Research: Is resection of tumours involving the pelvic ring justified? : A review of 49 consecutive cases

INTRODUCTION: Pelvic surgery is challenging and impacts significantly on limb and visceral function, thus, raising the question "is heroic surgery justifiable". This study assessed the functional, oncologic and surgical outcomes following pelvis tumour resections. METHODS: Between 1996-2003, 49 patients (mean age 43 years) underwent pelvic tumour resections- 38 primary malignant tumours, 5 secondary tumours and 6 benign tumours. Bone tumours comprised 5 osteosarcomas, 5 Ewings sarcomas, and 12 chondrosarcomas. Of the soft tumours, 9 were of neural origin. Tumours involved the ilium, acetabulum, pubic bones, sacrum or a combination of these. Functional assessment was performed and no patient had metastases at presentation. RESULTS: There were 41 limb sparing resections and 8 hindquarter amputations. Surgical margins were intralesional (1), marginal (13), wide (26), and radical (3). Of limb sparing surgery, prosthetic reconstructions were performed in 10 patients, biologic reconstructions in 6, a combination of these in 3 and no reconstruction in others. There was 1 intraoperative death, 7 local recurrences and 19 metastases. Death from disease occurred at a mean of 14.2 months with a mean followup of 27 (1-96) months. Amputation and periacetabular resections had worse functional outcomes. Emotional acceptance was surprisingly high. CONCLUSION: Pelvic resections are complex. Functional outcome is significantly affected by surgery. Disease control is similar to limb tumours. Emotional acceptance of surgery in survivors was surprisingly high. Major pelvic resection for malignancy appears justified.     

The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality.     

DNA-DNA hybridization evidence of the rapid rate of muroid rodent DNA evolution

Single-copy nuclear DNAs (scnDNAs) of eight species of arvicoline and six species of murine rodents were compared using DNA-DNA hybridization. The branching pattern derived from the DNA comparisons is congruent with the fossil evidence and supported by comparative biochemical, chromosomal, and morphological studies. The recently improved fossil record for these lineages provides seven approximate divergence dates, which were used to calibrate the DNA-hybridization data. The average rate of scnDNA divergence was estimated as 2.5%/Myr. This is approximately 10 times the rate in the hominoid primates. These results agree with previous reports of accelerated DNA evolution in muroid rodents and extend the DNA-DNA hybridization data set of Brownell.      

Cyclic AMP raises cytosolic Ca2+ and promotes Ca2+ influx in a clonal pancreatic beta-cell line (HIT T-15)

The effect on cytosolic Ca2+ concentration ([Ca2+]i) of cAMP analogues and the adenylate cyclase-stimulating agents forskolin, isoproterenol and glucagon has been examined in an insulin-secreting beta-cell line (HIT T-15) using fura 2. All these manipulations of the cAMP messenger system promoted a rise in [Ca2+]i which was blocked by the Ca2+ channel antagonists verapamil and nifedipine or by removal of extracellular Ca2+. The action of the adenylate cyclase activator forskolin was glucose-dependent. The results suggest that cAMP elevates [Ca2+]i in HIT cells by promoting Ca2+ entry through voltage-sensitive Ca2+ channels, not through mobilization of stored Ca2+. Activation of Ca2+ influx may be an important component of the mechanisms by which cAMP potentiates fuel-induced insulin release.     

Differential regulation of glucokinase activity in pancreatic islets and liver of the rat

The differential tissue-specific regulation of glucokinase activity in liver and pancreatic islet cells was investigated in the insulinoma-bearing rat. A transplantable insulinoma caused hyperinsulinemia and hypoglycemia in the host by 2-3 months after implantation. Suppression of the pancreatic B-cells by the high insulin and/or low glucose manifested itself by a decrease of insulin in islet tissue. Removal of the tumor initiated transient insulin deficiency and hyperglycemia with extremes of these changes at 24 h after tumor resection. These conditions markedly affected glucose phosphorylation in the islet cells: glucokinase activity was reduced 71% in islet samples from insulinoma-bearing rats, and the enzyme fully recovered within 24 h after tumor resection. Hexokinase activity, by contrast, was not affected by these manipulations. To evaluate the relative contributions of hypoglycemia and hyperinsulinemia in islet glucokinase adaptation, glucose was intravenously infused to insulinoma-bearing rats; glycemia in excess of 150 mg/100 ml combined with excessive hyperinsulinemia resulted in a partial recovery of islet glucokinase activity, first apparent after 9 h of glucose infusion and with doubling of the activity after 24 h after glucose loading. In contrast, liver glucokinase was increased nearly 4-fold at the time of extreme hypoglycemia and hyperinsulinemia and rapidly fell to control rates following tumor removal. Intravenous infusion of glucose for 24 h into the tumor-bearing rat (i.e. hyperglycemia combined with excessive plasma insulin) had no influence on liver glucokinase activity. Liver hexokinase was not influenced by any of these experimental manipulations. The data indicate that the activities of pancreatic islet and liver glucokinase are regulated in a differential manner. Insulin is apparently the primary determinant of liver glucokinase and glucose seems to control islet glucokinase. Biochemical mechanisms for differential organ-specific regulation of glucokinase activity seem to have evolved such that this enzyme may play a dual role in glucose homeostasis, namely to serve as insulin-dependent glucose sensor in the B-cells and as insulin-sensitive determinant of hepatic glucose use.     

