Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate.

This study investigates the response of the underlying sleep disorder associated with Chronic Fatigue Syndrome (CFS) and fibromyalgia (FM) to treatment. We retrospectively reviewed 118 cases clinically consistent with CFS or FM, treated in a neurology practice. Abnormal findings on sleep studies and associated human leukocyte antigen markers, and a clinical pattern suggestive of narcolepsy, are present in a high proportion of patients. When considered appropriate based on the clinical picture and test results, treatment with sodium oxybate was offered to these patients. Sixty percent of patients treated with oxybate experienced significant relief of pain, while 75% experienced significant relief of fatigue. We postulate that the response to oxybate in CFS and FM suggests a disturbance of sleep similar to narcolepsy. These findings support this novel approach to intervention and further research. The inability to distinguish CFS and FM by testing and response to treatment suggests that they may represent variations of the same disorder or may be closely related disorders.

A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia.

This study characterizes findings on sleep testing and Human Leukocyte Antigen (HLA) markers in a group of patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS). One hundred eighteen patients seen in a general neurology practice over 5 years meeting standard clinical criteria for FM or CFS were analyzed retrospectively. Cases of untreated sleep apnea or restless legs syndrome were excluded prior to inclusion in this study. Ninety-two patients had multiple sleep latency testing (MSLT). Seventy-three (80%) were abnormal by standard criteria. Of 57 females having positive MSLTs, 22 (39%) had one or more periods of sleep onset rapid eye movement (SOREM), and 5 of 16 (31%) males with positive MSLTs had one or more SOREM. Highly fragmented sleep, as previously described in FM, was seen but not analyzed quantitatively. HLA DQB1*0602 was obtained in 74 patients, and positive in 32 (43%), P < 0.0001 compared with published values in 228 populations. In our patients, who presented with neuromuscular fatigue or generalized pain, we found a sleep disorder characterized by objective hypersomnia. Some patients had characteristics of narcolepsy. Objective assessment by sleep studies can assist the diagnostic process, aid future research, and provide rationale for treatment.

Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.

Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.

The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates.

OBJECTIVE: Newborn screening laboratories vary in the values that are used to define congenital hypothyroidism. Defining congenital hypothyroidism is particularly complex in premature neonates because prematurely born infants often have a low free thyroxine value and low or normal TSH value, termed as transient hypothyroxinemia of prematurity. In a multicenter (n=11 sites) trial, we randomly allocated premature neonates with a gestational age of 23 to 29 and 6/7 weeks to one of two parenteral nutrition approaches. The primary objective of our trial was to measure the effect of two distinct strategies of parenteral nutrition on neonatal growth and blood amino acids. A protocol defined secondary aim of our clinical trial was the evaluation of the influence of gestational age, time and the degree of amino-acid supplementation on total thyroxine levels. We hypothesized that an increase of amino-acid supplementation would be associated with the normalization of serum amino acids and that this would improve thyroxine synthesis. STUDY DESIGN: Premature neonates (23 to 29 and 6/7 weeks) were randomly allocated to one of two approaches to intravenous amino-acid administration. In one group, amino-acid supplementation started at 1.0 g kg(-1) per day and advanced by 0.5 g kg(-1) per day to a maximum of 2.5 g kg(-1) per day (2.5 group). The other group received amino acids at 1.5 g kg(-1) per day and advanced by 1.0 g kg(-1) per day to a maximum of 3.5 g kg(-1) per day (3.5 group). Filter paper blood spots were obtained on the day of randomization, and on days 7 and 28 of age to monitor laboratory values. RESULT: Enrollment included 122 neonates, 64 in the 3.5 group and 58 in the 2.5 group. There were no differences in demographics or baseline characteristics between the two treatment groups. There were no significant differences in thyroid levels at baseline, on days 7 and 28 between the two treatment groups. Growth was similar in both groups. It was noted that thyroxine levels changed over time and that the changes with time were greatest in the most preterm neonates. CONCLUSION: The degree of amino-acid supplementation does not influence thyroxine levels and both time from birth and gestational age do influence thyroxine levels.

