Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion and/or proliferation of 26 human anterior pituitary adenomas secreting PRL alone (6 tumors), PRL and GH (18 tumors), or GH alone (2 tumors) were examined. Secretory studies were performed over 4 h, 4 days, and 21 days, and proliferation studies over 4 days. The acute effect of bFGF on secretion over 4 h was examined in 10 tumors. bFGF (10 nmol/L) increased PRL compared to that in controls (100%) in 2 tumors (126% and 290%; P < 0.05) and PRL and GH in a third tumor (183% and 133%, respectively; P < 0.05), whereas 7 tumors remained unaffected. Fourteen tumors were studied over 4 days. bFGF (10 nmol/L) increased PRL secretion in 9 of 11 tumors (117-525%; P < 0.05) cosecreting PRL and GH and in all 3 tumors secreting PRL alone (156%, 183%, and 691%; P < 0.01). Dose-response curves with 0.1, 1, and 10 nmol/L bFGF in 2 of these tumors cosecreting GH and PRL showed that stimulation was achieved with all 3 concentrations. bFGF (10 nmol/L) stimulated GH secretion in 2 of 11 mixed tumors (159% and 196%, respectively; P < 0.05). In 2 tumors studied over 3 weeks, 5 nmol/L bFGF stimulated PRL secretion progressively without affecting GH secretion (106% and 207%; P < 0.05). Tissue proliferation was determined by double immunostaining after bromodeoxyuridine incorporation for 1 h in 7 tumors after 4 days. The labeling index did not exceed 1.2% in any tumor, and there was no effect of 10 nmol/L bFGF on the proliferation of adenoma cells. These results suggest that bFGF may have a paracrine role in the stimulatory regulation of PRL secretion in human pituitary adenomas, and these effects are most likely due to increased hormonal synthesis. An in vitro cell culture system can be used to study proliferative potential. However, bFGF is not mitogenic for human anterior pituitary adenomas secreting PRL and PRL plus GH in vitro.

Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas.

The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P < 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors secreting FSH (28-266%, P < 0.05) and increased alpha-su secretion in all four tumors studied (36%, 63%, 91%, and 121%, P < 0.05). IGF-1 reduced LH secretion in four/nine tumors (13%, 23%, 32%, and 50%, P < 0.05). Dose response curves (1-100 nmol/L IGF-1) were performed on three tumors cosecreting FSH and LH. Stimulation of FSH was achieved with either 1 or 10 nmol/L IGF-1, a single tumor in which alpha-su was measured showed maximal stimulation at 10 nmol/L IGF-1, and one of three tumors showed LH inhibition with 100 nmol/L IGF-1. In situ viability of attached cells was assessed with fluorescein and propidium iodide in seven tumors. After 4 days' exposure to 100 nmol/L IGF-1, in situ viability was increased in five tumors (range 12-19%, 15 +/- 1.3% SEM, P < 0.05). The effects of IGF-1 on the adenoma cell proliferative S-phase fraction was determined in six tumors after 4 days of treatment using double immunostaining with bromodeoxyuridine incorporation for 1 h. In four/six adenomas that stained positive for bromodeoxyuridine in the controls (1-5.6%), the S-phase fraction was increased by 100 nmol/L IGF-1 [(range 2.1-10.6%, increase 90-220%) (P < 0.05)]. These results show that IGF-1 has differential effects on gonadotropins from human pituitary adenomas, stimulating intact FSH and alpha-su, inhibiting or being without effect on intact LH in vitro, and increasing both viability and number of tumorous glycoprotein-secreting cells entering into the S-phase of proliferation.

Effects of basic fibroblastic growth factor on the function and proliferation of human clinically non-functional pituitary adenomas which secreted glycoprotein hormones in vitro.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.

Apoptosis and p53 suppressor gene protein expression in human anterior pituitary adenomas.

