to manage, because little is known of their pathophysiology. We have mapped cerebral blood flow, and studied small vessel ultrastructure at different time points within the first three weeks of head injury, in patients with these lesions. A zone of ischaemic brain is always present around these lesions, and persists for weeks or months. This accords with astrocyte swelling and microvascular compression seen on electron microscopy. Focal zones of hyperaemia were also present in 42% of patients, within the first two weeks of injury, and this appeared only within apparently normal tissue as judged by late MRI or CT.


The role of computer based techniques in patient monitoring: technical note.

In this paper the requirements of Neurophysiology and Neurotraumatology monitoring are analyzed. As a result a set of designated systems were developed by the authors a short description of which is given in the paper. Finally the future perspectives and problems to be faced are briefly described.


Significance of endocrine studies in the general assessment and prediction of fatal outcome in head injury.

Serial basal blood glucose, serum insulin, cortisol, growth hormone, glucagon and catecholamine examinations were performed in 81 brain-injured patients. 32 patients with severe injuries of other parts of the body (chest, abdomen, limbs or polytrauma), and 17 patients with non-traumatic acute brain lesions served as double control. In the brain-injured patients there is a close relation between changes of the state of consciousness and those of basal blood glucose levels: the deeper coma the higher and wider is the pathological glucose-level range. Four types of blood-glucose changes could be identified in the background of which different alterations of each hormone level were observed. Fatal outcome could be predicted in a non-diabetic patient in the first days when seeing: 1) Fasting hyperglycaemia above 14 mmol/l; 2) Fluctuating basal blood glucose levels between 5 and 22 mmol/l; 3) Deeply depressed and unchanged basal insulin level; 4) Extremely high cortisol level; 5) Decreased plasma epinephrine level. These changes in the carbohydrate metabolism seen after acute brain lesions are not identical to diabetes mellitus.


Blunt basal head trauma: aspects of unconsciousness.

Two cases of street violence directed to the skull base level and transverse to the cervical axis are described. No skeletal damage. The violence resulted in the so-called "traumatic subarachnoid haemorrhage", an often used, unspecified forensic "diagnosis"; it was here revealed to be due to rupture of the wall of the posterior inferior cerebellar artery (p.i.c.a). However, this was only one of the possible explanations for the acute symptoms of unconsciousness (concussion) and almost immediate death. The careful examination of these two cases and of a series of control cases revealed that at the trauma, stress and strain may have occurred to arterial branches serving as feeding perforant vessels to the medulla oblongata; in these cases they were coursing directly from the p.i.c.a. region.--The type of direct impact has often been regarded as mild! However, its location suboccipitally as in these cases can become dangerous. The resulting direct or indirect deficit of brain stem functions are discussed in these cases as well as "concussion-related symptoms" resulting after other types of head and neck injury.


Primary traumatic benign midbrain haematoma in hyperextension injuries of the head.

Primary traumatic brain stem injury occurring in isolation is not universally recognized as a distinct pathological entity which may follow a head injury. We describe two patients with clinical and radiological evidence of primary posttraumatic midbrain haemorrhage occurring in isolation associated with good recoveries. It is suggested that paramedian midbrain syndromes associated with midbrain haemorrhages should be recognized as a distinct, although unusual, complication of hyperextension injury to the head which may have a benign course.


The prognostic value of some clinical and diagnostic factors in traumatic intracranial haematoma.

In order to carry out the analysis of predictive values of some clinical and diagnostic features, 146 patients of the Neurosurgical Clinic of the Silesian School of Medicine, were examined in 1980-1986. All the patients were in coma when admitted while CT findings showed traumatic intracranial haematomas. The examination included neurological diagnosis and CT examination. The analysis of statistical discrimination let us specify the probability of predicting death or survival of every patient. On the basis of 10 prognostic factors applied, the compatibility of prognosis and the real outcome for patients who survived was 78.2% and for those who died 91.2%.


Coexisting diffuse axonal injury (DAI) and outcome of severe head injury.

The importance of coexisting diffuse axonal injury (DAI) and outcome were studied in 107 patients with diffuse and focal brain injury. Comprehensive neuropathological study was undertaken in 26 fatal patients. There was a clear rank order of the mortality rate in the lesion type. The rank order of good recovery and moderate disability was also similar to the inverse of the mortality ranking. The pathological "marker" of DAI, macroscopic lesions in the corpus callosum and dorsolateral quadrant of the upper brainstem and histological evidence of axonal retraction balls, were commonly found not only in patients with diffuse brain injury but also in focal brain injury. The type of intracranial lesion in severe head injury is thus an important factor in determining outcomes and DAI of varying severity is the common subjacent lesion in the fatal patients.


Brain oedema and intracranial hypertension treatment by GLIAS.

The authors present their results regarding the use of a buffered solution of glycerol 30%-sodium ascorbate 20% (GLIAS) for the treatment of brain oedema and intracranial hypertension. GLIAS was perfused intravenously in 80 patients with several types of brain oedema. In every patients serum and urinary osmolarity, diuresis, main blood and urine parameters, and ICP were monitored. Following GLIAS infusion an increase in plasma osmolarity was observed, changing the average basal value plus 13.4% after 15 min., 10.5% after 30'. At the same time there was a reduction of ICP and improvement in cerebral compliance. In each case there was a decrease in intracranial hypertension and brain oedema without significant collateral effects.


Sedatives and antagonists in the management of severely head-injured patients.

Continuous intravenous sedation is often prescribed during the intensive treatment of severe head injury. It is known that intravenous hypnotics may prevent or treat the brief intracranial hypertension episodes associated with nociceptive stimuli, like tracheal intubation. However there is yet no clear evidence in the literature showing beneficial effects of sedation in severely head-injured patients on intracranial pressure control or outcome. Sedation should be primarily administered in neurotraumatology to allow good conditions for intensive treatment, while avoiding any depressive cardiovascular action. The abrupt reversal of sedation by means of specific antagonists may induce significant elevation of both cerebral blood flow and intracranial pressure and should be avoided.


Indomethacin (Confortid) in severe head injury and elevated intracranial pressure (ICP).

In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control ICP by hyperventilation and barbiturate sedation, indomethacin (Confortid) was used as a cerebral vasoconstrictor drug. In all patients indomethacin reduced ICP to below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in cerebral blood flow (CBF) at 2 hours. After 7 hours, ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In two patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. Outcome scaling has not yet been performed, but all patients left hospital without neurological deficits. The results suggest, that indomethacin is an alternative in the treatment of ICP-hypertension in head-injured patients.


Posttraumatic epilepsy in civilians: clinical and electroencephalographic studies.

Posttraumatic epilepsy (PTE) is a known consequence of head trauma. The factors involved in posttraumatic seizures generation and the relationship between acute seizures and posttraumatic epilepsy are not without controversy. This also applies to the evolution of the electroencephalographic characteristics. The study here reported was performed analysing data from patients with posttraumatic epilepsy (N = 205) and data from patients followed-up since trauma and considered as a high risk population for the development of PTE (patients with acute seizures and/or patients with focal lesions--contusion, haematomas or penetrating head injury) (N = 152). Seizure type was associated with age and trauma severity (children, elderly and worst trauma cases present with a higher proportion of partial seizures). Neurological deficit and lesion location were associated with the seizure occurrence. The increased incidence of seizures was found when the most diffused brain dysfunction was combined with neurological deficits. The analysis of sequential EEGs performed at first, at 6th and 12 months post trauma revealed a non-stationary pattern throughout these time periods with EEG focal abnormalities remaining frequent for more than two years after the trauma. Children and old people have a higher proportion of EEG abnormalities with more frequent abnormal generalized activity in children and more frequent abnormal focal EEG activity in the elderly.


