Supplementation with omega-3 fish oil has no effect on bone mineral density in adults with knee osteoarthritis: a 2-year randomized controlled trial.

UNLABELLED: This study aimed to determine the effect of fish oil on bone mineral density (BMD). There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD. This randomized controlled trial did not demonstrate any efficacy of omega-3 fatty acids on bone loss in adults. INTRODUCTION: The purpose of this study is to investigate whether supplementation with high dose omega-3 fish oil could have an impact on BMD. METHODS: In a multicentre, double-blind randomized controlled trial (RCT) (ACTRN 12607000415404), 202 Australian participants aged ≥40 with knee osteoarthritis (mean age, 61.0 ± 10.0 years; 49 % female) were randomized to receive either high dose (4.5 g eicosapentaenoic acid and docosahexaenoic acid daily) or low dose (0.45 g/day) omega-3 fish oil for 2 years. BMD was assessed at baseline and 2 years by dual energy X-ray absorptiometry. RESULTS: In subjects with baseline and 2-year assessments, mean standardized BMD at baseline for low or high dose group was 1198 ± 198 and 1157 ± 169 mg/cm(2), respectively, for the lumbar spine and was 1035 ± 165 and 1017 ± 174 mg/cm(2), respectively, for the femoral neck. There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD in the complete case regression analyses (lumbar spine 3.7, 95 % confidence interval (CI) -7.9 to 15.3 mg/cm(2) and femoral neck -5.5, 95 % CI -14.9 to 3.9 mg/cm(2)). The findings did not change with additional adjustments of age, gender, study centre and uses of bone-related drugs during the study period as well as using the intention-to-treat analysis or limiting to older participants (≥55 years at the baseline) (all P ≥ 0.25). Mild adverse events such as headache and gastrointestinal intolerance were common but did not occur more frequently in either group. There were no serious adverse events related to the intervention. CONCLUSION: A 2-year supplementation with high-dose omega-3 fish oil did not alter bone loss among men and women with knee osteoarthritis.

Correlation of VEGF production with IL1 alpha and IL6 secretion by human pituitary adenoma cells.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion. METHODS: Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1 alpha and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging. RESULTS: VEGF was detected in conditioned medium of HP75 cells (900+/-52 pg/ml) and in 82% of tumours tested (range 26-16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume, P = 0.056; VEGF, P < 0.001 (P values based on Spearman's test)) and IL1 alpha produced (volume, P < 0.005; VEGF, P < 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1 alpha, but not IL6, significantly increased VEGF production. CONCLUSIONS: The significant associations between VEGF and the levels of IL6 and IL1 alpha suggest an important role for these cytokines in the development of these tumours.

Cognitive outcome after aneurysm rupture: relationship to aneurysm site and perioperative complications.

We evaluated cognitive outcome in a group of 37 patients who had undergone surgery for rupture and repair of a single intracranial aneurysm at least 6 months previously. We compared outcome--assessed by tests of intelligence, attention, executive functions sensitive to frontal lobe lesions, memory, neglect, and mood, as well as by a specially devised questionnaire--between a group of 20 patients who had aneurysms of the anterior communicating artery and 17 patients who had aneurysms located on other branches of the internal carotid artery. There were no differences in cognitive outcome between patients with anterior communicating artery aneurysms and those with aneurysms on other branches of the internal carotid artery. The patient group as a whole, however, showed impairment in executive functions and some aspects of memory in comparison with normative data. Overall, 65% of the patients were impaired in at least one cognitive domain, with 19% showing executive impairments alone, 14% showing memory impairments alone, and 32% showing deficits in both domains. Cognitive outcome was most strongly predicted by postoperative neurologic events, although clipping of an anterior cerebral artery was associated with a higher impairment rating on a symptom profile completed by patients' relatives, and although preoperative rebleeding of aneurysms predicted impairment of executive function.

Aneurysmal SAH: cognitive outcome and structural damage after clipping or coiling.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) and surgical clipping of intracranial aneurysms are associated with substantial morbidity and mortality. OBJECTIVE: To compare cognitive outcome and structural damage in patients with aneurysmal SAH treated with surgical clipping or endovascular coiling. METHODS: Forty case-matched pairs of patients with aneurysmal SAH treated by surgical clipping or endovascular coiling were prospectively assessed by use of a battery of cognitive tests. Twenty-three case-matched pairs underwent MRI 1 year after the procedure. Matching was based on grade of SAH on admission, location of aneurysm, age, and premorbid IQ. RESULTS: Both groups were impaired in all cognitive domains when compared with age-matched healthy control subjects. Comparison of cognitive outcome between the two groups indicated an overall trend toward a poorer cognitive outcome in the surgical group, which achieved significance in four tests. MRI showed focal encephalomalacia exclusively in the surgical group. This group also had a significantly higher incidence of single or multiple small infarcts within the vascular territory of the aneurysm, but both groups had similar incidence of large infarcts and global ischemic damage. CONCLUSION: Endovascular treatment may cause less structural brain damage than surgery and have a more favorable cognitive outcome. However, cognitive outcome appears to be dictated primarily by the complications of SAH.

