Increased pediatric sub-specialization is associated with decreased surgical complication rates for inpatient pediatric urology procedures.

INTRODUCTION: Increased case volumes and training are associated with better surgical outcomes. However, the impact of pediatric urology sub-specialization on perioperative complication rates is unknown. OBJECTIVES: To determine the presence and magnitude of difference in rates of common postoperative complications for elective pediatric urology procedures between specialization levels of urologic surgeons. The Nationwide Inpatient Sample (NIS), a nationally representative administrative database, was used. STUDY DESIGN: The NIS (1998-2009) was retrospectively reviewed for pediatric (≤18 years) admissions, using ICD-9-CM codes to identify urologic surgeries and National Surgical Quality Improvement Program (NSQIP) inpatient postoperative complications. Degree of pediatric sub-specialization was calculated using a Pediatric Proportion Index (PPI), defined as the ratio of children to total patients operated on by each provider. The providers were grouped into PPI quartiles: Q1, 0-25% specialization; Q2, 25-50%; Q3, 50-75%; Q4, 75-100%. Weighted multivariate analysis was performed to test for associations between PPI and surgical complications. RESULTS: A total of 71,479 weighted inpatient admissions were identified. Patient age decreased with increasing specialization: Q1, 7.9 vs Q2, 4.8 vs Q3, 4.8 vs Q4, 4.6 years, P < 0.01). Specialization was not associated with race (P > 0.20), gender (P > 0.50), or comorbidity scores (P = 0.10). Mortality (1.5% vs 0.2% vs 0.3% vs 0.4%, P < 0.01) and complication rates (15.5% vs 11.7% vs 9.6% vs 10.9%, P < 0.0001) both decreased with increasing specialization. Patients treated by more highly specialized surgeons incurred slightly higher costs (Q2, +4%; Q3, +1%; Q4 + 2%) but experienced shorter length of hospital stay (Q2, -5%; Q3, -10%; Q4, -3%) compared with the least specialized providers. A greater proportion of patients treated by Q1 and Q3 specialized urologists had CCS ≥2 than those seen by Q2 or Q4 urologists (12.5% and 12.2%, respectively vs 8.4% and 10.9%, respectively, P = 0.04). Adjusting for confounding effects, increased pediatric specialization was associated with decreased postoperative complications: Q2 OR 0.78, CI 0.58-1.05; Q3 OR 0.60, CI 0.44-0.84; Q4 OR 0.70, CI 0.58-0.84; P < 0.01. DISCUSSION: Providers with proportionally higher volumes of pediatric patients achieved better postoperative outcomes than their less sub-specialized counterparts. This may have arisen from increased exposure to pediatric anatomy and physiology, and greater familiarity with pediatric techniques. LIMITATION: The NIS admission-based retrospective design did not enable assessment of long-term outcomes, repeated admissions, or to track a particular patient across time. The study was similarly limited in evaluating the effect of pre-surgical referral patterns on patient distributions. CONCLUSIONS: Increased pediatric sub-specialization among urologists was associated with a decreased risk of mortality and surgical complications in children undergoing inpatient urologic procedures.

Contribution of a real depth distance stereoacuity test to clinical management.

Measurement of Stereopsis forms an important part of the clinical assessment of patients with disorders of ocular motility. The introduction of a real depth distance stereoacuity test (FD2) was evaluated in clinical practice and to what extent the introduction affected clinical management. Seventy-three patients under evaluation before and following the introduction of the test were included. Combined thresholds were measured at near using the Frisby and TNO test and at distance using the FD2. Fifty healthy controls were included. Forty-five patients demonstrated Stereopsis using the FD2 and 23 of these had a change in their management based in part on their responses using the FD2. Patients with evidence of Stereopsis using the FD2 were significantly more likely to have change in their management than expected from the whole sample (P = .02). The introduction of a real depth distance stereoacuity test into clinical practice contributed to a change in management when used in conjunction with other tests. The usefulness of the FD2 is limited by its range at 6 m. Use at closer distances necessitates the calculation of binocular threshold from the combined and monocular threshold.