Monitoring of severe head-injured patients with transcranial Doppler (TCD) ultrasonography.

Intracranial haemodynamics were studied in 36 patients with severe head injury and experimental animals with acute intracranial hypertension by the use of TCD ultrasound. The mean flow velocity (FV) in the basal cerebral arteries commonly decreased on the side of the haematoma depending on intracranial pressure (ICP) elevation and cerebral perfusion pressure (CPP) reduction in focal brain injury. The FV decreased bilaterally and there was no difference between the right and left sides in diffuse brain injury without a clear relationship between the FV and CPP. The FV of the middle cerebral artery and blood flow in the internal carotid artery exhibited flow patterns which changed correlatively depending on CPP reduction in experimental animals. Monitoring with TCD ultrasound is valuable in evaluating compression ischaemia in focal brain injury. But many complicated factors are considerable in diffuse brain injury.


Risk factors for late posttraumatic epilepsy.

The usually accepted risk factors for late post-traumatic seizures (LPTS) are those identified years ago by Jennet: early post-traumatic seizure (EPTS), depressed fracture, intracranial haematoma. Prolonged unconsciousness (PTA greater than 24 hrs) is another factor usually added. More recently, personal experience of the Authors and the data of the literature, compel us to question the validity of known risk factors based on clinical data. Authors believe that the identification of patients at risk for LPTS depends mainly on the precise definition of trauma severity and on CT or surgically documented lesions of brain substance. Three groups of patients, characterized by the presence of one or more of the accepted risk factors of LPTS, have been studied. In our experience, while in adults the presence of documented cortico-subcortical lesions represents the main risk factor of LPTS, in children the appearance of EPTS per se increases the risk of LPTS, irrespective of the presence of documented brain lesions. Alteration of consciousness without a focal lesion, even if prolonged and severe, is not a risk factor for LPTS.


Mental deterioration at epilepsy onset: a hypothesis.

In this study, we hypothesized a type of mental deterioration in epilepsy, characterized as a discontinued, cascading process, i.e. a sudden mental decline in a limited time interval, immediately after the onset of the seizures. The posttraumatic epilepsy model (PTE) may appear to be exceptionally useful in avoiding one of the major methodological obstacles for testing this hypothesis, i.e. the unavailability of test results obtained with the same battery of tests prior to and directly after the onset of the seizures. We propose a multicentre study in which a large group of patients are assessed, after recovering from the direct aftermath of head injury, but before the onset of PTE. This baseline provides an opportunity for longitudinal follow-up. Full recovery from head injury before the onset of PTE is to be expected in the mild and moderate groups of closed head injury patients. In this category, approximately 2000 head injured patients have to be assessed to obtain a reasonable group of approximately 100-200 PTE patients. This group will be followed during the critical period of 2-3 years after the onset of epilepsy.


Rehabilitation after severe head injury.

123 survivors of severely head injured patients presenting with coma grade III show a decreasing mean duration of coma with increasing age. The numbers and frequency of good recovery decrease, whereas poor recovery increases with age. Increase of the duration of coma grade III produces an increase of the mean latency and time of recovery and of the frequency of poor recovery, regardless of the age of the patients. Increasing age does not increase the mean latency and time of recovery systematically. The important conclusion of this analysis is, that the clinical feature of coma grade III, corresponding to GCS score of 4 and RLS of 6 and 7, indicates a different kind of brain damage at various age groups. It represents a lesser degree of brain damage for younger patients under 20, than for those over 20. In our opinion our observations do not demonstrate a better capacity of recovery of the young patients: but the young patients show a more severe clinical picture than the older patients do, if only the clinical syndrome of coma grade III with extensor rigidity, is considered as a yardstick for comparison.


Social-economic impact of head injury.

The socio-economic costs of traffic road accidents were analysed data epidemiological studies and compared with reported data. The costs are calculated as a function of accident type and vehicle involved, severity of head trauma, patients individual characteristics, type of care--intensive and emergency services, other hospital bed costs, including recovering and rehabilitation such as in-and out-patient services. Finally the costs of repairing materials (cars, walls, roads, etc.) are also estimated. The author concludes that the medical doctor must take part in compiling the statistics so as to be able to discuss the economics of injury and the social priorities.


Comparative study of magnetic resonance and CT scan imaging in cases of severe head injury.

The distribution, frequency, and appearance of head injuries were evaluated with MRI and CT in a prospective study of 155 patients with acute (n = 124) and chronic (n = 31) head injuries. MRI was significantly more sensitive than CT in the detection of intraaxial injury at any stage. In severe cases, central structure lesions were detected in approximately 80% of patients. Severity on admission was compatible with MR findings. However it was difficult to decide on neurobehavioural prognosis from initial MRI findings only.


Oculo-dento-digital syndrome (Gorlin's syndrome): clinical and genetical report of a new family.

Here we report a family in which the Gorlin's syndrome or oculo-dento-digital dysplasia is transmitted with autosomal dominant inheritance of variant expressivity. Three cases, extensively studied, show also slight oligophrenia, symptom rarely described in this syndrome.


Hemianopic ataxic hemiparesis. A case report.

Ataxic hemiparesis and homonimous hemianopia developed in a hypertensive 60-year-old woman. Magnetic resonance imaging detected multiple lesions in the territory of distribution of the posterior cerebral artery and in the inferior region of the left cerebellar hemisphere. At computed tomography only a right hypodense area involving the posterior right thalamus, the postero-medial region of the temporal lobe and the occipital lobe was evident.


Effectiveness of oxiracetam therapy in the treatment of cognitive deficiencies secondary to primary degenerative dementia.

The effectiveness of oxiracetam (1600 mg/day) vs placebo was assessed in a group of 96 out-patients suffering from cognitive disorders secondary to primary degenerative dementia. The study, performed in double-blind, lasted 26 weeks and is expected to be continued in open conditions until a whole year of treatment is completed. The assessment of the results obtained at 6 months was carried out following both the methodology based on neuropsychological tests and scales, and the study of the simple reaction time by any of a computerised portable tachystoscope. The patients treated with oxiracetam showed a statistically significant improvement of cognitive function and simple reaction time. No significant variations in the scores of the tests used were observed in the placebo group. The patients themselves appeared in favour of oxiracetam. The drug tolerability proved to be very good for the whole duration of the treatment. The authors believe that oxiracetam favourably acts on the symptoms of senile cerebral deterioration and can improve the capability of information processing, as suggested by the better performances obtained at the reaction time tests.


Acute encephalopathy following lumbar myelography with iohexol.

We report an unusual case of an acute encephalopathy following injection of iohexol for myelographic study, which was reversible after a treatment with water restriction and glucocorticoids. The pathophysiologic mechanism appears to be related with hyponatremia. We conclude that drinking of large amounts of fluids must be not recommendable in order to avoid the developing of encephalopathy.


Metoclopramide-induced parkinsonism and depression.

A 46-year-old female patient with metoclopramide-induced parkinsonism and depression was reported in view of the rarity of the concurrent development of these side effects. A risk of metoclopramide administration is suggested.


Sneddon's syndrome, anticardiolipin antibodies and anticardiolipin cofactor. A case report.