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant.

OBJECTIVE: The primary aim of this study was to determine if an association exists between amino-acid levels and development of cholestasis. The secondary aim of our amino-acid dose comparison trial was to identify factors associated with the development of prolonged cholestatic jaundice. STUDY DESIGN: We compared demographic characteristics and amino-acid levels in neonates who developed cholestasis with those who did not. Parenteral-associated cholestatic liver disease was defined as a direct serum bilirubin above 5 mg per 100 ml any time during the first 28 days after birth in neonates with no history of biliary atresia or viral hepatitis. We obtained filter paper blood spots for amino acid and acylcarnitine measurements on the day of randomization and days 7 and 28 of age to identify a profile of values that could be used to identify neonates with evidence of abnormal liver function. RESULT: We enrolled 122 neonates in our study; 13 (10.7%) developed cholestasis. Neonates who developed cholestasis were more immature, had lower birth weight, were exposed to parenteral nutrition for a longer period, had a higher cumulative dose of amino acids, were less often on enteral nutrition by day 7 of age, more often had a patent ductus arteriosus and severe intraventricular hemorrhage and were more commonly treated with steroids by 28 days of age. Amino acid and acylcarnitine values were not different for the two groups on the day of randomization. On day 7 (parenteral phase of nutrition), blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher, and serine, glutamate and thyroxine levels were lower in the neonates who developed cholestasis than in who did not. CONCLUSION: Cholestasis remains an important complication of parenteral nutrition, and several clinical and biochemical factors may be helpful in identifying high-risk patients.

Functional and morphologic maturation of the superficial nephrons. Relationship to total kidney function.

The functional and morphologic pattern of superficial nephron development was studied in guinea pigs ranging in age between 2 h and 38 days. Concomitent measurements of total kidney function and glomerular counts were also performed. Superficial nephron glomerular filtration rate was found to increase from 0.92 to 19.32 nl/min. The filtration rate of the entire kidney rose from 0.19 to 1.31 ml/min. During the first 15 days of life the average rate of increase in glomerular filtration rate per nephron (0.48 nl/min.day), obtained by dividing the increase in total kidney glomerular filtration rate by glomerular number, was more than twice the observed rate of increase in the superficial nephrons (0.21 nl/min.day). During the remainder of the first month, the increase in superficial nephron glomerular filtration rate (0.97 nl/min.day) was greater than the average increase for all nephrons (0.71 nl/min.day). Thus, the initial increase in total kidney glomerular filtration rate was primarily a consequence of the activity of the deep nephrons, whereas during the ensuing period the superficial nephrons appeared to be the sole contributors to the change in total kidney glomerular filtration rate.The increase in superficial nephron glomerular filtration rate was found to correlate closely with the increase in proximal tubular length. Functional glomerulotubular balance was maintained throughout the entire period of renal maturation.

Postnatal changes in renal glomerular blood flow distribution in puppies.

