Should we abandon hormonal therapy in endometrial cancer? Outcomes of recurrent and metastatic endometrial cancer treated with systemic progestins.

PURPOSE: The objective of this study is to determine primary survival endpoints in women with recurrent and metastatic endometrial carcinoma (RMEC) treated with progestins. METHODS: A retrospective chart review was conducted at The Ottawa Hospital using electronic medical records. Inclusion criteria were a diagnosis of RMEC between 2000 and 2019, endometrioid histology, and ≥one line of progestin treatment. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Of 2342 cases reviewed, 74 met inclusion criteria. Sixty-six (88.0%) patients received megestrol acetate and 9 (12.0%) received a progestin alternative. The distribution of tumors by grade was: 1: 25 (33.3%), 2: 30 (40.0%), and 3: 20 (26.7%). The PFS and OS for the entire study sample was 14.3 months (95% CI 6.2-17.9) and 23.3 months (14.8-36.8), respectively. The PFS for patients with Grade 1-2 RMEC was 15.7 months (8.0, 19.5), compared to 5.0 months (3.0, 23.0) with Grade 3 disease. The OS for patients with Grade 1-2 versus Grade 3, was 25.9 months (15.3, 40.3) versus 12.5 months (5.7, 35.9), respectively. Thirty-four (45.9%) and 40 (54.1%) patients were treated with 0 and ≥1 line of chemotherapy. The PFS for chemotherapy-naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy-naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. CONCLUSIONS: This real-world data on RMEC suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy-naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy-OS was 29.1 months (17.9, 61.1) for chemotherapy-naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed.

Free carrier lifetime modification for silicon waveguide based devices.

We investigate the effect of silicon ion irradiation on free carrier lifetime in silicon waveguides, and thus its ability to reduce the density of two-photon-absorption (TPA) generated free carriers. Our experimental results show that free carrier lifetime can be reduced significantly by silicon ion implantation. Associated excess optical absorption from the implanted ions can be reduced to an acceptable level if irradiation energy and dose are correctly chosen. Simulations of Raman scattering suggest that net gain can be achieved in certain cases without the need for an integrated diode in reverse bias to remove the photo-generated free carriers.

Effect of growth hormone on bone: bone mineral density, trabecular bone volume, and alkaline phosphatase improve or are restored in the dwarf rat treated with growth hormone.

Studies were performed to determine whether serum total alkaline phosphatase (SAP), an index of bone formation; body weight; total body bone mineral density (BMD), measured by dual-energy X-ray absorptiometry; and tibial trabecular bone volume (TBV), measured by histomorphometry, are reduced in 2-week-old female sexually immature Lewis dwarf (dw/dw) rats (DW-CT, n = 9) with isolated growth hormone (GH) deficiency and, if so, whether recombinant human GH (rhGH), 200 micrograms/day subcutaneously for 4 weeks (DW-GH, n = 7), restores them. Studies were also performed to determine if 30% dietary restriction in 2-week-old female Lewis rats (LW-DR, n = 11) alters SAP, body weight, total BMD, or TBV compared with pair-fed controls (LW-CT, n = 7) given an ad libitum diet. Mean SAP (91 +/- 5 versus 109 +/- 5 U/l), body weight (102 +/- 11 versus 140 +/- 10 g), total BMD (88.5 +/- 0.3 versus 101.4 +/- 2.0 mg/cm2), and TBV (19.0 +/- 1.0 versus 27.0 +/- 1.4%) were significantly lower in DW-CT than in LW-CT animals, p < 0.05. In DW-GH, rhGH significantly increased mean SAP (130 +/- 7 U/l), body weight (133 +/- 10 g), total BMD (92.7 +/- 1.3), and TBV (24.0 +/- 1.9) compared with DW-CT animals. Compared with LW-CT rats, mean body weight and TBV were not different, but mean SAP was significantly higher (p < 0.01) and mean total BMD was significantly lower (p < 0.003) in DW-GH rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of pulsatile secretion and clearance of plasma cortisol in premature and term neonates using deconvolution analysis.

