The organization of frontostriatal brain wiring in non-affective early psychosis compared with healthy subjects using a novel diffusion imaging fiber cluster analysis.

BACKGROUND: Alterations in brain connectivity may underlie neuropsychiatric conditions such as schizophrenia. We here assessed the degree of convergence of frontostriatal fiber projections in 56 young adult healthy controls (HCs) and 108 matched Early Psychosis-Non-Affective patients (EP-NAs) using our novel fiber cluster analysis of whole brain diffusion magnetic resonance imaging tractography. METHODS: Using whole brain tractography and our fiber clustering methodology on harmonized diffusion magnetic resonance imaging data from the Human Connectome Project for Early Psychosis we identified 17 white matter fiber clusters that connect frontal cortex (FCtx) and caudate (Cd) per hemisphere in each group. To quantify the degree of convergence and, hence, topographical relationship of these fiber clusters, we measured the inter-cluster mean distances between the endpoints of the fiber clusters at the level of the FCtx and of the Cd, respectively. RESULTS: We found (1) in both groups, bilaterally, a non-linear relationship, yielding convex curves, between FCtx and Cd distances for FCtx-Cd connecting fiber clusters, driven by a cluster projecting from inferior frontal gyrus; however, in the right hemisphere, the convex curve was more flattened in EP-NAs; (2) that cluster pairs in the right (p = 0.03), but not left (p = 0.13), hemisphere were significantly more convergent in HCs vs EP-NAs; (3) in both groups, bilaterally, similar clusters projected significantly convergently to the Cd; and, (4) a significant group by fiber cluster pair interaction for 2 right hemisphere fiber clusters (numbers 5, 11; p = .00023; p = .00023) originating in selective PFC subregions. CONCLUSIONS: In both groups, we found the FCtx-Cd wiring pattern deviated from a strictly topographic relationship and that similar clusters projected significantly more convergently to the Cd. Interestingly, we also found a significantly more convergent pattern of connectivity in HCs in the right hemisphere and that 2 clusters from PFC subregions in the right hemisphere significantly differed in their pattern of connectivity between groups.

Circulating low-density lipoprotein ceramide concentrations increase in Holstein dairy cows transitioning from gestation to lactation.

Low-density lipoprotein (LDL) ceramide causes insulin resistance in obese diabetic nonruminants. Because previous work suggests that liver-derived ceramide may impair insulin action in postpartum cows, our objectives were to characterize peripartal changes in lipoprotein ceramides. We further studied the effects of prepartum adiposity on lipoprotein ceramide levels. Twenty-eight pregnant Holstein cows (parity = 3.65 ± 1.62) with lean (body condition score, BCS = 2.97 ± 0.16; body weight, BW = 630 ± 55.2 kg; n = 15) or overweight (BCS = 3.93 ± 0.27; BW = 766 ± 46.1 kg; n = 13) body condition 28 d before expected parturition were evaluated. Sampling occurred on d -20.5 ± 1.74, -13.8 ± 1.71, -7.84 ± 4.07, -6.71 ± 1.00, -3.92 ± 0.64, and -1.28 ± 0.61 (before parturition); daily until d 8 postpartum; and on d 10, 12, 14, 21, and 28. Adipose tissue and liver were biopsied on d -7.84 ± 4.07 and 10. Postpartum insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp. Lipoprotein fractions were isolated using liquid chromatography. Sphingolipids were quantified using mass spectrometry. Data were analyzed using a mixed model with repeated measures. Overweight cows had a higher BCS and BW at enrollment relative to lean cows, but BCS and BW were similar postpartum. Overweight cows lost more body condition (0.97 ± 0.36 vs. 0.55 ± 0.16 BCS units) and BW (291 ± 67.3 vs. 202 ± 54.5 kg) during transition relative to lean cows. Adipocyte volume and counts declined from prepartum to postpartum (50.4 and 13.7%, respectively), and adipocyte volume was greater (48.2%) in overweight cows prepartum relative to lean cows. Although DMI was comparable between BCS groups, milk yield tended to be greater in overweight cows. Plasma free fatty acid and ß-hydroxybutyrate and liver lipid levels were 40, 16, and 37% greater, respectively, in overweight cows compared with lean cows. Glucose infusion rate during the hyperinsulinemic-euglycemic clamp tended to be lower in overweight cows. Ceramide levels within triacylglycerol-rich lipoprotein fractions declined postpartum, whereas LDL ceramide increased postpartum. Overweight cows had lower triacylglycerol-rich lipoprotein C16:0-ceramide levels relative to lean cows. Prepartum LDL C24:0-ceramide levels were greater in overweight cows relative to lean cows. Independent of prepartum adiposity, we concluded that serum LDL ceramide levels are elevated in early-lactation cows experiencing adipose tissue free fatty acid mobilization and hepatic steatosis.

