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Biomedical subjects

F G Barker

Publications and source records attributed to F G Barker.

At least 37 records · Page 2Linked to original sources
PubMed1997

P16 deletion and mutation analysis in human brain tumors.

We screened human primary and recurrent malignant glioma, juvenile pilocytic astrocytoma, medulloblastoma, and meningioma tissue specimens for alterations in p16 gene structure. Single strand conformation polymorphism (SSCP) analysis was used to screen for point mutations, and a quantitative polymerase chain reaction-based assay was used to screen for homozygous gene deletions. In malignant glioma specimens, homozygous p16 gene deletions were significantly more common in high-grade tumors than in low-grade gliomas. Point mutations causing alteration in predicted protein structure were not detected. Medulloblastomas showed rare homozygous deletions and no point mutations. No mutations were detected in meningiomas.

Carrier Proteins↗
PubMed1997

Trigeminal numbness and tic relief after microvascular decompression for typical trigeminal neuralgia.

OBJECTIVE: After most operative treatments for trigeminal neuralgia, long-term tic relief is closely correlated with postoperative numbness in the trigeminal distribution. Microvascular decompression (MVD) is proposed to relieve tic through a nontraumatic mechanism. We investigated the relationship between postoperative trigeminal numbness and tic relief in a large, prospectively followed cohort of patients treated with MVD for typical trigeminal neuralgia. METHODS: Of 1204 patients who underwent MVD for typical tic during a 20-year period, 522 had single MVDs on a single side, had not undergone ablative trigeminal procedures before or after MVD, and were still being followed in 1994. In 1994, patients graded facial numbness using a questionnaire (response rate, 92%) with a 5-point scale. Multivariate Cox and logistic regression methods were used. The analyses were adjusted for the time that had passed between the performance of MVD and the completion of the questionnaire (minimum, 2 yr). RESULTS: Seventeen percent of patients reported some degree of persistent facial numbness. Decompression of a vein at MVD (odds ratio, 2.5) and failure to find compression by the superior cerebellar artery (odds ratio, 2.0) independently predicted postoperative facial numbness, which in turn predicted postoperative burning and aching facial pain (odds ratio, 5.2-5.9). A trend toward worse outcome was noted in patients with numb faces (P = 0.3). Similar findings were noted in subgroups of patients in whom the superior cerebellar artery was decompressed at MVD (n = 381) and in whom a superior cerebellar artery with no vein was found (n = 120). In the latter subgroup, facial numbness (5.8% of patients) significantly predicted worse long-term outcome (P = 0.03). CONCLUSION: We found no evidence that postoperative trigeminal numbness predicts relief of typical tic after MVD. Trigeminal numbness was related to operative findings at MVD and predicted postoperative burning and aching facial pain. To minimize postoperative facial dysesthesia, trauma to the trigeminal root during MVD should be avoided when possible.

Decompression, Surgical↗
PubMed1996

The long-term outcome of microvascular decompression for trigeminal neuralgia.

BACKGROUND: Several surgical procedures to treat trigeminal neuralgia (tic douloureux) are available, but most reports provide only short-term follow-up information. METHODS: We describe the long-term results of surgery in 1185 patients who underwent microvascular decompression of the trigeminal nerve for medically intractable trigeminal neuralgia. The outcome of the procedure was assessed prospectively with annual questionnaires. RESULTS: Of the 1185 patients who underwent microvascular decompression during the 20-year study period, 1155 were followed for 1 year or more after the operation. The median follow-up period was 6.2 years. Most postoperative recurrences of tic took place in the first two years after surgery. Thirty percent of the patients had recurrences of tic during the study period, and 11 percent underwent second operations for the recurrences. Ten years after surgery, 70 percent of the patients (as determined by Kaplan-Meier analysis) had excellent final results-that is, they were free of pain without medication for tic. An additional 4 percent had occasional pain that did not require long-term medication. Ten years after the procedure, the annual rate of the recurrence of tic was less than 1 percent. Female sex, symptoms lasting more than eight years, venous compression of the trigeminal-root entry zone, and the lack of immediate postoperative cessation of tic were significant predictors of eventual recurrence. Having undergone a previous ablative procedure did not lessen a patient's likelihood of having a cessation of tic after microvascular decompression, but the rates of burning and aching facial pain, as reported on the last follow-up questionnaire, were higher if a trigeminal-ganglion lesion had been created with radiofrequency current before microvascular decompression. Major complications included two deaths shortly after the operation (0.2 percent) and one brain-stem infarction (0.1 percent). Sixteen patients (1 percent) had ipsilateral hearing loss. CONCLUSIONS: Microvascular decompression is a safe and effective treatment for trigeminal neuralgia, with a high rate of long-term success.

Adolescent↗
PubMed1996

Necrosis as a prognostic factor in glioblastoma multiforme.

BACKGROUND: Many pathologists require the presence of tumor necrosis within an astrocytic neoplasm to establish the diagnosis of glioblastoma multiforme (GM). Two new grading systems for astrocytic neoplasms allow a tumor to be diagnosed at the highest level of anaplasia without requiring the presence of tumor necrosis. METHODS: To determine whether GMs without necrosis had biologic behavior most compatible with a diagnosis of GM or of anaplastic astrocytoma (AA), we examined the survival of 299 patients whose tumors were diagnosed as GM because they contained endothelial proliferation and who were treated according to prospective clinical protocols. Multivariate proportional-hazards survival analysis was used to assess the importance of tumor necrosis after adjustment for other prognostic factors. RESULTS: Of 275 patients with GMs containing endothelial proliferation, 88% had tumor necrosis. Absence of necrosis was associated with younger age and with less extensive surgical resection. The absence of necrosis predicted longer survival in univariate analysis (P = 0.02) and after adjustment for age, Karnofsky performance score, and extent of resection in a multivariate analysis (P = 0.04). However, the magnitude of the survival difference was not clinically important: patients without tumor necrosis had a median survival of 12.5 months, and those with tumor necrosis had a median survival of 10.9 months. Kaplan-Meier survival rates two years after diagnosis were 13.0% for patients with necrosis and 27.1% for patients without necrosis; the difference in 2-year survival was not statistically significant (difference in survival rates = 14.1%, 95% confidence interval -2.2% to 30.4%). CONCLUSIONS: The survival of patients with astrocytic neoplasms containing endothelial proliferation and no necrosis conforms best to the pattern expected for patients with GM rather than AA. This supports the classification of these tumors as GM in the revised World Health Organization grading system and as grade 4 astrocytomas in the St. Anne-Mayo grading system.

Adolescent↗
PubMed1996

Bromodeoxyuridine labeling index in glioblastoma multiforme: relation to radiation response, age, and survival.

PURPOSE: Various measures of the rate of tumor cell proliferation have been found to predict survival in patients with intracerebral gliomas. We correlated the bromodeoxyuridine labeling index (BrdUrd LI) with the response to radiation therapy, survival, and known prognostic factors in a series of patients with glioblastoma multiforme (GM) to test its utility as a prognostic factor. METHODS AND MATERIALS: The BrdUrd LI was determined in 200 newly diagnosed intracranial GMs. Age and sex were known for all patients. The response to radiation therapy was determined in 116 patients by comparing neuroimaging studies obtained before and after external beam radiation therapy. Survival was analyzed in 64 patients who were treated according to two consecutive prospective clinical protocols. RESULTS: The median BrdUrd LI was 6.5% (mean, 7.2%; range, 1.1-25.4%). The BrdUrd LI did not correlate significantly with age, sex, radiation response, or survival. Age and Karnofsky performance score were independent prognostic factors in our cohort. CONCLUSION: The proliferative rate as measured by BrdUrd LI was not a prognostic factor in our GM cohort. The BrdUrd LI did not correlate significantly with known prognostic factors in GM. There was no significant relationship between BrdUrd LI and radiation response.