Sneddon's syndrome is a rare entity characterized by idiopathic livedo reticularis and cerebrovascular lesions. A case of a young woman with livedo reticularis and progressive cerebral arteriopathy is described. Abnormalities of sexual and gonadotropic hormones were present. Anticardiolipin and anticardiolipin-cofactor complex antibodies were not found.


Neurological damage mediated by cytokines.

Our results suggest that CKs, in particular Interleukin-1 and Tumor Necrosis Factor (TNF)-alpha, are involved in the pathogenesis of some neurological disorders and HIV infection. Infact, we observed an exaggerated spontaneous release of TNF-alpha in patients with migraine without aura. Furthermore, in a broad spectrum of patients with HIV-infection we have also found increased amounts of serum TNF-alfa and IL-1. Interestingly, a strict correlation between plasma lipopolysaccharide (LPS) and IL-1 or TNF-alpha levels seems to exist in both group of patients, thus indicating that LPS could account for the production of CKs in the course of the above diseases.


Isolated amnesia following a bilateral paramedian thalamic infarct. Possible etiologic role of a whiplash injury.

A previously healthy 45 years old carpenter suffered a whiplash injury in a road accident on July, 18th, 1990. He continued to work in spite of occipital headache, episodic sweatening and slight hypersomnia. On August, 8th, 1990 while parking his car into the deck of a ferry-boat he was found slightly confuse and markedly amnestic. A post-traumatic subdural haematoma was suspected. As a CT-scan of the brain was normal, a toxic encephalopathy or an hysterical amnesia were proposed. However, a MRI performed on August, 22th, 1990, apart from a small infarct in the white matter of the left occipital lobe, showed two small bilateral paramedian thalamic infarcts. The last lesions usually follow a thrombotic or embolic occlusion of the "basilar communicating artery" (BCA) belonging to the vertebro-basilar system. The possible etiologic relationship between this syndrome and the previous whiplash injury has been considered. Six months later, while a control MRI showed a reduction of the brain lesions, a neuropsychological examination revealed a slight improvement of memory dysfunction evident also at a distance of further 6 months. This case is interesting because it tests the high sensitivity of MRI in amnestic syndromes and because of the possible role of a whiplash injury in the etiology of BPTI.


Verbalized anger and accusatory "you" messages as cues for anger and antagonism among adolescents.

This study investigated the impact of communications of negative feelings between adolescents in close relationships. High school boys and girls were asked to imagine discussing a relationship problem with a personally close partner and to rate likely reactions to four kinds of statements: assertively expressed distress, assertively expressed anger, aggressively expressed distress, and aggressively expressed anger. Accusatory "you" statements were rated as more aversive and evoked stronger antagonistic response inclinations than assertive "I" statements. Statements depicting anger were rated as more aversive and evoked stronger antagonistic response inclinations than statements depicting distress. Results were similar for boys and girls. Implications of the findings and directions for further research are discussed.


The effects of a psychoeducational program on adolescents' activity involvement, self-esteem, and locus of control.

Adolescents' participation in extracurricular activities is related to a number of variables, such as higher grade point average, increased self-esteem, and lower absenteeism. This research, part of a larger longitudinal study, was designed to determine whether a short, psychoeducational intervention, the personal empowerment program, would affect adolescents' level of involvement in activities, their self-esteem, or their locus of control. Fifty-two ninth-grade students who were average participators were randomly selected and assigned to either the empowerment program or control group. Students were surveyed six months after the program. Analyses of covariance using pretest scores as the covariates indicated that students who participated in the program maintained their level of activity involvement during the transition to high school, a time when participation generally decreases. The program did not produce significant changes in self-esteem or locus of control. Implications for future research are discussed.


Reliability and validity of the Korean Youth Depression Adjective Check List (Y-DACL).

To develop a Korean version of the Youth Depression Adjective Check List (Y-DACL), bilingual Koreans achieved consensus in their translation of the 22 adjectives. Four hundred and seventeen male and 412 female adolescents from 8th through 12th grade of four Korean public schools (mean age ranged from 13.4 to 17.3) completed the state form of the Y-DACL, the Beck Depression Inventory (BDI), and the Self-rating Depression Scale (SDS). Internal consistency was high (alpha = .87), split-half reliability was moderately high (.72), and test-retest reliability was low (.26) as expected. Estimates of concurrent validity indicated a moderate level of correlation between the Y-DACL and the BDI and SDS. The findings suggest that the Korean Y-DACL is suitable for use in research.


Evaluating the efficacy of short-term counseling on adolescents in a school setting.

This study evaluated the efficacy of short-term school-based counseling with forty-two high school adolescents (twenty-seven males, fifteen females) by measuring pre- and posttest scores on a self-report, self-esteem measure. While there was a significant decline in self-esteem ratings after counseling in the areas of social acceptance, job competence, and close friendship, counseled students showed a significant improvement in the consistency between their adequacy ratings and their judgments about what competencies they valued. Specific gender differences emerged, as females appeared to have benefited more from the counseling experience than did males.


The use of the MMPI special scales in the assessment of delinquent personality.

The MMPI was administered to 401 adjudicated male juvenile offenders, ages 13 to 17, who had been referred to a juvenile court mental health unit for recommendations in court disposition. Mean T scores generated by 86 MMPI clinical and supplementary scales were tabulated and analyzed as to their relationships with completed court offense histories. Twenty-eight of these scales that best described and discriminated between high and low levels of recidivism, crime severity, assault, and property offenses were identified, profiled, and discussed. Data were analyzed by a suggested T-score cutoff of 1.5 standard deviations, univariate, and multivariate (discriminant) analysis. Scales that best discriminated between high and low levels of recidivism and property offenses were Pd (Psychopathic Deviance), Ma1 (Amorality), Pd2 (Authority Problems), Re (Social Responsibility), and MAC (MacAndrew Alcoholism). Low scores on Re (Social Responsibility), Es (Ego Strength), Cn (Control), and St (Social Status) best discriminated between high and low levels of crime severity. High and low levels of assault were best differentiated by Ma3 (Imperturbability), Scale 5 (Masculinity-Femininity), and Pa2 (Poignancy). Although the linear combination of Scales F, 4, 8, and 9 has some utility in the areas of recidivism and property offenses, its discriminative ability is extremely poor for levels of assault and crime severity.


A comparison of the perceptions of the mother-daughter relationship of black pregnant and nonpregnant teenagers.

This study examined the relationship between mothers and their teenage daughters in order to determine if there was a significant difference in perceived relationships between pregnant and nonpregnant mother-daughter dyads in a predominantly black sample. Results indicated that the nonpregnant daughters and their mothers felt significantly more intimacy toward each other than did the pregnant daughters and their mothers. However, correlations of the mother and daughter scores revealed that the intimacy scores of the mothers of the pregnant daughters were positively correlated with their daughters' attachment scores, suggesting that the mothers and their pregnant daughters were more in agreement regarding their relationship than were the nonpregnant mother-daughter pairs.


The association between teacher attitudes, behavioral intentions, and smoking and the prevalence of smoking among seventh-grade students.

Seventh-grade students and teachers from twenty-three middle and junior high schools were surveyed to determine the association between teacher attitudes, behavioral intentions, and smoking behavior and the prevalence of student smoking. Teacher attitudes toward smoking policies were found to be strongly related to the current smoking behavior of the teacher but not consistently related to student smoking. In addition, teacher likelihood of intervening showed a modest association with teacher smoking status, with current smokers generally indicating being the least likely to intervene for student possession or use of cigarettes. Teacher intentions to intervene were strongly associated with the prevalence of smoking among boys but not girls.