Cytotoxic Effect of β-Amyloid on a Human Differentiated Neuron Is Not Mediated by Cytoplasmic Ca2+ Accumulation

Abstract: The effects of synthetic β-amyloid (Aβ1–42) on cell viability and cellular Ca²⁺ homeostasis have been studied in the human neuron-like NT2N cell, which differentiates from a teratocarcinoma cell line, NTera2/C1.D1, by retinoic acid treatment. NT2N viability was measured using morphological criteria and fluorescent live/dead staining and quantified using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide metabolism. Aβ1–42 dose-dependently caused NT2N cell death when it was present in the cell culture for 14 days but had no effect on viability when it was present for 4 days. The lowest effective concentration was 4 µ M , and the strongest effect was produced by 40 µ M . Control NT2N cells produced spontaneous cytosolic Ca²⁺ oscillations under basal conditions. These oscillations were inhibited dose-dependently (0.4–40 µ M ) by Aβ1–42 that was present in the cell culture for 1 or 4 days. Ca²⁺ wave frequency was decreased from 0.21 ± 0.02 to 0.05 ± 0.02/min, amplitude from 88 ± 8 to 13 ± 4 n M , and average Ca²⁺ level from 130 ± 8 to 58 ± 3 n M . The Ca²⁺ responses to 30 m M K⁺ and 100 µ M glutamate were not different between control and Aβ-treated cells. Thus, the results do not support the hypothesis that cytosolic early Ca²⁺ accumulation mediates Aβ-induced NT2N cell death.     

Alterations in pancreatic islet phosphate content during secretory stimulation with glucose.

Isolated rat pancreatic islets were perifused and analyzed for phosphate content immediately following the transient increase in the efflux of orthophosphate which occurs when insulin secretion is stimulated by glucose. In some instances, islets were perifused directly following isolation to minimize preparative delay; in others, islets were prelabeled during incubation with [32P]orthophosphate for 90 min prior to perifusion. In both experimental situations, total islet phosphate content declined 40--50% following exposure to stimulating concentrations of glucose and initiation of enhanced insulin release. In the experiments with prelabeled islets, tissue content of [32P]orthophosphate fell to a similar extent so that the specific radioactivity of islet orthophosphate was unaffected. Inhibited of heightened insulin release with Ni2+ did not modify the decrements in total or radioactive tissue orthophosphate, thus indicating that these responses to islet stimulation reflect events which are proximal to activated exocytosis. Simultaneous analyses for tissue ATP and ADP demonstrated that the efflux in orthophosphate and reduction in tissue orthophosphate content were not mediated via net changes in islet adenine nucleotides. The observations represent the first documentation that a net reduction of tissue inorganic phosphate is one of the early components of stimulus-secretion coupling in isolated pancreatic islets.     

Distribution of myo-Inositol in the Cat Cochlear Nucleus

Abstract: The distribution of myo -inositol, a substance that has been implicated in synaptic transmission, has been mapped within sections of the cat cochlear nucleus as well as some nearby regions. Highest values in the cochlear nucleus were found in regions of granule cells along the periphery of the anteroventral subdivision of the nucleus. Highest values overall were found in the molecular layer of the cerebellar flocculus. A fairly good correlation was found between myo -inositol levels and activities of the enzymes of acetyl-choline metabolism in the cat cochlear nucleus, supporting the possibility that myo -inositol may be involved in cholinergic synaptic transmission. No positive correlation was found between myo -inositol levels and the levels of glutamate, aspartate, glycine, or γ-aminobutyric acid (GABA). The most striking gradient of myo -inositol levels within a region was found in the auditory nerve, where different myo -inositol levels might be related to nerve fibers innervating different parts of the cochlea. The distribution of scyllo -inositol, a stereoisomer of myo -inositol, was also examined, and found to parallel closely the distribution of myo -inositol, with levels 4–5% as high.