Differential anaesthetic effects following microinjection of thiopentone and propofol into the pons of adult rats: a pilot study.

Identifying the central nervous system sites of action of anaesthetics is important for understanding the link between their molecular actions and clinical effects. The aim of the present pilot study was to compare the anaesthetic effect of bilateral microinjections of propofol and thiopentone (both 200 microg/microl, in Intralipid and 0.9% saline respectively) into a recently discovered anaesthetic-sensitive region in the rat brainstem, the "mesopontine tegmental anaesthetic area" (MPTA). Microinjections (1 microl per side) were made into the MPTA of fifteen male Sprague-Dawley rats. The effect of each agent on spontaneous behaviour, postural control and nociceptive responsiveness was subjectively assessed according to established criteria. The main finding was that thiopentone induced an "anaesthesia-like" state, including complete atonia and loss of righting ability, in 20% of the subjects. Overall, thiopentone significantly reduced postural control and had a moderate antinociceptive effect compared to saline microinjections (P < 0.01 and 0.05, respectively, Wilcoxon test). In contrast, propofol did not induce "anaesthesia" in any animal tested, although a similar antinociceptive effect to that of thiopentone was observed (P < 0.05, Wilcoxon test). In summary, propofol and thiopentone have different effects when microinjected into the MPTA. While both agents reduced reflex withdrawal to a nociceptive stimulus, only thiopentone induced an "anaesthesia-like" state.

Memory representation within the parahippocampal region.

The activity of 378 single neurons was recorded from areas of the parahippocampal region (PHR), including the perirhinal and lateral entorhinal cortex, as well as the subiculum, in rats performing an odor-guided delayed nonmatching-to-sample task. Nearly every neuron fired in association with some trial event, and every identifiable trial event or behavior was encoded by neuronal activity in the PHR. The greatest proportion of cells was active during odor sampling, and for many cells, activity during this period was odor selective. In addition, odor memory coding was reflected in two general ways. First, a substantial proportion of cells showed odor-selective activity throughout or at the end of the memory delay period. Second, odor-responsive cells showed odor-selective enhancement or suppression of activity during stimulus repetition in the recognition phase of the task. These data, combined with evidence that the PHR is critical for maintaining odor memories in animals performing the same task, indicate that this cortical region mediates the encoding of specific memory cues, maintains stimulus representations, and supports specific match-nonmatch judgments critical to recognition memory. By contrast, hippocampal neurons do not demonstrate evoked or maintained stimulus-specific codings, and hippocampal damage results in little if any decrement in performance on this task. Thus it becomes increasingly clear that the parahippocampal cortex can support recognition memory independent of the distinct memory functions of the hippocampus itself.

Co-expression of steroid hormone receptors in opioid peptide-containing neurons correlates with patterns of gene expression during the estrous cycle.

The anteroventral periventricular nucleus (AVPV) of the preoptic region represents an essential component of neural pathways regulating gonadotropin secretion, and contains sexually dimorphic populations of neurons that express dynorphin or enkephalin. In the present study we used in situ hybridization to measure prodynorphin (PDYN) and proenkephalin (PENK) mRNA in the AVPV of intact animals killed on each day of the cycle. Levels of PDYN mRNA were lowest in animals killed on the afternoon of proestrus and then increased by over 60% by the morning of the following day. Expression of PENK mRNA was generally stable during the cycle, but a small yet significant reduction was detected on proestrus relative to levels of PENK mRNA in animals killed on the day of diestrus. In addition, we used double in situ hybridization to demonstrate that the majority of PDYN mRNA-containing neurons express both estrogen (50%) and progesterone receptor (85%) mRNAs. Only one quarter of the PENK-containing neurons also co-express estrogen receptor mRNA, and fewer than 10% of the PENK mRNA neurons express PR mRNA. Thus, the differential expression of PDYN and PENK during the cycle generally correlates with distinct differences in the degree of colocalization of ER and PR mRNA in PDYN and PENK mRNA-containing neurons in the AVPV.

