Chromosome microarray proficiency testing and analysis of quality metric data trends through an external quality assessment program for Australasian laboratories.

Chromosome microarrays are an essential tool for investigation of copy number changes in children with congenital anomalies and intellectual deficit. Attempts to standardise microarray testing have focused on establishing technical and clinical quality criteria, however external quality assessment programs are still needed. We report on a microarray proficiency testing program for Australasian laboratories. Quality metrics evaluated included analytical accuracy, result interpretation, report completeness, and laboratory performance data: sample numbers, success and abnormality rate and reporting times. Between 2009 and 2014 nine samples were dispatched with variable results for analytical accuracy (30-100%), correct interpretation (32-96%), and report completeness (30-92%). Laboratory performance data (2007-2014) showed an overall mean success rate of 99.2% and abnormality rate of 23.6%. Reporting times decreased from >90 days to <30 days for normal results and from >102 days to <35 days for abnormal results. Data trends showed a positive correlation with improvement for all these quality metrics, however only 'report completeness' and reporting times reached statistical significance. Whether the overall improvement in laboratory performance was due to participation in this program, or from accumulated laboratory experience over time, is not clear. Either way, the outcome is likely to assist referring clinicians and improve patient care.

JRK is a positive regulator of ß-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer.

The loss of ß-catenin inhibitory components is a well-established mechanism of carcinogenesis but ß-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the ß-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a ß-catenin activator function, depletion of JRK in several cancer cell lines repressed ß-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of ß-catenin target genes and increased cell proliferation. This study shows that JRK is required for ß-catenin hyperactivity regardless of the adenomatous polyposis coli/ß-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer.

Reduced cortical BACE1 content with one bout of exercise is accompanied by declines in AMPK, Akt, and MAPK signaling in obese, glucose-intolerant mice.

Obesity and type 2 diabetes are significant risk factors in the development of neurodegenerative diseases, such as Alzheimer's disease. A variety of cellular mechanisms, such as altered Akt and AMPK and increased inflammatory signaling, contribute to neurodegeneration. Exercise training can improve markers of neurodegeneration, but the underlying mechanisms remain unknown. The purpose of this study was to determine the effects of a single bout of exercise on markers of neurodegeneration and inflammation in brains from mice fed a high-fat diet. Male C57BL/6 mice were fed a low (LFD; 10% kcal from lard)- or a high-fat diet (HFD; 60% kcal from lard) for 7 wk. HFD mice underwent an acute bout of exercise (treadmill running: 15 m/min, 5% incline, 120 min) followed by a recovery period of 2 h. The HFD increased body mass and glucose intolerance (both P < 0.05). This was accompanied by an approximately twofold increase in the phosphorylation of Akt, ERK, and GSK in the cortex (P < 0.05). Following exercise, there was a decrease in beta-site amyloid precursor protein cleaving enzyme 1 (BACE1; P < 0.05) and activity (P < 0.001). This was accompanied by a reduction in AMPK phosphorylation, indicative of a decline in cellular stress (P < 0.05). Akt and ERK phosphorylation were decreased following exercise in HFD mice to a level similar to that of the LFD mice (P < 0.05). This study demonstrates that a single bout of exercise can reduce BACE1 content and activity independent of changes in adiposity. This effect is associated with reductions in Akt, ERK, and AMPK signaling in the cortex.

A role for calcium/calmodulin kinase in insulin stimulated glucose transport.

Previous research has shown that the CAMK (calcium/calmodulin dependent protein kinase) inhibitor, KN62, can lead to reductions in insulin stimulated glucose transport. Although controversial, an L-type calcium channel mechanism has also been hypothesized to be involved in insulin stimulated glucose transport. The purpose of this report was to determine if 1) L-type calcium channels and CAMK are involved in a similar signaling pathway in the control of insulin stimulated glucose transport and 2) determine if insulin induces an increase in CAMKII phosphorylation through an L-type calcium channel dependent mechanism. Insulin stimulated glucose transport was significantly (p<0.05) inhibited to a similar extent ( approximately 30%) by both KN62 and nifedipine in rat soleus and epitrochelaris muscles. The new finding of these experiments was that the combined inhibitory effect of these two compounds was not greater than the effect of either inhibitor alone. To more accurately determine the interaction between CAMK and L-type calcium channels, we measured insulin induced changes in CAMKII phosphorylation using Western blot analysis. The novel finding of this set of experiments was that insulin induced an increase in phosphorylated CAMKII ( approximately 40%) in rat soleus muscle that was reversed in the presence of KN62 but not nifedipine. Taken together these results suggest that a CAMK signaling mechanism may be involved in insulin stimulated glucose transport in skeletal muscle through an L-type calcium channel independent mechanism.