Pulsatile secretion of cortisol (F) has not been documented in the newborn infant. Using repeated blood sampling and deconvolution analysis, we investigated F secretion and elimination dynamics in a group of five premature (gestational age, 24-34 weeks) and five term neonates. These infants had required placement of an umbilical arterial cannula for monitoring respiratory status, but were otherwise clinically stable. Blood samples were obtained at 15-min intervals for a 6-h period. All plasma F determinations were 58 nmol/L (2.1 micrograms/dL) or more, and pulsatile F secretion was observed in all infants. No significant differences were noted between the two groups with regard to 6-h mean plasma F concentration [350 +/- 129 (premature) vs. 277 +/- 54 nmol/L (term)], plasma corticosteroid-binding globulin (14 +/- 0 vs. 13 +/- 1 mg/L), F secretory burst frequency (4 +/- 0 vs. 5 +/- 1 bursts/6 h), mass of F secreted per burst [760 +/- 480 vs. 310 +/- 100 nmol/Lv [Lv, liter of F distribution volume)], F production rate (FPR; 2.7 +/- 1.4 vs. 1.1 +/- 0.2 mumol/Lv.6 h), or plasma F half-life (45 +/- 6 vs. 56 +/- 4 min). However, the premature infants had a significantly longer F secretory burst half-duration (63 +/- 18 vs. 6.7 +/- 4.0 min; P < 0.01) and a significantly lower maximal F secretory rate (9.4 +/- 3.4 vs. 100 +/- 26 nmol/Lv.min; P < 0.02) than the term infants. Body surface area and body weight were inversely correlated with F secretory burst half-duration (r = -0.74 and -0.75, respectively); both were also positively correlated with the maximal F secretory rate (r = 0.66 and 0.72). The two most premature infants had significantly greater mean plasma F and FPR than the other three premature and all of the term infants. Extrapolating to 24 h and correcting for the distribution volume of F and body surface area, we estimate FPR to be approximately 17-24 mumol/m2.24 h (6.6-8.8 mg/m2.24 h) for newborn infants of 34 weeks or more gestational age. These values are consistent with newer estimates of FPR in older children and adults determined using either deconvolution analysis or stable isotope dilution methods.

Spontaneous growth hormone release in term infants: changes during the first four days of life.

Healthy term infants have higher umbilical cord GH levels compared to older infants and children. In the sheep, GH concentrations rapidly fall within an hour of birth; the physiology of GH release after parturition in the human term infant is less well known. The purpose of this study was to investigate spontaneous 12-h GH release in male and female term infants of varying postnatal ages. We studied 14 infants (7 males and 7 females). Subjects were divided into those studied earlier following delivery (28.2 +/- 3.4 h of age, mean +/- SE) and into those studied at a later time (74.8 +/- 3.5 h, P < 0.0005). The age at study was defined as the age (hours) when blood sampling began. There were eight infants studied at an early age (four males and four females) and six studied at a later age (three males and three females). Subjects were comparable with respect to gestational age, birth weight, and length; all were biochemically euthyroid. One infant was large for gestational age although his head circumference was in the normal range. Blood (0.1 mL) was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double-antibody RIA using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor I (IGF-I) was measured following separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences in GH characteristics were found between male and female subgroups in the early or late study groups. In subsequent analysis, the data for the males and females are combined. The GH pulse frequency per 12 h was greater in the earlier studied group, 5.1 +/- 0.9 (mean +/- SE) vs. 2.5 +/- 0.7 in the later group (P < 0.05). The maximal pulse amplitude was 47.1 +/- 7.9 micrograms/L in the early and 27.1 +/- 4.1 in the later studied group (P < 0.06). The incremental pulse amplitude was 26.4 +/- 3.4 micrograms/L in the early and 12.8 +/- 2.7 in the later group (P = 0.01). The pulse width was greater in the later studied group (202.8 +/- 71.1 min vs. 84.1 +/- 21.6, P < 0.06).(ABSTRACT TRUNCATED AT 400 WORDS)

Greater secretion of growth hormone in black than in white men: possible factor in greater bone mineral density--a clinical research center study.