Influence of opsonization conditions on C3 deposition and phagocyte binding of large- and small-capsule Cryptococcus neoformans cells.

Previous studies demonstrated that, following opsonization with normal human serum (NHS), phagocytes bind greater numbers of small-capsule Cryptococcus neoformans cells than yeast cells with large capsules. The present study tested the hypothesis that suboptimal deposition of opsonic C3 fragments contributes to this disparity. C neoformans was grown under conditions promoting large or small capsules and was incubated at various concentrations in NHS. At low concentrations of yeast cells (125 cells per microl of NHS), the deposition of C3 fragments per unit of capsule volume and the binding of yeast cells to cultured human monocytes were similar for yeast cells having large and small capsules. However, at higher cell concentrations, large-capsule cells exhibited suboptimal coating with C3 fragments and markedly diminished monocyte binding compared with small-capsule cells. Thus, the inverse correlation between capsule size and phagocyte binding can be overcome by conditions promoting optimal C3 deposition.

Subarachnoid hemorrhage and aneurysms.

Ruptured intracranial aneurysms are the usual cause of acute subarachnoid hemorrhage (SAH). Noncontrast CT is the primary imaging procedure of choice for establishing the diagnosis of SAH. Conventional contrast angiography is the gold standard for establishing the presence of intracranial aneurysms, but CT and MRI have supplementary roles. The pathogenesis, presentation, and imaging of SAH and intracranial aneurysms are discussed.

Amygdala central nucleus lesions attenuate acoustic startle stimulus-evoked heart rate changes in rats.

Amygdala central nucleus (CNA) lesions were used to test the hypothesis that stimulus-evoked heart rate changes can reflect the development of fear during acoustic startle testing. A 120-dB white noise startle stimulus produced freezing as well as phasic heart rate accelerations and decelerations, and an abrupt decrease in tonic heart rate, in sham-operated rats. These responses were all significantly reduced in CNA-lesioned rats. In contrast, an 87-dB stimulus elicited only significant phasic decelerations that were similarly attenuated by the CNA lesions. In a follow-up experiment, the CNA lesions also attenuated phasic cardiac decelerations evoked by a conditioned stimulus-like, 85-dB pure tone. The results support the contention (B. J. Young & R.N. Leaton, 1994) that heart rate changes can reflect fear conditioned during acoustic startle testing and, in addition, suggest that the amygdala mediates responses to nonsignal acoustic stimuli.

Fear potentiation of acoustic startle stimulus-evoked heart rate changes in rats.

The present study examined the extent to which heart rate changes evoked by acoustic startle stimuli are affected by the development of fear during startle testing. The phasic heart rate responses of rats elicited by a 120-dB startle stimulus were characterized by decelerations that habituated across trials and accelerations that developed across trials in a manner that paralleled the development of freezing behavior. A 92-dB stimulus evoked little freezing or tachycardia, yet evoked decelerations of similar magnitude to the 120-dB stimulus. Pharmacological blockade of autonomic activity was used to uncouple freezing from the heart rate accelerations and to show that the accelerations were not an artifact of the habituating decelerations. These results indicate that heart rate responses to nonsignal stimuli depend critically on a rat's previous experience with those stimuli.

Correlates of hippocampal complex-spike cell activity in rats performing a nonspatial radial maze task.

