Biomedical subjects
Publications and source records attributed to G J Dohrmann.
This article chronicles the development of real-time ultrasound for use in operations in the central nervous system. Described are the technology and the various applications of ultrasound in the neurosurgical operating room. The use of real-time ultrasound to localize, characterize, and instrument lesions of the brain and spinal chord are discussed.
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In this study we describe the technique of intraoperative ultrasound imaging of brain and spinal cord in trauma patients. The images are shown and their interpretation is discussed. This intraoperative imaging allows for localization of hematomas, bone fragments and indriven foreign bodies (i.e., pieces of plastic, glass, metal, etc.). Disc material and bone fragments deep to the spinal cord can be localized with this technique. Real-time ultrasound can be used to guide instruments within the brain and, thereby, provide dynamic guidance for removal of bone fragments and foreign bodies dynamically. In summary, intraoperative real-time ultrasonic imaging is of use to the neurosurgeon in the treatment of the neurotrauma patient.
The accuracy of a novel frameless stereotactic system was determined during 10 surgeries performed to resect brain tumors. An array of three charge-coupled device cameras tracked the locations of infrared light-emitting diodes on a hand-held stylus and on a reference frame attached to the patient's skull with a single bone screw. Patient-image registration was achieved retrospectively by digitizing randomly chosen scalp points with the system and fitting them to a scalp surface model derived from magnetic resonance (MR) images. The reference frame enabled continual correction for patient head movements so that registration was maintained even when the patient's head was not immobilized in a surgical clamp. The location of the stylus was displayed in real-time on cross-sectional and three-dimensional MR images of the head; this information was used to predict the locations of small intracranial lesions. The average distance (and standard deviation) between the actual position of the mass and its stereotactically predicted location was 4.8 +/- 3.5 mm. The authors conclude that frameless stereotaxy can be used for accurate localization of intracranial masses without resorting to using fiducial markers during presurgical imaging and without immobilizing the patient's head during surgery.
The survival rate for patients with malignant gliomas is poor. We describe the results of a prospective study using concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for patients with malignant gliomas. Forty-two patients with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were treated with postoperative photon radiation 45 Gy/25 fraction (fxs) with concomitant continuous intravenous infusion of 5-fluorouracil at 300 mg/m2/day x 5 days and hydroxyurea 0.5 g orally every 12 hr for 6 days for 5 consecutive weeks, followed by a neutron boost of 450 N cGy/6 fxs delivered twice weekly. Adjuvant chemotherapy with procarbazine, CCNU, and vincristine (PCV) was given up to 1 year or until tumor progression. Thirty-four patients (81%) had GBM and 8 patients (19%) had AA. Sixteen patients (38%) were ineligible for the neutron boost because of large tumors or poor performance status and instead received a photon boost with concomitant chemotherapy for a total dose of 60-65 Gy to the tumor. The overall median survival is 68 weeks at a median follow-up of 203 weeks (range 166-302 weeks for the 11 patients remaining alive); 7/8 patients with AA are alive, 2 of these with progressive disease. For AA the median survival is not reached at a median follow-up of 203 weeks (range 166-302 weeks for the 7 patients alive with AA). Time to tumor progression for the 1 dead patient with AA was 35 weeks and the other 2 patients failed at 171 weeks and 179 weeks following treatment. The median survival for the 34 patients with GBM was 62 weeks; 4/34 patients with GBM are alive at 285, 238, 216, and 206 weeks. Multivariate survival analysis in the 34 patients with GBM revealed age and Karnofsky performance status as important prognostic factors. Extent of surgery and neutrons did not affect survival. Concomitant chemoradiotherapy was well tolerated by all patients. The only toxicities observed were mucositis < or = grade II in 3 patients (7%) and mild myelosuppression in 1 patient (2.4%). Adjuvant PCV was well tolerated. Continuous concomitant chemoradiotherapy was well tolerated by all patients with acceptable side effects. The survival rate for the patients with GBM suggests no significant impact on the prognosis for these patients. Patients with AA did well; however, the patient numbers are small.
