Robotic endoscopic transforaminal lumbar interbody fusion: A single institution case series.

Background: Robotic-assisted, endoscopic transforaminal lumbar interbody fusion (RE-TLIF) is a promising, minimally invasive surgical option for degenerative lumbar spondylosis/spondylolisthesis; however, outcomes data and efficacy are limited, especially in multilevel disease. Here, we present the first reported series of patients that underwent either single or multilevel RE-TLIF. Methods: A retrospective review was performed on 23 consecutive patients who underwent a single level or multilevel RE-TLIF by a single surgeon. Variables included demographics, perioperative results, pain scores, and functional outcome scores. Results: Eighteen patients (78.3 %) underwent single level RE-TLIF and 5 patients (21.7 %) underwent multilevel RE-TLIF. The median reduction of visual analog scale (VAS) for low back pain (LBP) of all subjects was 6 (IQR = 4.5, 6.5) with no significant difference between single level and multilevel RE-TLIF (p = 0.565). The median reduction of VAS for leg pain of all subjects 7 (IQR = 6, 8) with no significant difference between single level and multilevel RE-TLIF (p = 0.702). Median blood loss was 25 cc (IQR = 25, 25) and 50 cc (IQR = 25, 100) for single and multilevel RE-TLIF, respectively (p = 0.025), whereas median length of stay was 1 (IQR = 1, 1; mean = 1.0 ± 00.18) days and 1 (IQR = 1, 2; mean = 1.4 ± 00.54) days, respectively (p = 0.042). One major complication was observed requiring reoperation for demineralized bone matrix migration resulting in an L5 radiculopathy. Conclusions: Single and multi-level RE-TLIF appears to be a safe and efficacious approach with comparable outcomes to open and other minimally invasive approaches. Additionally, we observed favorable accuracy in robot-assisted pedicle screw, endoscope, and interbody device placement.

Maintenance of insulin release from pancreatic islets stored in the cold for up to 5 weeks.

Insulin content and release were measured from hand-dissected pancreatic islets from noninbred ob/ob mice after 1-5 wk storage in tissue culture medium 199 at various temperatures and glucose concentrations. After storage of islets for 1 wk at 37 degrees, 22 degrees, or 8 degrees C in 18 mM glucose medium and preincubation with 1 mM glucose, glucose-stimulated insulin release during the subsequent incubation was only 20-35% of that of fresh islets. The addition of a 4-h period at 37 degrees C with 18 mM glucose between the cold storage and perincubation restored glucose-stimulated insulin release from 8 degrees C stored islets to fresh-islet levels. Release throughout the 1-18 mM glucose range was strikingly parallel to that of fresh islets. Exposure of fresh islets to the same 4-h period increased basal release but did not affect maximal release. When islets were stored at 8 degrees C with 18 mM glucose for more than 1 wk, a short period at 37 degrees C every week was necessary for maintenance of release. After 5 wk of this procedure, glucose-stimulated insulin release was one-third that of fresh islets, or similar to that of islets stored for only 1 wk at 37 degrees C. Storage at 8 degrees C for 1 wk with 3 mM glucose, or continuously for 3 or 5 wk with 18 mM glucose, maintained islet insulin content, whereas release was lost. Thus, glucose-stimulated insulin release is best maintained by storage of pancreatic islets in tissue culture medium with a high concentration of glucose at 8 degrees C with short weekly periods at 37 degrees C.

Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster.

