Treatment barriers in PANS/PANDAS: Observations from eleven health care provider families.

INTRODUCTION: Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) are severe but highly treatable postinfectious inflammatory brain conditions. Despite published diagnostic and treatment guidelines for this condition, there are long delays in obtaining appropriate care. The reasons for these delays are poorly understood. We sought to identify health care system barriers to timely treatment by examining cases of PANDAS/PANS occurring in children of health care professionals. METHOD: We recruited families via e-mail request through the PANDAS Physicians Network. Participating parents completed a structured questionnaire and provided a written case description. RESULTS: Eleven families completed data collection, representing a broad spectrum of disease (child disease onset age 4-15, 7 males/4 females, mild to severe). Parents included 11 physicians, 2 mental health professionals, 2 nurses, and a PharmD. Nine cases (82%) had "very delayed" diagnosis and treatment (>4 weeks after onset). The most commonly encountered causes for treatment delay were clinician lack of awareness (82%), clinician skepticism (82%), overdependence on diagnostic testing (91%), and out-of-pocket expenses >$100 US (82%). Other common challenges included difficulties finding a provider to spearhead care (64%), psychological misdiagnosis (55%), and children's suppression of behaviors during assessments (55%). CONCLUSIONS: We found numerous barriers to treatment of PANDAS/PANS among children of health care providers. Our findings suggest that even among the medically sophisticated, PANDAS/PANS diagnosis and treatment remains challenging. Improvement in PANDAS/PANS education of clinicians who may encounter children with this disorder is 1 key step toward addressing our identified barriers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration.

Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation.

Differential gene expression between the porcine morula and blastocyst.

The survival and development of pre-implantation embryos are determinant factors affecting the outcome of animal reproduction. It is essential to transfer the expression of the genetic material from maternal sources, that is the ovum to the zygote before implantation to ensure successful development. Differentiation and transformation of blastomeres initiated during the morula and blastocyst stages is an important step of the embryonic development prior to implantation. We collected morula and early blastocyst samples from pure-bred Landrace pigs in vivo to study the differential gene expression patterns at these two stages. Total RNA was extracted from individual embryos and two rounds of amplification were employed. Two micrograms of antisense RNA, targets, were prepared and hybridized with each of four custom made oligo microarrays representing 24,000 porcine genes. The analyses of replicate hybridizations showed that among the 24,000 genes, 162 genes were expressed fivefold or greater in the morula compared to early blastocysts and 2126 genes were expressed fivefold or greater in early blastocysts compared to the morula. Of these differentially expressed genes, 1429 genes were functionally annotated with related human Gene Ontology terms. In addition to basic metabolic processes, genes related to signal transduction, transportation and cell differentiation were found in both stages and were up-regulated as embryo development proceeded. Real time polymerase chain reaction was utilized to quantify 12 genes differentially expressed in the 2 embryonic stages and validated the reliability of major evidences shown in microarrays. In conclusion, we have obtained a preliminary landscape of genes differentially expressed during the transition from morula to early blastocysts in pigs and showed a generally increased transcriptional activity, perhaps in preparation for implantation. Our results provide an opportunity to study the functions of these genes in relation to the development and survival of pre-implantation porcine embryos.

Development and potential clinical impairment of ultra-short-acting neuromuscular blocking agents.

Developing a non-depolarizing neuromuscular blocking agent that, like succinylcholine, has a rapid onset and a short duration of effect remains a goal of ongoing research. While rocuronium fills a portion of this need, the large doses required for rapid intubation render it a much longer-acting neuromuscular blocking agent. Postoperative residual neuromuscular block (NMB) is an increasingly recognized complication of non-depolarizing neuromuscular blocking agents. This occurs because of dosing choices for neuromuscular blocking agents and anticholinesterases as well as insensitivity of typically used monitors of depth of NMB. While antagonism of NMB is necessary with partial recovery, it is unnecessary with more complete recovery. Even when monitoring with an accelerograph, reversal of NMB is complicated. In addition to the pharmacodynamics of the individual neuromuscular blocking agents, factors such as timing of anticholinesterase administration, dose of anticholinesterase, concomitant medications, electrolyte abnormalities, and hepatic or renal disease can influence the degree of reversal. Sugammadex works differently than anticholinesterases and, when administered in appropriate doses, can reverse even profound block induced with vecuronium or rocuronium. Two new fumarate neuromuscular blocking agents have a rapid onset of effect and can be reversed at any time by administration of cysteine, which could significantly reduce the risk of postoperative residual NMB.