Single-sex versus coeducational environment and achievement in adolescent females.

For women, the nature and range of experiences during the high school years take on special significance, since it is during this period that they usually weigh their various roles and adjust their levels of aspirations accordingly. If the high school environment is successful in reducing the discrepancy between what are often viewed as conflicting roles, adolescent females may place greater emphasis on achievement. It is within this context that the present paper explored the differential benefits of single-sex and coeducational schooling. The issue explored is not whether one is preferable for females; rather, the concern here is how each of these settings influences both achievement and personal fulfillment.


Relationship between peer status and health behaviors.

Over the past decade, univariate studies have identified peer-rated popularity/sociability as a correlate of individual health practices (e.g., alcohol and drug use, exercise habits). Yet, the relationship between multiple health habits and broader social competencies rarely has been systematically examined. Accordingly, using a multivariate approach, the present study investigated the relative influence of background characteristics (i.e., age, gender, race, family type, and socioeconomic status) and peer status on health-related behaviors (i.e., physical activity, eating habits, smoking, alcohol use, and stress-related behaviors) in 589 junior high school students (ages 11-13). In this sample, peer popularity provided no significant increment in the prediction of health habits over and above the effects explained by demographics. These results are consistent with current perspectives on health and interpersonal behaviors, and have important practical implications for the initiation and maintenance of healthful and risky practices in the natural environment.


The cognitive and social-emotional correlates of color deficiency in children: a literature review and analysis.

Although color deficiency is a prevalent problem in childhood, little is known about the cognitive and social-emotional variables linked to this visual deficit. A review of the literature revealed just seven empirical articles designed to explore the psychological functioning of color-deficient children, with the results yielding contradictory findings. An analysis of the literature indicated that the equivocal nature of past research may be due to an inadequate rationale explaining what outcome variables should be tied to color deficiency. This weakness can be remedied, and as a means toward that end, specific investigative recommendations are made to provide a more valid theoretical link between color deficiency and selected cognitive and social-emotional variables.


Predictors of adolescent female decision making regarding contraceptive usage.

The relationship of cognitive capacity, cognitive egocentrism, and experience factors to decision making in a contraceptive usage problem was examined. Fifty sexually active, unmarried females, ages 14-19, served as subjects. Using correlational, regression, and canonical correlational analyses, cognitive capacity and cognitive egocentrism variables, not experience with contraceptives, were found to be significantly related to, and predictive of, five of seven decision-making variables. Forty-one percent of the variance was accounted for in predicting the canonical decision-making variable. The implications of these results for future research are discussed.


The effect of free or reduced-price lunches on the self-esteem of middle school students.

This study proposed to determine whether 52 middle school students who received free or reduced-price meals suffered lower general or area-specific self-esteem than did 52 sixth-, seventh-, and eighth-grade students who did not receive such benefits. It further sought to determine whether self-esteem varied according to grade level. Using the Piers-Harris Children's Self-Concept Scale, no significant differences were found for either group at any grade level for general or area-specific self-esteem. Interpersonal process resources, the use of a checklist, short-term relief, defensiveness, and external forces are considered as possible explanations.


Is parental divorce a critical stressor for young adolescents? Grade point average as a case in point.

Previous studies have shown parental divorce to be associated with poor functioning of children and adolescents. Almost all of the studies attempting to delineate these effects, and to shed light on the differences between boys and girls, have limited data collection to postdivorce. This practice has left a void in the picture of divorce--specifically in the area of predivorce effects. The purpose of the present study was to examine academic functioning of young adolescents with respect to both pre- and postdivorce effects. Fifty-eight young adolescents (29 from families which subsequently divorced and 29 from families which remained intact) were studied. Results indicated that boys from subsequently divorcing homes had significantly poorer academic functioning prior to their parents' divorce than did boys whose families remained intact and girls whose parents divorced. Differentially, girls from subsequently divorcing families showed a decline in academic functioning which began prior to divorce and continued beyond the time of divorce. Possible explanations for these gender differences are explored, and the importance of examining predivorce effects is addressed.


A profile of young adolescents attending a teen family planning clinic.

The purpose of this study was to assess the client records of adolescents attending a teen family planning clinic to determine the reported episodes of sexually transmitted diseases, sexual abuse, alcohol and drug use, and other dysfunctional situations in the family. In addition, information about the initiation of sexual activity and sexual partners was assessed in the record review. Data were obtained from a county health department located in a metropolitan area of a southeastern state. A review of the records of 183 adolescents 15 years of age or younger provided information on ethnicity, grade in school, and assessment data from the clinic interviews and exams. Twenty-five clients said they were not sexually active when they came to the family planning clinic for the first time, and were brought to the clinic by a parent (usually the mother). Those clients who came without parents said they were sexually active. Forty-one percent had their first sexual experience between 12 and 13 years of age, 18% between the ages of 14 and 15, and the remainder before the age of 12. While over 7% specifically stated that they had been sexually abused or raped, an additional 19% described situations in the home or exhibited symptoms associated with a history of sexual abuse. Eleven percent had a history of two to three different sexually transmitted diseases, and 26% had three or more diseases. Seventy-two percent indicated that there was conflict in the home; several had left home because of abuse. Fourteen percent admitted using drugs, mostly cocaine or marijuana, and 17% reported that they used alcohol at least occasionally.


Developmental profiles of adolescents and young adults choosing abortion: stage sequence, décalage, and implications for policy.

Three groups of unmarried females (ages 12-14, 17-19, and 23-25) electing to have an abortion in the first trimester of their first pregnancy were administered the Washington University Sentence Completion Test, the Rest Defining Issues Test, and a moral judgment interview of their reasons for choosing an abortion. Results indicated that there were clear developmental differences between the youngest group and the two older groups on the general measures of ego development and principled moral reasoning, as theory would have predicted. There were, however, no major differences across the three groups on the level of reasoning which directly assessed the specific decision concerning abortion. Further, all three groups were assessed at the self-protective level characterized by Stage 2 reasons of financial consequences and the need to rely exclusively on one's own self in such a difficult dilemma. These findings and developmental profiles are compared to national base rates, and the possible implications of apparent décalage, or discrepancy between the general stage assessments and the specific assessment on abortion, are discussed. In addition, the similarity between the older group of adolescents and the young adults was examined, particularly in light of the current controversy over mandatory parental consent.


The effects of gender, race, religion, and political orientation on the sex role attitudes of college freshmen.

Freshmen (N = 556) at a large eastern private university were administered a questionnaire during the first week of classes. A social learning perspective was used to examine the effects of gender, race (Asian, black, and white), religion (Catholic, Jewish, and Protestant), and political orientation (liberal and conservative) on four areas of sex role ideology--traditional attitudes toward female sexuality, justification of male dominance, negative attitudes toward homosexuality, and attitudes toward feminism. Although all four independent variables produced a significant effect on at least one measure of sex role ideology, religion and political orientation produced significant differences on all four sex role measures. Liberals as compared to conservatives and Jews as compared to Protestants were less traditional in their attitudes toward female sexuality, less accepting of male dominance and negative attitudes toward homosexuality, and more accepting of feminist attitudes. The results support the view that entering freshmen have established sex role belief systems that tend to be organized around constellations of traditional/conservative versus egalitarian/liberal attitudes.


Temperament and self-esteem in late adolescence.