Hereditary insulin-deficient diabetes mellitus occurs in certain sublines of nonobese Chinese hamsters. Several characteristics of this syndrome are similar to those seen in insulin-deficient human diabetics. Therefore, to characterize pancreatic islet function, dynamic insulin and glucagon release from normal and nonketotic diabetic hamster pancreases in response to glucose (300 mg/100 ml) and theophylline (10 mM), infused singly and together, was studied in vitro.20-min glucose infusions of normal hamster pancreases caused biphasic insulin release, consisting of a rapid first peak and a gradually rising second phase, similar to that reported for man in vivo. Both phases were significantly reduced in the diabetic pancreases. Theophylline alone stimulated similar nonphasic insulin release in both the normal and the diabetic pancreases. Glucose and theophylline together caused greater insulin release than either stimulant alone in both normals and diabetics; however, the diabetic response was still subnormal. Glucose suppressed glucagon release from normal pancreases; suppression was significantly impaired in diabetics. Theophylline stimulated nonphasic glucagon release in both the normals and diabetics. Glucose partially suppressed the theophylline-stimulated release in both groups.Insulin/glucagon molar ratios of the diabetics were consistently subnormal, although individual hormone levels often overlapped into the normal range. IN SUMMARY, THE PANCREASES OF GENETICALLY DIABETIC CHINESE HAMSTERS PERFUSED IN VITRO SHOWED: (a) decreased first and second phase insulin release in response to glucose-containing stimuli-only partially ameliorated by theophylline-, and (b) impaired suppression of glucagon in response to glucose, resulting in (c) a decreased insulin/glucagon molar ratio. These data support the suggestion that both alpha and beta cells of diabetic pancreases may be insensitive to glucose.

Glucose-stimulated 45Calcium efflux from isolated rat pancreatic islets.

Kinetics of (45)Ca efflux and insulin release were studied in collagenase-isolated rat islets during 2-h perifusions with calcium-depleted (0.05 mM) bicarbonate-phosphate buffer containing 2.2 mM glucose. Addition of glucose (16.7 mM) suppressed (45)Ca efflux by 30%. Removal of glucose caused an "off response" of insulin release. The perifusion of a normal concentration of Ca (2.3 mM) greatly stimulated (45)Ca efflux, indicating Ca <--> (45)Ca exchange. When Ca and glucose were superimposed, the effects on (45)Ca efflux and insulin release depended upon the order of presentation of the stimuli: when Ca was added to an ongoing 16.7-mM glucose perifusion, biphasic patterns of (45)Ca and insulin release were seen; when glucose was superimposed on a Ca perifusion, an inhibition of the Ca-stimulated (45)Ca efflux occurred, and a reduced but clearly biphasic insulin response was seen. The subsequent insulin off response after with-drawal of the glucose was also reduced. Mathematical "peeling" of (45)Ca efflux curves from unstimulated islets suggests that there are at least two, and probably three, different intracellular Ca compartments (not including the extracellular sucrose space). At the beginning of perifusion, these three compartments (I, II, III) contain 25, 56, and 19% of the intracellular (45)Ca, and their rates of efflux are 6.7, 1.2, and 0.1%/min, respectively. Glucose appears to suppress efflux from the largest compartment (II); Ca appears to exchange with (45)Ca from a more inert compartment (III). The relationship between insulin and (45)Ca release is not stoichiometric.

Effect of continuous low-dose insulin treatment on subsequent incidence of diabetes in genetically prediabetic Chinese hamsters.

In an attempt to prevent the onset of diabetes, young, genetically prediabetic (but not yet hyperglycemic) Chinese hamsters were treated continuously with insulin via minipump for 4 wk beginning 1 wk before the predicted age of onset of glucosuria (age 7 wk). Continuous insulin infusion which increased the plasma insulin levels by 70%, did not cause hypoglycemia, nor did it reduce the incidence or severity of diabetic symptoms over the ensuing year of observation. In fact, early treatment with exogenous insulin tended to cause increased hyperglycemia and glucosuria. No plasma anti-insulin antibodies were detected 3 and 9 months after stopping insulin treatment.

Abnormalities in glucose-stimulated insulin release, 45Ca uptake, and 86Rb efflux in diabetic Chinese hamster islets.

