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Biomedical subjects

S L Wald

Publications and source records attributed to S L Wald.

At least 19 recordsLinked to original sources
PubMed2000

Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells.

OBJECTIVE: Recent experimental data have shown that dietary soy isoflavones such as genistein can significantly suppress invasiveness and growth of a number of human malignancies. In this study we examined whether genistein, at a concentration typical of plasma levels following soy formula intake, in combination with cisplatin or vincristine exhibited an additive or synergistic inhibitory effect on the growth of medulloblastoma cells. METHODS: Three human medulloblastomas cell lines (HTB-186, CRL-8805 and MED-1) were treated with genistein at 6 microM, the maximum reported dietary plasma level in children, combined with cisplatin (0-10 microM) or vincristine (0-1 microM). Monolayer cell growth and cytotoxicity, as measured by colonigenic survival in soft agarose, were then compared in control and drug-treated cultures. Presence of apoptosis, using the DNA ladder assay and laser scanning cytometry, was investigated in all cell lines at those concentrations at which an enhancement of antiproliferative effect of cisplatin and vincristine in presence of genistein was observed. RESULTS: Genistein at 6 microM led to a 2.8-fold increase in the monolayer growth inhibitory effect of cisplatin (0.05 microM) in HTB-186 cells (p = 4.5 x 10(-4) by one-tailed t test). Genistein increased colonigenic survival inhibition of HTB-186 2.6-fold at the same cisplatin concentration (p = 1.5 x 10(-4)). Genistein caused a 1. 3-fold increase in antiproliferative effect of cisplatin (0.5 microM) in CRL-8805 cells (p = 3.1 x 10(-4)). Similarly the inhibition of colonigenic survival was enhanced 2.0-fold in CRL-8805 (p = 1.22 x 10(-5)). The addition of genistein to 0.5 microM cisplatin led to a 1.7-fold increase in monolayer growth inhibition and 2.4-fold increase in colonigenic survival inhibition of MED-1 cells (p = 8.3 x 10(-4) and p = 1.1 x 10(-4) respectively). These effects were primarily synergistic but also additive in nature. The combination of genistein and vincristine, as compared to vincristine alone, caused a minimal-to-modest increase in antiproliferative effect on medulloblastoma cells studied here. We were unable to detect apoptosis by two methodologies in any of the medulloblastoma lines when genistein was combined with cisplatin or vincristine. CONCLUSION: These results indicate that genistein at typical dietary plasma levels can significantly enhance the antiproliferative and cytotoxic action of cisplatin and, to a lesser extent, vincristine. The implication for treatment of medulloblastomas of early childhood may be a reduction in the chemotherapeutic dose recommendations of these agents and subsequently a decrease in the risk of treatment sequelae for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Computed tomographic angiography as a screening modality for blunt cervical arterial injuries: preliminary results.

BACKGROUND: The diagnosis of blunt cervical arterial injury (CAI) is made difficult by its infrequent occurrence and delayed presentation. Beginning in January of 1995, we used computed tomographic angiography (CTA) of the neck to screen for CAI. We hypothesized that CTA could be incorporated into the workup of patients sustaining blunt neck injury as a screening modality for CAI and that CTA would increase the early detection of CAI. METHODS: Retrospective review of all CAI for the years January of 1988 to June of 1997 at a Level I trauma center. CAI diagnosed before introduction of CTA (pre-CTA; January of 1988 to December of 1994) were compared with those after (post-CTA; January of 1995 to June of 1997). RESULTS: The overall incidence of CAI for the entire time period was 0.11%. Motor vehicle crash (53%) was the most common mechanism, with focal neurologic deficit (23%) or seizures (17.6%) the most common presenting clinical symptoms. CTA added only a few additional minutes to the time required for the workup of patients sustaining blunt neck injury in whom CAI was suspected. The incidence of CAI increased from 0.06% pre-CTA to 0.19% post-CTA (p = 0.02; Fisher exact test). CTA was associated with a decrease in mean time to make the diagnosis of CAI (156 hours pre-CTA vs. 5.9 hours post-CTA). In addition, CTA was associated with a decrease in the incidence of permanent neurologic sequelae from CAI (50% pre-CTA vs. 0% post-CTA; p = 0.07; Fisher exact test). CONCLUSION: We conclude that CTA does not significantly increase the time of the diagnostic workup of the patient with injuries caused by blunt trauma. The introduction of CTA at our institution was associated with an increase in the detection rate of CAI. Earlier detection of CAI may allow for more timely therapeutic intervention and potentially prevent permanent neurologic sequelae.