Evidence for the involvement of a phospholipase C--protein kinase C signaling pathway in insulin stimulated glucose transport in skeletal muscle.

The primary purpose of this investigation was to determine the relationship between phospholipase C (PLC) and diacylglycerol (DAG) sensitive protein kinase C isoforms in insulin signaling in skeletal muscle. Using an in vitro preparation of rat soleus muscle we found that insulin (0.6 nM) stimulated glucose transport was inhibited approximately 20 and 25% by the PKC inhibitor GF109203X and the phospholipase C inhibitor U73122 respectively (p<0.05). The combined effects of these inhibitors were no greater than the inhibitory effects of either compound alone. Western blot analysis revealed that insulin induced a redistribution of PKC beta II from the cytosol to the membrane that was reversed in the presence of GF109203X (1 microM) and U73122 (20 microM). Similarly, U73122 and GF109203X reversed the insulin induced increase in membrane associated phosphorylated (ser 660) PKC beta II. The novel finding of this investigation is that insulin induces an increase in PKC beta II translocation and phosphorylation through a U73122 sensitive pathway in quantatively the most important insulin responsive tissue, skeletal muscle. Furthermore, these results imply that PKC beta II may be one of the DAG sensitive isoforms involved in glucose transport.

A male genital tract-specific carbohydrate epitope on human CD52: implications for immunocontraception.

The identification of unique sperm surface epitopes that are not expressed or exposed in the female reproductive tract is a key element in the development of antibody-based contraceptives. Western blotting and immunohistochemistry were performed to define the tissue distribution of the S19 epitope, which has been proposed as a target for immunocontraception. S19 is an IgG1 murine monoclonal antibody (mAb) directed to an N-linked carbohydrate epitope on a 15-25 kDa glycoprotein, sperm agglutination antigen-1 (SAGA-1), containing a peptide core identical to that of the lymphocytic surface protein CD52. In this study, the S19 epitope was shown to be absent from human lymphocytes, demonstrating a distinction between this epitope and the CAMPATH epitope that is recognized by an antibody against the terminal tripeptide and GPI-anchor of CD52. Further tissue specificity analysis identified the S19 epitope in the epithelium of the human epididymis and vas deferens, as well as on both epididymal and ejaculated spermatozoa. In contrast, the S19 epitope was absent in the five human female reproductive tract and 18 other somatic tissues tested. These results support the use of the S19 epitope as a contraceptive immunogen and the suitability of the S19 mAb as an intravaginal contraceptive. To test the agglutinating activity of the S19 mAb in a formulation designed for vaginal use, S19 mAb were bound to the surface of Novasomes, a multilamellar liposome delivery vehicle. S19-Novasome formulations agglutinated human spermatozoa and were as effective as unbound S19 mAb, demonstrating the feasibility of spermistatic contraceptives targeted to the male reproductive tract specific carbohydrate epitope.

The effects of phospholipase C inhibition on insulin-stimulated glucose transport in skeletal muscle.

Previous research has demonstrated that phospholipase C (PLC) is involved in insulin-stimulated glucose transport in 3T3-L1 adipocytes. The purpose of the current investigation was to determine if PLC is also involved in insulin-stimulated glucose uptake in rat skeletal muscle. To that end, we used an in vitro muscle preparation of the rat soleus muscle to test the effects of the PLC inhibitor, U73122, on glucose transport. The PLC inhibitor, U73122, led to a concentration-dependent inhibition of insulin (0.6 nmol/L)-stimulated glucose transport, whereas it had no effect on basal glucose transport. Specifically 10, 20, 50, and 150 micromol/L U73122 inhibited insulin (0.6 nmol/L)-stimulated glucose transport approximately 17%, 20%, 26%, and 38%, respectively, while an equal molar concentration of U73343 (inactive form of U73122) and/or carrier media (dimethyl sulfoxide [DMSO]) did not influence glucose uptake. A secondary aim of this investigation was to determine if increasing the concentration of insulin from a physiologic concentration (0.6 nmol/L) to a supraphysiologic concentration (6.0 nmol/L) could ameliorate the inhibitory effects of U73122. A 10-fold increase in insulin eliminated the inhibitory effects of U73122 on insulin-stimulated glucose uptake in soleus muscle. In summary, this preliminary report provides evidence to suggest that a PLC signaling mechanism modifies insulin-stimulated glucose uptake in skeletal muscle via its influence on insulin sensitivity.

Posterior fossa meningiomas: surgical experience in 161 cases.

BACKGROUND: We report the clinical, radiological, and surgical findings of patients with posterior fossa meningiomas surgically treated at our institution over the last 6 years. METHODS: We reviewed 161 consecutive cases of posterior fossa meningiomas operated on between April 1993 and April 1999 at The George Washington University Medical Center. RESULTS: There were 128 female and 33 male patients (mean age 47 years, range of 10-81 years). Meningiomas were classified as petroclival (110 cases), foramen magnum (21 cases), cerebellar hemispheric, lateral tentorial (14 cases), cerebellopontine angle (9 cases), and jugular foramen (7 cases). Mean tumor equivalent diameter (TED) = (D1xD2xDE)(1/3) was 3.1 cm (range of 0.53-8.95). Head pain (50% of cases) and disturbance of gait (44%) were the most common presenting symptoms, and cranial neuropathies the most common neurological signs on admission. Mean preoperative performance status (Karnofsky scale) was 80.2 (range 40-100). Surgical approaches to these tumors included partial labyrinthectomy petrous apicectomy, fronto-temporal/fronto-temporal orbitozygomatic osteotomy, retrosigmoidal, extreme lateral, transpetrosal, and combined. In 38 cases a staged procedure was performed. Gross-total resection was achieved in 57% of patients, and subtotal/partial in 43%. Surgical mortality was 2.5% and complications were encountered in 41% of patients. Postoperative CSF leak occurred in 22 cases (13.6%). The mean follow-up was 19 months, ranging from 0.2 to 63.6, and the mean performance status of patients with a follow-up of at least 12 months was 77 (range of 40-100). Recurrence or progression of disease was found in 13.7% of cases (follow-up 2 years or more). CONCLUSION: Our experience suggests that although posterior fossa meningiomas represent a continuing challenge for contemporary neurosurgeons, such tumors may be completely or subtotally removed with low rate of mortality and acceptable morbidity, allowing most of these patients to achieve a good outcome in a long-term follow-up.

Lowering of blood glucose to nondiabetic levels in a hyperglycemic pig by allografting of fetal pig isletlike cell clusters.

BACKGROUND: Fetal pig isletlike cell clusters (ICCs) will differentiate when grafted into the thymus gland of outbred immunosuppressed nondiabetic pigs for up to 3 months. Whether these cells will survive for a similar period in a diabetic recipient and will mature with secretion of insulin to ameliorate the hyperglycemia is unknown. METHODS: Between 40,000 and 125,000 ICCs (7,000 to 11,400 ICCs/kg) were injected into the thymus gland of five juvenile pigs immunosuppressed with cyclosporine and deoxyspergualin, and the animals were subsequently made diabetic by the injection of streptozotocin. Insulin was administered subcutaneously, with one pig dying from hypoglycemia. The animal with the least number of ICCs transplanted was killed 81 days later, and the graft was analyzed histologically. Blood glucose levels and porcine C-peptide in the remaining animals were monitored for a median of 101 days. RESULTS: Histological analysis of the graft showed numerous epithelial cell clusters; the percentage of cells that contained insulin, glucagon, somatostatin, and pancreatic polypeptide were 61%, 64%, 25%, and 18%, respectively. Some cells contained more than one hormone. Porcine C-peptide was detected from 21 days after induction of diabetes but not before. In the pig receiving the most ICCs, blood glucose levels were lowered to nondiabetic levels 109 days after transplantation. Plasma C-peptide levels in response to glucagon in this pig steadily increased after grafting; peak levels were 0, 0.21, 0.45, and 0.52 ng/ml at 4, 21, 49, and 80 days after induction of diabetes compared to 0.09 ng/ml in control diabetic pigs. The secretion of C-peptide in response to oral and intravenous glucose and arginine also was greater than in untransplanted diabetic pigs, the pattern of secretion being consistent with developing fetal beta cells as the source of the C-peptide. Pancreatic insulin content was 0.1 mU/mg, 4% of that in nondiabetic pigs, and the number of beta cells per islet was 3 to 6 compared to 90 in nondiabetic controls. CONCLUSIONS: ICCs will differentiate and function for up to 111 days when transplanted into outbred immunosuppressed pigs rendered diabetic. Blood glucose levels can be lowered to nondiabetic levels when sufficient numbers of ICCs are grafted.

Chordomas and chondrosarcomas of the skull base: results and complications of surgical management.

OBJECT: Chordomas and chondrosarcomas are rare and difficult to treat tumors for which the optimum treatment modality remains controversial. The aim of this study was to evaluate the surgery-related results and complications in a series of patients in whom radical resection was the treatment of choice. METHODS: The authors conducted a retrospective analysis of the surgery-related results and complications associated with chordoma and chondrosarcoma in 64 patients of whom 33 (52%) had previously undergone some form of treatment. Total or near-total excision was achieved in 56% and this rate increased to 68% in patients without prior treatment. The main complications were postoperative cerebrospinal fluid leakage, intraoperative arterial injury, and new-onset cranial nerve deficits. Arterial injury occurred only and perioperative death occurred more often in patients who had undergone previous treatment. CONCLUSIONS: Analysis of the results provides support for a policy of radical excision of chordomas and chondrosarcomas at the time of first presentation. A higher incidence of procedure-related complications is found in patients who have already undergone surgery and radiotherapy.

The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats.

In operant conditioning experiments, two methods are commonly used to motivate laboratory rats to perform designated tasks. The first is restricting food so that rats are forced to lose 20% of body weight within one week, followed by maintenance at 80% of the baseline weight for the remainder of the experiment. The second is restricting access to water to 15 min in each 24 h period. These methods are effective in motivating the animals. There is, however, little information available on the effects on performance in tests of behaviour that are not related to operant conditioning. In addition, it is not clear if these commonly used methods of food and water restriction will lead to physiological stress as indicated by an elevation of serum corticosterone. Male rats were either food-restricted to reduce and maintain their weight at 80% of baseline weight, or were restricted to 15 min access to water every 24 h. Activity in the open field was significantly greater in food-restricted rats than in water-restricted or control rats, but freezing behaviour was similar in all experimental groups. Food-restricted rats had a higher mean serum corticosterone level than water-restricted and control rats 37 days after the start of the experimental period. These data suggested that chronically restricting food and maintenance of body weight at 80% of baseline body weight led to significant behavioural changes and physiological stress. In contrast, water restriction did not lead to changes in behaviour or corticosterone levels. A second experiment was conducted to compare the effects of food restriction to 80% of baseline body weight, as described above, with a less stringent protocol in which test rats were initially reduced to 80% of baseline weight, but were then maintained at 80% of an ad libitum fed control rat's weight. Serum corticosterone levels and adrenal gland weights were measured after the initial week of forced weight loss and after maintenance for 21 days. Forced loss of 20% of body weight in the first week led to significantly increased serum corticosterone levels and adrenal gland weights compared to ad libitum fed controls. Serum corticosterone levels and adrenal gland weights in rats maintained at 80% of their initial body weight for 21 days remained higher than ad libitum fed control rats. However, rats maintained at 80% of an ad libitum fed control rat's weight did not differ from control rats in serum corticosterone levels or adrenal gland weights at the end of the 21-day study period. Adjustment of the feeding regimen in this manner eliminated physiological evidence of chronic stress.

Management of Zone III Missile Injuries Involving the Carotid Artery and Cranial Nerves.

Carotid and cranial nerve injuries from zone III (high cervical/cranial base) missile injuries are rare and difficult to treat. We have treated five patients with such injuries. We present our management scheme, and compare it to the management of the same injuries in other reports. Five consecutive zone III missile injuries presented to our institution. Trauma assessment by the trauma team, followed by detailed neurological assessment and radiographs (angiogram and computed tomography) were obtained on admission. All patients presented with dysphagia and carotid artery injury with good collateral flow, documented by angiogram. Two patients had facial nerve injury, one had trigeminal nerve injury, one patient presented with tongue weakness, and one patient suffered conductive hearing loss. No patient had evidence of stroke clinically or radiographically. Carotid artery injury was managed with bypass (3 of 5) or ligation (2 of 5). Cranial nerve injuries were documented and treated aggressively with surgery if needed. All patients were discharged to home. Patients presenting with zone III missile injuries should receive an expeditious neurological exam and four-vessel angiogram after initial trauma survey and resuscitation. Bypass of the injured portion of carotid artery is a valid treatment in the hemodynamically stable patient. The unstable patient should undergo ligation to stop hemorrhage and protect against immediate risk for stroke, with the option to bypass later. Cranial nerve injuries should be pursued and aggressively treated to minimize morbidity and prevent mortality.

Near infrared spectrophotometry for the diagnosis of vasculogenic erectile dysfunction.

A specialized near infrared spectrophotometry instrument for noninvasive, continuous monitoring of the hemodynamic events of erection in the human penis has been developed. Its potential application for the diagnostic evaluation of erectile dysfunction was investigated. Thirty-eight patients and 18 volunteer subjects underwent penile near infrared spectrophotometry using an optical sensor probe with wavelength selectivity for hemoglobin absorption spectra. Penile blood volume changes and their time courses were measured following intracavernous pharmacostimulation in patients and visual sexual stimulation in volunteers. Spectrophotometric results were compared with results obtained simultaneously using color duplex ultrasonography, strain gauge penile circumference monitoring, penile tonometry, and clinical assessments. Spectrophotometric recordings of penile erection showed measurable blood volume changes consistent with the hemodynamic events of this biological function. Blood volume per cent (BV%) increase correlated with clinical ratings of erection quality (P < 0.001), penile rigidity measurements (P < 0.005), and penile circumference increases (P < 0.0001), and it correlated with mean peak systolic velocity measurements when BV% increase was restricted to values less than 50% (P < 0.001). The time to reach half the maximum blood volume change (BV T1) correlated directly with the time to reach half the maximum penile circumference size increase (P < 0.001), whereas BV T4 correlated inversely with mean resistive index measurements only when BV T(1/2) was restricted to values greater than 120 s (P < 0.05). Spectrophotometric criteria consisting of BV % less than 35% and BV T(1/2) greater than 120 s affirmed the diagnosis of severe erectile impairment with a similar degree of accuracy as standard ultrasonographic criteria (P < 0.002). Penile near infrared spectrophotometry is a safe, inexpensive and simply used biomedical optics technique that provides quantitative measurements of the vascular physiology of penile erection and appears to offer clinical utility in the diagnosis of vasculogenic erectile dysfunction.

A comparison of the sensitivity of pig and human peripheral blood mononuclear cells to the antiproliferative effects of traditional and newer immunosuppressive agents.

Difficulty in preventing rejection of fetal pig islet-like cell clusters (ICCs) transplanted into pigs using traditional forms of immunotherapy has been reported. An in vitro study of the efficacy of seven different immunosuppressive agents to inhibit proliferation of pig peripheral blood mononuclear cells (PBMC) was performed, and a comparison was made between the human and pig to determine if the efficacy of these agents differed between species. The efficacy of cyclosporine (CsA), azathioprine (Aza), methylprednisolone (MP), FK506, rapamycin (RAP), mycophenolate mofetil (MMF) and deoxymethylspergualin (MeDSG) to inhibit pig and human PBMC proliferation in mitogenic experiments using phytohaemagglutinin (PHA) as a stimulus was performed. Further, allogeneic pig mixed lymphocyte reactions (MLR) were used to determine the activity of these agents in a model more comparable to the allograft rejection process. It was found that pig PBMC stimulated with PHA or in a MLR were inhibited by the agents tested, with the exception of MeDSG that was ineffective in mitogenic experiments. The inhibitory effects of these agents differed between PHA and MLR, the respective (50% inhibitory concentration) IC50 values for pig PBMC being 1.7 and 0.08 microg/ml for CsA, 1.4 and 4.4 microg/ml for Aza, 0.11 and 0.002 microg/ml for MP, 3.0 and 2.8 ng/ml for FK506, 2.1 and 0.3 ng/ml for RAP and 10.8 and 454 ng/ml for MME Pig PBMC were less sensitive than human PBMC to the antiproliferative effects of CsA, Aza, FK506, RAP and MMF, but not MP on PHA stimulation, the ratio of the pig to human IC50 values being 19, 11, 13, 2.3, 1.4, and 0.4, respectively. These data suggest that the doses of most immunosuppressive agents administered to prevent rejection in pigs need to be higher than those used to achieve therapeutic benefit in humans.

A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species.

Two nontoxic, antimicrobial nanoemulsions, BCTP and BCTP 401, have been developed. These emulsions are composed of detergents and oils in 80% water. BCTP diluted up to 1:1000 inactivated>90% of Bacillus anthracis spores in 4 h and was also sporicidal against three other Bacillus species. This sporicidal activity is due to disruption of the spore coat after initiation of germination without complete outgrowth. BCTP 401 diluted 1:1000 had greater activity than BCTP against Bacillus spores and had an onset of action of <30 min. Mixing BCTP or BCTP 401 with Bacillus cereus prior to subcutaneous injection in mice reduced the resulting skin lesion by 99%. Wound irrigation with BCTP 1 h after spore inoculation yielded a 98% reduction in skin lesion size, and mortality was reduced 3-fold. These nanoemulsion formulas are stable, easily dispersed, nonirritant, and nontoxic compared with other available sporicidal agents.

Proposed grading system to predict the extent of resection and outcomes for cranial base meningiomas.

OBJECTIVE: This investigation was performed to construct a grading system for cranial base meningiomas that augments the current system of topographic labeling. This new system classifies cranial base meningiomas based on predicted surgical resection and patient outcomes. METHODS: Two hundred thirty-two consecutive patients with cranial base meningiomas were surgically treated by the two senior authors between April 1993 and August 1997. Using standard statistical tests, a large number of preoperative, intraoperative, and follow-up findings were analyzed for correlation with the extent of resection. These included the presence of previous radiotherapy, Cranial Nerve III, V, and VI palsies, multiple fossa involvement, and vessel encasement. RESULTS: Analysis revealed that each variable tested was independently and inversely correlated with total tumor resection (P < 0.002). We were able to construct a grading system based on these variables; when more variables are present, the grade is higher. With the grading system, lower-grade tumors were correlated with increased probabilities of total resection (r2 = 0.9947) and better patient outcomes, as measured by Karnofsky performance scale scores (r = 0.9291). We also found that, as a group, patients who underwent subtotal resection exhibited worse Karnofsky performance scale scores and had longer hospital stays. CONCLUSION: The current system of classifying cranial base meningiomas provides no information regarding the tumor except location and no information concerning patient prognosis. We present a more useful system to categorize these tumors. Our scheme must be tested at other centers to corroborate our findings. This new grading system should serve to guide surgical treatment, inform patients, and improve communication among surgeons.

Differentiation of fetal pig endocrine cells after allografting into the thymus gland.

BACKGROUND: The thymus of large animals, such as the pig, is thought to be an appropriate site for transplanting adult islets, which contain numerous beta cells, for the purpose of reversing diabetes. Whether fetal islet-like cell clusters (ICCs), which contain few beta cells, will develop at this site, so that adequate amounts of insulin can be produced, is unknown. METHODS: Between 15,000 and 40,000 ICCs were injected into the thymus gland of six juvenile immunosuppressed pigs, and the animals were killed up to 30 days later. The graft was then examined histologically and comparisons made with untransplanted ICCs and those grafted into the omentum of immunosuppressed pigs. RESULTS: At transplantation, the percentage of cells in the ICCs containing insulin, glucagon, somatostatin, or pancreatic polypeptide was 9+/-1%, 13+/-2%, 9+/-1%, and 3+/-1% respectively. Within 9-30 days of transplantation into the thymus, the percentage of all endocrine cells increased, insulin to 41+/-3%, glucagon to 43+/-6%, somatostatin to 26+/-4%, and pancreatic polypeptide to 9+/-3%. There was co-localization of more than one hormone in some cells. Omental grafts contained a similar percentage of insulin and glucagon-containing cells, but significantly fewer somatostatin and pancreatic polypeptide-containing cells. CONCLUSIONS: Endocrine cells from the fetal pig pancreas will differentiate when transplanted into the thymus gland of the pig, making this a suitable site for grafting ICCs to test their ability to normalize blood glucose levels of diabetic recipients.

Variations of the extreme-lateral craniocervical approach: anatomical study and clinical analysis of 69 patients.

OBJECT: The aim of this study was to describe six variations of the extreme-lateral craniocervical approach, their application, and treatment results. METHODS: During a 4-year period 69 patients underwent surgery in which six variations of the extreme-lateral craniocervical approach were performed. The variations included: the transfacetal approach (TFA), performed to treat four lesions in the upper cervical spine anterior or anterolateral to the spinal cord; the retrocondylar approach, to treat five intradural lesions located anterolateral to the medulla oblongata and six vascular lesions to expose the extradural segment of the vertebral artery (VA); the partial transcondylar approach (PTCA), to treat 18 intradural lesions located anterior to the medulla oblongata; the complete transcondylar approach (CTCA), to treat 13 extradural lesions that involved the lower clivus and anterior upper cervical spine; the extreme-lateral transjugular approach, to treat 14 jugular foramen tumors; and the transtubercular approach with or without division of the sigmoid sinus, to treat complex VA and vertebrobasilar junction aneurysms. An anatomical prosection was performed to study the surgical exposure of each of the six variations of the extreme-lateral craniocervical approach. Total removal was achieved in 35 (69%) of the patients with tumor; subtotal resection was achieved in 16 (31%) of those patients. In the 12 patients with VA aneurysms, seven underwent clipping, three underwent trapping and a vein graft bypass procedure, and two underwent trapping without the use of a bypass procedure. In five other patients, different cystic, inflammatory, and other vascular lesions were successfully treated. Fifty percent of the patients who underwent surgery via the TFA, 83% via the of the CTCA, and 11% via the PTCA required an occipitocervical fusion procedure. The mean Karnofsky Performance Scale score was 74.7 preoperatively and 76.4 postoperatively. Major complications were hydrocephalus (nine patients), cerebrospinal fluid leakage (seven patients), worsened cranial nerve function (seven patients), vertebrobasilar vasospasm (one patient), and sigmoid sinus thrombosis (one patient). CONCLUSIONS: To treat lesions in the region of the foramen magnum and surrounding areas, the approach should be tailored to each specific lesion to provide the needed exposure without unnecessary operative steps.

Partial labyrinthectomy petrous apicectomy approach to neoplastic and vascular lesions of the petroclival area.

OBJECTIVE: To study the value of an improvement of the presigmoid petrosal approach to the petroclival area by the addition of partial labyrinthectomy and petrous apicectomy and to document hearing and other results. METHODS: Thirty-six consecutive patients treated by this technique during a 2-year period were studied prospectively. The lesions treated included 33 petroclival neoplasms (25 meningiomas, 5 chordomas, 1 chondrosarcoma, 1 trigeminal schwannoma, and 1 epidermoid cyst) and 3 vertebrobasilar aneurysms. The patients underwent clinical, radiological, and neuro-otological examinations. RESULTS: There was no perioperative mortality. Cranial nerve deficits involving Cranial Nerves III, IV, V, and VI occurred in 17 patients (47%) postoperatively. Cerebrospinal fluid leak occurred in 12 patients (33%). Four of these patients were treated by lumbar drainage, two patients were treated by lumboperitoneal shunt, and six patients required reoperation and repacking of the middle ear. Hydrocephalus occurred in five patients (13.9%). There was one case of meningitis and another of systemic sepsis. All 36 patients underwent postoperative audiometric evaluation. When serviceable hearing was present preoperatively (Gardner-Robertson Grades I or II), it was determined to be preserved at postoperative follow-up in 81% of the patients (26 of 32 patients). CONCLUSION: The partial labyrinthectomy petrous apicectomy approach provided improved access to neoplasms of the clivus and petrous apex and the posterior cavernous sinus area and to vertebrobasilar aneurysms in the midclival area. This improvement in access permits more controlled and thorough treatment of these lesions, with reduced brain retraction and acceptable morbidity with respect to auditory function.