The purpose of this study was to investigate the relationship between temperament and self-esteem (or social competence) among late adolescents. The Dimensions of Temperament Scale and the Short Form of the Texas Social Behavior Inventory were administered to 186 students. It was found that Adaptability, Attention/Distractibility, and Reactivity all showed significant correlations with self-esteem. An interactive framework suggested that temperament may mediate how each individual perceives and experiences social demands and constraints, thereby influencing the level of positive regard and success during development.


Demographic, clinical, and personality variables associated with male prostitution by choice.

This research compared demographic, clinical and personality variables in a sample of 15 male prostitutes and 15 nonprostitutes from the same cohort. Unlike previous samples of male prostitutes, these young men specifically reported that they were involved by choice, primarily to earn extra money. Significant findings included heavier drug and alcohol use, more limited vocational success and aspirations, and greater alcohol use among family members of male prostitutes. Male prostitutes were also more likely to identify themselves as drug or alcohol addicted. No significant differences were found in personality characteristics between the two groups, although there was limited support for the hypothesis that male prostitutes are more antisocial.


Adolescent self-perception as a function of vision loss.

The potential effect of vision loss on adolescents' self-perception has been the subject of limited research. Several previous studies have failed to shed much light on this relationship. This study, utilizing a sample of adolescents with visual problems and a comparison sample with normal vision, found significant differences in dimensions of perceived self-concept between these groups. Some possible interpretations of these results are offered. The need for new research in this field of inquiry is emphasized.


An evaluation of parental assessment of the Big Brothers/Big Sisters program in New York City.

This study used a self-report survey to assess parents' impressions of the impact of the Big Brothers/Big Sisters program on their children. Parents rated program success on each of seven outcome variables (school attendance, grades, getting along with family members, getting along with friends, self-esteem, staying out of trouble, and being more responsible), and two program variables (frequency of contact and length of time in program). While children were rated by their parents as benefiting significantly from the program, children's frequency of contact did not have a significant effect on the outcome measures. However, a trend of increased success with greater time spent in the program was found. Frequency of contact between parents and Big Brothers/Big Sisters was positively correlated with reported success.


Holistic attitudes of high school students toward themselves and their school experiences.

This study was based on an analysis of essays written by 47 teacher education students in response to the question, "If you could live your high school days over again, what, if anything, would you change?" The responses were organized into 20 different categories and tabulated according to students' age and sex. In retrospect, 38% of these students would have improved their attitude toward high school. Thirty-six percent indicated that high school was a positive experience, though this attitude was often unrelated to academic achievement. The responses strongly suggest that for many high school students, general attitude toward school affects achievement more than do attitudes toward specific school characteristics.


The validity and devolution of a concept: student alienation.

This study examined the correspondence between conceptual and empirical dimensions of student alienation. Responses from 2,056 secondary school students were analyzed using a multivariate technique, smallest space analysis. Except for a few items, there was a basic correspondence between a multidimensional conceptualization of alienation and empirical dimensions articulated by students. Such a correspondence for both intermediate and high school students serves to strengthen confidence in the concept of multidimensional alienation specific to the school context.


Cytokine activation of killer cells in mycobacterial immunity.

Mycobacterium avium-intracellulare (MAI) is an ubiquitous soil contaminant that rarely causes disseminated disease in adults, regardless of immunological status. In AIDS patients, however, this microorganism invades virtually every tissue and organ, and most conventional chemotherapeutic agents are usually ineffective against MAI. We report here that monocytes, in which MAI has established an intracellular parasitic stage, appear to be under the control of natural killer (NK) cells. Autologous large granular lymphocytes (LGL), purified from human peripheral blood mononuclear cells (PBMC), were capable of efficiently lysing MAI-infected monocytes in a 5 hr 51Cr-release assay. More importantly, interleukin 2 (IL-2) was able to activate the LGL to a high degree of lysis of infected monocytes. Additionally, 3 to 4 days of incubation of LGL with MAI resulted in the induction of killer cells capable of killing bacterially-infected monocytes, as well as tumor cells. Northern blot analysis of RNA from MAI-stimulated LGL revealed specific messages for both IL-2 receptor proteins (p55 and p70). Thus, MAI can directly activate killer cells, which may therefore play a role in containment of MAI infection by lysis of parasitized monocytes before the bacteria can multiply and spread to other sites.


"Inverse" effects of cortisone in experimental infection of mice.

Hydrocortisone (HC) ameliorated the course of experimental infection with E. coli given intraperitoneally. In experiments with Staphylococcus aureus and treatment with endotoxin on the day of infection, HC had also a beneficial effect, however only when LPS was injected intraperitoneally and bacteria intravenously. With the footpad swelling reaction as a model for cellular immunity it could be shown that HC alone reduced the reactivity by 75 per cent. Under endotoxin treatment, however, HC induced further inhibition when LPS was given intraperitoneally the day of sensitization but changing to a stimulatory effect when LPS was given two days later. In case of intravenous application of LPS, HC had no effect.


Determination of the antiinfectious activity of RU 41740 (Biostim) as an example of an immunomodulator.

Evaluation of the anti-infectious activity of an immunomodulator performed either in vitro or in vivo in animals as in humans must answer three questions: what are the targets? what models should be used to study the mechanism of action? what methodology should be selected for the assessment of therapeutic benefit? In the case of RU 41470 (Biostim), an immunomodulator with a known structure and of biological origin affects immunocompetent cells and two essential mediators: II1 and CSF. Because of multiple interactions between anti-infectious, anti-inflammatory and anti-allergic responses, as well as the pleiotropism of mediators, there exists no absolute predictive index of activity in vivo and, independently of models of immune deficiency, experimental infections are a particularly useful pharmacological model for study of the anti-infectious activity of any immunomodulator. In this model, RU 41470 tested by oral, intraperitoneal and aerosol administration, proved to be active regardless of the type of infectious agent for extracellular bacteria, intracellular bacteria, viruses or yeasts. Because of special local features of anti-infectious defences (pulmonary, cutaneous), the target organ must be identified when studying mechanism of action. RU 41740 stimulates the metabolic activities of alveolar macrophage and the target organ is the respiratory tract. From a clinical pharmacology standpoint, stimulation of different immune components has been investigated with RU 41470 at different dosages, using double-blind versus placebo designs. Target pathology, regardless of severity, includes a risk of infection and the existence of an immunological deficiency. Chronic bronchitis is a reference pathology since patients are subject to episodes of infection, resulting in acute decompensation and contributing to worsening of the ventilatory obstructive disorder. Clinical efficacy in terms of anti-infectious prophylaxis must be evaluated by a strict methodological approach: randomized double-blind placebo-controlled trials with prolonged follow-up. RU 41470 is effective in prophylaxis of respiratory infections in chronic bronchitis (reduction in the number of respiratory infections, their duration and in antibiotic consumption) and in prophylaxis of respiratory tract infections in children over one year old. Clinicians faced with the perplexity of the mechanism of action of immunomodulators and their number are preoccupied above all by the response which such an anti-infectious immunomodulator can offer in a context of clinical reality.(ABSTRACT TRUNCATED AT 400 WORDS)


Enhancement of host resistance to opportunistic infections by ubenimex (bestatin).

Ubenimex is a low molecular biological response modifier (BRM) which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the effect of ubenimex on infection with Candida albicans was investigated in normal and immunosuppressed mice, and it showed a prophylactic effect. In normal mice, ubenimex prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with cyclophosphamide 4 days before infection, ubenimex at 5 mg/kg for 5 days significantly increased the number of survivors. Significant improvement in peritoneal leukocyte counts and in function of neutrophils including phagocytosis and release of activated oxygen was observed in ubenimex-treated mice. These results indicate that ubenimex is a potent BRM for prevention against opportunistic infections.