A frameless stereotactic device interfacing an electromagnetic three-dimensional (3-D) digitizer to a computer workstation is described. The patient-image coordinate transformation was found by retrospectively registering a digitizer-derived model of the patient's scalp with a magnetic resonance (MR) imaging-derived model of the same surface. This procedure was performed with routine imaging data, eliminating the need to obtain special-purpose MR images with fiducial markers in place. After patient-image fusion was achieved, a hand-held digitizing stylus was moved over the scalp and tracked in real time on cross-sectional and 3-D brain images on the computer screen. This device was used for presurgical localization of lesions in 10 patients with meningeal and superficial brain tumors. The results suggest that the system is accurate enough (typical error range 3 to 8 mm) to enable the surgeon to reduce the craniotomy to one-half the size advisable with conventional qualitative presurgical planning.
Two glioma tumor lines and specimens from five patients with gliomas were analyzed to determine genic expression of four growth factors found in human brain. Messenger RNA encoding for interleukin-1 beta, interleukin-6, and basic fibroblast growth factor was found to be expressed in significant amounts in some of these tumors, while mRNA for interleukin-3 was found in small quantities in only the tumor lines. Multiple species of mRNA for basic fibroblast growth factor were found. Expression of growth factor genes may play a role in the growth of human gliomas.
The transfacial approach to the anterior cranial fossa for tumor removal provides for excellent surgical exposure, improved postoperative appearance, and a minimum of complications. The technique is different from previously reported combined craniofacial ablative procedures in that the head and neck surgeon and the neurosurgeon approach the anterior fossa mass through the same facial incision, thus avoiding the need for a separate craniotomy incision. The formation of a vascularized nasofrontal bone flap allows for better wound healing regardless of preoperative and postoperative radiotherapy and/or chemotherapy. This report presents 42 cases in which the transfacial approach was exclusively used in a combined manner to remove nasal, paranasal sinus, and nasopharyngeal neoplasms. The transfacial technique offers a significant advantage over previously described approaches to the anterior skull base.
Through the technical advances in molecular biology during the past decade, important new insights into the fundamental chromosomal changes associated with brain tumors have been gained. The pace of such research is accelerating, and most of the published reports have appeared outside the neurosurgical literature. Furthermore, many neurosurgeons may not be sufficiently familiar with the terminology and techniques involved to remain abreast of the field. In this review, we discuss through specific examples of recent work on brain tumors the basic techniques of molecular biology, including the Southern and Northern blots, restriction enzyme digestion of DNA, molecular cloning of genes, and mapping of chromosomal deletions. Gene amplification and rearrangements are discussed through review of recent work on the N-myc gene in neuroblastoma and the epidermal growth factor receptor (EGFR) gene in glioblastoma. The molecular cloning of the gli gene from a glioblastoma illustrates the powerful analytic nature of these laboratory techniques and the investigative potential of a cloned gene. The concept of the "recessive oncogene" is discussed through a summary of recent work analyzing restriction fragment length polymorphisms (RFLPs) in families of patients with meningioma, acoustic neurinoma, and bilateral acoustic neurofibromatosis (BANF; NF-2). Throughout this article, emphasis is placed on ways in which molecular biology may soon affect clinical practice.
In an attempt to investigate the role of tissue fibrinolytic activity in the resolution of intracerebral hematoma, an experimental model of intracerebral hematoma was developed in the rat. The fibrinolytic activity was studied using a histochemical fibrin slide technique. A total of 59 adult male rats were studied. Twenty-nine rats were used for developing the intracerebral hematoma model via injection of autologous whole blood into the left frontal lobe; in the remaining 30 rats, the intracerebral hematomas were studied sequentially. Intracerebral hematoma formation was unsuccessful in six (21%) of 29 rats. Four rats died in the immediate postoperative period and two showed no intraparenchymal clot. Intense fibrinolytic activity was demonstrated in the blood vessel walls of the normal brain, especially in the meninges, choroid plexus, and ependymal cell layer. In the initial stages of hematoma resolution, fibrinolytic activity was not seen in the hematoma or parenchyma except in the preexisting blood vessels. However, 3 to 5 days later, fibrinolytic activity was observed in the capillary buds surrounding the hematoma and among the infiltrating mononuclear cells. This activity increased for 7 to 10 days following formation of the hematoma and decreased after 21 to 28 days. It is concluded that tissue fibrinolytic activity associated with newly formed blood vessels appears to be important in lysis of intracerebral hematomas.
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The pathophysiology of cervical spondylotic myelopathy and syringomyelia is incompletely understood. Only 50-60% of the former group of patients and only 30-40% of the latter group of patients show long-term improvement. One possible cause for this might be continued anterior compression of the spinal cord in the former and incomplete drainage of the fluid-filled cavities in the latter. Intraoperative ultrasound imaging can be done in the operating room (4-6, 16-18) and can identify whether an adequate decompression has been done in patients with cervical spondylotic myelopathy and whether there has been complete drainage in shunting of patients with syringomyelia. Intraoperative ultrasound imaging aids the neurosurgeon in checking to see if he did what he set out to do. It is useful in operative procedures for cervical spondylotic myelopathy and syringomyelia.