Accidents, Traffic↗
PubMed1999

Pediatric blunt carotid injury: a review of the National Pediatric Trauma Registry.

Blunt carotid injury (BCI) is an uncommon yet potentially devastating entity which has received little attention in the pediatric literature. In an attempt to better characterize pediatric BCI, a review of the National Pediatric Trauma Registry was performed. Records were obtained from all children diagnosed with internal or common carotid injury associated with blunt trauma. The incidence of BCI was 0.03% (15 of 57,659 blunt trauma patients). Variables examined included: age, gender, mechanism of injury, associated injuries, various injury severity scores, and outcome. Various injuries were associated with an increase in BCI incidence including chest trauma (4-fold), combined head and chest trauma (6-fold), basilar skull fractures (4-fold), intracranial hemorrhage (6-fold), and clavicle fractures (8-fold). Thirty-three percent of the patients diagnosed with BCI suffered neurological complications directly attributable to their carotid injuries. Current practices regarding screening, diagnosis, and treatment are reviewed.

Adolescent↗
PubMed1998

Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial.

BACKGROUND: Experimental and clinical work has suggested that hypertonic saline (HTS) would be better than lactated Ringer's solution (LRS) for the resuscitation of patients with head injuries. No clinical study has examined the effect of HTS infusion on intracranial pressure (ICP) and outcome in patients with head injuries. We hypothesized that HTS infusion would result in a lower ICP and fewer medical interventions to lower ICP compared with LRS. METHODS/DESIGN: Prospective, randomized clinical trial at two teaching hospitals. RESULTS: Thirty-four patients were enrolled and were similar in age and Injury Severity Score. HTS patients had a lower admission Glasgow Coma Scale score (HTS: 4.7+/-0.7; LRS: 6.7+/-0.7; p = 0.057), a higher initial ICP (HTS: 16+/-2; LRS: 11+/-2; p = 0.06), and a higher initial mean maximum ICP (HTS: 31+/-3; LRS: 18+/-2; p < 0.01). Treatment effectively lowered ICP in both groups, and there was no significant difference between the groups in ICP at any time after entry. HTS patients required significantly more interventions (HTS: 31+/-4; LRS: 11+/-3; p < 0.01). During the study, the change in maximum ICP was positive in the LRS group but negative in the HTS group (LRS: +2+/-3; HTS: -9+/-4; p < 0.05). CONCLUSION: As a group, HTS patients had more severe head injuries. HTS and LRS used with other therapies effectively controlled the ICP. The widely held conviction that sodium administration will lead to a sustained increase in ICP is not supported by this work.

Adult↗
PubMed1996

Multiple intradural spinal lipomata with intracranial extension.

An intradural, intramedullary lipoma originating within the upper cervical cord with significant extension into the posterior fossa is reported in an infant. Two additional lipomas were found in the lumbar region. This constellation of findings represents the first description of multiple intradural, intramedullary spinal lipomas with extensive intracranial involvement.

Cerebral Ventricle Neoplasms↗
PubMed1995

Advances in the early management of patients with head injury.

The last decade has seen continual improvement in our skills of visualizing and diagnosing the many types of human head injury. As we continue to unravel the complex biochemistry and molecular changes caused by trauma, we expect to find new methods and agents to enhance the extracellular milieu of injured but salvageable neurons and supporting cells, resulting in continued improvement in outcome for patients with severe head injury.

Brain Injuries↗
PubMed1995

Spinal anesthesia for repair of meningomyelocele in neonates.

The use of spinal anesthesia for meningomyelocele repair in neonates has received minimal attention. Spinal anesthesia may lessen the stress response to surgery and decrease postoperative respiratory complications. We therefore examined the efficacy of spinal anesthesia in 14 neonates requiring repair of lumbar or sacral meningomyelocele. All neonates were positioned prone with a small chest roll. Hyperbaric 0.5% tetracaine with epinephrine was injected into the caudal end of the meningomyelocele sac. If necessary, supplemental tetracaine was administered directly into the intrathecal space by the surgeon during the operation. Blood pressure, heart rate, and oxyhemoglobin saturation were measured throughout surgery. Neonates were monitored with transthoracic impedance apnea monitors, electrocardiogram (ECG), and pulse oximetry for 36 h after surgery. Spinal anesthesia was successful in all cases. Seven patients received one supplemental tetracaine injection; one patient received two supplemental injections. Arterial blood pressure decreased an average of 5 mm Hg with the largest decrease being 10 mm Hg. Two postoperative respiratory events occurred in the first 8 h after surgery. Both neonates had received intraoperative midazolam for sedation. Neurologic function was assessed pre- and postoperatively. Twelve patients had no change in neurologic function after surgery, while two infants demonstrated improved function. We conclude that spinal anesthesia can be safely used for meningomyelocele repair.

