Biomedical subjects
I Ciric
Publications and source records attributed to I Ciric.
Absence of constitutively activating mutations in the GHRH receptor in GH-producing pituitary tumors.
The molecular events leading to the development of GH-producing pituitary tumors remain largely unknown. We hypothesized that activating mutations of the GHRH receptor might occur in a subset of GH-producing pituitary tumors. Genomic DNA samples from 54 GH-producing pituitary tumor tissues were screened for mutations of the GHRH receptor. Eleven homozygous or heterozygous nucleotide substitutions [169G > A (A57T), 338C > T (P113L), 363G > T (E121D), 409C > T (H137Y), 547G > A (D183N), 673G > A (V225I), 749G > A (W250X), 760G > A (V254M), 785G > A (S262N), 880G > A (G294R), 1268G > A (C423Y)] were found in 12 patients (22.2%). The 169G > A substitution (A57T) appears to be a polymorphism (4 patients, 7.4%). E121D and V225I were each found in 2 patients. In 1 patient with the V225I sequence, the substitution was not found in genomic DNA from peripheral leukocytes, suggesting a somatic mutation. A patient with a heterozygous W250X mutation was homozygous for the C423Y substitution. These variant GHRH receptors were studied in transfected TSA-201 cells to evaluate the functional consequences of the amino acid changes. None of the GHRH receptor variants was associated with basal elevation of intracellular cAMP. GHRH induced variable cAMP responses. With the W250X and G294R variants, there was no cAMP stimulation by GHRH, indicating that the mutations are inactivating. Expression of the W250X GHRH receptor on the cell membrane was severely decreased and GHRH binding to the G294R GHRH receptor was impaired. Although GHRH receptor variants are common in GH- producing pituitary adenomas, constitutively activating mutations, as a mechanism for GH-producing pituitary tumors appear to be rare.
Perspective in pituitary adenomas: an end of the century review of tumorigenesis, diagnosis, and treatment.
Significant advances have been made in the molecular biological understanding of pituitary tumorigenesis. These advances will have an impact on the gene therapy of pituitary tumors in the coming century. Transsphenoidal surgery remains the mainstay of treatment for the majority of pituitary adenomas, with endoscopic surgery being used at some centers in select patients. Pharmacotherapy of pituitary adenomas has made great strides in the management of prolactinomas and GH-secreting pituitary adenomas. Finally, radiosurgery has become a very important adjuvant therapy in the treatment of hypersecreting pituitary adenomas.
Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience.
OBJECTIVE: The primary objectives of this report were, first, to determine the number and incidence of complications of transsphenoidal surgery performed by a cross-section of neurosurgeons in the United States and, second, to ascertain the influence of the surgeon's experience with the procedure on the occurrence of these complications. The secondary objective was to review complications of transsphenoidal surgery from the standpoint of their causation, treatment, and prevention. METHODS: Questionnaires regarding 14 specific complications of transsphenoidal surgery were mailed to 3172 neurosurgeons. The data reported were analyzed from the 958 respondents (82%) who reported performing the operation. The neurosurgeons surveyed were asked to estimate the number of transsphenoidal operations performed, to identify any complications observed, and to estimate the percentage of operations that had resulted in any of the 14 specific complications. The 958 respondents were placed into three experience groups, based on the number of transsphenoidal operations performed. The data were analyzed by using chi 2 tests and Spearman correlation coefficients. The secondary objectives were met through a detailed review of the literature, in light of our experience. RESULTS: Of the respondents, 87.3% reported having performed < 200 operations and 9.7% reported 200 to 500 previous operations. The remaining 3% reported more than 500 previous operations. More extensive previous experience with transsphenoidal surgery was associated with a greater likelihood of having witnessed each specific complication. The mean operative mortality rate for all three groups was 0.9%. Anterior pituitary insufficiency (19.4%) and diabetes insipidus (17.8%) were complications with the highest incidence of occurrence. The overall incidence of cerebrospinal fluid fistulas was 3.9%. Other significant complications, such as carotid artery injuries, hypothalamic injuries, loss of vision, and meningitis, occurred with incidence rates between 1 and 2%. An inverse relationship was found between the experience group and the likelihood of complications, as indicated by significant negative Spearman correlation coefficients for all but 2 of the 14 complications listed in the survey (P < 0.05). Thus, increased experience with transsphenoidal surgery seems to be associated with a decreased percentage of operations resulting in complications. Some caution should be exercised in interpreting these data, because they are based on the respondents' estimates. CONCLUSION: Transsphenoidal surgery seems to be a reasonably safe procedure, with a mortality rate of less than 1%. However, a significant number of complications do occur. The incidence of these complications seems to be higher, with statistical significance, in the hands of less experienced surgeons. The learning curve seems to be relatively shallow, because a statistically significantly decreased incidence of morbidity and death could be documented after 200 and even 500 transsphenoidal operations. Better understanding of the indications for transsphenoidal surgery and improved familiarity with the regional anatomy should further lower the incidence of death and morbidity resulting from this procedure in the hands of all neurosurgeons.