To determine why blacks have a higher bone mineral density (BMD) and lower incidence of osteoporosis and fractures than whites, we investigated whether the secretion of GH is higher in black than in white men. Measurements of GH were obtained at 20-min intervals over 24 h and analyzed by deconvolution. BMD was determined by dual energy x-ray absorptiometry in 16 normal black and 17 normal white men, aged 20-40 yr. The 24-h integrated GH concentration 942 +/- 174 vs. 602 +/- 104 micrograms/L; P = 0.0495) and GH secretory burst amplitude (0.499 +/- 0.163 vs. 0.169 +/- 0.027 micrograms/L.min; P = 0.0482) were higher in black than in white men. GH burst frequency, half-duration, mass, and half-life were not different in the 2 groups. The serum 17 beta-estradiol level (162 +/- 12 vs. 108 +/- 11 pmol/L; P = 0.0011) was higher, and the serum insulin-like growth factor-binding protein 3 level (2.2 +/- 0.1 vs. 2.8 +/- 0.1 microgram/mL; P = 0.0001) was lower in black than in white men. BMD values for total body (1.22 +/- 0.02 vs. 1.14 +/- 0.02 g/cm2; P = 0.0041), forearm (0.69 +/- 0.01 vs. 0.66 +/- 0.01 g/cm2; P = 0.0211), trochanter (0.91 +/- 0.03 vs. 0.77 +/- 0.03 g/cm2; P = 0.0003), and femoral neck (1.08 +/- 0.03 vs. 0.93 +/- 0.03 g/cm2; P = 0.0007) were higher in black than in white men. Thus, serum 17 beta-estradiol level, GH secretion, and BMD values for the total body, forearm, trochanter, and femoral neck are greater in black than in white men. As estrogen is known to increase GH secretion and GH to increase bone mass, increases in circulating 17 beta-estradiol may contribute to the higher GH secretion and bone mass in black men.

Demonstration of a lack of racial difference in secretion of growth hormone despite a racial difference in bone mineral density in premenopausal women--a Clinical Research Center study.

We previously found GH secretion to be higher in black than white men. Therefore, we performed studies to determine whether this racial difference in GH secretion also occurs in women. Measurements of GH were obtained at 20-min intervals over 24 h and analyzed by deconvolution in 12 healthy black and 12 healthy white premenopausal women. Bone mineral density (BMD) was determined by dual energy x-ray absorptiometry, and GM allotypes were measured as a genetic marker for race. Racial distribution of the groups, as determined by analysis of GM haplotypes, were typical for black and white American populations. Twenty-four-hour integrated GH concentration, GH secretory burst amplitude, burst frequency, half-duration, mass, and half-life were not different in the two groups. Serum testosterone was modestly, but significantly, greater in the black than in the white women (1.1 +/- 0.1 vs. 0.9 +/- 0.1 nmol/L; P < 0.05). Serum 17 beta-estradiol and insulin-like growth factor (IGF)-binding protein-3 were not different in the two groups. However, the IGF-I/IGF-binding protein-3 molar ratio was significantly greater in the black than the white women (2.0 +/- 0.1 vs. 1.6 +/- 0.1; P < 0.02). The BMD of total body (1.12 +/- 0.02 vs. 1.07 +/- 0.02 g/cm2; P < 0.05) and total hip (0.96 +/- 0.04 vs. 0.86 +/- 0.04 g/cm2, P < 0.05) were greater in the black (n = 13) than in the white (n = 12) women. There was a trend toward greater BMD of the forearm in the black women (0.58 +/- 0.01 vs. 0.56 +/- 0.01 g/cm2; P = 0.06) and no racial difference in the BMD of the spine. When examining all subjects together, the BMD of the total body, trochanter, and spine correlated with total integrated GH secretion. Thus, the racial difference in GH secretion that we had previously found in men does not occur in women despite the higher BMD values at several skeletal sites in black women.

Spontaneous pulsatile growth hormone release in male and female premature infants.