Human anterior pituitary adenomas proliferate and express the p53 tumour suppressor gene protein, but it is not known if apoptosis (programmed cell death) occurs. Therefore, the detection of apoptosis was undertaken in tumorous human anterior pituitary tissue and compared with p53 protein expression, tumour type and tumour size. Apoptosis (detected by the in situ end labelling technique) and p53 suppressor gene protein (detected by DO.1-antibody immunocytochemistry) were determined in formalin-fixed and paraffin-embedded tissue from 37 human pituitary adenomas (2 macroprolactinomas, 9 somatotrophinomas and 26 non-functioning adenomas). Two normal anterior pituitaries were also included in this study. Pre-operative tumour size was scored 1 to 4 from magnetic resonance imaging radiology. Apoptosis was found in 7 of 29 tumours (24%), 11% of somatotrophinomas and 33% of non-functioning adenomas, although this difference was not significant. The p53 tumour suppressor protein was found in 7 of 31 tumours (23%), 33% of somatotrophinomas and 19% of non-functioning adenomas. Apoptosis and p53 protein expression were not found in normal anterior pituitary. In conclusion, apoptosis occurs in human anterior pituitary adenomas, but no significant association was found between apoptosis and p53 protein expression, tumour type or tumour size.

Ophthalmic manifestations of Rathke's cleft cysts.

PURPOSE: We studied the neuro-ophthalmic features of patients with symptomatic Rathke's cleft cysts, to distinguish features of Rathke's cleft cysts from those of craniopharyngioma. METHODS: Eleven patients who had undergone surgery for symptomatic Rathke's cleft cysts in the Liverpool University Department of Neurological Science were identified from the records. Histopathologic analyses, clinical notes, and radiologic investigations were reviewed. RESULTS: Eight of the 11 patients initially had visual problems. Reduced visual acuity, visual field defect, or both, were detected in nine patients. Optic atrophy was observed in eight patients. Other initial features included headaches, epilepsy, and endocrine disturbance. All patients recovered from surgery, and an improvement in the visual acuity or visual field defect was noted in six patients. CONCLUSIONS: Symptomatic Rathke's cleft cysts often manifest as visual disturbance. Every effort to distinguish Rathke's cleft cysts from craniopharyngiomas should be made preoperatively. Rathke's cleft cysts only require limited surgical intervention, and radiotherapy is not necessary. Early recognition and treatment can lead to improvement in visual function.

Intramedullary enterogenous cyst of the spinal cord. Case report.

The authors describe a case of intramedullary enterogenous cyst of the spinal cord, and review the clinical aspects f this entity together with the histological classification. Discussions on the embryogenesis and pathogenesis of this rare lesion are reviewed and summarized.

A comparison of proliferation indices in human anterior pituitary adenomas using formalin-fixed tissue and in vitro cell culture.

The authors compared detection methods for cell proliferation in human anterior pituitary adenomas using histological sections and dispersed cell culture. After tumor cells had been grown for 4 days in dispersed culture, bromodeoxyuridine (BUdR), proliferating cell nuclear antigen (PCNA), and Ki-67 were compared by double immunostaining and contrasted with single staining of PCNA and Ki-67 indices in the corresponding histological sections from 12 human pituitary adenomas. In vitro, the BUdR labeling index was positive in six of 12 tumors (range < 0.1-5.1%), 10 of 12 tumors were PCNA-positive (range < 0.1-100%), and Ki-67 was positive in 10 of 12 adenomas (range < 0.1-8%). In vitro, BUdR and Ki-67 gave similar proliferative indices for 10 of 12 adenomas. In vivo, the PCNA labeling index was positive in 12 of 12 adenomas (range 0.9-95%) and Ki-67 was positive in 11 of 12 adenomas (range < 0.1-2%). Tumors with a labeling index less than 0.1% were considered to be negative for proliferation. High PCNA values were found in vitro and in vivo, whereas Ki-67 labeling indices were similar in vitro and in vivo for nine of 12 adenomas. It is concluded that Ki-67 proliferative indices in vivo reflect those found in vitro, at least after 4 days in dispersed culture, but that PCNA overestimates pituitary adenoma proliferation in histological sections as well as in dispersed culture.

The surgical treatment of cervical myelopathy due to spondylosis and disc degeneration.

A personal prospective study of the surgical treatment of cervical myelopathy due to spondylosis and disc protrusion is presented. One hundred and thirty-seven patients with severe disability have undergone surgery according to a protocol involving both the anterior approach of Cloward and decompressive laminectomy. Fifty-two percent of patients have returned to full employment, 39% to light employment and 9% remained disabled though improved from their pre-operative status. The pathenogenesis, natural history and treatment are discussed and reasons advanced to suggest that the disability resulting from severe forms of the condition may be alleviated in the majority of cases.

The surgical treatment of large pituitary adenomas.