Diaphragma sellae meningiomas.
Despite their unique clinical, radiological, and surgical considerations, diaphragma sellae meningiomas remain largely undistinguished from tuberculum sellae meningiomas. On the basis of our experience with 12 patients with diaphragma sellae meningiomas and our review of the literature, we classify these tumors into three groups: Type A, originating from the upper leaf of the diaphragma sellae anterior to the pituitary stalk; Type B, originating from the upper leaf of the diaphragma sellae posterior to the pituitary stalk; and Type C, originating from the inferior leaf of the diaphragma sellae. Each type has specific clinical symptoms. Type A mainly presents with unilateral visual disturbances and visual field defects resembling those of tuberculum sellae meningiomas, although preoperative diabetes insipidus occurred in patients with large tumors. Type B causes fewer visual disturbances, but memory disturbance and hypopituitarism occur. Type C closely resembles nonfunctioning pituitary adenomas; bitemporal hemianopsia and hypopituitarism are common. Multiplanar magnetic resonance images can accurately diagnose the tumor and establish its type. Surgical approaches include the cranio-orbital approach for Types A and B and the transcranial-transsphenoidal approach for Type C. Surgery is more difficult than for tuberculum sellae meningiomas because of the deep location and the difficulty of dissecting Types A and B from the pituitary stalk. Repair of the sphenoid sinus to prevent cerebrospinal fluid leakage is mandatory for Type C tumors.
Temporal arteritis masquerade syndrome.
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Paul C. Bucy, M.D.
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Tentorial and posterior cranial fossa meningiomas: operative results and long-term follow-up: experience with twenty-six cases.
In spite of significant recent advancements in imaging technology, monitoring [12] and surgical techniques [1,5,7,18,21,24], complete and safe removal of tentorial and posterior fossa meningiomas remains a formidable challenge for most neurosurgeons [6,8,9,14,15,17]. This paper reviews our experience with 28 patients with tentorial and posterior fossa meningiomas.
Paul C. Bucy. 1904-1992.
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Paul C. Bucy, M.D.
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Aggressive surgery for malignant supratentorial gliomas.
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Pigmented villonodular synovitis in a vertebra. A case report.
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Laser-assisted nerve repair in primates.
Studies on the peripheral nerves in rats and other species have helped in the development of laser-assisted nerve anastomosis (LANA), but offer little in evaluating the efficacy of this technique in primates. The authors present a study of LANA in the peripheral nerves of rhesus monkeys. Twelve adult rhesus monkeys underwent bilateral resection of a portion of the peroneal nerve followed by placement of autogenous sural nerve interposition fascicular grafts. The grafts were completed with conventional microsurgical suture technique on one side and with LANA on the other. At 5, 8, 10, and 12 months, the grafted nerves were evaluated for continuity, nerve conduction, and histology (both light and electron microscopy). No significant difference in continuity, conduction velocity, nerve degeneration, nerve regeneration, axon fiber number, or axon fiber density was found in any animal between grafts performed by conventional microsuture and LANA grafts. There was no difference in distal or proximal myelinated fiber density between the LANA grafts and the conventional microsuture grafts. It was concluded that LANA is as effective as microsurgical suture nerve anastomosis in a primate model of nerve repair and grafting.
Pathology of laser-induced experimental aneurysms.
Aneurysms were produced in the common carotid artery of 35 rats by milliwatt CO2 laser welding of an adventitia patch over a hole. The aneurysmal sac was formed by collagen; the lumen was covered by an endothelial-like lining and partially thrombosed. The pathology of these aneurysms is similar to spontaneously occurring intracranial human aneurysms. This aneurysm model has properties (reliability, spontaneous bleeding tendency, minimal vessel manipulation, and pathological features) that make it theoretically advantageous for the induction of experimental intracranial aneurysms in larger animals.