Inter-site and inter-scanner diffusion MRI data harmonization.

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Simultaneous saccharification and fermentation of steam exploded duckweed: Improvement of the ethanol yield by increasing yeast titre.

This study investigated the conversion of Lemna minor biomass to bioethanol. The biomass was pre-treated by steam explosion (SE, 210°C, 10 min) and then subjected to simultaneous saccharification and fermentation (SSF) using Cellic® CTec 2 (20 U or 0.87 FPU g(-1) substrate) cellulase plus ß-glucosidase (2 U g(-1) substrate) and a yeast inoculum of 10% (v/v or 8.0×10(7) cells mL(-1)). At a substrate concentration of 1% (w/v) an ethanol yield of 80% (w/w, theoretical) was achieved. However at a substrate concentration of 20% (w/v), the ethanol yield was lowered to 18.8% (w/w, theoretical). Yields were considerably improved by increasing the yeast titre in the inoculum or preconditioning the yeast on steam exploded liquor. These approaches enhanced the ethanol yield up to 70% (w/w, theoretical) at a substrate concentration of 20% (w/v) by metabolising fermentation inhibitors.

Chemical characterisation and analysis of the cell wall polysaccharides of duckweed (Lemna minor).

Duckweed is potentially an ideal biofuel feedstock due to its high proportion of cellulose and starch and low lignin content. However, there is little detailed information on the composition and structure of duckweed cell walls relevant to optimising the conversion of duckweed biomass to ethanol and other biorefinery products. This study reports that, for the variety and batch evaluated, carbohydrates constitute 51.2% (w/w) of dry matter while starch accounts for 19.9%. This study, for the first time, analyses duckweed cell wall composition through a detailed sequential extraction. The cell wall is rich in cellulose and also contains 20.3% pectin comprising galacturonan, xylogalacturonan, rhamnogalacturonan; 3.5% hemicellulose comprising xyloglucan and xylan, and 0.03% phenolics. In addition, essential fatty acids (0.6%, α-linolenic and linoleic/linoelaidic acid) and p-coumaric acid (0.015%) respectively are the most abundant fatty acids and phenolics in whole duckweed.

Microbiota of plaque microcosm biofilms: effect of three times daily sucrose pulses in different simulated oral environments.

AIM: To explore the Ecological Plaque Hypothesis for dental caries. To test modification of the microbiota of dental plaque microcosm biofilms by sucrose pulsing during growth in two different simulated oral fluids, and with a urea-induced plaque pH elevation. METHODS: Plaque microcosm biofilms were cultured in an 'artificial mouth' with and without 6-min 5% w/v sucrose pulses every 8 h in an environment of continuously supplied saliva-like defined medium with mucin (DMM), or basal medium mucin (BMM, a high-peptone-yeast extract oral fluid analogue), and also in DMM + 10 mmol/l urea, with sucrose pulsing. Forty plaque species were quantified by checkerboard DNA:DNA hybridization analysis. RESULTS: Sucrose pulsing extended rapid plaque growth in DMM and BMM, inducing major microbiota changes in DMM but not in BMM. In DMM, some streptococci and lactobacilli were unaffected while others implicated in caries, together with Candida albicans and Capnocytophaga gingivalis, increased. Aerobic, microaerophilic and major anaerobic species decreased. Elevation of the pH(max) from 6.4 to 7.0 had almost no effect on the microbiota. BMM plaques were distinct from DMM plaques with particularly low levels of Candida albicans and Actinomyces. CONCLUSIONS: Modest sucrose exposure in a saliva-like environment causes profound changes in the developmental self-organization of plaque microcosms, supporting the Ecological Plaque Hypothesis. Nevertheless, there is significant stability in microbial composition with varying pH near neutrality. Increases in levels of specific bacteria in response to sucrose could be characteristic of organisms particularly important in caries.