Although premature infants have high umbilical cord GH levels, little is known about spontaneous GH release in these individuals. The purpose of our study was to investigate spontaneous 12-h GH release in appropriate for gestational age male and female premature infants. We studied 22 premature infants (15 males and 7 females) of appropriate length and weight for age. Gestational ages, birth weights, birth lengths, and ages at the time of study were similar in male or female infants. All infants were biochemically euthyroid. Blood was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double antibody RIA, using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor-I and -II (IGF-I and -II) levels were measured after separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences were found between males and females in the pulse characteristics of frequency, maximal amplitude, incremental amplitude, width, or area. The GH pulse frequency per 12 h was 3.2 +/- 0.3 (mean +/- SE) in males and 3.0 +/- 0.7 in females. The maximal pulse amplitude was 50.7 +/- 6.2 micrograms/L in males and 44.7 +/- 9.0 micrograms/L in females. The incremental pulse amplitude was 24.3 +/- 3.2 micrograms/L in males and 20.2 +/- 3.9 micrograms/L in females. The mean 12-h GH level was 37.1 +/- 4.8 micrograms/L in males and 35.8 +/- 8.5 micrograms/L in females; the average GH nadir was 26.1 +/- 4.0 micrograms/L in males and 24.4 +/- 8.3 micrograms/L in females. Both IGF-I and IGF-II concentrations were similar in males and females. The mean IGF-I levels were 10.7 +/- 1.5 ng/mL in males and 7.5 +/- 1.1 ng/mL in females; IGF-II levels were 96.0 +/- 12.0 ng/mL in males and 115.4 +/- 17.1 ng/mL in females. These results demonstrate similar pulsatile GH release in male and female premature infants at a mean age of 32-33 weeks. Compared with previously reported values for mean GH concentration and average GH nadir in older children, the values in these premature infants were much higher. We speculate that the higher GH levels in premature infants may result from decreased negative feedback associated with low IGF-I levels. The premature infant's somatotrophs may also not fully respond to the GH inhibitory action of somatostatin.

Spontaneous and stimulated growth hormone release in adolescents with type I diabetes mellitus: effects of metabolic control.

Abnormalities in GH release have been found in adults with poorly controlled type I diabetes mellitus. During puberty, circulating GH concentrations transiently increase. To investigate in pubertal diabetic adolescents, the physiological relationship between metabolic control and GH release, we compared spontaneous and GH-releasing hormone (GHRH)-stimulated GH release in six pubertal subjects during poor (study A) and improved (study B) metabolic control. The subjects included two females and four males (mean age +/- SE, 15.5 +/- 1 yr; duration of diabetes, 8.6 +/- 0.9 yr; Tanner stages II-V). Serum samples for glucose and GH determinations were obtained at 20-min intervals over a 24-h period. Significant pulses of GH release were identified using a pulse detection algorithm (Cluster). Fourier expansion time series was used to document the occurrence of significant periodicities in the GH concentration-time data series. All subjects received 1.0 microgram/kg GHRH-44, iv, at 0800 h on the day after the 24-h monitoring for GH. After GHRH administration, samples were taken for glucose and GH determinations over 90 min. The overall mean glucose level (+/- SE) during the 24-h monitoring was 11.5 +/- 0.2 mmol/L during study A and 7.2 +/- 0.2 during study B (P = 0.0001). During the 4 weeks of improved control, glycated hemoglobin fell from 13.9 +/- 1.4% to 11.7 +/- 0.8% (mean +/- SE; P < 0.025). All subjects had significant pulses of GH release during poor or improved metabolic control. Relative to that at night, the daytime pulse frequency was higher in study A (P < 0.025). The overnight pulse frequency increased during study B (P < 0.01). Other pulse parameters, including maximal and incremental pulse amplitudes, pulse width, and interpulse valley mean, did not change during improved control. The mean +/- SE 24-h GH concentration was 4.1 +/- 0.7 micrograms/L during study A and 4.3 +/- 0.8 during study B. The amplitude of the circadian GH rhythm was not different by Fourier analysis. The overall mean glucose +/- SE after GHRH administration was 15.3 +/- 0.2 mmol/L in study A and 6.8 +/- 0.1 in study B. In spite of the marked hyperglycemia during study A, the GH responses were similar during studies A and B. Maximal GH levels were obtained at 15-30 min (mean +/- SE) and were 36.0 +/- 16.9 micrograms/L in study A and 38.7 +/- 18.9 in study B.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of a high-protein, low-fat, ketogenic diet on adolescents with morbid obesity: body composition, blood chemistries, and sleep abnormalities.