Induction of experimental aneurysms on the rat common carotid artery using a microsurgical CO2 laser.
Aneurysms were produced on the common carotid artery of rats by milliwatt CO2 laser welding of an adventitia patch over a hole. Sixty-nine animals were operated on. Aneurysms were present in 35 animals (51%), 7 of which ruptured spontaneously. The time to aneurysm formation was 1 week or longer. The adventitia patch aneurysm model has features (reliability, minimal vessel manipulation, histology similar to human berry aneurysm, and spontaneous bleeding tendency) that make it theoretically suitable for the induction of intracranial aneurysms in experimental animals. The microsurgical skills required to create and dissect the aneurysm make our experimental aneurysm useful as a teaching model in the development of microneurovascular surgery skills.
Supratentorial gliomas: surgical considerations and immediate postoperative results. Gross total resection versus partial resection.
Forty-two patients with supratentorial gliomas not involving the basal ganglia (extraganglionic) were studied pre- and postoperatively with computed tomographic (CT) scans to evaluate the effect of the extent of surgical resection on the immediate postoperative results. Thirty-three patients (79%) had malignant astrocytic gliomas (glioblastoma or anaplastic astrocytoma), 4 patients (10%) had well-differentiated astrocytomas, and 5 (12%) had oligodendrogliomas. The median age was 58 years, and the median Karnofsky rating was 70. There was no operative mortality. Six patients (14%) had surgical complications. A gross total resection was defined as the absence of any abnormal enhancement on the postoperative CT scan. A nearly gross total resection had been accomplished when less than 10% of the preoperatively enhancing mass was still seen. A partial resection was indicated by the presence of more than 10% of the enhancing lesion on the postoperative CT scan. A gross total or nearly gross total resection was accomplished in 36 patients (86%), and an improved or stable postoperative neurological status was present in 35 of these patients (97%). In contrast, the rate of neurological morbidity after a partial resection was 40%. Supratentorial extraganglionic gliomas, regardless of their histological type, generally were well-circumscribed lesions except at the level of the ventricular wall, where glioblastomas and anaplastic astrocytomas blended with the subependymal white matter from which they seemed to arise.
Effect of the extent of surgical resection on survival and quality of life in patients with supratentorial glioblastomas and anaplastic astrocytomas.
Thirty-one patients operated upon for supratentorial glioblastomas or anaplastic astrocytomas were studied to evaluate the effect of the extent of surgical resection on the length and quality of survival. The median age was 50 years and the median preoperative Karnofsky rate was 80. Twenty-one patients (68%) had glioblastoma multiforme, and 10 patients (32%) had anaplastic astrocytoma. Early postoperative enhanced computed tomography was used to determine the extent of tumor resection. Gross total tumor resection was accomplished in 19 patients (61%), and subtotal resection was performed in 12 patients (39%). The two groups were comparable regarding age, sex, pathological condition, preoperative Karnofsky rating, tumor location, postoperative radiation therapy, and postoperative chemotherapy (P greater than 0.05). The gross total resection group lived longer than the subtotal resection group by life table analysis (P less than 0.001; median survival of 90 and 43 weeks, respectively). Postoperatively, the mean functional ability measured by the Karnofsky rating was significantly increased in the gross total resection group (P = 0.006), but not in the subtotal resection group (P greater than 0.05). The difference in degree of change between preoperative and postoperative Karnofsky rating in the two groups was statistically significant (P = 0.002). The gross total resection group spent significantly more time after the operation in an independent status (Karnofsky rating greater than or equal to 80) compared to the subtotal resection group (P = 0.007; median time of 185 and 12.5 weeks, respectively). Gross total resection of supratentorial glioblastomas and anaplastic astrocytomas is feasible and is directly associated with longer and better survival when compared to subtotal resection.
Technique of experimental aneurysm formation in the rat common carotid artery using the milliwatt carbon dioxide laser and the adventitia patch model.
Aneurysms were induced in the rat common carotid artery by using the milliwatt carbon dioxide laser to weld an adventitia patch over a hole. This technique proved to be effective and reliable as demonstrated by the 100% incidence of aneurysm formation at the patch site in 28 rats killed 1 week or later after the procedure. It is suggested that this technique may be used to produce intracranial aneurysms in experimental animals due to the minimal vessel manipulation required.