Central mechanisms underlying short- and long-term regulation of the cardiovascular system.

1. Sympathetic vasomotor nerves play a major role in determining the level of arterial blood pressure and the distribution of cardiac output. The present review will discuss briefly the central regulatory mechanisms that control the sympathetic outflow to the cardiovascular system in the short and long term. 2. In the short term, the sympathetic vasomotor outflow is regulated by: (i) homeostatic feedback mechanisms, such as the baroreceptor or chemoreceptor reflexes; or (ii) feed-forward mechanisms that evoke cardiovascular changes as part of more complex behavioural responses. 3. The essential central pathways that subserve the baroreceptor reflex and, to a lesser extent, other cardiovascular reflexes, have been identified by studies in both anaesthetized and conscious animals. A critical component of these pathways is a group of neurons in the rostral ventrolateral medulla that project directly to the spinal sympathetic outflow and that receive inputs from both peripheral receptors and higher centres in the brain. 4. Much less is known about the central pathways subserving feed-forward or 'central command' responses, such as the cardiovascular changes that occur during exercise or that are evoked by a threatening or alerting stimulus. However, recent evidence indicates that the dorsomedial hypothalamic nucleus is a critical component of the pathways mediating the cardiovascular response to an acute alerting stimulus. 5. Long-term sustained changes in sympathetic vasomotor activity occur under both physiological conditions (e.g. a change in salt intake) and pathophysiological conditions (e.g. heart failure). There is evidence that the paraventricular nucleus in the hypothalamus is a critical component of the pathways mediating these changes. 6. Understanding the central mechanisms involved in the long-term regulation of sympathetic activity and blood pressure is a major challenge for the future. As a working hypothesis, a model is presented of the postulated central mechanisms that result in sustained changes in sympathetic vasomotor activity that are evoked by different types of chronic stimulation.

Prediction of stable walking for a toy that cannot stand.

Previous experiments [M. J. Coleman and A. Ruina, Phys. Rev. Lett. 80, 3658 (1998)] showed that a gravity-powered toy with no control and that has no statically stable near-standing configurations can walk stably. We show here that a simple rigid-body statically unstable mathematical model based loosely on the physical toy can predict stable limit-cycle walking motions. These calculations add to the repertoire of rigid-body mechanism behaviors as well as further implicating passive dynamics as a possible contributor to stability of animal motions.

The cardiovascular effects of angiotensin-(1-7) in the rostral and caudal ventrolateral medulla of the rabbit.

Previous studies in the rat have indicated that the heptapeptide angiotensin-(1-7) has an excitatory action on pressor neurons in the rostral ventrolateral medulla that is equipotent to that evoked by angiotensin II, but which is mediated by separate receptors. In this study we have compared the cardiovascular effects and mechanisms of action of angiotensin-(1-7) with angiotensin II in the rostral and caudal ventrolateral medulla of the rabbit, a species which, unlike the rat, contains a high density of angiotensin receptors, similar to that observed in humans. Microinjections of angiotensin-(1-7) into the rostral and caudal ventrolateral medulla evoked dose-dependent increases and decreases, respectively, in arterial pressure and renal sympathetic nerve activity, but in comparison to angiotensin II much higher doses (approximately 50-fold higher) were required to produce cardiovascular response of similar magnitude. The cardiovascular effects of angiotensin-(1-7) were blocked by prior injection of the selective antagonist [D-Ala(7)]-Ang-(1-7) but were also blocked by the selective AT(1) receptor antagonist losartan. The results demonstrate that in the rabbit angiotensin-(1-7) can excite pressor and depressor neurons in the ventrolateral medulla, but indicate that these effects are mediated by AT(1) receptors. The much lower potency of angiotensin-(1-7) as compared to angiotensin II may be explained as a consequence of it having a much lower affinity to AT(1) receptors. Thus, in contrast to the rat, the results do not indicate that angiotensin-(1-7) has a biologically significant action in the ventrolateral medulla of the rabbit.

GABA and responses to GABA in the stomatogastric ganglion of the crab Cancer borealis.