The intrarenal distribution of radionuclide microspheres injected into the thoracic aorta was used to examine glomerular blood flow distribution (GBFD) in 26 healthy, unanesthetized puppies, ranging in age from 5 h to 42 days, and in 5 adult dogs. For analysis, the cortex was divided into four equally thick zones designated zone I (subcapsular) to zone IV (juxtamedullary). During the first 36 h of life, the highest flow rate was in zone II, which received 35.5+/-2.0%/g, compared with 26.8+/-1.4% to zone I, 23.7+/-1.4% to zone III, and 13.4+/-1.4% to zone IV. At age 6 wk, zone I had the highest rate of perfusion (48.6+/-2.1%, compared with 28.8+/-1.4% in zone II, 15.8+/-0.8%, in zone III, and 6.8+/-0.6% in zone IV). The 6-wk old animals resembled the adult animals, except for relatively greater perfusion per gram of zone I in the former group. Changes in relative GBFD did not correlate with those in arterial pressure or peripheral hematocrit. The distribution of glomeruli among the four zones of the cortex followed its own pattern of development. At birth and at 6 wk, the greatest density of glomeruli was in zone I (50.6+/-5.4 and 42.7+/-3.9%/g respectively, as compared with 24.1+/-2.9% in adults); in adults zone II contained the greatest density (39.1+/-1.6%). At birth the relative perfusion of glomeruli in zone I was only one-fifth that of glomeruli in zone IV, with intermediate values in zones II and III. By 6 wk of age, increased perfusion of the outer cortical glomeruli resulted in rates of flow in the four zones that did not differ significantly from each other. Relative perfusion in zone I continued to increase, so that in the adult animals perfusion in that zone was significantly greater than in the three deeper zones. These data demonstrate the marked hemodynamic changes that take place within the kidney during the first few weeks of life. The relatively greater blood flow of the most deeply situated nephrons in the early postnatal period suggests ascendancy of this population of nephrons and may have important functional implications.

Role of multiple site blood cultures to document the clearance of bacteremia in neonates.

OBJECTIVE: To evaluate the usefulness of two-site blood cultures for the documentation of bacterial clearance during initial treatment of culture proven neonatal sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had blood cultures drawn for evaluation of possible sepsis. A positive diagnostic blood culture was followed by repeat blood cultures from two different peripheral sites after initiation of antimicrobial therapy. RESULTS: Follow-up two-site cultures were drawn on 25 occasions at a median interval of 3 days after start of antimicrobial therapy for culture-proven sepsis in 15 neonates. On 12 occasions, follow-up blood cultures were both negative. On eight occasions, follow-up blood cultures grew the same organisms from both sites. However, follow-up two-site cultures on five occasions in four of the 15 infants grew organisms from one site but not the second site. CONCLUSIONS: Two-site blood cultures seem necessary to document bacterial clearance in response to antimicrobial therapy for culture-proven sepsis, and may help determine the appropriate duration of antimicrobial therapy by reducing false-negative results.

Impact of l-carnitine supplementation on metabolic profiles in premature infants.

OBJECTIVE: To describe the influence that of l-carnitine supplementation on acylcarnitine (AC) profiles and hospital outcomes in premature infants. STUDY DESIGN: This study is a secondary analysis of previously reported work. Metabolic profiles were obtained using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 h after birth and on approximately days 7, 28 and 42 of life, or at the time of discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. l-Carnitine was added to parenteral nutrition in 390 (39%) study subjects; 592 (60%) did not receive supplementation. Non-supplemented infants were more likely to develop low levels of free carnitine (FC; <7 µm) on day 28; (41% vs 5%, P<0.01); and FC values were lower on day 7. Despite higher levels of FC and fewer patients with significant carnitine deficiencies, we found no evidence that l-carnitine supplementation was associated with improved short-term hospital outcomes. CONCLUSION: l-Carnitine supplementation is common in prematurely born neonates and is associated with higher carnitine levels, but is not associated with improved short-term hospital outcomes.

Anthropometric trends from 1997 to 2012 in infants born at ⩽28 weeks' gestation or less.

OBJECTIVE: Postnatal growth failure is common after preterm birth, in particular for infants born at ⩽28 weeks' gestation, but it is unknown if growth-to-term equivalent age has improved over the years as neonatal intensive care in general, and infant nutrition in particular, have improved. The objective of the study was to evaluate anthropometric trends at NICU discharge for infants born at ⩽28 weeks' gestation using a large national database. STUDY DESIGN: Analysis of growth in weight, length, head circumference and body mass index (kg m2) in 23 005 infants born in 1997 to 2012 who survived to neonatal intensive care unit discharge at ⩽41 weeks' postmenstrual age. RESULTS: Discharge weight, length, head circumference and body mass index were converted to Z-scores using a reference database, and growth trends over the 16 years were summarized. Discharge results also were summarized for common neonatal morbidities, including chronic lung disease. Gestational age at birth and postmenstrual age at discharge were similar across the 16 years. Discharge weight, length and head circumference Z-scores were all below the median, but head circumference Z-scores consistently were closer to the median than were weight and length. In 1997 compared with 2012, the weight Z-score improved from -1.5 to -0.6; the length Z-score increased the least, from -1.68 to just -1.16; the head circumference Z-score improved from -0.68 to -0.30; and the body mass index Z-score increased from -0.66 to 0.19. Percent small-for-gestational age at birth was stable across the years at 8.4 to 9.3%, and the frequency of postnatal growth failure at discharge improved from 55.4% in 1997 to 19.6% in 2012. CONCLUSIONS: Growth-to-discharge progressively improved from 1997 to 2012, but Z-scores remained below the reference median for weight, length and head circumference. Length Z-scores were consistently significantly less than for weight, and body mass index Z-scores have been above the reference median since 2002. Prospective studies are needed to quantify anthropometric trends in relation to body composition and to current nutritional strategies.

Major anomalies and birth-weight influence NICU interventions and mortality in infants with trisomy 13 or 18.

OBJECTIVE: To describe neonatal intensive care unit (NICU) medical interventions and NICU mortality by birth weight and major anomaly types for infants with trisomy 13 (T13) or 18 (T18). STUDY DESIGN: Retrospective cohort analysis of infants with T13 or T18 from 2005 to 2012 in the Pediatrix Medical Group. We classified infants into three groups by associated anomaly type: neonatal surgical, non-neonatal surgical and minor. Outcomes were NICU medical interventions and mortality. RESULTS: 841 infants were included from 186 NICUs. NICU mortality varied widely by anomaly type and birth weight, from 70% of infants <1500 g with neonatal surgical anomalies to 31% of infants ⩾2500 g with minor anomalies. Infants ⩾1500 g without a neonatal surgical anomaly comprised 66% of infants admitted to the NICU; they had the lowest rates of NICU medical interventions and NICU mortality. CONCLUSIONS: Risk stratification by anomaly type and birth weight may help provide more accurate family counseling for infants with T13 and T18.

A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis.

BACKGROUND: The optimal number of blood cultures needed to document sepsis in an ill neonate has undergone little critical evaluation. Multiple site cultures may improve pathogen detection if intermittent bacteremia occurs, or if a low density of bacteria is present in the blood. We hypothesized, however, that bacterial clearance is slower and bacteremia more continuous in septic neonates, so that a single site blood culture should be sufficient to accurately document true septicemia. OBJECTIVE: To determine the need for multiple site blood cultures in the evaluation of neonates for sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had 269 pairs of blood cultures taken from two different peripheral sites for the evaluation of possible sepsis. A minimum of 1 ml of blood was obtained from the two peripheral sites within 15-30 min of each other. Based on prior retrospective data, we determined that 203 infants would need to have two site blood cultures to demonstrate a significant improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%) power. RESULTS: A total of 186 culture pairs were taken for evaluation of early-onset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late-onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were evaluated more than once, and 12 neonates were evaluated for both early- and late-onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven sepsis at a median age of 18 days. All neonates with positive cultures had the same organism with a similar sensitivity pattern obtained from the two different peripheral sites. The other 196 study neonates had negative blood cultures from both sites. The single episode of early-onset sepsis was caused by Listeria monocytogenes, while all remaining episodes were late-onset with the following organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone (2), late-onset Group B beta-hemolytic Streptococcus (GBS) (2), Klebsiella pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia marcescens (1). Since no infant grew organisms from only one of the two sites, the data indicate that the diagnosis of sepsis would have been made correctly in all infants with a single site culture. CONCLUSIONS: Two site blood cultures for the initial evaluation of neonatal sepsis do not have a better yield in pathogen detection. Sepsis in neonates can be detected with no loss of accuracy with a single site blood culture with blood volume of>or=1 ml.

The complete blood cell count in a refined cohort of preterm NEC: the importance of gestational age and day of diagnosis when using the CBC to estimate mortality.

OBJECTIVE: The value of the white blood cell count (WBC) in necrotizing enterocolitis (NEC) is controversial. One reason for this confusion may be that the various WBC lineages change substantially with increasing gestational age and thereby age of NEC onset. This study postulated that if a data set was large enough and the diagnosis of NEC clean enough, absolute WBC counts would facilitate prediction of NEC mortality. The objective of this study was to determine whether absolute WBC counts enhance the prediction of NEC mortality. STUDY DESIGN: A de-identified data subset from the Pediatrix national data set specific to the diagnoses of NEC in patients who had a CBC drawn on the day of diagnosis (exclusive of the diagnoses of spontaneous intestinal perforations and congenital anomalies) was the target for analysis. Values of primary interest included: gestation, day of diagnosis, absolute WBC count, platelet count, hematocrit, mortality and the day of diagnosis. Stepwise regression analysis was used to predict mortality. RESULT: A total of 4059 (79%) survivors and 1107 (21%) infants who died with a diagnosis of medical or surgical NEC were included in the data set. Associations with mortality were found with low gestational age, low platelet count, low hematocrit, high band/segmented neutrophil ratio, earlier day of diagnosis, high birth weight z-score, non-white race, no antenatal steroids in gestations above 24 weeks, absolute lymphocyte count adjusted for gestational age, and absolute monocyte count high and low values. A stepwise regression analysis yielded a receiver-operator curve of 0.819 with a sensitivity of 65% and specificity of 84%. CONCLUSION: Absolute WBC values enhance prediction of NEC survival when used in combination with readily available data on the day of NEC diagnosis.

The epidemiology, prevalence and hospital outcomes of infants with gastroschisis.

OBJECTIVE: The purpose of this study is to evaluate recent trends in prevalence of gastroschisis among infants admitted for neonatal intensive care in the United States. STUDY DESIGN: Retrospective review of a de-identified patient data. The current study extends our observations through the end of 2007 to 2015. RESULTS: During the study period (1 January 1997 to 12 December 2015), there were 1 158 755 total discharges; 6023 (5.2/1000) had gastroschisis and 1885 (1.6/1000) had an omphalocele. Between 1997 and 2008, the reported rate of gastroschisis increased from 2.9 to 6.4/1000 discharges. From 2008 to 2011, the values have slowly decreased from 6.4 to 4.7/1000 discharges and since 2011 have been stable. The largest drop in the prevalence was in mothers who were <20 years old. In contrast, the reported rate of omphalocele was stable at 1 to 2/1000 discharges. CONCLUSION: The prevalence of gastroschisis increased from 1997 to 2008, and then declined thereafter.

NMR measurement of intracellular water volume in rat kidney proximal tubules.

Knowledge of cell water volume is essential for the measurement of concentrations of intracellular ions and metabolites in kidney proximal tubules. We have developed a method which utilizes 35Cl-NMR as a measure of extracellular volume and 2H-NMR, in combination with a membrane-impermeable shift-reagent [Dy-DTPA]2-, as a measure of the ratio of intra- and extracellular water volumes. Measurement of extracellular volume by 35Cl-NMR is possible, since the resonance of intracellular 35Cl is too broad to be detectable in kidney cells. The 2H-NMR measurement exploits the fact that only extracellular water is in direct contact with [Dy-DTPA]2-. However, rapid exchange of water across the cell membrane results in only a single 2H2O resonance at a chemical shift which is a weighted average of the shifted extra- and unshifted intracellular water resonances. Expression of the extracellular volume as a fraction of the total volume by fCl and as a fraction of the total water-volume by fD, permits the calculation of the fractional cell-water content fw = [(1/fD)-1]/[(1/fCl)-1]. This approach was applied to proximal tubular suspensions prepared from the rat kidney. The water content was found to be 76.9 +/- 1.8% (n = 6) at 37 degrees C. Increasing extracellular osmolality from 295 to 390 mOsm/kg H2O, by addition of mannitol, decreased the water content by 21%. Our results are in good agreement with those obtained by the gravimetric method.

NMR measurements of intra- and extravesicular sodium in renal microvilli.

Previous attempts to separate the nuclear magnetic resonances of intra- and extravesicular Na+ in brush-border membrane vesicles (BBMV) were unsuccessful and led to the proposal of rapid exchange of Na+ via sodium channels in BBMV. However, passive conductance of Na+ in this membrane has been found to be relatively small. This inconsistency prompted us to use a different shift reagent to reassess the issue. In guinea pig renal BBMV (15-30 mg protein/ml) equilibrated with Na+ (130 mequiv. 1), using the impermeant Na+ shift reagent dysprosium tripolyphosphate (3 mM), the resonances of intra- (3.3%) and extravesicular (96.7%) Na+ were resolved by 6 ppm. Increases in Na+ conductance induced by gramicidin D did not alter the characteristics of intra- and extravesicular Na+ resonances. By contrast, addition of glucose caused a transient increase in the area of the intravesicular Na+ resonance. The clear separation between the intra- and the extravesicular Na+ resonances allowed us to measure the relaxation times of Na+, which depend on its interactions with its immediate environment. The longitudinal relaxation time of intravesicular Na+ (13 +/- 1 ms) was much shorter than that of the extravesicular Na+ (44.0 +/- 0.4 ms). Thus, in intact renal BBMV, as well as in membranes treated with the cationophore gramicidin D, the exchange of Na+ between the intra- and the extravesicular compartments is slow on the NMR time scale, consistent with the low Na+ channel density of this membrane. In contrast, the increase in intravesicular Na+ induced by glucose, is consistent with a significant contribution of the glucose cotransport pathway to Na+ flux across these membranes. The short longitudinal relaxation time of Na+ in the intravesicular space indicates interaction of Na+ with BBMV binding sites or ordering of these ions in the intravesicular compartment.

Quantitative computer analysis of the sounds of isolated motor unit action potentials.

To develop quantitative measures of motor unit action potential (MUAP) sounds, we correlated Fourier domain features of isolated, individual MUAPs with classic time domain measurements. There were moderate correlations between amplitude or duration measurements, and absolute low-frequency (39 to 234 Hz) energy and amplitude of the peak frequency, and high correlations between the composite time domain feature of amplitude x duration, and total energy, amplitude of the peak frequency, and absolute low-frequency energy. Polyphasic potentials have multiple peaks in the magnitude component of the Fourier transform. Phase information appears to convey the "crisp" sound of MUAPs close to the recording electrode. The clinical description of "large" or "small" MUAPs by sound is likely based on absolute low-frequency energy, and incorporates both amplitude and duration information. We conclude that features of isolated MUAPs may be analyzed in the Fourier domain, and that they correlate closely with traditionally used measures of known diagnostic significance. The sound of the EMG used by clinical electromyographers is amenable to quantitative analysis.

The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial.

Neuropathic pain is often severe, persistent, and responds poorly to analgesic medications. Recent evidence suggests that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective in the treatment of neuropathic pain. The present trial was designed to test the efficacy of acute administration of the NMDA receptor antagonist amantadine in relieving surgical neuropathic pain in patients with cancer. The study sample consisted of 15 cancer patients with the diagnosis of surgical neuropathic pain. Two 500 ml infusions of either 200 mg amantadine or placebo were administered over a 3 h period, in a randomized order, 1 week apart from each other. Spontaneous and evoked pain were measured for 48 h before treatment, during treatment, and for 48 h following treatment. An average pain reduction of 85% was recorded at the end of amantadine infusion vs. 45% following placebo administration. The difference in pain relief between the two treatments was statistically significant (P = 0.009). Mean pain intensity remained significantly lower during the 48 h following amantadine treatment as compared with the 48 h prior to treatment (31% reduction; P = 0.006), whereas no such effect was found with the placebo (6% reduction; P = 0.40). Amantadine, but not the placebo, also reduced 'wind up' like pain (caused by repeated pinpricking) in four patients. We conclude that amantadine infusion is a safe and effective acute treatment for surgical neuropathic pain in cancer patients. Further trials with long-term oral or parenteral amantadine treatment should be conducted.

Sudomotor function in sympathetic reflex dystrophy.

Sudomotor functions were studied in 27 patients suffering from reflex sympathetic dystrophy (RSD) according to the criteria established by Bonica (18 women, 9 men; mean age 50 +/- 12.3 years; median duration of disease 8 weeks, range 2-468 weeks). To measure local sweating rates, two small chambers (5 cm2) were affixed to corresponding areas of hairy skin on the affected and unaffected limbs. Dry nitrogen gas was passed through the chambers (270 ml/min) and evaporation was recorded at both devices with hygrometers. Thermoregulatory sweating (TST) was induced by raising body temperature (intake of 0.5 1 hot tea and infra-red irradiation). Local sweating was also induced through an axon reflex (QSART) by transcutaneous iontophoretic application of carbachol (5 min, 1 mA). In addition, skin temperature was measured on the affected and unaffected side by infra-red thermography. Mean skin temperature was significantly higher on the affected side (P < 0.003). In spite of the temperature differences, there was no difference in basal sweating on the affected and unaffected side. However, both methods of sudomotor stimulation lead to significantly greater sweating responses on the affected compared to the unaffected side (TST: P < 0.05, QSART: P < 0.004). Latency to onset of sweating was significantly shorter on the affected side under both test conditions (P < 0.04 and P < 0.003, respectively). Sweat responses were not correlated to absolute skin temperature but were probably related to the increased blood flow on the affected side. Our findings imply a differential disturbance of vasomotor and sudomotor mechanisms in affected skin. Whereas vasoconstrictor activity is apparently lowered, sudomotor output is either unaltered or may even be enhanced.

No lumbar puncture in the evaluation for early neonatal sepsis: will meningitis be missed?

OBJECTIVE: We performed this investigation to assess whether selective approaches to performing lumbar puncture (LP) in the early neonatal period will result in a missed or delayed diagnosis of bacterial meningitis. DESIGN: A retrospective review was conducted of the medical records of all neonates born in US Army hospitals from 1988 through 1992 who developed culture-positive meningitis during the first 72 hours of life. RESULTS: In total, 169,849 infants were born during the 5-year study period. The incidence of meningitis in the first 72 hours of life was 0.25 per 1000 live births. Forty-three infants had organisms isolated from their cerebrospinal fluid (30, group B streptococcus; 10, Escherichia coli; 1, Listeria monocytogenes; 1, Streptococcus pneumoniae; and 1, Citrobacter diversus). The median age of infants at evaluation was 12 hours, and the mean gestational age was 38.8 weeks (7 < 37 weeks), whereas mean birth weight was 3163 g (7 < 2500 g). If we had used currently advocated selective criteria as the basis for not performing an LP, the diagnosis of bacterial meningitis would have been missed or delayed in 16 of 43 infants (37%): 5 infants born prematurely with suspected respiratory distress syndrome, 3 asymptomatic infants born at term with positive blood cultures, and 8 infants born at term with no central nervous system symptoms and negative blood cultures. CONCLUSIONS: If LPs are omitted as part of the early neonatal sepsis evaluation, the diagnosis of bacterial meningitis occasionally will be delayed or missed completely.