Cryostat section assay of oestrogen and progesterone receptors in meningiomas: a clinicopathological study.

Oestrogen receptors and progesterone receptors were measured in the cytosols from cryostat sections of 45 meningiomas from 40 patients (12 men, 28 women) using an isoelectric focusing technique. Near fascimile adjacent sections from the same tissue blocks were stained and examined to determine the histological subtype of the neoplasms. Appreciable levels of progesterone receptor (greater than 10 fmol/mg cytosol protein) were present in 24 (53.3%) of of the neoplasms, but no clinically important oestrogen receptor was detected in any of the tumours. Competitive binding studies on control tissue confirmed the specificity of the assay procedures. No correlation was found between progesterone receptor state and the age, sex, or menopausal state of the patients, or the histological subtype and site of the neoplasms. Four of the patients studied had multiple intracranial neoplasms, which in two were of differing progesterone receptor state. The presence of specific progesterone receptor in meningioma cytosols raises the possibility of hormonal manipulation in the treatment of this group of neoplasms.

Cytogenetic studies in 50 meningiomas.

In a series of 50 meningiomas, cytogenetic studies showed that almost half had a normal diploid karyotype. The remainder had monosomy 22, some with a normal diploid line also present. The initial monosomy was often followed by further chromosome loss, and occasionally by structural abnormalities, some with distinctive characteristics. Chromosomes most often involved in structural rearrangements were 1, 14, 10, and 19, and those most often lost were 17 and Y. The type of chromosome abnormalities seen were similar to those described for senescent human cell cultures, which suggests that common chromosomal mechanisms may be operative in benign tumors and senescent cells. Although meningiomas occur more commonly in females, the chromosomally abnormal tumors are distributed evenly between males and females. Within the group of tumors with structural chromosomal abnormality, there seems to be a bias toward meningotheliomatous histology, but otherwise the karyotype changes seen independent of the histologic type of tumor.

Long-term follow up of progesterone receptor status in benign meningioma: a prognostic indicator of recurrence?

OBJECT: A long-term prospective analysis of patients with benign meningioma was undertaken to determine whether progesterone receptor (PR) status of the excised tumor has any influence on recurrence. METHODS: Between 1983 and 1985, a total of 62 meningiomas in 53 patients (age range 19-79 years, mean age 55.6 years) were studied for clinical, histological, and pathological characteristics, including hormone receptor status and DNA features. Progesterone receptor status was quantified by cryostat section assay, and then factors affecting recurrence were analyzed. During 1997 all case records were reviewed to determine whether tumor had recurred in any patient, and PR status was correlated with tumor recurrence. Of the 62 tumors, 60 were benign, and of the benign tumors 29 (48%) were PR positive. Patients harboring 14 of the 60 benign tumors were lost to follow up. Of the 46 tumors included in the final analysis, 13 were recurrent (all within 5 years) and 33 were nonrecurrent. Of the 33 nonrecurrent tumors, 14 had not recurred 5 to 10 years postresection and 19 had not recurred after more than 10 years. Chi-square analysis of the results did not show an association between recurrence and patient's sex, extent of resection, histological subtype, or tumor site but did show an association between recurrence and PR negativity (p = 0.013). CONCLUSIONS: The results indicate that benign meningiomas that are PR positive are less likely to recur, a finding that has prognostic and therapeutic implications.

The prediction of recurrence in meningiomas. A flow cytometric study of paraffin-embedded archival material.

Despite the complete macroscopic excision of meningiomas, there is a significant rate of recurrence approaching 20% at 20 years. The prediction of recurrence by clinical and histopathological means is inadequate. Flow cytometric analysis of deoxyribonucleic acid (DNA) in meningiomas has shown a correlation between a high proliferative index based on tumor cell-cycle stage (%S + %G2/M) and clinically aggressive behavior. Accordingly, the DNA analysis of meningioma tissue may be of value in predicting recurrence of these tumors. To test this hypothesis, the DNA of paraffin-embedded archival tissue from known recurrent meningiomas was compared with an age- and sex-matched nonrecurrent group. Both groups had comparable follow-up periods. Forty patients with total macroscopic removal at the time of surgery were analyzed. The paraffin blocks of these tumors were retrieved and reclassified histologically according to the World Health Organization system. Sections were then taken for flow cytometric study. The DNA analysis showed that the proliferative index of the recurrent group was significantly higher than that of the nonrecurrent group (p less than 0.002), although the histological subtyping of the two groups was similar. These results support the suggestion that flow cytometry may be of value in the prediction of recurrence of histologically benign, macroscopically removed meningiomas.

DNA in meningioma tissues and explant cell cultures. A flow cytometric study with clinicopathological correlates.