OBJECTIVE: To evaluate the efficacy and metabolic impact of a high-protein, low-carbohydrate, low-fat ketogenic diet (K diet) in the treatment of morbidly obese adolescents with initial weights of >200% of ideal body weight. METHODS: Six adolescents, aged 12 to 15 years, weighing an average of 147.8 kg (range, 120.6-198.6 kg) and having an average body mass index of 50.9 kg/m (39.8-63.0 kg/m), consumed the K diet for 8 weeks. Daily intake consisted of 650 to 725 calories, which was substantively in the form of protein (80-100 g). The diet was very low in carbohydrates (25 g) and fat (25 g). This was followed by 12 weeks of the K diet plus two carbohydrates (30 g) per meal (K+2 diet). MAIN OUTCOME MEASURES: Anthropometric data and blood and urine were collected at enrollment, during week 1, and at 4-week intervals throughout the course of the study. Resting energy expenditure was measured by indirect calorimetry. Body composition was estimated using dual-energy x-ray absorptiometry, bioelectrical impedance analysis, and urinary creatinine excretion at enrollment and on completion of each phase of the diet. Nocturnal polysomnography and multiple sleep latency testing were conducted at baseline and repeated after an average weight loss of 18.7 kg to determine sleep architecture, frequency and duration of apneas, and daytime sleepiness. RESULTS: Subjects lost 15.4 +/- 1.4 kg (mean +/- SEM) during the K diet and an additional 2.3 +/- 2.9 kg during the K+2 diet. Body mass index decreased 5.6 +/- 0.6 kg/m(2) during the K diet and an additional 1.1 +/- 1.1 kg/m(2) during the K+2 diet. Body composition studies indicated that weight was lost equally from all areas of the body and was predominantly fat. Dual-energy x-ray absorptiometry showed a decrease from 51.1% +/- 2.1% body fat to 44.2% +/- 2.9% during the K diet and then to 41.6% +/- 4.5% during the K+2 diet. Lean body mass was not significantly affected. Weight loss was accompanied by a reduction in resting energy expenditure of 5.2 +/- 1.8 kcal/kg of fat-free mass per day. Blood chemistries remained normal throughout the study and included a decrease in serum cholesterol from 162 +/- 12 to 121 +/- 8 mg/dL in the initial 4 weeks of the K diet. An increase in calcium excretion was accompanied by a decrease in total-body bone mineral content. A paucity of rapid eye movement sleep and excessive slow-wave sleep were seen in all subjects at enrollment. Weight loss led to an increase in rapid eye movement sleep (P < .02) and a decrease in slow-wave sleep (P < .01) to near normal levels. CONCLUSIONS: The K diet can be used effectively for rapid weight loss in adolescents with morbid obesity. Loss in lean body mass is blunted, blood chemistries remain normal, and sleep abnormalities significantly decrease with weight loss.

In Vitro andIn Vivo induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene.

It has been well established that bone morphogenetic protein-2 (BMP-2) can induce bone formation bothin vivo andin vitro, although high concentrations (up to milligrams) of BMP-2 have been required to achieve this effectin vivo. Further, clinical applications are usually limited to a single dose at the time of implantation. In an attempt to prolong the transforming effect of BMP-2 we used a recombinant adenoviral vector carrying the human BMP-2 gene (Adv-BMP2) to transduce marrow-derived mesenchymal stem cells (MSC) of skeletally mature male New Zealand white rabbits. The pluripotential MSC were incubated with Adv-BMP2 overnight followed by culture in growth medium for 1 week. Assays on tissue cultures demonstrated that these Adv-BMP2 transduced MSC produced BMP-2 protein, differentiated into an osteoprogenitor line, and induced bone formationin vitro. These MSC had increased alkaline phosphatase activity, increased expression of type I collagen, osteopontin, and osteocalcin mRNA, and induced matrix mineralization compared with both nontransduced cells and cells transduced with a control adenoviral construct. To analyze the osteogenic potentialin vivo, Adv-BMP2-transduced MSC were autologously implanted into the intertransverse process space between L5 and L6 of the donor rabbits. The production of new bone was demonstrated by radiographic examination 4 weeks later in areas implanted with cells transduced with Adv-BMP2, whereas no bone was evident at sites implanted with cells transduced with the control adenoviral construct. Histological examination further confirmed the presence of new bone formation. These accumulated data indicate that it is possible to successfully transduce mesenchymal stem cells with a recombinant adenoviral vector carrying the gene for BMP-2 such that these cells will produce BMP-2, differentiate into an osteoprogenitor line, and induce bone formation bothin vitro andin vivo. Moreover, incubation of the Adv-BMP2-transduced cells for an additional 7 days in culture before transplantation enhances the success rate in bone formation (three out of three) as compared with our previous report (one out of five, Calcif Tissue Int 63:357-360, 1998).