The problems associated with the treatment of large pituitary adenomas are discussed with reference to 41 patients operated on by the author. All adenomas had either suprasellar extensions greater than 2 cm and/or more than two intracranial extensions. Ninety-five per cent were suffering from chiasmal compression pre-operatively. All underwent transfrontal surgery with 76% being deemed totally excised and 24% being subtotal. After surgery 29% regained normal vision, 53% had improved vision and 18% had unchanged vision. Thirty-four per cent had no postoperative complications and the majority had a variety of complications, some minor and some major. Other aspects, including endocrinology and recurrence, are also discussed.

Early complications and results of surgery for ruptured intracranial aneurysms.

A personal prospective study has been carried out on 91 consecutive patients undergoing direct surgery for aneurysms of the anterior Circle of Willis. The protocol particularly involved maintaining normotension for each patient during surgery, and operating on all patients in Grades I, II, and III and on those patients in Grades IV and V suffering from coincidental hydrocephalus or intra-cranial haematoma. The results are discussed with particular regard to earlier complications following surgery.

Experiences with head injuries in a regional neurosurgical unit.

A review of all patients with major head injuries transferred to a regional neurosurgical unit for the years 1975 and 1976 has been carried out for comparison with the total number of patients with head injury admitted to district general hospitals of the region. Fifty-four per cent of patients admitted to the neurosurgical unit have resumed their old occupation and 20 per cent died. The significance of these figures is discussed, particularly in the light of the need for a more comprehensive policy for treating head injuries within the United Kingdom.

Mucous-secreting choroid plexus adenoma--case report and review of the literature.

Choroid plexus tumours are rare, and mucous-secreting choroid plexus adenomas are even rarer. The authors report the first case of mucous-secreting choroid plexus adenoma in childhood and review the relevant literature.

Common carotid ligation for the treatment of ruptured posterior communicating aneurysms.

Sixty-four consecutive cases of ruptured posterior communicating aneurysms were investigated. Fifty-one cases were treated by abrupt ligation of the common carotid artery with no operative mortality and a small temporary operative morbidity.

The use of the CAT scanner in the management of patients with head injury transferred to the regional neurosurgical unit.

The use of computerized tomography (CAT scanning) in the management of 204 severely head-injured patients transferred to a regional neurosurgical unit has been evaluated. The experiences gained with CAT scan have been contrasted with those of a period immediately before when the CAT scan was not available. The CAT scan has resulted in a major reduction in burr-holes without worsening the long-term result.

Relative risk of alternative admission policies for patients with head injuries.

During 1975 and 1976, 10 200 patients with head injuries were admitted for observation to sixteen general hospitals serving 2.1 million people. The neurological condition of 60 (0.59%) patients subsequently deteriorated, including 27 (0.26%) who died. The effect of alternative admission policies on outcome and bed occupancy was calculated. If no patients were admitted solely for observation, 35 beds would be released for elective surgery but 30 patients with severe intracranial injuries would be sent home each year. Alternatively, if only patients with a history of loss of consciousness were admitted, 18 beds would be released but 11 patients with severe injuries, including 7 with unrecognised skull fractures, would be sent home. The effect of introducing a standard policy for routine skull radiography has also been determined. If, in England and Wales, post-traumatic skull radiography was restricted to patients with alteration in level of consciousness when examined, with neurological signs, with physical signs (e.g., a palpable fracture), or with a history of loss of consciousness, each year 163 patients with unrecognised skull fractures and potentially lethal intracranial injuries would be sent home and not be admitted for observation. Can the expected annual saving of 3 million pounds on routine skull radiography justify the risk to these patients?

Avoidable factors contributing to the death of head injury patients in general hospitals in Mersey Region.

In 1975 and 1976 190 head injury patients died after admission to 19 general hospitals in Mersey Region or after transfer to the regional department of neurosciences. Their hospital case-notes were examined. Avoidable factors definitely contributing to death were identified in 58 (30%), and those possibly contributing to death in another 45 (24%). Of the avoidable factors 38% occurred in patients who "talked and died" and 77% in patients with intracranial haematomas. The most common avoidable factors were failure to recognise the development of a haematoma, respiratory difficulty leading to hypoxia, hypotension, and convulsions. The following recommendations are made: hospital case-notes of all head injury deaths should be assessed by a panel of senior consultants; all patients unconscious for 4 h in primary surgical wards in general hospitals should be transferred to the regional department of neurosciences; and fewer patients with minor head injuries should be admitted for observation.