Cytokines and anti-fungal immunity.

In summary, we have defined a unique host resistance circuit that has not previously been investigated. For the host control of an opportunistic fungal pathogen such as C. albicans, we have definitive evidence to indicate that LGL can respond to C. albicans by producing key cytokines, i.e. TNF, IFNg, and GMCSF, to activate neutrophil function against C. albicans. The cytokine-producing LGL differs from the spontaneous tumoricidal LGL by being DR+; otherwise other markers are identical, i.e., CD2(+)-CD16+CD4-CD8-CD15-. From the point of view of the neutrophils, they can respond to these cytokines readily within 2 hr of activation and may utilize any of the 3 antifungal pathways, i.e., oxidative radical production, enzyme degranulation, and lactoferrin release, to control Candida. It is of importance to note that TNF and GMCSF have also been shown to have chemotactic properties on neutrophils (27,28). Thus, the cytokines produced by LGL may have bifunctional roles for PMN, in not only activating them but in mobilizing them to the site of fungal invasion. In addition, we have defined that C. albicans as well as the bacterial polysaccharide, LPS, can activate PMN to produce TNF. Since TNF is a neutrophil activating factor, this implies that neutrophils may self-regulate function in an autocrine manner or utilize released TNF to recruit neighboring PMN. The possibility exists that other cytokines may also be produced by neutrophils when activated with C. albicans. Future studies should indicate the true role of neutrophils in host resistance to infection and may lead to a new identity for neutrophils as an active participant in the afferent phase of the immune response rather than an end effector cell population, waiting for outside signals to mobilize and activate them.


Effects of medicinal plants on hemopoietic cells.

It has been found that Juzentaihoto (TJ-48), one of the traditional Japanese kampo (herbal) medicines, improves the general condition of cancer patients receiving chemotherapy and radiation therapy. We analyze how TJ-48 elicits such effect, and show that oral administration of TJ-48 accelerates recovery from hemopoietic injury induced by radiation and the anti-cancer drug mitomycin C. The effects are found to be due to its stimulation of spleen colony-forming units. Based on the present findings, we propose that the administration of TJ-48 should be of benefit to patients receiving chemotherapy, radiation therapy or bone marrow transplantation.


Immunomodulation of C3H/HeJ cells by endotoxin associated protein and lipopolysaccharide endotoxin.

Protein kinase C plays a vital role in the activation of C3H/HeJ B lymphocytes by endotoxin associated protein; however, it is unlikely that G proteins are involved in the early signals stimulated by EP. On the other hand, LPS suppresses C3H/HeJ B cell DNA synthesis induced by EP which may be the result of PKC down regulation. LPS inhibits C3H/HeJ B cells from progressing through the G1 phase of the cell cycle blocking RNA synthesis within the first 12 hr after the cells are stimulated. Finally, this inhibition extends to activation of the arachidonic acid metabolism in C3H/HeJ macrophages and T cell proliferation to a limited extent.


BRM activities of low-toxic Bordetella pertussis lipopolysaccharides.

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.


Direct approach to the difficult anterior neck region.

This article presents an alternative method to correct the sagging neck with a local dermolipectomy and median platysma duplication. The technique is recommended mainly for the older patient with redundant skin and fat in that region and who, for some reason, does not want to undergo a facelift.


Hypoplasia of the lower medial quadrant of the breast.

A corrective surgical technique is described for a newly defined deformity: hypoplasia of the lower medial quadrant of the breast. It involves reducing the usually enlarged nipple-areola complex and reshaping the breast by turning a glandular pedicled flap from the fairly large upper two quadrants on a medial base into the underdeveloped site of the medial lower quadrant. The method proved uniformly successful in 11 cases and 17 breasts involved.


Ultrasonic liposculpturing.

The author describes a revolutionary body contouring technique based on the surgical use of ultrasonic energy. It allows the selective destruction of only excess adipose tissue. The technique is based on three fundamental steps: (1) preparation of the areas to be treated with a large infiltration of a special solution, (2) treatment of the areas with ultrasonic energy through special titanium probes, (3) manual remodeling of the treated areas to eliminate the fluid from the bursted adipocytes (fatty acids). The advantages of this new technique are selective destruction of just the undesired tissues, elimination of the fluid from the adipose tissues, and the possibility of a real "lifting" of the skin of the treated areas, and a reduction of physical strain on the surgeon. The author has already treated more than 280 patients with excellent results and without contraindications or undesired side effects. The fundamental steps of ultrasonic liposculpturing, including a description of the physical principles on which the technique is based, are presented.


Influence of suction-assisted lipectomy on coagulation.

Suction-assisted lipectomy is the most commonly performed surgical aesthetic procedure in North America today. The procedure is not without significant morbidity, as death as well as serious nonfatal complications have been reported. Thromboembolic disease as a complicating factor of various types of surgical procedures and trauma has been well documented in the literature. Stasis, injury, and hypercoagulation--the limbs of Virchow's triad--contribute to predisposition for morbidity. The effects of stasis and injury are experienced with most operative procedures. We questioned whether suction-assisted lipectomy, in the appropriately selected and managed patient, would demonstrate a predisposition toward a hypercoagulable state and subsequent thromboembolic disease. In our group of ten female patients who underwent large-volume liposuction, a carefully selected assay of hematological factors demonstrated alterations consistent with a controlled response to tissue injury, but did not demonstrate a predisposition to a hypercoagulable state or subsequent increased risk of thromboembolic sequelae.


External skin excision in the sebaceous nose and supratip deformity.

Some sebaceous noses cannot be properly reduced in size because of redundant skin. After standard rhinoplasty some noses develop a supratip deformity that recurs even after subcutaneous removal of the scar tissue. These noses can be corrected only by wedge-shaped skin excision. Most patients much prefer a pleasantly shaped nose, even at the cost of a midline scar on the nose. Most surgeons are hesitant to add scars to the face. However, the vast experience with wounds following accidents, tumor excisions, or corrections of malformations has shown that generally scar formation on the nose is inconspicuous. Nineteen patients were treated successfully by skin excision at the time of primary rhinoplasty or by a second operation.


Local anesthesia in reduction mastoplasty for out-patient surgery.

To perform a breast reduction under local anesthesia we need a large amount of anesthetic with lasting effects. For this I use a solution of 25 cc of lidocaine, 25 cc of bupivacaine, and 1 cc of epinephrine in 350 cc of saline solution. The bupivacaine allows a 4-6-hour operation. Once the breast is infiltrated, a great amount of anesthetic is lost in the incision, in the dissection, and in the resected tissue. Thus, a low dose remains subcutaneously to be metabolized by the liver. The serum lidocaine levels are low during these operations, as demonstrated by fluorescence polarization immunoassay. Under analgesic sedation the submammary sulcus and the retroglandular space are infiltrated, blocking the perforants of the intercostal nerves, under the areola, beneath the skin where the incision is made and where the areola is placed. This procedure has been applied to many techniques of breast reduction by modifying the infiltration under the incision lines. For hypertrophy up to 1000 g, 200-300 cc of anesthetic solution is used for both breasts at one stage, while for gigantomastia, about 400 cc of anesthetic is used, infiltrating and reducing one after the other. As the blood loss is minimal and the recovery very fast, with an appropriate adhesive bandage and a "soutien," the patient could be discharged in the afternoon. Our experience includes 94 reduction mastoplasties with local anesthesia, and also 74 other mastoplasties with equally good results. There were no patient complaints and, in general, they felt very comfortable, awakening without pain or side effects.