Adjacent fracture-dislocations of the lumbosacral spine: case report.

OBJECTIVE AND IMPORTANCE: Traumatic fracture-dislocations of the lumbosacral junction are rare, with all previously reported cases involving fracture-dislocations at a single level. No cases of multiple fracture-dislocations of contiguous spinal segments in the lumbosacral spine have been reported. A case of traumatic adjacent fracture-dislocations of the fifth lumbar segment is presented. CLINICAL PRESENTATION: An 18-year-old male patient sustained open lumbar spinal trauma after a motor vehicle accident. A neurological examination revealed an L4 level. Radiographic evaluation of the spine revealed a three-column injury at L5 with spondyloptosis of the L5 vertebral body. Aorto-ilio-femoral angiography revealed no evidence of vascular injury. INTERVENTION: The patient was treated with a combined anterior and posterior approach in a two-stage operation. Six months postoperatively, he was neurologically unchanged; however, he was able to walk with the aid of a cane. Plain films revealed normal alignment of the lumbosacral spine. CONCLUSION: The management of traumatic lumbosacral fracture-dislocations requires careful consideration of retroperitoneal structures and possible exploration of the iliac vessels in addition to spinal reconstruction.

Vertebral artery injury in C1-2 transarticular screw fixation: results of a survey of the AANS/CNS section on disorders of the spine and peripheral nerves. American Association of Neurological Surgeons/Congress of Neurological Surgeons.

OBJECT: The 847 active members of the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Section on Disorders of the Spine and Peripheral Nerves were surveyed to quantitate the risk of vertebral artery (VA) injury during C1-2 transarticular screw placement. METHODS: This retrospective study elicited the number of patients treated with transarticular screws, the number of screws placed, the incidence of VA injury and subsequent neurological deficit, and the management of known or suspected VA injury. Two hundred thirteen (25.1%) of the 847 surgeons responded. One hundred one respondents (47.4%) had placed a total of 2492 C1-2 transarticular screws in 1318 patients. Thirty-one patients (2.4%) had known VA injuries and an additional 23 patients (1.7%) were suspected of having injuries. However, only two (3.7%) of the 54 patients with known or suspected VA injuries exhibited subsequent neurological deficits and only one (1.9%) died of bilateral VA injury. Other iatrogenic complications included dural tears, screw fractures, screw breakout, fusion failure, infection, and suboccipital numbness. CONCLUSIONS: Including both known and suspected cases, the risk of VA injury was 4.1% per patient or 2.2% per screw inserted. The risk of neurological deficit from VA injury was 0.2% per patient or 0.1% per screw, and the mortality rate was 0.1%. The choice of management of intraoperative VA injuries was evenly divided between placing the patient under observation and initiating immediate postoperative angiography with possible balloon occlusion.

Complex cervical spine neoplastic disease: reconstruction after surgery by using a vascularized fibular strut graft. Case report.

The authors report a case of an aggressive chordoma in the cervical spine of a 15-year-old girl who underwent radical resection followed by reconstruction using an anterior vascularized fibular strut graft and posterior arthrodesis prior to receiving immediate postoperative radiation therapy. The patient had successful graft incorporation 4 months postoperatively. The authors review the advantages of using vascularized fibular strut grafts for the treatment of multilevel cervical spine neoplastic disease and discuss the theoretical advantages of using vascularized grafts that tolerate therapeutic levels of radiation.

Just taller or more bone? The impact of growth hormone on osteogenesis imperfecta and idiopathic juvenile osteoporosis.