The multifunctional neural circuits in the crustacean stomatogastric ganglion (STG) are influenced by many small-molecule transmitters and neuropeptides that are co-localized in identified projection neurons to the STG. We describe the pattern of gamma-aminobutyric acid (GABA) immunoreactivity in the stomatogastric nervous system of the crab Cancer borealis and demonstrate biochemically the presence of authentic GABA in C. borealis. No STG somata show GABA immunoreactivity but, within the stomatogastric nervous system, GABA immunoreactivity co-localizes with several neuropeptides in two identified projection neurons, the modulatory proctolin neuron (MPN) and modulatory commissural neuron 1 (MCN1). To determine which actions of these neurons are evoked by GABA, it is necessary to determine the physiological actions of GABA on STG neurons. We therefore characterized the response of each type of STG neuron to focally applied GABA. All STG neurons responded to GABA. In some neurons, GABA evoked a picrotoxin-sensitive depolarizing, excitatory response with a reversal potential of approximately -40 mV. This response was also activated by muscimol. In many STG neurons, GABA evoked inhibitory responses with both K(+)- and Cl(-)-dependent components. Muscimol and beta-guanidinopropionic acid weakly activated the inhibitory responses, but many other drugs, including bicuculline and phaclofen, that act on vertebrate GABA receptors were not effective. In summary, GABA is found in projection neurons to the crab STG and can evoke both excitatory and inhibitory actions on STG neurons.

The operative management of screen-detected breast cancers.

BACKGROUND: Mammographic screening for breast cancer not only reduces the overall mortality from breast cancer but allows greater opportunities for breast-conserving operations. The predicted degree of breast conservation is not being realized, but is increasing in centres that have published their results. METHODS: The operative management of breast cancers diagnosed by BreastScreen Central and Eastern Sydney Screening and Assessment Service were compared between two time periods: January 1988-December 1992 (group 1) and January 1993-December 1995 (group 2). The rate of breast conservation, and other data were compared between the two periods. An attempt was made with multivariate analysis to identify some of the factors that made mastectomy rather than conservation more likely. RESULTS: There were 723 cancers detected that were suitable for analysis (group 1, n = 273; group 2, n = 450). In group 1 the breast conservation rate was 42.9%; this increased significantly to 60.4% in group 2 (P < 0.001). The data were examined to determine if there was any other factor that had changed over the time periods which might account for the increased rate of breast conservation. The use of pre-operative diagnostic techniques such as fine needle aspirate cytology and core biopsy increased significantly. Multivariate analysis comparing the differences in patient age, diagnostic technique, tumour type, grade, size, location and lymph node status, both independently and compositely did not account for the increase in breast conservation in group 2. CONCLUSION: The increase in breast conservation is due to other factors such as the surgeons' approach and patient attitude. The use of pre-operative, minimally invasive tissue sampling techniques is increasing.

Use of unopposed estrogen in women with uteri: prevalence, clinical implications, and economic consequence.

OBJECTIVE: Hormone replacement therapy with estrogen/progestin is the treatment of choice for relieving postmenopausal vasomotor symptoms and preventing urogenital atrophy and osteoporosis in women with intact uteri. However, despite the known increased incidence of endometrial hyperplasia when unopposed estrogen is used in such women, this progestin regimen has not been universally adopted. DESIGN: This study was conducted in a managed care organization to determine the extent of the use of unopposed estrogen in women with intact uteri. Pharmacy claims data for all women 55 years or older with claims for estrogen only from September 1, 1996, to December 31, 1996, were reviewed. A total of 5,209 records were identified, from which 480 were randomly selected. A survey of the members' physicians was then carried out to determine hysterectomy status and was confirmed by chart audit. RESULTS: Thirty-three (11%) of the members identified had not undergone hysterectomy. Follow-up physician contact revealed that five women did not have a uterus. Use of estrogen without opposing progestin was documented in a substantial percentage of files reviewed. It is of concern that with the documentation of the risks of endometrial hyperplasia and carcinoma in the intact uterus, unopposed therapy still occurs. In addition to the clinical costs, there are economic consequences to this practice. An economic model of unopposed estrogen use was created. A management cost of $1,504 for 3 years was estimated. CONCLUSIONS: Further educational efforts are needed to ensure the use of opposed estrogen in the woman with an intact uterus.

Arabidopsis RelA/SpoT homologs implicate (p)ppGpp in plant signaling.

Arabidopsis RPP5 is a member of a large class of pathogen resistance genes encoding nucleotide-binding sites and leucine-rich repeat domains. Yeast two-hybrid analysis showed that RPP5 specifically interacts with At-RSH1, an Arabidopsis RelA/SpoT homolog. In Escherichia coli, RelA and SpoT determine the level of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), which are the effector nucleotides of the bacterial stringent response. Functional analysis in E. coli and in Streptomyces coelicolor A3 (2) showed that At-RSH1 confers phenotypes associated with (p)ppGpp synthesis. We characterized two additional Arabidopsis RelA/SpoT homologs, At-RSH2 and At-RSH3. At-RSH genes may regulate a rapid plant (p)ppGpp-mediated response to pathogens and other stresses.

A point-mass model of gibbon locomotion.

In brachiation, an animal uses alternating bimanual support to move beneath an overhead support. Past brachiation models have been based on the oscillations of a simple pendulum over half of a full cycle of oscillation. These models have been unsatisfying because the natural behavior of gibbons and siamangs appears to be far less restricted than so predicted. Cursorial mammals use an inverted pendulum-like energy exchange in walking, but switch to a spring-based energy exchange in running as velocity increases. Brachiating apes do not possess the anatomical springs characteristic of the limbs of terrestrial runners and do not appear to be using a spring-based gait. How do these animals move so easily within the branches of the forest canopy? Are there fundamental mechanical factors responsible for the transition from a continuous-contact gait where at least one hand is on a hand hold at a time, to a ricochetal gait where the animal vaults between hand holds? We present a simple model of ricochetal locomotion based on a combination of parabolic free flight and simple circular pendulum motion of a single point mass on a massless arm. In this simple brachiation model, energy losses due to inelastic collisions of the animal with the support are avoided, either because the collisions occur at zero velocity (continuous-contact brachiation) or by a smooth matching of the circular and parabolic trajectories at the point of contact (ricochetal brachiation). This model predicts that brachiation is possible over a large range of speeds, handhold spacings and gait frequencies with (theoretically) no mechanical energy cost. We then add the further assumption that a brachiator minimizes either its total energy or, equivalently, its peak arm tension, or a peak tension-related measure of muscle contraction metabolic cost. However, near the optimum the model is still rather unrestrictive. We present some comparisons with gibbon brachiation showing that the simple dynamic model presented has predictive value. However, natural gibbon motion is even smoother than the smoothest motions predicted by this primitive model.

Different proctolin neurons elicit distinct motor patterns from a multifunctional neuronal network.

Distinct motor patterns are selected from a multifunctional neuronal network by activation of different modulatory projection neurons. Subsets of these projection neurons can contain the same neuromodulator(s), yet little is known about the relative influence of such neurons on network activity. We have addressed this issue in the stomatogastric nervous system of the crab Cancer borealis. Within this system, there is a neuronal network in the stomatogastric ganglion (STG) that produces many versions of the pyloric and gastric mill rhythms. These different rhythms result from activation of different projection neurons that innervate the STG from neighboring ganglia and modulate STG network activity. Three pairs of these projection neurons contain the neuropeptide proctolin. These include the previously identified modulatory proctolin neuron and modulatory commissural neuron 1 (MCN1) and the newly identified modulatory commissural neuron 7 (MCN7). We document here that each of these neurons contains a unique complement of cotransmitters and that each of these neurons elicits a distinct version of the pyloric motor pattern. Moreover, only one of them (MCN1) also elicits a gastric mill rhythm. The MCN7-elicited pyloric rhythm includes a pivotal switch by one STG network neuron from playing a minor to a major role in motor pattern generation. Therefore, modulatory neurons that share a peptide transmitter can elicit distinct motor patterns from a common target network.

Incidence of deep vein thrombosis after laparoscopic vs minilaparotomy cholecystectomy.

OBJECTIVES: To determine the frequency of deep vein thrombosis (DVT) associated with minimally invasive cholecystectomy and to determine, using minilaparotomy cholecystectomy as a control operation, the influence of the laparoscopic pneumoperitoneum on DVT formation. DESIGN: Prospective nonrandomized control trial. SETTING: Tertiary care university hospital. PATIENTS: One hundred consecutive patients intended to undergo either laparoscopic cholecystectomy (59 patients) or minilaparotomy cholecystectomy (41 patients) with either of 2 surgeons were prospectively enrolled between April 1996 and April 1997. The minilaparotomy cholecystectomy group served as controls to isolate the effect of the pneumoperitoneum. Patient details, operative details, and any thromboembolic or bleeding complications were recorded. The same thromboprophylaxis regimen was prescribed for each group; namely, preoperative and postoperative subcutaneous low-molecular-weight heparin (LMWH), graduated compression stockings, and intraoperative intermittent calf compression. INTERVENTION: Minimally invasive cholecystectomy. MAIN OUTCOME MEASURE: Frequency of DVT. Bilateral lower limb venous color duplex scanning was used to detect DVT. Scans were performed on 3 occasions: (1) preoperatively on admission to hospital, (2) on the first postoperative day, and (3) between 2 and 4 weeks postoperatively. RESULTS: Three patients in the laparoscopic group and 2 patients in the minilaparotomy group underwent conversion to conventional open cholecystectomy. There were no significant differences between patients in the 2 groups for age, sex, body mass index, preoperative white blood cell count, platelet count, prothrombin time, or activated partial thromboplastin time. There were no significant differences between the 2 groups for elective vs emergency operations, public hospital vs private hospital admissions, or consultant vs resident surgeon. Macroscopic gallbladder pathology grades for both groups were not significantly different, and there was no significant difference in the duration of postoperative hospital stay. Operative cholangiography was performed in a significantly larger proportion of laparoscopic cases (86% vs 66% in the minilaparotomy group; chi(2) test, P=.002), and the duration of anesthesia was significantly longer for the laparoscopic operation (118 minutes vs 98 minutes; t test, P=.05). Ninety-seven patients received preoperative LMWH and all patients received graduated compression stockings, intraoperative intermittent calf compression, and postoperative LMWH. Two of the 100 patients had postoperative DVT, 1 after laparoscopic cholecystectomy and 1 after minilaparotomy cholecystectomy. Both DVTs were detected by duplex examination on the first postoperative day. The DVT found after laparoscopic cholecystectomy was in 1 of the 3 patients who did not receive preoperative LMWH. There were no DVTs in any of the 40 patients who had an additional duplex scan between 2 and 4 weeks after operation. CONCLUSIONS: Despite the theoretical risk of thromboembolic disease due to use of the laparoscopic pneumoperitoneum, the frequency of DVT after either laparoscopic cholecystectomy or minilaparotomy cholecystectomy is low if adequate thromboprophylaxis is provided.

Splenectomy for HIV-related immune thrombocytopenia: comparison with results of splenectomy for non-HIV immune thrombocytopenic purpura.

OBJECTIVE: To determine the effectiveness and safety of splenectomy for patients with human immunodeficiency virus (HIV)-related immune thrombocytopenia, using the results of splenectomy for patients with non-HIV immune thrombocytopenic purpura as a control group for comparison. DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PATIENTS: Fourteen patients who underwent splenectomy for symptomatic, medically refractory HIV-related immune thrombocytopenia at this hospital from 1988 to 1997. During the same period, 20 patients had splenectomy for treatment of non-HIV immune thrombocytopenic purpura. INTERVENTION: Splenectomy. MAIN OUTCOME MEASURES: Platelet response, need for postsplenectomy medical therapy, progression of HIV disease, and complications. RESULTS: All patients with HIV-related thrombocytopenia had a complete early platelet response to splenectomy, with an elevation of the platelet count to greater than 100X10(9)/L. After a median follow-up of 26.5 months, all but 1 patient had a sustained complete remission with no need for medical therapy for thrombocytopenia. Splenectomy was more effective in the HIV-related thrombocytopenia group than in the non-HIV immune thrombocytopenic purpura group, with significantly higher platelet counts at 1 week and 1 month after splenectomy in the HIV group (t test, P=.02 and P=.009, respectively). There were significantly fewer patients needing medical therapy for thrombocytopenia after splenectomy in the HIV group (chi2 test, P=.02). There were no remarkable short- or long-term complications in the patients with HIV infection, including no overwhelming postsplenectomy infections. Three patients have died, and 2 patients have developed AIDS since operation. CONCLUSIONS: Splenectomy is effective treatment for patients with symptomatic HIV-related thrombocytopenia that is resistant to medical therapy. The effectiveness of this treatment suggests that the predominant mechanism of thrombocytopenia in HIV-infected patients is increased destruction of platelets because of platelet-associated immunoproteins.

Sympathoinhibition evoked from caudal midline medulla is mediated by GABA receptors in rostral VLM.

The present study was performed to determine whether the powerful depressor and sympathoinhibitory response that can be evoked from neurons in the caudal midline medulla is mediated by gamma-aminobutyric acidergic (GABAergic) inhibition of sympathoexcitatory neurons in the rostral part of the ventrolateral medulla (VLM). In anesthetized barointact and barodenervated rabbits, bilateral micro-injections of bicuculline into sympathoexcitatory sites in the rostral VLM resulted in a sustained increase in renal sympathetic nerve activity and abolished or reversed the depressor and sympathoinhibitory response evoked by glutamate micro-injection into the caudal midline medulla. By contrast, the sympathoinhibitory response evoked from the caudal midline medulla persisted when the background level of renal sympathetic nerve activity was reflexly raised by baroreceptor unloading. The results indicate that 1) the depressor and sympathoinhibitory response evoked by stimulation of neurons in the caudal midline medulla is mediated by a GABAergic synapse in the rostral VLM and 2) there are also sympathoexcitatory neurons in the caudal midline medulla whose presence is revealed by blockade of the more powerful sympathoinhibitory response.

Cholecystectomy in cardiothoracic organ transplant recipients.

OBJECTIVES: To assess the risks associated with cholelithiasis and cholecystectomy in cardiothoracic organ transplant recipients at this hospital and to identify any differences with potential causal significance between the group with known gallstones and the transplant recipient group as a whole. DESIGN: Medical records survey. SETTING: Tertiary care university hospital. PATIENTS: Six hundred forty-five patients had cardiothoracic organ transplantation at this hospital between February 1, 1984, and May 31, 1996. Gallstones were detected in 37 (5.7%) of these patients and 32 patients underwent cholecystectomy, of which 29 operations were performed primarily for symptomatic gallstone disease. All cholecystectomies were performed after transplantation. MAIN OUTCOME MEASURES: Mortality, morbidity, postoperative biliary disease. RESULTS: Patients with gallstones were significantly older than the transplant patient group as a whole (Student t test, P=.001); they were more likely to be female (chi2 test, P=.05); and they had a higher body mass index (t test, P=.001). There were no significant differences in the maximum serum bilirubin level during the transplantation admission, incidence of diabetes mellitus, cholestyramine use, or cyclosporine dosage during the first 12 months after transplantation. Cholecystectomy was performed after a median 5-month symptomatic period, mostly by the minilaparotomy method. Forty-five percent of cholecystectomies were urgent or semi-urgent. One patient died of lung infection on the second postoperative day. The median postoperative stay was 3 days. At a median 33 months' follow-up, 4 patients have had further biliary problems (2 patients with common bile duct stones, 1 patient with intrahepatic stones, and 1 patient with biliary dyskinesia). Four other patients with asymptomatic gallstones who did not receive cholecystectomy have remained asymptomatic for between 15 and 67 months. CONCLUSIONS: Cholecystectomy by the minilaparotomy or laparoscopic methods, with routine operative cholangiography, is the preferred treatment for symptomatic gallstones in cardiothoracic organ transplant recipients. Although the optimum management of asymptomatic gallstones in these patients remains unclear, our favorable experience with a policy of reserving cholecystectomy for symptomatic cases seems noteworthy.

Gastric cancer in the bypassed segment after operation for morbid obesity.

A case is reported in which two separate adenocarcinomas were detected in the bypassed distal stomach 13 years after gastric stapling with loop gastro-enterostomy was performed for the treatment of morbid obesity. Retrograde endoscopy via the afferent loop was used to establish the diagnosis. Although gastritis and metaplasia have been described in the bypassed stomach, only one case of carcinoma in this area has previously been reported.