We loaded islets from normal and diabetic Chinese hamsters with 86Rb (an analogue for K+) and measured 86Rb efflux during stimulation with 20 mM D-glucose. Genetically diabetic Chinese hamsters were selected from a subline (L) known for subnormal pancreatic insulin release and excessive pancreatic glucagon release in vitro. 86Rb accumulation in 1 mM glucose was normal in the diabetic islets. Similar to the pattern of 86Rb efflux previously seen from normal rat and mouse islets, 20 mM glucose suppressed 86Rb efflux within 1-2 min, and efflux remained suppressed until return to 1 mM glucose in both normal and diabetic hamster islets. After the first 2 min of 20 mM glucose, suppression of 86Rb efflux was somewhat greater in the diabetic hamster islets than in the normals. In addition, glucose-stimulated insulin release and 45Ca uptake were significantly reduced in the diabetic islets. Therefore, in the diabetic hamster islets, there is at least no impairment in the initial suppression of 86Rb efflux by glucose. This suggests that the diabetic beta-cells recognize glucose and carry out the initial steps in the stimulus-secretion coupling sequence normally. The later, excessive suppression of 86Rb efflux may be due to impaired Ca2+-induced changes in 86Rb efflux, suggesting that defective regulation of intracellular Ca2+ activity, rather than defective regulation of K+ permeability, may lead to the impaired insulin secretion.

Responses to arginine of the perfused pancreas of the genetically diabetic Chinese hamster.

Nonketotic, genetically diabetic Cinese hamsters show subnormal pancreatic insulin release and impaired suppression of glucagon in response to glucose. To study the pancreatic effects of other agents, dynamic insulin and glucagon release was measured from the in vitro perfused pancreases of normal and diabetic Chinese hamsters in response to various combinations of arginine (20mM), glucose (100 or 150 mg. per 100 ml.), and theophylline (10 mM). Theophylline alone caused identical insulin and glucagon release in diabetics and normals. Glucose, alone and in the presence of theophylline, caused subnormal insulin release and less suppression of glucagon release in the diabectics than in the normals. Arginine, in the presence of glucose and theophylline, caused excessive glucagon release but nearly normal insulin release in the diabetics. Arginine, in the absence of glucose or theophylline, caused excessive glucagon release in the diabetics and undetectable insulin release in either diabetics or normals. Pancreatic content after perfusion did not correlate with release during perfusion. Infusion of arginine alone markedly decreased the amount of extractable pancreatic insulin and glucagon. These results indicate that the pancreatic alpha cell of the diabetic Chinese hamster responds excessively to arginine, as is seen in the human diabetic. This defect is not related to acute insulin release or the presence of glucose. Further, these results confirm that the diabetic Chinese hamster's alpha and beta cells respond normally to theophylline, but are relatively insensitive to glucose.

Insulinopenic diabetes after rodenticide (Vacor) ingestion: a unique model of acquired diabetes in man.

A clinical syndrome, characterized by acute diabetic ketoacidosis associated with a toxic neuropathy, developed in five men who intentionally ingested a recently introduced rodenticide (Vacor) containing N-3-pyridylmethyl-N'-p-nitrophenyl urea (RH-787). A 7-yr-old boy, who accidentally ingested this poison, died within 14 h. Marked insulinopenia, without a reduction in glucagon levels, suggested a specific beta-cytotoxic effect, which was supported after autopsy in three cases by histopathologic evidence of extensive beta cell destruction. Lethal effects in rats prevented investigation of RH-787's diabetogenicity in vivo; however, studies in isolated rat islets confirmed a direct inhibitory effect, which was prevented by concomitant incubation with nicotinamide, suggesting a mechanism of action similar to that of streptozotocin. We detected islet cell-surface antibodies in two of four patients studied. These findings indicate that this nongenetic, acquired form of insulinopenic diabetes, which has persisted in the surviving patients for up to 3 yr, presents a unique opportunity to test in man the concept that hyperglycemia and the accompanying metabolic consequences of insulinopenia can induced diabetic microangiopathy in the absence of genetic predisposition.

Recorded and reported sleep in chronic primary insomnia.

Sleep polygraph and questionnaire data of 18 chronic primary insomniacs were compared with those of 18 age- and sex-matched controls. The insomniacs had significantly longer sleep latencies, less total sleep, less sleep efficiency, more terminal wake time, and less delta sleep. There were significant discrepancies between the insomniacs' and controls' subjective assessments of their sleep and the sleep-polygraph data, but in opposite directions. The insomniacs' recorded sleep also showed more night-to-night variability than that of the controls. However, the controls, in contrast to the insomniacs, reported sleeping worse in the laboratory than at home. Significant differences between insomnia subtypes validly reflected the insomniacs' subjective complaints and were generally in accord with expectations based on them.