There are scant data to date on the use of GH therapy in osteogenesis imperfecta (OI) or in idiopathic juvenile osteoporosis (IJO). In OI, we review three clinical trials (aggregate study population 46), and 13 patient reports from the NCGS, and two independent patient reports. Based on evidence of increased growth rate versus some reported increased fracture rate, we conclude that GH should probably not be used as first-line therapy in OI, pending further data from clinical trials. There are no published reports of the use of GH therapy in IJO and only one patient with documented IJO enrolled in the NCGS. Since IJO presents in the immediate prepubertal period and appears to improve naturally during puberty, it is difficult to differentiate the effects of GH therapy from those of puberty; therefore, we conclude that GH in IJO should currently be used only for research and not in clinical practice.

Exploring prison buprenorphine misuse in the United Kingdom: a qualitative study of former prisoners.

The United Kingdom Ministry of Justice recently highlighted the extent of buprenorphine (Subutex) misuse in English andWelsh prisons, naming it the third most misused drug overall. Yet little is known regarding how illicit buprenorphine is obtained in prison and what influences prisoners to use it. Qualitative research was used to explore prison drug using practices. Thirty men who were former prisoners with a history of injecting drug use were interviewed in depth about their illicit prison drug use, including buprenorphine. Interviews were conducted over 18 months, from August 2006 to January 2008 and were analysed using Framework. The misuse of Subutex by snorting emerged as a significant theme. Accounts suggested that the diversion of prison prescribed Subutex was widespread and prisoners used various tactics to obtain the medication. Various complex and interlinked reasons were given to explain why Subutex was snorted in prison. The main motivation for snorting was to experience a prolonged euphoric opiate effect, believed to help to combat the boredom of being in prison. The price of illicit Subutex in prison was linked to its availability, but it was generally cheaper than heroin, thus contributing to its use. Participants'narratives identified the belief that snorting Subutex in prison was not risk free, but risks were lower than continuing to use other drugs, particularly injecting illicit opiates. The implications of prison Subutex misuse for prisoners, prison medical services, commissioners, and prescribing policy and practice are discussed.

Non-commercial clinical trials of a medicinal product: can they survive the current process of research approvals in the UK?

Over recent years, considerable attention has been paid to the National Health Service (NHS) research governance and ethics approvals process in the UK. New regulations mean that approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) is now also needed for conducting all clinical trials. Practical experience of gaining MHRA and sponsorship approval has yet to be described and critically explored in the literature. Our experience, from start to finish, of applying for these four approvals for a multicentre randomised controlled trial of two licensed drugs for opiate detoxification in the prison setting is described here. In addition, the implications of the approvals process for research projects, particularly clinical trials, in terms of time and funding, and also indirect implications for NHS patients are discussed. Inconsistencies are discussed and suggestions that could improve and streamline the overall process are made. The current approvals process could now be hindering non-commercial clinical trials, leading to a loss of important evidence-based medical information.

Verification of nerve root decompression during minimally-invasive lumbar microdiskectomy: a practical application of surgeon-driven evoked EMG.

Lumbar microendoscopic diskectomy (MED) has gained widespread acceptance as an alternative to conventional open microdiskectomy due to several potential advantages, including reductions in postoperative pain and recovery time. However, constraints in visualization and working space present technical difficulties in the verification of nerve root decompression and the identification of sequestered disc fragments. This study was undertaken to investigate whether a surgeon-driven, evoked EMG paradigm could be used for intraoperative verification of nerve root decompression within the technical and mechanical confines of lumbar MED. Twenty-two patients underwent intraoperative EMG stimulation threshold recordings during lumbar microendoscopic diskectomy. In this series, the EMG threshold recorded directly from the nerve root immediately prior to diskectomy was 8.6 +/- 4.4 mA. Following decompression, the threshold was 4.2 +/- 2.1 mA. The difference in pre- and post-decompression EMG stimulation threshold, 4.4 +/- 4.0 mA, was statistically significant (p < 0.001). In two of the 22 cases (9.1 %), the EMG threshold was initially unchanged following diskectomy, and further exploration revealed sequestered disc fragments. After removal of these fragments, an appropriate decrease in the EMG threshold was observed. The results from this study suggest that surgeon-driven, evoked EMG threshold testing may provide a simple, effective adjunct to lumbar microendoscopic diskectomy for intraoperative verification of nerve root decompression.