Glucose utilization in vivo and hexokinase activity and mitochondrial oxygen consumption in vitro were measured in a series of human brain tumors. Several relatively slow-growing tumors appeared to have depressed electron-transport activities coupled with a compensatory elevated glucose utilization. These data suggest that a decrease in oxidative metabolism and a corresponding increase in glycolysis are not necessarily correlated with malignancy in certain human brain tumors.
The significance and management of cervical carotid artery tortuosity are controversial. One hundred eighteen cases of angulation of the common carotid artery and over 800 cases of elongation of the internal carotid artery have been reported. The etiology, presentation, diagnosis, and treatment of each entity are reviewed. Angulation of the common carotid artery is often managed conservatively. For clarity, elongations of the internal carotid artery should be classified as either tortuosities or kinks. Some patients with kinks of the internal carotid artery will have episodes of cerebrovascular insufficiency related to the position of their heads. Such patients merit thorough diagnostic evaluation. When other etiologic factors have been eliminated, patients in this group may benefit from a surgical procedure directed at the vascular abnormality. Applicable surgical techniques are discussed.
It has been recognized for some time that malignant cells have a diminished respiratory rate coupled with an excessive rate of aerobic glycolysis. Subsequent studies indicated, however, that this pattern was neither unique to malignant tumors nor an essential characteristic of all varieties of cancer. In attempting to synthesize the data on oxygen consumption of human brain tumors, it is difficult to relate activity to malignancy, and the integrity of the mitochondrial electron transport chain has not been systematically examined. In this study, oxygen consumption was measured using a whole cell mixture and subsequently with isolated mitochondria prepared by routine differential centrifugation from a variety of human brain tumors. It is clear from these data that low oxidative respiration is not uniquely characteristic of malignant tumors, but that a number of benign tumors such as meningiomas and pituitary adenomas display very low levels of oxygen consumption. Many of these tumors have normal respiration, with isolated mitochondria using substrates that enter at different points in the electron transport pathway. However, several of the tumors in this series showed defects in respiration at various points in the electron transport pathway. These data suggest that both benign and malignant brain tumors have depressed respiratory capacities secondary to either a decrease in mitochondria per cell or defects in electron transport activities.
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A population-based study of astrocytomas occurring in children is reported. A population-based study eliminates referral bias and the bias of a series based on the experience of a given medical center or a particular surgeon. In a 42-year period, 179 such cases were diagnosed. The average age at diagnosis was 8.9 years. Over one-half of the astrocytic tumors were located in the cerebellum. A peak in the number of astrocytomas was noted between 1965 and 1970. Cumulative probability of survival of children with intracranial astrocytomas at 6 months and at 1, 2, and 5 years was 0.824, 0.752, 0.732, and 0.667; by 10 years and 20 years the cumulative probability of survival had fallen to 0.607 and 0.538. The shortest survival was observed with brainstem tumors, with an average survival of 19 months. Longer survivals were noted with tumors of the cerebral hemispheres: 0.779, 0.748, 0.678 and 0.628 at 1, 2, 5, and 10 years, respectively. The longest survivals were in those children with cerebellar astrocytomas: at 1 year they had an 0.837 probability of survival and at 20 years, 0.675.
Thoracic disc herniation is uncommon. One of the main problems in the treatment of thoracic disc herniation has been the lack of accuracy of diagnostic tests. Now, with the use of computed tomographic scanning with and without metrizamide in the subarachnoid space, this accuracy has greatly improved. Computed tomography scanning can demonstrate the type and level of the lesion even when the myelographic study is negative. We have reviewed 280 cases; a peak incidence was noted in the fourth decade with 75% of the protruded discs occurring below T-8. Back pain was the most common presenting symptom followed by sensory disturbances. By the time of diagnosis, 70% of the patients had signs of spinal cord compression. A small group of patients could be identified that invariably had a good prognosis. They had a history of trauma, symptoms lasting less than a month, and soft disc herniation. Regarding the results of surgical treatment, there was a success rate ranging from 57% for decompressive laminectomy to over 80% for the posterolateral, lateral, and transthoracic approaches.