The observation of hippocampal place cells forms a major line of evidence supporting the view that the hippocampus is dedicated to spatial processing. However, most studies demonstrating the spatial properties of hippocampal unit activity have employed tasks that emphasize spatial cues but minimize nonspatial cues. In the present experiment we recorded the activity of hippocampal complex-spike cells from rats performing a nonspatial radial maze task. Performance in this task was guided by local visual-tactile cues on the maze arms, while distal spatial cues were minimized and made irrelevant. The influence of three variables on unit activity was examined:type of cue on an arm, spatial location of an arm, and the relative position of the animal on an arm. Of the units recorded, almost one-fifth were classified as "cue cells" in that their activity was associated with cue type but not spatial location. Conversely, a similar proportion of the units were classified as "place cells" in that their activity was associated with location, but not cue type. In an additional similar proportion of units, firing was influenced only by relative position and not by local cues or spatial locations. For the majority of units, however, firing was related to combinations of these three variables, indicating that most hippocampal neurons encoded conjunctions or relations between spatial and local cue information. This pattern of results indicates that when local rather than distal spatial cues are emphasized, hippocampal neural activity is strongly influenced by salient nonspatial cues and shows no overwhelming predominance of place coding. These findings are at odds with the hypothesis that the hippocampus is selectively involved in spatial processing and, conversely, support the broader view that the hippocampus encodes both spatial and nonspatial relations among important experimental variables.

Occurrences, immunoglobulin classes, and biological activities of antibodies in normal human serum that are reactive with Cryptococcus neoformans glucuronoxylomannan.

Serum obtained from normal human subjects contains antibodies reactive in an enzyme-linked immunosorbent assay with the glucuronoxylomannan (GXM) of Cryptococcus neoformans. The frequency of occurrence of class-specific antibodies among normal subjects was 28% for immunoglobulin G (IgG), 98% for IgM, and 3% for IgA. Anti-GXM antibodies with kappa light chains occurred in 98% of normal subjects, while the occurrence of lambda light chains was 28%. Each of five subjects with high levels of anti-GXM IgG antibodies had readily detectable antibodies of the IgG2 isotype; two of the five subjects had readily detectable IgG1 antibody. An examination of sera from human immunodeficiency virus-infected patients showed that human immunodeficiency virus infection was accompanied by a significant decrease in the occurrence of IgM antibodies and anti-GXM antibodies with kappa light chains; these decreases occurred early in infection when CD4 counts were still > or = 500 cells per microliter. A slight but not statistically significant decrease in the occurrence of anti-GXM IgG antibodies was seen only in patients with CD4 levels of < 200 cells per microliter. Sera from normal subjects with high levels of anti-GXM IgG antibodies were examined to identify any contribution of the antibodies to complement activation or to opsonization of the yeast cells. An analysis of the kinetics for activation and binding of C3 to the yeast cell showed no pattern of quantitative or qualitative differences between sera with high or low levels of anti-GXM IgG antibodies. Phagocytosis studies showed that the naturally occurring IgG antibodies did not contribute to opsonization of the yeast cells.

Endophthalmitis as a presentation of meningococcal septicaemia.

Meningococcal infections can present in diverse clinical forms ranging from fulminant, occult, chronic meningococcaemia to meningitis. Rare presentations may include conjunctivitis, sinusitis, pneumonia, pericarditis, arthritis, and osteomyelitis. We present a very unusual case of meningococcaemia presented as an endophthalmitis.

Accelerated decay of C3b to iC3b when C3b is bound to the Cryptococcus neoformans capsule.

Incubation of encapsulated and nonencapsulated Cryptococcus neoformans in normal human serum (NHS) leads to activation and binding of potentially opsonic fragments of complement component C3 to the yeast cells. Analysis of the molecular forms of C3 after incubation of encapsulated cryptococci in NHS showed that the percentage of bound C3 occurring as iC3b approached 100% after 8 min. The percentage of bound C3 occurring as iC3b on nonencapsulated cryptococci never exceeded 70%, even after 60 min of incubation in NHS. Conversion of C3b to iC3b was assessed further by incubating C3b-coated cryptococci for various times with a mixture of complement factors H and I at 40% of their respective physiological concentrations. Most, if not all, of the C3b on encapsulated cryptococci was converted to iC3b at a single fast rate. Conversion of C3b to iC3b on nonencapsulated cryptococci did not follow a single rate constant and appeared to have a fast and a slow component. Studies of the requirements for factors H and I in cleavage of C3b to iC3b showed steep dose-response curves for both factors in the case of encapsulated cryptococci and shallow curves with C3b bound to nonencapsulated cryptococci. Taken together, our results indicate that C3b molecules bound to encapsulated cryptococci have a uniformly high susceptibility to conversion to iC3b by factors H and I. In contrast, a significant portion of the C3b bound to nonencapsulated cryptococci is very resistant to conversion to iC3b by factors H and I.

Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans.

Incubation of encapsulated cells of Cryptococcus neoformans in normal human serum leads to activation of the alternative complement pathway and deposition of opsonic fragments of C3 into the capsule. We determined whether the variation in capsular structure that occurs among the four major cryptococcal serotypes was reflected in the kinetics for activation and binding of C3. We also examined the effects on activation kinetics of de-O-acetylation or periodate oxidation of the capsule. Binding kinetics were characterized in terms of the time required to deposit 5% of the maximal amount of C3 on the yeast (t5%), the first-order rate constant for amplification of C3 deposition (k'), and the maximum amount of C3 that could be deposited in the capsule (C3max). Our results showed that variations in the capsular structure that characterized each serotype had no significant influence on C3max but that the rate of C3 deposition depended significantly on the serotype. C3 accumulated at a higher rate on cells of serotypes A and D than on cells of serotypes B and C. There was a significant correlation between capsular volume and C3max, although the relationship was not linear. Periodate treatment of encapsulated cryptococci of all four serotypes led to decapsulation. Periodate-oxidized encapsulated cells displayed kinetics for activation and binding of C3 that were identical to kinetics observed with nonencapsulated cryptococci. Finally, de-O-acetylation led to a significant but relatively minor increase in C3max.

Characterization of tailshock elicited withdrawal reflexes in intact and spinal rats.

The tail flick withdrawal reflex (TFR) was generated by applying graded electric current to the tail of intact and spinally transected rats. In Experiment 1, separate groups of rats were tested 1, 3, 7, 10, 14, or 21 days after spinal transection. The latency, amplitude, and magnitude of the TFR was highly related to current intensity in both intact and spinal animals. However, the TFR changed dramatically as a function of the number of days between spinalization and TFR measurement. Compared to intact controls, the current intensity at which TFR was initiated (threshold) in spinal rats was elevated 1 and 3 days after transection, did not differ at 7 and 10 days, and was reduced at 14 and 21 days. Latency of TFR in spinal rats did not differ from controls 1 day after transection, but decreased steadily thereafter. Amplitude and magnitude of TFR in spinal rats remained depressed, but did show recovery toward control levels as the interval between transection and testing increased. Changes in the TFR of spinal rats was correlated with recovery of tailpinch-elicited hindlimb withdrawal. Experiment 2 demonstrated that the dose-response curve relating systemic morphine treatment to increases in TFR thresholds was shifted to the right in chronic spinal rats. Threshold increases in both spinal and intact rats were not necessarily accompanied by changes in TFR performance. These experiments establish the segmental organization of tailshock-elicited TFR and supports its use as a measure of nociceptive transmission at spinal levels.

Compliance with follow-up of patients treated for non-seminomatous testicular cancer.

Many patients with Stage 1 non-seminomas are now treated by orchidectomy and close follow-up along. Chart review indicated that a group of such patients, compared with patients treated with chemotherapy, tended to be less compliant with follow-up. A questionnaire given to a second sample of patients confirmed that surgical patients underestimated the dangers of the disease and chances of relapse, and doubted the value of follow-up.

Effects of systemic and intra-amygdaloid diazepam on long-term habituation of acoustic startle in rats.