Tissue suction of the male and female breast.

Liposuction has been used either alone or combined with resection for the correction of male and female breast deformities. The majority of the 32 patients in our study were treated for gynecomastia (69%). Other indications were Madelung's disease, gender dysphoria, asymmetry, hypertrophy, postburn and postreconstruction deformities. In 54% of the gynecomastia cases, suction alone gave a satisfactory result. In all but one male patient suction permitted us to avoid incisions other than periareolar incisions. Thirteen aspirates from gynecomastias and three glands resected secondarily after suction were examined histologically. All aspirates included glandular tissue. We conclude that breast tissue is accessible to the suction cannula, and that this is a valuable tool for correcting gynecomastia and for use in many aesthetic procedures on female patients.


Male reduction mammoplasty in serious gynecomastias.

This article is a report on long-term followup of a total of 44 serious gynecomastia cases in the stages I-III (according to Deutinger). The treatment consisted of either a semicircular incision and subcutaneous mastectomy or a superiorly or an inferiorly based nipple transposition while performing male reduction mammoplasty. Aesthetically pleasing results could be obtained by a periareolar approach and mastectomy. This inconspicuous procedure is feasible even in massive gynecomastia cases (stage III) or in cases of male breast asymmetry. On the other hand, all cases with breast reduction plasty and nipple transposition resulted in wing-shaped, mainly broad scars, and subjectively unfavorable results. Consequently, we favor the semicircular approach in male reduction mammoplasty in treating serious gynecomastias. With regard to possible male breast cancer etiology, the histological specimen of the mammary gland in gynecomastia is excised prior to any additional liposuction for supplementary body contouring.


Inferior pedicle reduction technique for larger forms of gynecomastia.

The treatment of larger types of gynecomastia is significantly different than that of less severe gynecomastias. Special concerns of the former include areola enlargement, nipple-areola ptosis, and redundant skin. Many procedures have been described to address these issues, none of which is completely satisfactory; these are reviewed here. Unsatisfactory results may be due to residual breast hypertrophy, skin redundancy, complications related to nipple-areola placement, form and viability, and cosmetically unacceptable scars. We describe a new technique that uses an inferior pedicle to reposition the nipple-areola complex and to maintain its neurovascular integrity and form. A superiorly based chest wall flap in conjunction with suction-assisted lipectomy maximizes chest wall contour. There are no breast mound scars, only a periareolar and inframammary scar.


Periareolar mastopexy with mammary implants.

We present our experience with using a periareolar mastopexy technique combined with prosthesis implantation to correct mammary ptosis, misplaced areolas, and tuberous hypoplastic breasts. We draw a circle around the areola and deepidermize the skin between them. We enter the glandular tissue and introduce the implant in a submuscular pocket. A purse string suture of nonabsorbable material is used to gather the excess skin. Results were satisfactory in all cases. During the immediate postoperative weeks the shape was flatter and protruded less, but a progressive correction was observed. The tuberous breast could be released and reshaped adequately. Misplaced areolas can also be replaced correctly by drawing the periareolar circle and ellipse in eccentric forms. This technique does not allow great elevation of the areola (no more than 4-5 cm), but it is good and safe for correcting minor to moderate ptosis combined with volume augmentation.


The use of leeches for treatment of venous congestion of the nipple following breast surgery.

The medicinal leech, Hirudo medicinalis, played a central role in the evolution of medieval and folk medicine. Today, for the first time in history, the leech actually has a real and valuable purpose in medicine as a useful adjunct for the plastic surgeon: It provides relief of venous congestion. For over 2000 years, leeches were needlessly applied for a multitude of maladies as an adjunct to blood-letting. Their use in Europe peaked between 1830 and 1850, however, shortages led to a subsequent decline in leech application. Today there is a real clinical use for leeches which had led to a resurgence in their use in plastic surgery. Plastic surgeons use leeches in microsurgery to salvage congested flaps, whose viability is uncertain due to venous congestion. We present our experience with two patients where leeches were used to treat isolated venous engorgement of the nipple following breast surgery. Leech therapy is painless, well tolerated, and does not result in significant scarring. Prompt initiation of treatment is mandatory and produces dramatic resolution of venous congestion.


Mandibular angle implants.

A new type of implant designed to increase the angle of the mandible in three dimensions is described. Made of silicone and shaped like a saddle, this implant makes the technique of implantation relatively simple, and its versatility makes it a desirable addition to the tools for skeletal framework reconstruction of the face. The satisfaction rate has been high and the complications easy to manage. The surgical technique consists of an intraoral incision and the development of a subperiosteal pocket at the mandibular angle area, often performed under local anesthesia.


Infracture technique for the zygomatic body and arch reduction.

In the Orient, prominent malar regions are considered unaesthetic and the majority of women with a prominent malar want to reduce the zygoma. Various operative procedures such as shaving or chiseling the zygomatic body or the zygomatic arch have been used for reducing malar eminence, but the zygomatic arch cannot be reduced sufficiently by these methods. By combining intraoral shaving of the zygomatic body and a new effect arch infracture technique through a temporopreauricular incision, we have obtained very satisfactory results in 19 cases and notable minimal complications over the last three years.


Association of age with regional cerebral oxygen utilization: a positron emission tomography study.

Positron emission tomography scans were performed on 14 normal subjects over the age of 50. Cerebral metabolic rate for oxygen (CMRO2) was assessed in a number of cortical and subcortical regions. There was a trend for a decrease in CMRO2 with age but this was significant only in the parietal lobe. There was a suggestion that the age/CMRO2 correlation became less strong with advancing age. CMRO2 in the occipital lobe, subcortical regions and cerebellum was not related to age. The relationship between CMRO2 and age is discussed.


Factors related to long-term stay in hospital by elderly people in a Japanese city.

The characteristics and social backgrounds of 61 elderly patients with long hospital stays and those of 179 incapacitated elderly people living at home in a Japanese city were compared. Discriminant function analysis was performed to clarify the factors associated with long-term use of hospital beds by elderly people. In addition to this analysis, the elderly patients with long hospital stays were divided into two subgroups according to the likelihood of discharge, and these subgroups were compared in the same way. The elderly patients with long hospital stays were more likely to be women, persons with low ADL, living alone and not living with a spouse or a second generation, compared with incapacitated elderly people living at home. Analysis of the subgroups of the elderly subjects with long hospital stays showed that use of a urethral catheter and not undergoing rehabilitation were the medical factors related to difficulty of discharge, while being women, of advanced age and not having their own room at home were the non-medical factors associated with long-term occupation of hospital beds.


Age-associated changes in mesenteric arteries.

Vascular disease increases in incidence with age and is the commonest cause of morbidity and mortality among elderly people. Hypertension is associated with hypertrophy of the arterial media. This study was designed to investigate changes in arterial structure that may occur with age independent of blood pressure. Collapsed sections of human mesenteric arteries (external diameter 2-3 mm) were measured using a semi-automatic image analysis system. There was a nonlinear increase in both the wall/lumen area ratio and the relative intimal area with age. There were no significant relationships between blood pressure and either the wall/lumen ratio or the relative intimal area.


Can elderly diabetic patients co-operate with routine foot care?