Adolescent↗
PubMed1996

Patients with polycystic kidney disease would benefit from routine magnetic resonance angiographic screening for intracerebral aneurysms: a decision analysis.

Autosomal dominant polycystic kidney disease (ADPKD) is associated with increased prevalence of cerebral aneurysms and increased risk of subarachnoid hemorrhage. A decision analysis by Levey et al. in 1983 demonstrated that patients with ADPKD would not significantly benefit from routine arteriographic screening for cerebral aneurysms. We reexamined this conclusion in light of new clinical data and the introduction of magnetic resonance imaging (MRI) as a screening method. We compared an MRI screening strategy with a nonscreening strategy. The screening strategy specified MRI screening and then neurosurgical management of detected aneurysms. The nonscreening strategy specified cerebrovascular care only in the event of subarachnoid hemorrhage. The decision tree incorporated estimates derived from the clinical literature for the prevalence of asymptomatic aneurysms in patients with ADPKD (15%), the annual incidence of aneurysmal rupture (1.6%), the morbidity and mortality rates associated with subarachnoid hemorrhage (70 and 56%, respectively), the risk of transfemoral arteriography (0.2%), the sensitivity and specificity of MRI, the morbidity and mortality rates associated with surgical treatment of an unruptured aneurysm (4.1 and 1.0%, respectively), and the life expectancy of patients with ADPKD. The model predicted that the screening strategy would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD. A sensitivity analysis showed that the model was most sensitive to estimates of the prevalence of aneurysms in ADPKD, the annual incidence of rupture, and the morbidity and mortality rates associated with rupture. A financial analysis showed that a screening strategy is likely to cost less than a nonscreening strategy. The model predicts that an MRI screening strategy would increase the life expectancy of young patients with ADPKD and reduce the financial impact on society of ADPKD.

Adult↗
PubMed1996

Analysis of the relationship between long-term operative success and a transient or delayed operative side effect.

OBJECTIVE: Investigators sometimes correlate the success of an operative procedure with the presence of an operative side effect that is thought to reflect the efficacy of the procedure in some way. When the prevalence of the side effect increases or decreases with time, this type of analysis can introduce a systematic bias. METHODS: Monte Carlo-simulated patient cohorts with independently and randomly generated operative success and presence of side effects were generated. Kaplan-Meier analyses of operative success were stratified by the presence of side effects at various times after the "operation." RESULTS: When the side effect (such as numbness after an ablative procedure) resolved during the study period in a significant proportion of patients, stratification by presence of the side effect at the end of the study period introduced a serious bias in favor of apparent better pain relief in patients without numbness. When the prevalence of the side effect increased with time (such as the requirement for a subsequent operation for radiation necrosis after brachytherapy or radiosurgical treatment of a glioma), the analysis was biased in favor of apparent longer survival for patients who experienced the side effect (i.e., those who required subsequent operations). CONCLUSION: Analyses of operative success stratified by the presence of postoperative side effects with time-varying prevalence may be seriously biased and should be interpreted with caution.

Bias↗
PubMed1996

Transfacial transclival approach for midline posterior circulation aneurysms.

OBJECTIVE: To evaluate the use of an anterior, transfacial transclival approach to midline posterior circulation aneurysms in five patients. SURGICAL APPROACH: A skin incision is made on the right side of the nose with subsequent bony and cartilaginous disarticulation of the nasal complex. The nose remains attached along the left side and is reflected laterally. Removal of the nasal septum and bilateral ethmoidectomy, medial maxillectomy (usually bilateral), and opening of the sphenoid yield a large triangular exposure of the anterior clivus. After removal of the clivus with a drill, the vertebral and basilar arteries are exposed through a midline dural opening. RESULTS: The approach provided excellent exposure of basilar artery trunk aneurysms with room available for temporary clip placement in three patients. In a fourth patient, a midline posterior inferior cerebellar artery aneurysm was clipped using this technique. A basilar trunk dissection was treated by proximal basilar occlusion through this exposure in a fifth patient. Although three patients developed transient cerebrospinal fluid leaks with symptoms of meningitis, no permanent neurological morbidity resulted from the use of the approach. CONCLUSION: The transfacial transclival approach to midline aneurysms of the basilar trunk and its branches provided excellent exposure for surgical treatment in five patients. No patient had postoperative palatal dysfunction and cosmetic results were excellent. Cerebrospinal fluid leak and meningitis continue to be the major drawbacks to the use of this approach, although the availability of modern broad-spectrum antibiotics lessens the chance of permanent neurological sequelae.

Adult↗
PubMed1996

Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis.

The authors report findings from a metaanalysis of all published randomized trials of prophylactic nimodipine used in patients who have experienced subarachnoid hemorrhage (SAH). Seven trials were included with a total of 1202 patients suitable for evaluation. Eight outcome measures were examined, including good versus other outcome, good or fair outcome versus other outcome, overall mortality, deficit and/or death attributed to vasospasm, infarction rate as judged by computerized tomography (CT), and deficit and/or death from rebleeding. Nimodipine improved outcome according to all measures examined. The odds of good and of good plus fair outcomes were improved by ratios of 1.86:1 and 1.67:1, respectively, for nimodipine versus control(p<0.005 for both measures). The odds of deficit and/or mortality attributed to vasospasm and CT-assessed infarction rate were reduced by ratios of 0.46:1 to 0.58:1 in the nimodipine group (p<0.008 for all measures). Overall mortality was slightly reduced in the nimodipine group, but the trend was not statistically significant. The rebleeding rate was not increased by nimodipine. A metaregression yielded findings indicating that the treatment effect of nimodipine in individual trials was positively correlated with the severity of SAH in enrolled patients. Although the majority of individual trials examined did not have statistically significant results at the p<0.01 level according to most outcome measures, the metaanalyses confirmed the significant efficacy of prophylactic nimodipine in improving outcome after SAH under the conditions used in these trials.

Brain Ischemia↗
PubMed1996

Radiation response and survival time in patients with glioblastoma multiforme.

The determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external- beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p< 0.001 for radiation response and p=0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

Adolescent↗
PubMed1996

Long-term outcome after operation for trigeminal neuralgia in patients with posterior fossa tumors.

During a 20-year period, 26 patients with typical symptoms of trigeminal neuralgia were found to have posterior fossa tumors at operation. These cases included 14 meningiomas, eight acoustic neurinomas, two epidermoid tumors, one angiolipoma, and one ependymoma. The median patient age was 60 years and 69% of the patients were women. Sixty-five percent of the symptoms were left sided. The median preoperative duration of symptoms was 5 years. The distribution of pain among the three divisions of the trigeminal nerve was similar to that found in patients with trigeminal neuralgia who did not have tumors; however, more divisions tended to be involved in the tumor patients. The mean postoperative follow-up period was 9 years. At operation, the root entry zone of the trigeminal nerve was examined for vascular cross-compression in 21 patients. Vessels compressing the nerve at the root entry zone were observed in all patients examined. Postoperative pain relief was frequent and long lasting. Using Kaplan-Meier methods the authors estimated excellent relief in 81% of the patients 10 years postoperatively, with partial relief in an additional 4%.

Adult↗
PubMed1995

The extent of heterocellular communication mediated by gap junctions is predictive of bystander tumor cytotoxicity in vitro.

Herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir (GCV) viral-directed enzyme prodrug gene therapy causes potent, tumor-selective cytotoxicity in animal models in which HSV-tk gene transduction is limited to a minority of tumor cells. The passage of toxic molecules from HSV-tk+ cells to neighboring HSV-tk- cells during GCV therapy is one mechanism that may account for this "bystander" cytotoxicity. To investigate whether gap junction-mediated intercellular coupling could mediate this bystander effect, we used a flow cytometry assay to quantitate the extent of heterocellular coupling between HSV-tk+ murine fibroblasts and both rodent and human tumor cell lines. Bystander tumor cytotoxicity during GCV treatment in a coculture assay was highly correlated (P < 0.001) with the extent of gap junction-mediated coupling. These findings show that gap junction-mediated intercellular coupling contributes to the in vitro bystander effect during HSV-tk/GCV therapy and that retroviral transduction of tumor cells is not required for bystander cytotoxicity.

Animals↗
PubMed1995

Uterine junctional zone: function and disease.

The myometrium is usually thought of as a homogeneous mass of smooth muscle fibres. However, magnetic resonance studies of the uterus have revealed two distinct zones--the subendometrial myometrium or junctional zone and the outer myometrium. The junctional zone is not only structurally but also functionally different from the outer myometrium. For instance, myometrial contractions in a non-pregnant woman originate exclusively from the junctional zone, and their amplitude, frequency, and direction depend on the phase of the cycle. Irregular thickening of the junctional zone has been proposed as the magnetic resonance criterion for the diagnosis of diffuse adenomyosis. However, this magnetic resonance appearance relies on the disruption of the inner myometrial architecture secondary to smooth muscle hyperplasia but does not provide proof of mucosal invasion of the myometrium. We postulate that adenomyosis is a dichotomous disease characterised primarily by disruption of the inner myometrial architecture and function, with secondary infiltration of endometrial elements into the myometrium under certain circumstances. This hypothesis focuses on the inner myometrium and may explain the high incidence of superficial adenomyosis in dysfunctional uterine bleeding.

Endometriosis↗
PubMed1995

Endovaginal ultrasonography in the diagnosis of adenomyosis uteri: identifying the predictive characteristics.

OBJECTIVE: To evaluate prospectively the role of endovaginal ultrasonography in the diagnosis of adenomyosis and to identify predictive characteristics. SETTING: In Vitro Fertilisation Unit, Hammersmith Hospital. SUBJECTS: Fifty-six women with menorrhagia and dysmenorrhea. DESIGN: Endovaginal sonography was performed and uterine body morphometry and myometrial echogenicity were assessed. The sonographic suspicion of adenomyosis was scored high or low depending on the degree of uterine enlargement, uterine asymmetry not due to fibroids and heterogenicity of myometrial echoes. The sonographic diagnosis was compared either with the histological findings after hysterectomy (n = 34) or to the appearances on magnetic resonance imaging (n = 22). RESULTS: Adenomyosis was diagnosed in 28 patients: 15 by histology and 13 by magnetic resonance imaging. Endovaginal ultrasound demonstrated a sensitivity of 86%, a specificity of 50%, a positive predictive value of 86%, and a negative predictive value of 77%. Uterine morphometry alone did not predict adenomyosis: although the mean length of the longitudinal, anteroposterior and transverse axis was larger in uteri with, compared with those without, adenomyosis, this did not reach statistical significance. The uterine asymmetry ratio was 1.43 (SD 0.6) and 1.34 (SD 0.4) (P = 0.26) in uteri with and without adenomyosis, respectively, but in the presence of adenomyosis the mean posterior wall was significantly thicker than the mean anterior wall: 25.6 (SD 6.6) mm compared with 21.8 (SD 5.0) mm, P = 0.02. Therefore, adenomyosis was best predicted on the basis of ill-defined myometrial heterogeneity. However, leiomyomas and various echogenic shadows and artefacts often complicate subjective assessment of the myometrial echogenicity. CONCLUSION: Endovaginal sonography in symptomatic patients can be a sensitive but not a specific procedure for the diagnosis of adenomyosis.

Adult↗
PubMed1995

Sarcomas subsequent to cranial irradiation.

The development of sarcoma subsequent to cranial irradiation is a rare but serious and potentially fatal event. We describe seven patients who had undergone cranial irradiation (range, 1600-6000 cGy) to treat their primary disease and who developed sarcomas within the irradiated field. The median time from radiation therapy to the development of a sarcoma was 8 years (range, 4 to 15 yr). Fibrosarcomas developed in four patients, and malignant fibrous histiocytomas developed in three. Despite aggressive treatment, the prognosis was poor; the median survival from the diagnosis of sarcoma was 19 months. Sarcoma should be considered in the differential diagnosis of a new lesion or a lesion that progresses several years after radiation therapy.

Adolescent↗
PubMed1995

Microvascular decompression for hemifacial spasm.

The authors report the results of 782 microvascular decompression procedures for hemifacial spasm in 703 patients (705 sides), with follow-up study from 1 to 20 years (mean 8 years). Of 648 patients who had not undergone prior intracranial procedures for hemifacial spasm, 65% were women; their mean age was 52 years, and the mean preoperative duration of symptoms was 7 years. The onset of symptoms was typical in 92% and atypical in 8%. An additional 57 patients who had undergone prior microvascular decompression elsewhere were analyzed as a separate group. Patients were followed prospectively with annual questionnaires. Kaplan-Meier methods showed that among patients without prior microvascular decompression elsewhere, 84% had excellent results and 7% had partial success 10 years postoperatively. Subgroup analyses (Cox proportional hazards model) showed that men had better results than women, and patients with typical onset of symptoms had better results than those with atypical onset. Nearly all failures occurred within 24 months of operation; 9% of patients underwent reoperation for recurrent symptoms. Second microvascular decompression procedures were less successful, whether the first procedure was performed at Presbyterian-University Hospital or elsewhere, unless the procedure was performed within 30 days after the first microvascular decompression. Patient age, side and preoperative duration of symptoms, history of Bell's palsy, preoperative presence of facial weakness or synkinesis, and implant material used had no influence on postoperative results. Complications after the first microvascular decompression for hemifacial spasm included ipsilateral deaf ear in 2.6% and ipsilateral permanent, severe facial weakness in 0.9% of patients. Complications were more frequent in reoperated patients. In all, one operative death (0.1%) and two brainstem infarctions (0.3%) occurred. Microvascular decompression is a safe and definitive treatment for hemifacial spasm with proven long-term efficacy.

Adolescent↗
PubMed1995

Phineas among the phrenologists: the American crowbar case and nineteenth-century theories of cerebral localization.

In 1848, Mr. Phineas Gage suffered destruction of his left frontal lobe in a unique fashion: passage of a metal rod through his head after a freak explosion. His change in character after the accident is the index case for personality change due to frontal lobe damage. Yet, from 1848 to 1868, it was widely believed among American physicians that he was mentally intact. The case was used as evidence against phrenology, a crude precursor of modern cerebral localization theories. The two original reports of the case by Drs. John Harlow (Gage's physician) and Henry J. Bigelow show subtle differences in attitude toward Gage's posttraumatic character change. In his 1848 report, Harlow promised a further communication that would address Gage's "mental manifestations." Bigelow's article portrayed Gage as fully recovered. Although delayed by 20 years, Harlow's second report rapidly changed the perception of the case in the medical community, as reflected by contemporary citations. The educational backgrounds of Harlow and Bigelow are examined to explain their differing attitudes toward the case. Harlow's interest in phrenology prepared him to accept the change in character as a significant clue to cerebral function which merited publication. Bigelow had learned that damage to the cerebral hemispheres had no intellectual effect, and he was unwilling to consider Gage's deficit significant. Although Bigelow's paradigm was initially more influential, Harlow's more closely matched emerging theories of cerebral localization. His version of the case was used by David Ferrier as the keystone in the first modern theory of frontal lobe function, and this is how the case is remembered today.

Brain Injuries↗