Contribution of intracranial vertebral artery asymmetry to vestibular neuropathy.

OBJECTIVES: To test the hypothesis that vertebral artery hypoplasia (VAH) may affect the lateralisation of vestibular neuropathy (VN), probably through haemodynamic effect on the vestibular labyrinth. METHODS: 69 patients with unilateral VN were examined with a magnetic resonance angiographic (MRA) and caloric test. 50 healthy subjects served as controls. The diagnosis of intracranial VAH was based on MRA if <0.22 cm in VA diameter and a diameter asymmetry index >40%. The authors then correlated the canal paretic side with the VAH side. RESULTS: MRA study revealed 29 VAH (right/left: 23/6) in VN subjects and six VAH in controls (right/left: 5/1). The RR of VAH in VN subjects compared with controls was elevated (RR=2.2; 95% CI 1.8 to 2.8). There was a high accordance rate between the side of VAH and VN. Among 29 patients with unilateral VAH, 65.5% (N=19) had an ipsilateral VN, in which left VAH showed a higher accordance rate (83.3%) than the right side (60.9%). VN subjects with vascular risk factors also had a higher VAH accordance rate (81%) than those without (25%). CONCLUSIONS: VAH may serve as a regional haemodynamic negative contributor and impede blood supply to the ipsilateral vestibular labyrinth, contributing to the development of VN, which could be enhanced by atherosclerotic risk factors and the left-sided location.

Neuromuscular dose-response studies: determining sample size.

BACKGROUND: Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. METHODS: The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED50 for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED50 was varied from ±10-20%. RESULTS: The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED50 is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). CONCLUSIONS: On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.

Determining the potency of neuromuscular blockers: are traditional methods flawed?

BACKGROUND: Traditionally, the clinical potency of neuromuscular blocking drugs has been measured using linear regression analysis (LRA) after log dose and probit or logit data transformation. However, probit and logit analyses are meant to handle only quantal responses with binomial error distributions, not continuous data such as per cent of maximal response. Some statisticians now consider this approach outmoded and assert that non-linear regression (NLR) is the preferred way to analyse sigmoidal dose-response relationships. We were interested in the degree to which the method of regression analysis alters calculated ED(50) and ED(95) values. METHODS: We analysed raw data for succinylcholine, rocuronium, rapacuronium, and cisatracurium from previously published studies using both LRA and NLR to determine the ED(50) and ED(95) values and the respective slopes of the dose-response relationships. We also estimated drug potency using the Hill equation (HE) using the slopes obtained from LRA and NLR. RESULTS: ED(50) values calculated by NLR, LRA, or the HE were interchangeable. LRA resulted in ED(95) values that were 13-18% lower than those determined by NLR. The 95% confidence limits (CL) for the ED(50) did not exceed +/-8% of the estimated value no matter how it was calculated vs +/-20-30% for the ED(95). CONCLUSIONS: The ED(50) is a very robust parameter. When comparing the potency of neuromuscular blockers, it is this value rather than the ED(95) that should be used. The CL for the ED(95), regardless of how it is calculated, are so wide that this parameter must be viewed, at best, as an approximation.

M(1)-like muscarinic acetylcholine receptors regulate fast-spiking interneuron excitability in rat dentate gyrus.

Cholinergic transmission through muscarinic acetylcholine receptors (mAChRs) plays a key role in cortical oscillations. Although fast-spiking (FS), parvalbumin-expressing basket cells (BCs) are proposed to be the cellular substrates of gamma oscillations, previous studies reported that FS nonpyramidal cells in neocortical areas are unresponsive to cholinergic modulation. Dentate gyrus (DG) is an independent gamma oscillator in the hippocampal formation. However, in contrast to other cortical regions, the direct impact of mAChR activation on FS BC excitability in this area has not been investigated. Here, we show that bath-applied muscarine or carbachol, two mAChR agonists, depolarize DG BCs in the acute brain slices, leading to action potential firing in the theta-gamma bands in the presence of blockers of ionotropic glutamate and gamma-aminobutyric acid type A receptors at physiological temperatures. The depolarizing action persists in the presence of tetrodotoxin, a voltage-gated Na(+) channel blocker. In voltage-clamp recordings, muscarine markedly reduces background K(+) currents. These effects are mimicked by oxotremorine methiodide, an mAChR-specific agonist, and largely reversed by atropine, a non-selective mAChR antagonist, or pirenzepine, an M(1) receptor antagonist, but not by gallamine, an M(2/4) receptor antagonist. Interestingly, in contrast to M(1)-receptor-mediated depolarization, M(2) receptor activation by the specific agonist arecaidine but-2-ynyl ester tosylate down-regulates GABA release at BC axons-the effect is occluded by gallamine, an M(2) receptor antagonist. Overall, muscarinic activation results in a net increase in phasic inhibitory output to the target cells. Thus, cholinergic activation through M(1)-like receptor enhances BC activity and promotes the generation of nested theta and gamma rhythms, thereby enhancing hippocampal function and associated performance.

Estimating intracellular Ca2+ concentrations and buffering in a dendritic inhibitory hippocampal interneuron.

Calcium is known to regulate several phenomena like neuronal excitability and plasticity. Interestingly, the spatiotemporal profile of dendritic calcium depends on several processes, specific to each neuronal type. In this study, we investigated Ca(2+) buffering and action potential (AP)-evoked Ca(2+) signaling in the dendrites of anatomically identified oriens lacunosum-moleculare (O-LM) cells, a major type of dendrite-targeting interneurons in the hippocampal CA1 region, using a combination of whole-cell patch-clamp recording and fast Ca(2+) imaging in acute rat brain slices. Cells were loaded with fluorescent Ca(2+) indicators fura-2 or Oregon Green BAPTA-1 (OGB-1) via patch-clamping electrode, and the effect of fura-2 on AP-evoked dendritic Ca(2+) transients was determined by ratiometric Ca(2+) imaging. To estimate intracellular Ca(2+) concentrations ([Ca(2+)](i)) and endogenous Ca(2+)-binding ratio (kappa(s)) in the proximal dendrite, fluorescence signals were converted into [Ca(2+)](i) using the ratioing method and were analyzed on the basis of the "single compartment model." Resting [Ca(2+)](i) was 22+/-5 nM and the build-up of [Ca(2+)](i) during a single AP was up to 656+/-226 nM. Analysis of Ca(2+) transients revealed that O-LM cells have a relatively low endogenous Ca(2+)-binding ratio (kappa(s)): the kappa(s) was 20+/-8 estimated during fura-2 loading and 27 estimated under steady-state fura-2 concentrations, respectively. To further examine the spatial profile of dendritic Ca(2+) transients, we measured somatic AP-evoked Ca(2+) transients beyond proximal dendrites using OGB-1. Dendritic Ca(2+) transients evoked by single APs or AP trains are not limited to regions close to the soma. The amplitude and decay of [Ca(2+)](i) associated with backpropagating APs are relatively independent of the distance from the soma. In sum, O-LM cells exhibit low endogenous Ca(2+)-binding ratios and relatively distance-independent Ca(2+) dynamics in the dendrites. These special features of Ca(2+) signaling in O-LM cells may have important functional implications for both normal and pathological conditions.

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss.

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.

Dissolved air flotation of polishing wastewater from semiconductor manufacturer.

The feasibility of the dissolved air flotation (DAF) process in treating chemical mechanical polishing (CMP) wastewater was evaluated in this study. Wastewater from a local semiconductor manufacturer was sampled and characterised. Nano-sized silica (77.6 nm) with turbidity of 130 +/- 3 NTU was found in the slightly alkaline wastewater with traces of other pollutants. Experimental results indicated removal efficiency of particles, measured as suspended particle or turbidity, increased with increasing concentration of cationic collector cetyltrimethyl ammonium bromide (CTAB). When CTAB concentration was 30 mg/L, pH of 6.5 +/- 0.1 and recycle ratio of 30%, very effective removal of particles (> 98%) was observed in saturation pressure range of 4 to 6 kg/cm2, and the reaction proceeded faster under higher pressure. Similarly, the reaction was faster under the higher recycle ratio, while final removal efficiency improved slightly as the recycle ratio increased from 20 to 40%. An insignificant effect of pH on treatment efficiency was found as pH varied from 4.5 to 8.5. The presence of activator, Al3+ and Fe3+, enhanced the system performance. It is proposed that CTAB adsorbs on silica particles in polishing wastewater through electrostatic interaction and makes particles more hydrophobic. The increase in hydrophobicity results in more effective bubble-particle collisions. In addition, flocculation of silica particles through bridging effect of collector was found; it is believed that flocculation of particles also contributed to flotation. Better attachment between gas bubble and solid, higher buoyancy and higher air to solid ratio all lead to effective flotation.

Changes in immunolocalisation of beta-dystroglycan and specific degradative enzymes in the osteoarthritic synovium.

OBJECTIVE: To investigate the immunolocalisation of beta-dystroglycan (beta-DG) and specific matrix metalloproteinases (MMPs)-3, -9, -13 and a disintegrin like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) within the joint tissues of patients with osteoarthritis (OA) and unaffected controls. DESIGN: Cartilage, synovium and synovial fluid were obtained from the hip joints of five osteoarthritic (patients undergoing total hip replacement) and five control hip joints (patients undergoing hemiarthroplasty for femoral neck fracture). The samples were analysed for beta-DG protein using Western blot technique and by immunohistochemistry for tissue distribution of beta-DG, MMP-3, -9, -13, and ADAMTS-4. RESULTS: beta-DG was detected in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Importantly, beta-DG was detected in endothelium of blood vessels of OA synovium, but not in the control endothelium. In the endothelium of osteoarthritic synovial blood vessels, beta-DG co-localised with MMP-3 and -9. MMP-13 and ADAMTS-4 showed no endothelial staining, and only weak staining of the vascular smooth muscle was found. In contrast, we did not detect beta-DG protein in cartilage or synovial fluid. CONCLUSIONS: beta-DG has been shown to have a role in angiogenesis, and our results demonstrate for the first time that there are clear differences in beta-DG staining between OA and control synovial blood vessels. The specific immunolocalisation of beta-DG within endothelium of inflamed OA blood vessels and its co-localisation with MMP-3 and -9, reported to have pro-angiogenic roles and believed to be involved in beta-DG cleavage, may also suggest that beta-DG plays a role in angiogenesis accompanying OA.

Polypharmacy and inappropriate medication use in Singapore nursing homes.

INTRODUCTION: At present, 7.2% of the population in Singapore is in the geriatric age group, which will increase to 18.4% in the year 2030. The frailest segment of the geriatric population live in nursing homes. They suffer from multiple co-morbidities requiring multiple medication use. Polypharmacy and inappropriate medication use have been considered as quality indicators for nursing home care. As no data of these indicators are available in Singapore, this study was planned to assess the prevalence of polypharmacy and inappropriate medication use in Singapore nursing homes. MATERIALS AND METHODS: A total of 454 residents in the geriatric age group residing in 3 randomly selected nursing homes were involved in the study. Case notes were reviewed for demographic information, clinical history and medication use. The data were analysed for polypharmacy (5 or more medication orders) and inappropriate medication use (based on established criteria). RESULTS: Residents were on an average of 5.32 medications. Polypharmacy and inappropriate medication use were seen in 266 (58.6%) and 318 (70.0%) residents, respectively. There was significant association between polypharmacy and inappropriate medication use [P < 0.001, chi2 = 82.56 at 95% confidence interval (CI)]. The most common medication-related problems were the use of medication without proper indication (n = 302), significant potential for adverse drug reactions (n = 281) and drug interactions (n = 141). CONCLUSION: The prevalence of polypharmacy and inappropriate medication use is high in Singapore nursing homes. Current practice of medication use in the nursing homes may lead to significant adverse drug reactions and drug interactions. A multidisciplinary approach involving geriatricians, nursing home physicians, nurses and pharmacists may potentially reduce polypharmacy and inappropriate medication use in Singapore nursing homes.

Use of polymerase chain reaction for early detection and management of hepatitis C virus infection after needlestick injury.

Infection with hepatitis C virus (HCV) is a matter of great concern because of its potentially grave consequences. Instead of relying on the conventional anti-HCV antibody test to detect HCV infection after needlestick incidents, we used the polymerase chain reaction (PCR) to achieve earlier detection, to manage a patient more effectively, and to exclude possible infection more quickly. Fourteen incidents were studied in which the source patients were positive for both the anti-HCV antibody and HCV RNA, and the exposed subjects were negative for anti-HCV antibody at the time of the incidents. In one of the exposed subjects, a nurse, the result of the PCR test for HCV RNA was positive at 2 wk after the needlestick incident; the nurse's viral load was very low (800 copies/ml) and she responded well to immediate medical treatment. She never developed acute hepatitis C; her serum anti-HCV antibody level and alanine aminotransferase (ALT) activity did not become elevated, and results of her PCR test for HCV RNA were negative following treatment. In the other 13 needlestick incidents, the results of PCR tests of the exposed subjects were negative for HCV RNA throughout the study and possible infections were quickly ruled out.

Helicobacter pylori infection in recurrent abdominal pain in children--a prospective study.

A total of 40 children was recruited to assess the role of Helicobacter pylori infection in children with recurrent abdominal pain syndrome. Among 40 children, seven (17.5%) cases were confirmed to have H. pylori infection. All H. pylori-positive patients had active chronic gastritis histologic findings (p < 0.0001); however, the majority of the H. pylori-negative patients had minimal to mild gastritis histologic findings (p = 0.001). Grossly, chronic gastritis picture was present in all children infected with H. pylori and antral nodular gastropathy present in 43%. 71% of H. pylori-positive patients had elevated anti-H. pylori IgG titer; however, 15% in H. pylori-negative patients (p = 0.006). Serum H. pylori assay had a sensitivity of 71% and specificity of 85%; however, sensitivity and specificity of rapid urease test were 86% and 100% respectively. Antral nodularity is a specific, peculiar endoscopic finding of children infected with H. pylori (p = 0.004). Although the present study suggests that H. pylori-related chronic gastritis may play an etiological role in a subgroup of children with RAP syndrome, but the routine screening of H. pylori infection in children with RAP is not recommended, since no compelling data support the significant association between H. pylori infection and RAP syndrome.

Pretreatment of bakery wastewater by coagulation-flocculation and dissolved air flotation.

The pretreatment of wastewater from a large-scale bakery was studied. In the coagulation-flocculation reaction, it was found that both alum and FeCl3 were effective in the jar tests. When at coagulant dosage of 90 to 100 mg/l, 55% of COD and 95 to 100% of SS could be removed. The optimum pH was at 6.0. In addition, the removal of SS was affected by pH more significantly, while the removal of COD was not affected in the pH range of 6.0 to 8.0. In the DAF experiments, 48.6% of COD and 69.8% of SS were removed in 10 min at a pressure of 4 kg/cm2, recycle ratio of 0.3 l/min, and pH of 6.0. Upon the addition of 100 mg/l of alum, the removal efficiency of COD did not increase while SS removal increased to 82.1%. It was found that 5-min flocculation time did improve the COD removal while it had little effect on SS removal. Flocculation for longer than 5 min did not enhance the flotation performance. Similar phenomena were observed when FeCl3 was used as the coagulant, except that flocculation had an insignificant effect on COD and SS removal. It was also found that FeCl3 was relatively more effective than alum. In summary, both coagulation-flocculation and DAF were efficient for the pretreatment. The advantages and disadvantages were discussed.

Postoperative narcotic requirement after microscopic lumbar discectomy is not affected by intraoperative ketorolac or bupivacaine.

STUDY DESIGN: Prospective, randomized, double-blind study. OBJECTIVE: To assess the efficacy of ketorolac and bupivacaine in reducing postoperative pain after microsurgical lumbar discectomy. SUMMARY OF BACKGROUND DATA: Microsurgical lumbar discectomy often is performed as an ambulatory procedure. Pain, nausea, and urinary retention may delay discharge. It was hypothesized that intraoperative ketorolac or bupivacaine would reduce postoperative pain as measured by morphine demand. METHODS: After Institutional Review Board (IRB) approval and informed consent, 30 patients undergoing single-level microsurgical lumbar discectomy under general anesthesia randomly received either intravenous ketorolac, intramuscular bupivacaine, or placebo before wound closure. After surgery, all patients received intravenous, MSO4, patient-controlled analgesia. MSO4 demand was compared between groups at 30 minutes and at 1, 4, 8, 16, 20, and 24 hours after surgery by one-way ANOVA. Pre- and postoperative pain was assessed by using a standard scale and was correlated to postoperative MSO4 demand by Pearson correlation. Significance was assumed at P < 0.05. RESULTS: There were no group differences in age, gender, weight, disc level, preoperative pain, or preoperative use of pain medication. Neither ketorolac nor bupivacaine decreased pain or nausea scores, MSO4 demand, or time to void and ambulation. Preoperative pain was significantly correlated to postoperative narcotic demand (r = 0.46, P < 0.01). Preoperative narcotic or NSAID use was not correlated to either preoperative pain scores or postoperative MSO4 requirement. CONCLUSIONS: Neither ketorolac nor bupivacaine decreased the postoperative narcotic requirement in patients undergoing microsurgical lumbar discectomy. Postoperative narcotic requirements are increased in patients who are in severe pain before surgery, regardless of preoperative narcotic use.