Foot care education is widely promoted as a preventive strategy for reducing foot ulceration in diabetes. We describe a simple method of assessing the ability of elderly diabetic patients to co-operate with foot care advice. Using small self-adhesive red spots, foot lesions can be simulated and patients advised and prompted to detect and inspect these 'lesions'. Nineteen young non-diabetic volunteers and three groups of 14 elderly patients were assessed: diabetic patients with a foot ulcer, diabetic patients with no history of foot ulceration and non-diabetic patients. Eleven (39%) of the diabetic patients were unable to reach their toes and remove the lesions and only 6 (14%) of all elderly patients could respond to plantar lesions. It is therefore unlikely that unsupported foot care education can be effective in reducing the morbidity of foot problems in the elderly diabetic patient.


Prevalence of biliary lithiasis in the elderly people of a small town in Sicily.

The aim of the present study was to determine the prevalence of biliary lithiasis (BL) and its major associated factors in the elderly people of a small town in Sicily. All inhabitants over the age of 65 were interviewed and underwent a general physical examination, blood tests and ultrasonography of the gallbladder and biliary tracts. The final group included 328 subjects (162 men and 166 women), representing 63.1% of the population asked to participate, with a mean age of 74.3 +/- 6.8 years (range 65-95). The prevalence of BL (lithiasis in progress + subjects cholecystectomized for previous calculosis) was 18.6%. No male subject had been cholecystectomized. Prevalence was higher in women than in men, but there was no progressive increase with age. There was no significant correlation between number of pregnancies and BL and there was no statistically significant difference between subjects with and without lithiasis for total cholesterol, triglycerides, HDL-cholesterol, A-I and B apoprotein values; a significant difference was found only for body weight values (p less than 0.01). Stones were more often multiple and more radiopaque than in younger subjects; specific symptoms and positive family histories were found in 22% and 18% of the study group, respectively.


Use of drugs by non-institutionalized urban Finns born in 1904-1923 and the association of drug use with mood and self-rated health.

The purpose of this study was to examine the use of drugs by elderly people and to investigate its associations with various other factors. Random sampling was used to select 800 interviewees born in 1904-13 and a further 800 born in 1914-23. The average number of prescribed drugs per person was 2.2. Women used a greater number of prescribed drugs than did men; and this difference increased with age. The use of vitamins and trace elements seemed to decline with increasing age. Among women a significant association between the use of prescribed drugs and depressive symptoms was found. Women in the older age group used prescribed drugs more often than women in the younger age group. One fifth of the subjects had a greater number of drugs in simultaneous use than is generally recommended. It seems that, especially among elderly women, depression often remains undiagnosed and treatments are chiefly provided for the associated symptoms.


Sex differences in cancellous and cortical bone strength, bone mineral content and bone density.

The purpose of this study was to examine sex differences in cancellous and cortical bone strength, bone mineral content (BMC) and bone density of excised cadaver vertebral and phalangeal bones. The samples were age-matched. Bone strength was measured as the mechanical force required to crush or break the bones. Two parameters of bone strength were used on the vertebrae; the force at the first deviation from linearity and the mean force during the consolidation before final failure. The force at first deviation from linearity was not significantly different between the sexes, but there was a significant difference in the consolidation force. The mean men's phalangeal strength was twice that of the women's. BMC and BMC/BW of both types of bone were statistically different between the sexes. Radiographic photodensity measures on the vertebrae showed no sex differences. Cortical diameters of the finger bones were significantly greater in males.


The role of age in susceptibility to pneumococcal infections.

Whether or not age by itself increases susceptibility to pneumococcal infections separate from the effects of chronic disease is controversial. To address this issue, data collected for a retrospective cohort study of pneumococcal infections among 63 middle-aged and older veterans and 126 uninfected controls were reanalysed. Univariate analysis suggested a linear increase in risk with increasing age for patients 50 years old and older (p = 0.03). Subjects over age 80 years seemed to be at particularly high risk when compared with patients under 50 (odds ratio = 4.3, p less than 0.03). The odds of pneumococcal infection increased by an estimated factor of 1.33 (95% confidence interval = 1.03, 1.71) for each 10-year increase in age. Controlling for other risk factors did not appreciably change the point estimate of the age effect, but statistical significance was lost. This result however suggests that age has an independent association with the risk of pneumococcal infections. The potential impact of this finding on public policy urges that the association of age with the risk of pneumococcal disease be re-examined in a study of sufficient sample size to resolve the issue.


Alcohol and acute medical admission of elderly people.

In a prospective study of 539 consecutive elderly medical admissions (mean age 77.3 years; 275 men), 42 patients (7.8%; 36 men) were identified as alcohol abusers, 41 by an alcohol intake history and one by a positive response to the CAGE questionnaire; none was identified by laboratory screening (gamma glutamyltransferase and red cell mean corpuscular volume) alone. Thirteen admissions (2%) were alcohol-related. In alcohol abusers, 24% of admissions (n = 10; p less than 0.001) were alcohol-related. Alcohol abusers were predominantly men (86%; p less than 0.001) and independently mobile (88%; p less than 0.001), suggesting greater physical fitness. In these more active men (n = 167), the prevalence of alcohol abuse was 19.8% and 6% of admissions were alcohol-related. While the sensitivities of the CAGE questionnaire and laboratory screening were too low to be clinically useful, an alcohol intake history may allow for a significant opportunity in preventive medicine in this age group, particularly in the fitter men.


Pulmonary function in gastro-oesophageal reflux disease of elderly people.

An effect of gastro-oesophageal reflux disease (GORD) on respiratory function was studied in elderly patients. Twenty-seven patients with, and 29 patients without, abnormal gastro-oesophageal reflux (GOR) in 24-hour pH monitoring were included in the study. Symptoms suggestive of gastrooesophageal reflux disease were recorded and spirometry was performed in all the patients. Patients with abnormal GOR had lower vital capacity (percentage of predicted value) (VC%) than those with normal pH monitoring result (92 vs 102, p = 0.032). Forced vital capacity (FVC%) and forced expiratory volume in one second (FEV1%) did not differ between these two groups. Thirty-two per cent of patients with slight and 73% of patients with moderate or severe reflux in pH monitoring had abnormal VC%, FVC%, or FEV1% (less than 80% of predicted value) at spirometry (vs 30% of patients without reflux, p = 0.039). When patients were divided according to their symptoms suggestive of GORD, lower VC%, FVC%, and FEV1% were found in patients with than in those without symptoms (87 vs 102, p = 0.0018; 76 vs 91, p = 0.0099; 80 vs 93, p = 0.0026). In conclusion, mainly a restrictive ventilatory defect was associated with GORD in elderly patients.


The selective protection afforded by ebselen against lipid peroxidation in an ROS-dependent model of inflammation.

The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.


Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet-activating factor.

The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED50 values in the range 20-30 mg/kg/3 days. Both were also equipotent in suppression of PMN infiltration induced by PAF with ED50 values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen-induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis.


RP 54745, a potential antirheumatic compound. I. Inhibitor of macrophage stimulation and interleukin-1 production.

RP 54745 is an amino-dithiole-one compound found to be active at micromolar concentration on the metabolism of stimulated macrophages, for example, the hexose monophosphate pathway (HMP) and the exocytosis of lysosomal enzymes. LPS-induced interleukin-1 (IL-1) production by murine peritoneal macrophages was also diminished by this compound in vitro as well as in vivo. This effect was confirmed at the mRNA level; at the concentration of 3 x 10(-6) M, the IL-1 alpha and beta mRNA signals were inhibited, whereas the TNF alpha mRNA signal was only slightly lessened. These observations were confirmed in vivo, with a dose of RP 54745 of 25 mg kg-1. These results led us to consider that RP 54745 might influence certain cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies.