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Biomedical subjects

A L Wolf

Publications and source records attributed to A L Wolf.

At least 19 recordsLinked to original sources

The effects of naltrexone on alcohol and cocaine use in dually addicted patients.

Concurrent dependence on cocaine and alcohol is common among patients seeking addiction treatment. This study was undertaken to explore the effectiveness of naltrexone (150 mg) as a potential treatment for patients who are alcohol and cocaine dependent. Of 15 subjects enrolled in the 12-week, open medication trial, 7 subjects did not complete the study. Relapse to clinically significant drinking occurred in 7 subjects (47%). There was a reduction in the average daily amount of alcohol consumed from pretreatment to treatment (p < .001) and the percentage of days engaged in drinking behavior (p < .001). Similarly, there was a reduction in the average weekly amount spent on cocaine from pretreatment to treatment (p = .001) and the percentage of days using cocaine (p < .001). This preliminary study suggests that naltrexone (150 mg) may be tolerable in patients dependent upon alcohol and cocaine and may be effective in reducing both cocaine and alcohol use. The results of this study provide a rationale for a double-blind placebo-controlled study of the efficacy of naltrexone in this difficult to treat but prevalent population.

Adult↗

Gender differences in comorbidly depressed alcohol-dependent outpatients.

UNLABELLED: Clinical profiles of alcohol-dependent male and female outpatients were evaluated at treatment entry to compare the level of clinical severity in alcoholics with a coexistent comorbid depressive disorder to alcoholics who have never been depressed. Due to a higher proportion of females than males in the depressed alcoholic population, selected patient groups were oversampled to create a study group with equivalent number of males and females with and without comorbid depression. Clinical severity was assessed by examining both the extent of alcohol problems, and depressive symptomatology at treatment entry with respect to gender differences (unrelated to depression), effects of comorbid depression (unrelated to gender), and effects from the interaction of gender and depression. There were 93 DSM-III-R alcohol-dependent outpatients (50 males, 43 females), half of whom had a current or lifetime DSM-III-R depressive disorder. The amount of drinking in the 90 days before treatment entry, the degree of alcohol severity, and the number of lifetime drinking-related consequences were collected in the first week after detoxification. Diagnoses of lifetime and current depression were determined via the Structured Clinical Interview for DSM-III-R, and depressive symptoms were evaluated with rating scales 1 week after detoxification. In most cases, a depressive disorder was diagnosed only if sometime in the patient's history depressive symptoms had either predated problem drinking or been present during a 6-month abstinent period. RESULTS: depressed males had a more severe clinical profile with respect to their alcoholism (i.e., more drinking, drinking-related problems, and alcohol severity than depressed females and never-depressed males). Surprisingly, females who had never been depressed (also no family history of depression) reported drinking the same quantities of alcohol in the 90 days before treatment and had comparable alcohol severity and number of consequences as males who had never been depressed. Depressed females, however, were more severely depressed (i.e., reported more intensive depressive symptoms than depressed male alcoholics). Thus, determining the type and extent of clinical severity at treatment entry in comorbidly depressed alcoholics depends on the gender of the patient The significant interaction between gender and the presence of comorbid depression that was found in this study may have important implications for predicting success in treatment.

Alcohol Drinking↗

Focal cortical resections for the treatment of extratemporal epilepsy in children.

Epilepsy in children is a common and disabling disorder. Approximately 10% to 20% of patients who develop seizures will have medically intractable epilepsy. This group of patients may be candidates for epilepsy surgery. Unlike adults, epilepsy in children frequently arises in extratemporal sites. The surgical treatment of this extratemporal epilepsy is discussed in this article.

Adolescent↗

Cytokine-gene expression in measles-infected adult human glial cells.

The expression of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF) alpha transcripts in cultured human glial cells was examined using reverse transcription followed by polymerase chain reaction (PCR) amplification and Southern blot quantitation. Microglial cultures derived from brain biopsy specimens from three different individuals expressed transcripts for the three cytokines under basal culture conditions. This expression was enhanced in response to measles virus (MV) infection (IL-1 beta, 2.2-8.8-fold; IL-6, 2.5-8.4-fold; TNF alpha, 2.2-3.2-fold). Neither IL-1 beta nor TNF alpha transcripts were detectable in undissociated brain tissue from two individuals, suggesting that the basal expression of these cytokines in culture may have been induced by tissue dissociation or by the culture conditions. Oligodendrocytes did not express cytokine transcripts under basal culture conditions, and IL-1 beta and IL-6 but not TNF alpha transcripts could be induced by MV. Similarly, meningeal fibroblasts expressed IL-1 beta and IL-6 but not TNF alpha in response to MV-infection, suggesting that the production of TNF alpha is more cell type-restricted than either IL-1 beta or IL-6. The results indicate that adult human microglia can participate in the inflammatory response to MV infection in the CNS by producing cytokines that contribute to inflammation and demyelination. In addition, besides their role in myelination, oligodendrocytes can potentially influence immunoreactivity in the CNS by producing IL-1 beta and IL-6.

Adolescent↗

Melanoma arising in a cervical spinal nerve root: report of a case with a benign course and malignant features.

A 20-year-old caucasian woman with a 5-year history of right arm, neck, and back pain sought treatment when an automobile accident (4 months before admission) exacerbated her pain. Magnetic resonance imaging revealed an intra- and extradural mass compressing the spinal cord at the C5-C6 level. It also extended into and widened the neural foramen, mimicking a neurofibroma. A single cafe-au-lait spot was discovered in the inguinal region. A two-staged surgical resection was performed on an apparent hemorrhagic C6 nerve root mass. The mass exhibited diagnostic features of a malignant melanoma histologically, immunocytochemically, and ultrastructurally. A search for a primary lesion outside the nervous system or other metastases during an 8-year period from the onset of symptoms has been negative. The patient's chronic history, evidence of neural foraminal enlargement, and the absence of other malignant melanoma lesions or subsequent metastases indicates that this lesion may be a primary melanoma of the nerve root with a benign course.

Adult↗

Thoracic epidural abscess.

Twenty-one cases of thoracic spinal epidural abscess occurring over a 10-year period were retrospectively reviewed. Diagnosis was made by MRI or myelography and confirmed in the operative cases. A bacterial agent was isolated in 18 of the cases (86%). When measured, the erythrocyte sedimentation rate was elevated in all cases. Four patients who presented without neurologic deficits remained intact. All patients who presented with neurological deficits underwent surgical intervention in addition to intravenous antibiotics. Of the 15 patients who presented with a paraparesis of less than antigravity strength, five eventually were independent ambulators and continent. A good outcome resulted in 80% of those who underwent decompression within 24 h, as opposed to only 10% of the patients decompressed after 24 h. Good results can be obtained despite severe neurologic compromise when treated by rapid diagnosis and decompression of the spinal canal.

Abscess↗

Epidural abscess in the cervical spine.

A ten-year retrospective review of 23 cases of documented spinal epidural abscess in the cervical spine was undertaken to define the clinical features and establish current diagnostic and therapeutic criteria. Diagnosis was made by magnetic resonance imaging or myelography. Risk factors included intravenous drug abuse, diabetes mellitus, previous trauma, and a positive serologic test for the human immunodeficiency virus. A bacterial agent was isolated in 21 cases (91%). Neurologic deficits were present in 20 of the cases (87%) at the time of diagnosis. Erythrocyte sedimentation rate was elevated in all patients in whom it was measured. All patients were treated with appropriate antibiotics, usually for 6 to 8 weeks. Twenty-one patients underwent operative procedures using percutaneous aspiration (1 patient), the anterior approach (14 patients) or the posterior approach (4 patients), or a combination of the two approaches (2 patients). Four of ten patients who initially had less than antigravity strength were eventually ambulatory and continent; in each case, operative decompression was performed within 36 hours of initial consultation. Three patients who had no initial neurologic deficits remained intact.

Abscess↗

Effect of THAM upon outcome in severe head injury: a randomized prospective clinical trial.

Although mortality and morbidity rates from head injury have been reduced substantially by improved prehospital interventions, intensive care, and aggressive management of intracranial pressure (ICP), successful treatment of the primary brain injury has been elusive. In experimental models, tromethamine (THAM) has been effective in treating head injury; this drug acts by entering the cerebrospinal fluid compartment, reducing cerebral acidosis and ICP, and reversing the adverse effects of prophylactic hyperventilation on early recovery. In this randomized prospective clinical trial, THAM was studied to determine if it had beneficial effects in the early management of severe head injuries and if the adverse effects of hyperventilation could be prevented. A total of 149 patients with severe head injury (Glasgow Coma Scale scores of < or = 8) were randomly assigned to either a control or a THAM group. Both groups of patients matched in terms of clinical parameters, including age, sex, number of surgical mass lesions, number in each Glasgow Coma Scale stratum, and first ICP measurement. All patients were treated by a standard management protocol, intubated, mechanically ventilated, and maintained in the pCO2 range of 32 to 35 mm Hg for 5 days. Tromethamine was administered as a 0.3-M solution in an initial loading dose (body weight x blood acidity deficit, average 4.27 cc/kg/hr) given over 2 hours, followed by a constant infusion of 1 ml/kg/hr for 5 days. Outcome was measured at 3, 6, and 12 months postinjury. Although analysis indicated no significant difference in outcome between these two groups at 3 months, 6 months, and 1 year, there was a difference regarding ICP. The time that ICP was above 20 mm Hg in the first 48 hours postinjury was less in patients treated with THAM (p < 0.05). Also, the number of patients requiring barbiturate coma was significantly less in the THAM group (5.48% vs. 18.4%, p < 0.05). The authors conclude that THAM ameliorates the deleterious effect of prolonged hyperventilation, may be beneficial in ICP control, and warrants further study as to the dosage and timing of administration.

Adolescent↗

Human T-cell leukemia virus type I infection of monocytes and microglial cells in primary human cultures.

The pathogenesis of progressive spastic paraparesis [HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)], a serious consequence of human T-cell leukemia virus type I (HTLV-I) infection, is unclear. T and B lymphocytes can be naturally infected by HTLV-I, but the susceptibility to HTLV-I infection of other cell types that could contribute to the pathogenesis of HAM/TSP has not been determined. We found that a human monocyte cell line (THP-1), primary human peripheral blood monocytes, and isolated microglial cells but not astrocytes or oligodendroglial cells derived from adult human brain were infected by HTLV-I in vitro. Infection with HTLV-I enhanced the secretion of interleukin 6 in human microglial cell-enriched cultures but did not stimulate the release of interleukin 1 from monocytes or microglial cells. Tumor necrosis factor alpha production was stimulated by HTLV-I infection of monocytes and microglial cells and could be enhanced by suboptimal amounts of lipopolysaccharide. Since both tumor necrosis factor alpha and interleukin 6 have been implicated in inflammatory demyelination and gliosis, our findings suggest that human microglial cells and monocytes infected with and activated by HTLV-I could play a role in the pathogenesis of HAM/TSP.

Brain↗

Spinal epidural abscess: a report of 40 cases and review.

Despite modern medical advances, the morbidity and mortality rates associated with spinal epidural abscess remain significant, and the diagnosis often is elusive. A retrospective study was undertaken to define better the incidence and clinical features of this infection, and to establish current diagnostic and therapeutic guidelines. Forty cases of spinal epidural abscess were encountered at our institution between July 1979 and March 1991. All medical records and radiological images were reviewed. We report a significant increase in the incidence of epidural abscess after June 1988 (p = 0.0195). Sixteen patients used drugs intravenously, and six had undergone spinal procedures. Twelve patients were misdiagnosed in various emergency rooms or clinics and discharged. Localized back pain, fever, and neurological deficit remained the typical clinical manifestations. Erythrocyte sedimentation rate was elevated uniformly when measured (21 cases). Magnetic resonance imaging was diagnostic specifically in 23 of 24 instances. The majority of patients underwent surgical drainage, but five selected patients were managed nonoperatively. The highly variable presentation of spinal epidural abscess may confuse the diagnosis and delay indicated surgical intervention. Localized back pain in a febrile patient at significant risk for epidural abscess warrants erythrocyte sedimentation rate measurement. The presence of erythrocyte sedimentation rate elevation or evidence of spinal cord compression on physical examination are indications for immediate magnetic resonance imaging examination with contrast enhancement. Surgical drainage with sustained intravenous antibiotic treatment remains the cornerstone of therapy. Nonoperative management may be considered in selected cases.

Adolescent↗

Bodysurfing accidents resulting in cervical spinal injuries.

During the summers of 1987 and 1988, 14 cervical spine injuries sustained during bodysurfing accidents at the beaches around Ocean City, Maryland presented to our Neurotrauma service. All the patients were men, predominantly in their middle years (mean age = 40), and otherwise healthy. Likely mechanisms of injury suggested by radiography and computed tomography-myelography included hyperflexion, hyperextension, and axial loading. Clinically, neurologic deficits were found in 10 patients (71%), of whom 2 were complete sensorimotor quadriplegics below the level of injury, and 8 were incomplete injuries. Of the eight incomplete injuries, two-thirds were central cord syndromes associated with narrow spinal canals and prominent osteophytes, and one-third had Brown-Sequard or anterior cord syndromes. After initial anatomic realignment by closed or open reduction, the injured cervical spines were stabilized either externally or internally. Two patients underwent laminectomies. These bodysurfing accidents, in marked contrast to other types of shallow water-diving accidents, predominantly involved older men and produced incomplete injuries. It is concluded that bodysurfing is peculiarly hazardous to healthy, middle-aged men, especially those endowed with a narrow spinal canal with or without osteophyte formation.

Adult↗

Myelographic and enhanced computed tomographic appearance of acute traumatic spinal cord avulsion.

The neuroradiological findings that revealed spinal cord transection/laceration in 6 patients with acute, blunt spinal trauma are described. Four patients suffered cervical spine injuries, and two had thoracic injuries. Initially, all patients had complete neurological deficit at the level of injury. The deficit improved in only 1 patient. On the basis of clinical history and spinal radiographs, spinal hyperflexion with distraction was the predominant mechanism of injury in our patients. Computed tomography with intrathecal contrast was performed on all patients and was always diagnostic. Visualization of intrathecal contrast material accumulating within the cord or the absence of cord shadow within the contrast column established the diagnosis in all cases. A dural tear was noted in 3 patients. Thoracic myelography was performed in 2 patients and, in both, demonstrated contrast pooling within the spinal cord at the level of the laceration. Magnetic resonance imaging was obtained in 1 patient and revealed an irregular, low-signal-intensity, intramedullary region extending to the cord surface on T1-weighted axial images. The myelographic and enhanced computed tomographic appearances of acute, traumatic spinal cord avulsion/laceration, which have been infrequently reported in the literature, are described.

Acute Disease↗

Allografts of CNS tissue possess a blood-brain barrier. II. Angiogenesis in solid tissue and cell suspension grafts.

Angiogenesis and patency of blood vessels were analyzed qualitatively in solid CNS and peripheral tissue syngeneic, allogeneic, and xenogeneic grafts and in individual cell suspension grafts of astrocytes, fibroblasts, PC12, and three additional tumor cell lines placed intracerebrally in adult host mice. Postgrafting survival times were 1 day through 4 weeks. The patency of graft vessels was determined in sections from immersion-fixed tissues incubated to reveal the endogenous peroxidase activity of host red cells trapped within the lumen of blood vessels. Additionally, horseradish peroxidase (HRP) was administered intravenously to live hosts; HRP labels host brain and graft vessels on the luminal surface and reveals the presence or absence of a blood-brain barrier (BBB) within the grafts. The origins of blood vessels supplying solid tissue xenografts were identified immunohistochemically with primary antibodies against host (athymic AKR mice) and donor (fetal Lewis rats) major histocompatibility complex (MHC) class I. Blood vessels supplying solid CNS grafts at 1-7 days post-transplantation were identified ultrastructurally and possessed interendothelial tight junctional complexes; however, they were not perfused with either host blood or blood-borne HRP prior to 8 days. Graft vessels at 10 days were outlined consistently by peroxidase-positive red cells in immersion-fixed material and labeled with blood-borne HRP. These vessels provided a BBB to the circulating HRP and exhibited interendothelial tight junctions. Evidence of angiogenesis within solid anterior pituitary grafts and the variety of cell suspension grafts was obtained prior to 3 days post-transplantation in immersion-fixed preparations; the vessels, with the notable exception of those supplying astrocyte cell suspensions, failed to present a BBB to blood-borne peroxidase. Endothelia in the solid pituitary allografts and the PC12 cell grafts were highly fenestrated and exhibited open interendothelial junctions; those in the tumor and fibroblast cell grafts, for the most part, appeared nonfenestrated, and many possessed open interendothelial junctional complexes. Immunostaining for host and donor MHC class I revealed that donor blood vessels predominate over host vessels in CNS xenografts and supply pituitary xenografts exclusively; in both preparations, donor vessels were not identified within the host CNS. Because cell suspension grafts were derived from endothelia-free preparations grown in culture, blood vessels supplying these grafts were necessarily of host CNS origin and manifested a morphological transformation from a BBB to a non-BBB endothelium. The data suggest that angiogenesis in solid CNS grafts placed into the adult host CNS, compared to similarly placed solid peripheral tissue/cell suspension grafts, is not rapid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Complete temporal lobectomy for surgical resuscitation of patients with transtentorial herniation secondary to unilateral hemispheric swelling.

Transtentorial herniation is an ominous finding in the patient with head injuries. We report our experience with 10 patients suffering from acute transtentorial herniation secondary to posttraumatic unilateral hemispheric swelling who were treated aggressively with temporal lobectomy. Eight patients were men and 2 were women. Their ages ranged from 22 to 61 years, with a mean of 37 years. Their preoperative Glasgow Coma Scale scores ranged from 3 to 6, with a mean of 4. All patients had both computed tomographic and clinical evidence of unilateral hemispheric shift and acute herniation without a significant subdural or epidural hematoma. Seven patients had unilateral nonreactive pupils and 3 had bilateral nonreactive pupils. All were taken to the operating room within 2 hours of clinical signs of herniation. Complete unilateral temporal lobectomies including the mesial structures, amygdala, and uncus were performed. In this series, the mortality rate was 30%, including a single patient who was neurologically stable but died from nonneurological injuries. Of the 7 survivors, 4 were functionally independent and 3 required minimal assistance with the activities of daily living. Aggressive, early decompression via complete temporal lobectomy may thus significantly improve the outcome in patients with transtentorial herniation accompanying posttraumatic hemispheric swelling and midline shift.

Adult↗

Posterior spinal osteosynthesis for cervical fracture/dislocation using a flexible multistrand cable system: technical note.

Cervical instability secondary to fracture/dislocation or traumatic subluxation involving the posterior elements may be treated by a variety of fusion techniques. The rigidity of the stainless steel wires used in posterior cervical fusions often leads to difficulty with insertion, adequate tension, and conformation of the graft construct. This report describes a technique of posterior cervical fusion employing a wire system using flexible stainless steel cables. The wire consists of a flexible, 49-strand, stainless steel cable connected on one end to a short, malleable, blunt leader with the opposite end connected to a small islet. The cable may be used in occipitocervical, atlantoaxial, facet-to-spinous process, and interspinous fusion techniques. The cable loop is secured by using a tension/crimper device that sets the desired tension in the cable. In addition to superior biomechanical strength, the flexibility of the cable allows greater ease of insertion and tension adjustment. In terms of direct operative instrumentation in posterior cervical arthrodesis, involving both the upper and lower cervical spine, the cable system appears to be a safe and efficient alternative to monofilament wires.

Bone Wires↗

Acute traumatic midbrain hemorrhage: experimental and clinical observations with CT.

Traumatic brain stem hemorrhage (TBH) after blunt head impact is an uncommon injury and has historically been associated with high mortality. Retrospective clinical review identified 64 patients with TBH admitted during a 5-year period. Complete imaging and clinical records for 45 of these patients demonstrated that TBH could be categorized into three groups. The most frequent site of hemorrhage, in 31 (69%) of 45 patients (group 1), was the midline rostral anterior brain stem, posterior to the interpeduncular cistern, and this injury was associated with a 71% survival rate. This pattern was also associated with a predominantly anterior site of head and/or face impact. Eight (18%) patients (group 2) had miscellaneous foci of acute brain stem hemorrhage with seven (88%) surviving. Six (13%) patients (group 3) had brain stem hemorrhage associated with transtentorial herniation and brain stem compression, with 100% mortality. Experimental findings in a canine model and clinical results indicate that the anterior rostral midbrain is a common site of TBH and appears to arise from sudden craniocaudal displacement of the brain at impact. Survival is unexpected high with this location of traumatic midbrain hemorrhage.

Acute Disease↗

Angiogenesis and the blood-brain barrier in solid and dissociated cell grafts within the CNS.

Available evidence suggests that blood vessels indigenous to solid CNS and peripheral tissues grafted to the brain are sustained and maintain the morphological and permeability characteristics they manifest in normal life. Furthermore, these vessels of graft origin anastomose (albeit not rapidly) with vessels of the surrounding host tissue predominantly at the host-graft interface and less so, or not at all, within the graft itself. For these reasons, blood-brain and brain-blood barriers, evident in the late fetal and neonatal CNS, can be expected to exist within CNS grafts placed intracerebrally or extracerebrally, providing the graft remains viable. Peripheral neural and non-neural tissues not possessing cellular barriers to circulating macromolecules do not acquire such barriers subsequent to their transplantation within the CNS. The absence of a blood-brain barrier in the adrenal gland grafted intracerebrally may be relevant for the treatment of Parkinson's disease with blood-borne therapeutics. Compared to solid tissue grafts, cell suspension grafts have the potential of becoming vascularized rapidly. That cell suspensions of neurons and of glia are supplied with BBB vessels of host origin and that the permeability characteristics of host BBB vessels are altered by a tumor cell suspension reaffirm the belief that the type of transplanted cell/tissue indeed determines the permeability characteristics of the blood vessels supplying it. The suspected immunologic privilege of the CNS is not absolute. Eventual host rejection of allografts placed within the third ventricle may be a dual consequence of the absence of a BBB at the level of the host median eminence and involvement of the minor histocompatibility complex.

Animals↗