Two experiments were conducted to examine the effects of the anxiolytic drug, diazepam, on long-term habituation of the acoustic startle response. The experiments were based upon the hypothesis that manipulations that reduce fear should enhance long-term response decrements by reducing a fear-like sensitization process. In Experiment 1 rats given intraperitoneal injections of 0.5, 1.2, or 2.5 mg/kg showed larger decrements of startle amplitude than vehicle-injected controls both over trials within sessions and over days. In Experiment 2 rats injected with 35 micrograms of diazepam bilaterally into the amygdala showed larger decrements of startle amplitudes over days than vehicle-injected controls. No within-session startle effects were detected in Experiment 2. Freezing behavior was measured in Experiment 2 as an index of fear, and the amygdala injections of diazepam retarded the development of fear in the startle chamber. This index of fear was not possible in Experiment 1 because of the sedating effects of systemic diazepam. We conclude that diazepam, acting at least in part through the amygdala, attenuates the fear-like sensitization process associated with the acoustic startle stimulus. By attenuating sensitization diazepam produces larger than normal reductions in startle amplitudes over trials and days without significantly affecting initial responsiveness.

Regulation of estrogen receptor messenger ribonucleic acid in rat hypothalamus by sex steroid hormones.

Sex steroid hormone receptors are thought to mediate the actions of their respective hormones by functioning as ligand-activated nuclear transcription factors that alter the expression of specific sets of hormone-responsive genes. Particularly high densities of estrogen receptor (ER)-containing neurons are located in the arcuate nucleus (ARH) and ventrolateral part of the ventromedial nucleus (VMHvl) of the hypothalamus, and these cell groups are thought to play key roles in the neuroendocrine control of reproductive function. Thus, hormonal regulation of ER gene expression in ARH and VMHvl neurons represents a direct mechanism by which circulating sex steroids could affect the responsiveness of these neurons to hormonal activation. We used in situ hybridization histochemistry to evaluate the influence of estradiol and testosterone on levels of ER mRNA within the ARH and VMHvl of adult male and female rats. In female rats, estradiol treatment reduced levels of ER mRNA in the ARH and VMHvl within 24 h relative to levels in both ovariectomized control animals and intact estrous females. Comparable results were obtained in male rats, except that testosterone did not significantly attenuate ER mRNA hybridization in the VMHvl until after 3 days of hormone treatment, and only a minor decrease was noted in the ARH, which was not statistically significant. In both male and female animals, the overall density of labeling found over individual cells in emulsion-dipped autoradiograms was consistently lower in hormone-treated animals compared with that over cells in gonadectomized controls, suggesting that the observed decreases in ER mRNA hybridization measured over the ARH and VMHvl are due to changes in cellular levels of ER mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen differentially regulates neuropeptide gene expression in a sexually dimorphic olfactory pathway.

The posterodorsal part of the medial nucleus of the amygdala (MeAp) receives its major sensory input from the accessory olfactory bulb and projects massively to the medial preoptic nucleus and other sexually dimorphic hypothalamic nuclei thought to play key roles in mediating steroid-sensitive reproductive functions. A combined axonal transport/double-immunohistochemical method was used to show that at least one-quarter of the cholecystokinin-immunoreactive cells in the MeAp cocontain substance P and that a substantial proportion of these cells project to the medial preoptic nucleus. In situ hybridization histochemistry was then used to demonstrate that estrogen regulates the expression of preprocholecystokinin in these cells at the mRNA level in male and female rats. In contrast, levels of preprotachykinin mRNA within the MeAp do not appear to be sensitive to acute changes in circulating gonadal steroids in either sex. Although posttranscriptional regulation of mRNA stability may contribute to the observed effects, it appears likely that estrogen stimulates preprocholecystokinin expression within the MeAp by selectively inducing transcription of the corresponding gene, thereby altering the relative amounts of cholecystokinin and substance P coexpressed within individual neurons of the MeAp that project to the hypothalamus.