Flow cytometry was performed on stored frozen tissues and explant cell cultures from 39 meningiomas using ethidium bromide and mithramycin in a selective staining technique for deoxyribonucleic acid (DNA). The ploidy index and percentage of cells in the G0/G1, S, and G2/M phases were calculated for each specimen. The results were compared with the age and sex of the patients; the site, the histological subtype, and mitotic rate of the neoplasms; and the estrogen- and progesterone-receptor levels assayed in cytosol-enriched supernatants from cryostat-cut sections. Sixteen neoplasms (41%) were aneuploid. These included two recurrent neoplasms, seven of the eight neoplasms from patients with multiple meningiomas, and three clinically aggressive neoplasms (one hemangiopericytic and two anaplastic meningiomas). Significant correlations were found between values for the ploidy index (r = 0.75, p less than 0.01), the percentage of S-phase cells (r = 0.82, p less than 0.01), and the percentage of G2/M-phase cells (r = 0.69, p less than 0.05) in vivo and in vitro. The results support the suggestion that flow cytometry for DNA in meningiomas may be of value in predicting the behavior of these neoplasms, and indicate that under controlled conditions explant cell cultures may provide a useful model for the proliferative characteristics of meningiomas in vivo.

Relationships between psychological symptoms, somatic complaints and menopausal status.

The importance of distinguishing climacteric symptoms from other psychological and somatic complaints has been repeatedly stressed, but as yet no detailed guidelines are available to assist the clinician in the day-to-day management of patients. Previous epidemiological surveys of climacteric symptoms have been criticised because of inadequate methodology. We have attempted to overcome most of these problems and to provide a more detailed analysis of the relationships between menopausal status and psychological and somatic symptoms. Eight hundred and fifty pre-, peri- and post-menopausal women, aged 45-65 yr, took part in a cross-sectional survey of general health, psychosocial factors and current symptomatology. They were a non-menopause clinic sample and were blind to the purpose of the study. Using a principal components analysis, the relationships between symptoms were examined. Certain psychological and somatic symptoms occurred together in specific clusters. Some of these symptom clusters, e.g., vasomotor symptoms and sexual difficulties, were best predicted solely by menopausal status, while others, such as psychological and somatic symptoms, were more clearly associated with psychosocial factors. On the basis of these results, guidelines for the assessment of climacteric and post-menopausal women can be suggested.

Extruded aneurysm coils found at craniotomy: report of two cases.

The operative findings are presented in two patients following inadequate coil embolization. At craniotomy, part of the coil mass had extruded through the fundus of both aneurysms. It is unclear if this phenomenon is confined to aneurysms that demonstrate significant regrowth and if there is an increased risk of rebleeding.

Exploratory burr holes.

The ability to enter the cranial cavity rapidly and effectively is a mandatory skill for those managing the head-injured patient. It may be increasingly required now that earlier computed tomography diagnosis of non-traumatic intracranial lesions is made in centres without the immediate assistance of a neurosurgeon.

Do we need variable pressure shunts?

We describe our experience using a variable pressure cerebrospinal fluid shunting system, over a period of 5 years. These valves appear to be reliable and have the advantage of allowing pressure setting adjustments to be made in the out-patient clinic. An analysis of the cost-effectiveness of this system, allowing for materials, theatre time and hospital stay, suggests that over pounds 21,000 was saved, by avoiding shunt revision procedures, over this period.

Intraoperative ultrasound-guided biopsy of intracranial lesions: comparison with freehand biopsy.

Achieving the required accuracy during such relatively straightforward procedures as tumour biopsy or abscess aspiration remains a challenge especially for the more junior neurosurgeon. A study comparing freehand biopsy with ultrasound-guided biopsy is presented. The use of intraoperative ultrasound increases the accuracy at the expense of a slightly longer operating time. Diagnostic tissue was always obtained using this technique.

Birth injury: a possible contributory factor in the aetiology of primary basilar impression.

Adult patients with primary basilar impression were four times more likely to have a history of birth injury than a control group. Distortion of basicranial synchondroses during birth is suggested as a possible mechanism and, in association with hindbrain herniation and arachnoid adhesions, may contribute towards the development of syringomyelia.

Inherited multiple meningiomas: a clinical, pathological and cytogenetic study of an affected family.

The clinical features of a family with inherited multiple meningiomas as the major manifestation of neurofibromatosis are presented. The value of noninvasive radiological screening investigations is emphasised. The results of cytogenetic and pathological studies on the family are presented and discussed with a review of the relevant literature.

Sigmoidoscopic neurosurgery? Treatment of an unusual complication of ventriculoperitoneal shunting.

A 16-year-old male with acute hydrocephalus due to bilateral acoustic neuromata was treated successfully with a ventriculoperitoneal shunt before formal neuroma resection. However, 2 years postoperatively, he noticed the distal shunt per rectum while defaecating. Subsequent removal was successfully performed using a flexible sigmoidoscope.