Successful separation of depressed, normal, and insomniac subjects by EEG sleep data.

Data from all-night EEG sleep studies were used to distinguish normal subjects, primary depressed patients, and primary insomniac patients. In part 1, we compared 41 normal subjects, 56 depressed patients, and 18 insomniacs. In a univariate comparison with normal subjects, depressed patients showed less total sleep, longer sleep latency, more early morning awake time, more intermittent awake time, less delta sleep, less sleep efficiency, and shorter rapid eye movement (REM) latencies; compared with insomniacs, depressed patients showed greater early morning awake time, shorter REM latency, greater REM index, and greater REM density. Using multivariate discriminant analysis, 82% of the sample were correctly classified by diagnosis: 100% of the normal subjects, 72% of the depressed patients, and 77% of the insomniacs. Eight variables contributed to the multivariate separation of depressed individuals from insomniacs and normals: total sleep time, total recording period, sleep efficiency, sleep latency, early morning awake time, awake time, REM time and REM%. When the discriminant functions were applied to a second group of 18 primary depressed patients, 82% were correctly classified as depressed. These results suggest that primary depressed patients and primary insomniac patients may show relatively characteristic patterns of sleep abnormality.

Effects of K+ and arginine on insulin, glucagon, and somatostatin release from the in vitro perfused rat pancreas.

Rat pancreases were perfused in vitro for 5-min periods with K+ alone (8, 10, and 12 mM) or in the presence of arginine (10 mM). Alone, K+ caused bursts of insulin, glucagon, and somatostatin (SRIF) release; with arginine, it caused a burst of insulin and sustained SRIF release, but caused sustained suppression of glucagon. This suppression correlated better with SRIF than insulin release. Therefore, if a paracrine effect is responsible for the inhibition of glucagon secretion under these circumstances, SRIF is a more likely candidate than insulin.

Low polarization dependent diffraction grating for wavelength demultimlexing.

A low polarization dependent, high diffraction efficiency grating for wavelength demultiplexer is proposed, manufactured by standard crystallographic etching of Si surface. Light is incident and diffracted inside the wafer, which is covered with reflecting metal. Optimized groove form results in a flat spectral response for TE and TM polarizations.

Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell.

To characterize insulin release and cytoplasmic free Ca2+ ([Ca2+]i) levels in the diabetic Chinese hamster islet B cell, islets from genetically normal (subline M) and diabetic (subline L) hamsters were collagenase isolated. Insulin release and glucose utilization (conversion of D-[5-(3H)]glucose to 3H2O) were measured in whole islets; [Ca2+]i levels were measured in single islet cells using fura-2. The Ca2+ channel agonist, 12 mmol/l perchlorate, ClO4-, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not normalize it. Glucose utilization measured over a 2-h period was normal. Glucose induced an initial decrease and then a rise in [Ca2+]i in 85% of the normal (presumably B) cells. In diabetic cells, the [Ca2+]i response was delayed, subnormal and only observed in 23% of the cells. When perchlorate or another Ca2+ channel agonist, 10 mumol/l CGP 28392, was added with glucose, a larger proportion of the diabetic cells (61-67%) showed increased [Ca2+]i and the mean [Ca2+]i response was not different from normal. However, neither perchlorate nor CGP 28392 could normalize glucose-stimulated insulin release, and K(+)-induced insulin release was decreased in diabetic islets. The K(+)-induced [Ca2+]i rise was essentially normal in all the diabetic islet cells. Therefore, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ channel agonists markedly improve the subnormal [Ca2+]i response but not the insulin response. Glucose-induced elevation of [Ca2+]i and exocytosis appear defective in the diabetic Chinese hamster B cell.

Effect of perchlorate on glucose-stimulated insulin release and 45Ca2+ uptake in pancreatic islets from diabetic Chinese hamsters.

Insulin release and 45Ca2+ uptake were studied in isolated islets from Chinese hamsters of genetically diabetic and normal sublines. The calcium channel agonist, perchlorate (ClO4-, 12 mmol/L), augmented both 45Ca2+ uptake and insulin release from normal islets in the presence of 20 but not 1 mmol/L glucose. The agonist also amplified the glucose-stimulated 45Ca2+ uptake and insulin release from diabetic islets but did not normalize the insulin release despite normal insulin concentration in the diabetic Chinese hamster islets. The dry weight of the diabetic islets was subnormal (54%, p < 0.005) but the insulin concentration (insulin per dry weight of islet tissue) was not different from normal (122%). It appears that there are defective mechanisms in addition to the glucose-stimulated influx of Ca2+ in diabetic islet B cells.

Islet morphology in young, genetically diabetic Chinese hamsters during the hyperinsulinemic phase.

Plasma glucose and insulin levels were measured in genetically diabetic (subline L) hamsters from 2 1/2 weeks to over 1 year of age. This nonobese subline is known for subnormal pancreatic insulin release. Hyperglycemia was seen from 4 weeks onward. A short period of hyperinsulinemia was seen at 6 weeks of age, after which plasma insulin levels were not different from normal. During the hyperinsulinemia phase (age 6 weeks), pancreatic insulin content was subnormal, islet volume (as percent of pancreas cross-sectional area) and islet size (as islet cross-sectional area in micron2) were not different from normal, islet morphology appeared normal in electron micrographs, but granule volume was slightly but significantly below normal. Because the islets appeared morphologically normal, except for the slight degranulation during the hyperinsulinemic phase, these data suggest (a) that the islets "hypersecrete" to reduce hyperglycemia; but (b) synthesis does not increase enough to maintain a normal pancreatic insulin content; (c) that the first sign of pancreatic failure may be degranulation and decreased insulin synthesis or content; (d) that early peripheral resistance to insulin, rather than early islet failure, may cause the early hyperglycemia, and (e) that early hyperglycemia or insulin resistance contributes to the later islet exhaustion, which is seen in these diabetic animals when adult.

Elemental composition in the pancreatic B cell is normal in the prediabetic Chinese hamster.

To clarify whether elemental changes are present before the onset of diabetes, freeze-dried pancreas sections from young (18-19 days old), genetically prediabetic Chinese hamsters were subjected to proton bombardment and the concentrations of 15 elements (Na, Mg, Al, P, S, Cl, K, Ca, Mn, Fe, Cu, Zn, Rb, Cd, and Pb) in B cells and exocrine pancreas were calculated from the x-rays emitted. We have previously shown that islet B cells and exocrine pancreas from adult, overtly diabetic Chinese hamsters contain subnormal levels of Al (-61%, -88%) and excess levels of Cu (+92%, +59%), Rb (+13%, +13%), and Mg (+6%, +6%) in B cells and exocrine pancreas, respectively (Juntti-Berggren et al., Biosci Rep 1976;7:33-41). In the present study the prediabetic B cells contained normal levels of all 15 elements, whereas the prediabetic exocrine pancreas contained a subnormal level of Fe (-10%; p less than 0.005). Hence, the development of diabetes in the Chinese hamster does not seem to be associated with an early change in the elemental composition of the pancreatic B cells. In fact, the overt diabetic condition may cause changes in the body's handling of some elements.

Tumor Fas (APO-1/CD95) up-regulation results in increased apoptosis and survival times for rats with intracranial malignant gliomas.

OBJECTIVE: The cellular "death" receptor Fas has been proposed to be a potential specific target for anti-glioma therapy. However, little is known regarding the effects of Fas expression on glioma viability in vivo. The goal of this study was to clarify the relationships among Fas expression, apoptosis, and survival rates for high-grade astrocytomas. METHODS: Fas expression was measured in several human glioblastoma multiforme cell lines and a malignant rat glioma cell line (36B10), before and after Fas up-regulation by gene transfer. Expression was correlated with the degree of Fas-mediated cytotoxicity and apoptosis induced after Fas activation. Subsequently, rats underwent intracranial implantation of either wild-type or genetically altered 36B10 cell lines, for study of the effects of Fas up-regulation on survival rates. RESULTS: Low levels of cell surface Fas expression in glioblastomas multiforme were correlated with their limited susceptibility to Fas-mediated cytotoxicity. Through Fas receptor up-regulation, relationships among increased Fas expression, Fas-mediated cytotoxicity, and apoptosis were demonstrated. The percentage of cells undergoing apoptosis after exposure to a Fas ligand-producing cell line increased from 4% in the sham-transfected line (36B10-) to 27% in the Fas-transfected line (36B10-Fas). After intracranial implantation of these tumors into rats, the median survival time increased significantly from 14 days (36B10 and 36B10-) to 24.5 days (36B10-Fas), which represents a 75% increase in the survival time for the greater Fas-expressing group (P = 0.0005). CONCLUSION: It seems that the overall low rate of apoptosis in high-grade astrocytomas is related to low levels of cell surface Fas expression. With increases in cellular Fas expression, rates of Fas-mediated apoptosis and survival rates were increased.

Antisense oligonucleotide-induced inhibition of adrenocorticotropic hormone release from cultured human corticotrophs.

OBJECT: Available therapies for Cushing's disease are often inadequate or involve the risk of significant morbidity. Accordingly, the need arises for the development of novel treatments, especially for cases caused by corticotroph hyperplasia, a condition difficult to treat using standard therapies. In this study, the authors investigated the use of phosphorothioate antisense oligonucleotides as a potential treatment for Cushing's disease. METHODS: Corticotrophs, obtained from a patient with Cushing's disease in whom pathological findings showed multifocal areas of corticotroph adenoma and hyperplasia, were grown in tissue culture. By assessing cell viability and using immunoradiometric assay techniques, it was determined that these cells grew autonomously and secreted adrenocorticotropic hormone (ACTH) in vitro. A fully phosphorothioated antisense oligonucleotide was constructed to be complementary to the first 25 bp of the region coding for ACTH in exon 3 of the proopiomelanocortin precursor. After incubation of the corticotrophs with liposome-coated phosphorothioate antisense oligonucleotides, a greater than 90% decrease in ACTH release was noted on Days 3 and 6, compared with nonsense-treated controls (p < 0.05). CONCLUSIONS: Antisense oligonucleotides may prove to be a useful adjunct in treating Cushing's disease by targeting one of its fundamental problems, ACTH hypersecretion.

Teaching a biopsychosocial approach on medical attending rounds.

The ascent of the biotechnical, disease-oriented model of medicine threatens to relegate the integrated, patient-oriented approach to a secondary position. In response to this, a program to teach medical housestaff a biopsychosocial approach was implemented in a setting of attending rounds by having a psychiatrist participate regularly as a member of the rounding team. The effectiveness of this program's teaching effort was significantly influenced by the psychological styles and level of training of the housestaff officers. Residents were the most teachable and potentially the most effective teachers with respect to the biopsychosocial model. Interns, appearing to respond to the stresses of internship with defensive behavior, e.g., turning passive into active and isolation of affect, were less receptive. The medical attending's attitude, however, was the most important factor affecting the teaching of this approach on rounds. Three medical-attending-teaching styles were characterized, one of which appeared incompatible with teaching a biopsychosocial approach on rounds. The psychiatrist had to learn to specifically adapt his teaching efforts to each of these three attending styles, as well as to the training level related needs and the defensive styles of the housestaff.

Assessing residents' performance in C-L psychiatry. Work in progress.

The scores from the Psychiatry Resident In Training Examination (PRITE) provide useful information concerning residents' acquired knowledge about consultation-liaison (C-L) psychiatry. However, a comparable method for assessment of C-L residents' clinical skills has not been developed. A task force was commissioned by the Consultation-Liaison Psychiatry Section of the Association for Academic Psychiatry to develop such an assessment system. This paper presents the work of that task force and includes a methodology for assessing clinical performance, a prototype evaluation form, and instructions for its use.