Anesthesia, Spinal↗
PubMed1995

Primary diffuse chiasmatic germinomas: differentiation from optic chiasm gliomas.

Primary germ cell tumors confined to the optic nerves and chiasm without suprasellar extension are uncommon. These tumors appear similar to chiasmatic gliomas on both computed tomography and magnetic resonance imaging, potentially resulting in treatment errors if the diagnosis is based on radiologic criteria alone. Unlike chiasmatic gliomas, suprasellar germinomas characteristically present with a clinical triad of endocrine abnormalities, diabetes insipidus, and visual complaints. We report the case of a 9-year-old boy who presented with a 5-month history of fatigue, 16-pound weight gain, polydipsia, polyuria, visual complaints, and intermittent headache. Imaging studies demonstrated findings consistent with a glioma of the chiasm with infiltration into the optic tracts. At surgery, the chiasm and optic tracts were diffusely enlarged with no other suprasellar abnormalities. Biopsy specimens were characteristic of germ cell tumor. Based on this result, the patient received a treatment regimen different from that used at our institution for chiasmatic gliomas. We feel it is imperative to biopsy chiasmatic lesions that radiologically appear to be gliomas if symptoms do not adhere to the classical clinical presentation.

Biopsy↗
PubMed1994

Prophylactic vena cava filter insertion in patients with traumatic spinal cord injury: preliminary results.

Pulmonary embolism (PE) is a devastating complication in patients with traumatic spinal cord injury (SCI). Prophylactic measures such as venous compression hose or low-dose heparin are only partially protective in reducing the risk of venous thromboembolism and are contraindicated in some patients. Because of extended perturbations in fibrinolytic activity, catecholamine effects on platelet aggregation, increased activity of complement and acute phase reactants, abnormally high factor VIII concentrations, and persistent venous stasis with ongoing endothelial damage, the patient with an SCI remains at prolonged risk for venous thromboembolism. A retrospective 5-year review at the Medical Center Hospital of Vermont revealed seven patients with eight documented PEs (three fatal; 2.7%) in 111 SCI patients (6.3%). Six PEs (75%) occurred after discharge from the acute care facility. Median time to PE after injury was 78 days (range, 9-5993). Although comprising only 4% of all trauma admissions, SCI accounted for 31% of all PEs in the total trauma population (2525 patients). Beginning in July 1991, a new prophylaxis protocol was instituted, which included the percutaneous insertion of vena cava filters under local anesthesia in all SCI patients with paraplegia or quadriplegia. Fifteen patients have undergone the insertion of titanium filters. Impedance plethysmography was performed weekly to detect deep venous thrombosis. No complications were associated with vena cava filter insertion. No patients developed deep venous thrombosis during their acute hospitalization (median, 22 d), and no patients have developed PE after filter insertion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The effect of hypotension and hypoxia on children with severe head injuries.

Survival of children (< 17 years) with severe head injuries (Glascow Coma Scale [GCS] score < 8) has been shown to be better than that of adults. The addition of hypotension (HT) or hypoxia (H) has a deleterious effect on outcome in adults but no information is currently available about their effects in children. Over a 5-year period, 58 children with GCS scores < 8 were admitted and prospectively evaluated at this institution. Patients were divided into two groups on the basis of systolic blood pressure (SBP) and arterial blood gasses. Patients exhibiting HT, defined as a SBP < 90 mm Hg, and patients demonstrating H with a PaO2 < 60 mm Hg were compared with normoxic, normotensive children. Survival was increased fourfold in patients with neither H nor HT as compared with children with either H or HT (P < .001). To validate these observations we reviewed the data from the National Pediatric Trauma Registry for similar patients and included our cohort in the analysis. In total, 509 children had sufficient data for analysis and were studied. Hypoxia alone was not associated with increased mortality in normotensive patients (P = .34). Hypotension significantly increased mortality in these children even without concomitant H (P < .00001). If both HT and H were found together, mortality was only slightly increased over those children with HT alone (P = .056). These data confirm that HT with or without H causes significantly increased mortality in head-injured children to those levels normally found in adults (P = .9), alleviating any age-related protective mechanisms normally afforded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The epidemiology of injury in a rural state: 5,322 cases over 6 years.

Presently, descriptions of rural trauma are complications of national sample statistics and local data from states projected to rural areas. This study reviews all hospital discharges (36,866) for children (aged 0 to 18 years) from January 1985 through December 1990 in an entirely rural state. Fourteen percent of admissions (5,322) were due to traumatic injury and 63% of these occurred in boys. Injury rates were age dependent with children 15 to 18 years experiencing an incidence of 110/10,000; 10 to 14 years 55/10,000; 5 to 9 years 39/10,000; 1 to 4 years 35/10,000; and < 1 year 39.5/10,000. Mean age for the entire population was 11.4 +/- 5.7 years. Thirty-five percent of children had more than one major site of injury. Sixty-three percent of admissions were for blunt trauma and only 4.8% were penetrating. The remainder were due to burns, hanging, ingestion, and other toxic agents. Falls constituted the most prevalent cause of injury in this population occurring in 25.9%, motor vehicle accidents 22.9%, struck by an object 9.6%, suicide attempts 8.5%, poisoning 4.7%, fire 1.2%, drowning 0.7%, and farm machinery 0.3%. The vast majority of motor vehicle accidents involved the child as an operator or occupant of the vehicle. Less than 10% involved a pedestrian being struck and less than 5% involved a child being struck while on a bicycle. Less than 6% of all injuries involved a bicycle. Child maltreatment was recorded in less than 2% of this population. Only 3.3% of injured children required transfer to another acute care facility (1/3 because of a motor vehicle accident and 1/4 because of a fall).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The effect of secondary insults on mortality and long-term disability after severe head injury in a rural region without a trauma system.

Outcome after head injury appears to be adversely affected by secondary insults such as hypoxia or hypotension. Previous work examining the influence of these secondary insults on outcome has originated from urban environments with organized systems of trauma care. We hypothesized that secondary insults would be more frequent and that outcome of severe head injury would be worse in a rural region without a trauma system. To validate these hypotheses we retrospectively reviewed the course and outcome of all patients admitted to the Medical Center Hospital of Vermont with severe head injuries between 1980 and 1985. A cohort of 170 patients was assigned to one of two groups: group I had neither hypotension nor hypoxia at the time of admission; group II had either hypotension or hypoxia at the time of admission. The groups were similar in terms of demographics, incidence of mass lesions, frequency of craniotomy, and incidence of intracranial hypertension. Only 23% of group II patients made a good recovery compared with 56% of group I patients (p < 0.01). The mortality rate of group II patients was twice that of group I patients (66% vs. 33%; p < 0.01). When compared with data provided by the National Trauma Coma Data Bank from urban areas with trauma systems, there was no difference in outcome of patients similarly grouped according to the presence or absence of secondary insults between Vermont's rural cohort and the urban cohort. We conclude that hypotension and hypoxia adversely effect the outcome of severe head injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The clinical utility of computed tomographic scanning and neurologic examination in the management of patients with minor head injuries.

The evaluation and management of patients with minor head injury (MHI: history of loss of consciousness or posttraumatic amnesia and a GCS score greater than 12) remain controversial. Recommendations vary from routine admission without computed tomographic (CT) scanning to mandatory CT scanning and admission to CT scanning without admission for selected patients. Previous reports examining this issue have included patients with associated non-CNS injuries who confound the interpretation of the data and affect outcome. We hypothesized that patients with MHI and no other reason for admission with normal neurologic examinations and normal CT scans would have a negligible risk of neurologic deterioration requiring surgical intervention. To validate this hypothesis we studied 2766 patients with an isolated MHI admitted to seven trauma centers between January 1, 1988, and December 31, 1991. There were 1898 male patients and 868 female patients; injury was blunt in 99%. A neurologic examination and a CT scan were performed on 2166 patients; 933 patients had normal neurologic examinations and normal CT scans and none required craniotomy; 1170 patients had normal CT scans and none required craniotomy; 2112 patients had normal neurologic examinations and 59 required craniotomy. The sensitivity of the CT scan was 100%, with positive predictive value of 10%, negative predictive value of 100%, and specificity of 51%. The use of CT alone as a diagnostic modality would have saved 3924 hospital days, including 814 ICU days, and $1,509,012 in hospital charges. Based on these data, we believe that CT scanning is essential in the management of patients with MHI and that if the neurologic examination is normal and the scan is negative patients can be safely discharged from the emergency room.

Adolescent↗
PubMed1992

The deleterious effects of intraoperative hypotension on outcome in patients with severe head injuries.

Prehospital or admission hypotension doubles the mortality for patients with severe head injury (SHI = Glasgow Coma Scale score less than or equal to 8). To our knowledge no study to date has determined the effects of intraoperative hypotension [IH: systolic blood pressure (SBP) less than 90 mm Hg] on outcome in patients with SHI. This study examined 53 patients who had SHI and required early surgical intervention (surgery within 72 hours of injury). All patients were initially normotensive on arrival. There were 17 patients (32%) who developed IH and 36 (68%) who remained normotensive throughout surgery. The mortality rate was 82% in the IH group and 25% in the normotensive group (p less than 0.001). The duration of IH was inversely correlated with Glasgow Outcome Scale using linear regression (R = -0.30; p = 0.02). Despite vigorous fluid resuscitation in the IH group, additional pharmacologic support was used in only 32%. These data suggest that IH is not uncommon after SHI (32%) and that it does have a significant effect on patient outcome.

Adult↗
PubMed1992

An analysis of the relationship between fluid and sodium administration and intracranial pressure after head injury.

Severe head injury is the leading cause of traumatic death. When a severe head injury is combined with hypotension the mortality doubles. The use of asanguineous salt solutions to maintain blood pressure, however, may contribute to cerebral swelling and intracranial hypertension. For this reason, restrictions of fluids (FLD) and sodium (Na) have been advocated. To our knowledge, however, there are no clinical data to support this recommendation. We hypothesized that in adult patients sustaining severe head injuries (Glasgow Coma Scale score less than or equal to 8) with or without associated injuries: (1) FLD balance and total Na administered during the initial 72 hours of hospital admission are positively and significantly correlated with each other, and (2) total FLD, FLD balance, and total Na administration during the initial 72 hours are significantly and positively correlated with changes in ICP and adverse outcome. We retrospectively studied 40 adult trauma patients with severe head injuries. We found a significant correlation between total Na and FLD balance (R2 = 0.54; p less than 0.05). However, we found no significant correlation between total FLD and maximum ICP (R2 = 0.081), ICP score (R2 = 0.01), or outcome (R2 = 0.066), no significant correlation between FLD balance and maximum ICP (R2 = 0.000), ICP score (R2 = 0.000), or outcome (R2 = 0.01), and no significant correlation between total Na and maximum ICP (R2 = 0.000), ICP score (R2 = 0.001), or outcome (R2 = 0.02). We conclude that Na and FLD administration are not independent determinants of ICP during the initial 72 hours after brain injury.

Adolescent↗
PubMed1992

Chronic or recurrent meningitis. Neurosurgical perspectives.

Chronic meningitis is not a commonly encountered clinical problem in the day-to-day patient care responsibilities of neurosurgeons. It is, however, important for the neurosurgeon to be familiar with the clinical problems, diagnostic challenges, and therapeutic options required to establish a definitive diagnosis. This article concentrates on specific entities causing chronic or recurrent meningitis that may require neurosurgical participation.

Chronic Disease↗
PubMed1984

Compressive myelopathy associated with type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome).

Spinal cord compression with resultant myelopathy is a frequent occurrence in patients with mucopolysaccharidoses. Etiological factors include developmental abnormalities of the cervical spine and infiltration of the dura mater by the accumulated products of mucopolyssacharide metabolism. Compression at the thoracolumbar junction is rare, but was found in a child with the characteristic physical and biochemical stigmata of the Maroteaux-Lamy syndrome (mucopolysaccharidosis VI). An anterolateral approach to remove the compressing bony elements resulted in symptomatic improvement. Careful radiological evaluation is required so that all surgical options can be considered. Patients with metabolic storage diseases and the capacity for normal intellectual function warrant aggressive surgical care to optimize neurological function.

Child↗