Miracle-dz/UniFAR-FTUs huggingface dataset:
Endotoxin release from Escherichia coli after exposure to tobramycin: dose-dependency and reduction in cefuroxime-induced endotoxin release.

OBJECTIVE To study the release of free endotoxin from Escherichia coli exposed to varying concentrations of the penicillin-binding protein (PBP) 3-specific beta-lactam antibiotic cefuroxime, the aminoglycoside tobramycin, and a combination of the two, and to test the relationship between bacterial killing rate and endotoxin release. METHODS A clinical isolate of Escherichia coli in logarithmic phase was exposed to 0.1, 2, 10, and 50 x minimum inhibitory concentration (MIC) of cefuroxime, tobramycin, and a combination of the two. Samples for viable counts and endotoxin analysis were drawn immediately before and after the addition of the antibiotics and at 1, 2, 4, 6, and 24 h. All experiments were performed in triplicate. For the analysis of endotoxin, a chromogenic limulus amoebocyte lysate assay was used. RESULTS Endotoxin liberation was found to be proportional to the number of killed bacteria for each antibiotic regimen at each concentration level justifying the endotoxin-liberating potential to be expressed as release of endotoxin per killed bacterium, an expression that was independent of the inoculum size. At all concentration levels there was a statistically significant difference between the treatments, with the highest release of endotoxin per killed bacterium for cefuroxime, lower for tobramycin and the lowest for the combination of the two drugs (P < 0.001). With increasing doses, there was a significant reduction (P < 0.001) in the propensity to release endotoxin. When the bacterial killing rate was correlated to the propensity to release endotoxin in bacteria exposed to tobramycin or the combination of tobramycin and cefuroxime, a significant negative correlation was found (P < 0.01). This reduction in endotoxin release was not caused by an unspecific endotoxin binding of tobramycin. CONCLUSIONS Addition of tobramycin reduced the cefuroxime-induced endotoxin release per killed bacterium to a level which was even lower than that of tobramycin alone in spite of an increased killing rate. Increasing concentrations of tobramycin led to reduction in endotoxin release, which may be of benefit when dosing aminoglycosides once daily.
Predicting the insertion length for gastric tube placement in neonates.

OBJECTIVE To compare error rates of three existing methods of predicting the gastric tube insertion length in a group of neonates <1 month corrected age: age-related, height-based (ARHB); direct distance nose-ear-xiphoid (NEX); and direct distance nose-ear-mid-umbilicus (NEMU). DESIGN Randomized controlled trial. SETTING Five neonatal care units in a large midwestern city. PARTICIPANTS One hundred and seventy-three hospitalized neonates. METHODS Neonates were randomly assigned to one of three groups: ARHB, NEX, or NEMU. For primary analysis, only tubes placed too high with the tube tip in the esophagus or at the gastroesophageal junction were considered to be misplaced. For secondary analysis, a stricter definition was used, and low placements (pylorus or duodenum) were also considered to be misplaced. All radiographs were blinded and read by a pediatric radiologist. RESULTS For the primary analysis, the differences in percentages of correctly placed tubes among the three methods was statistically significant (χ(2) =34.45; p<. 0001), with NEMU and ARHB more accurate than NEX (NEMU χ(2) =18.59, p<. 0001; ARHB χ(2) =21.34, p<. 0001). Using the stricter definition for placement, ARHB was not significantly different from NEX (p=.0615). A new ARHB equation was developed specific for neonates <1 month corrected age. CONCLUSIONS Direct distance nose-ear-xiphoid should no longer be used as an nasogastric/orogastric (NG/OG) tube insertion-length predictor in neonates. Either NEMU for NG/OG tubes or the new ARHB equation for NG tubes should be used.
Divergent transcription of pdxB and homology between the pdxB and serA gene products in Escherichia coli K-12

We report the DNA sequence and in vivo transcription start of pdxB, which encodes a protein required for de novo biosynthesis of pyridoxine (vitamin B6). The DNA sequence confirms results from previous minicell experiments showing that pdxB encodes a 41-kilodalton polypeptide. RNase T2 mapping of in vivo transcripts and corroborating experiments with promoter expression vector pKK232-8 demonstrated that the pdxB promoter shares its -10 region with an overlapping, divergent promoter. Thus, pdxB must be the first gene in the complex pdxB-hisT operon. The steady-state transcription level from these divergent promoters, which probably occlude each other, is approximately equal in bacteria growing in rich medium at 37 degrees C. The divergent transcript could encode a polypeptide whose amino-terminal domain is rich in proline and glutamine residues. Similarity searches of protein data bases revealed a significant number of amino acid matches between the pdxB gene product and D-3-phosphoglycerate dehydrogenase, which is encoded by serA and catalyzes the first step in the phosphorylated pathway of serine biosynthesis. FASTA and alignment score analyses indicated that PdxB and SerA are indeed homologs and share a common ancestor. The amino acid alignment between PdxB and SerA implies that PdxB is a 2-hydroxyacid dehydrogenase and suggests possible NAD+, substrate binding, and active sites of both enzymes. Furthermore, the fact that 4-hydroxythreonine, a probable intermediate in pyridoxine biosynthesis, is structurally related to serine strongly suggests that the pdxB gene product is erythronate-4-phosphate dehydrogenase. The homology between PdxB and SerA provides considerable support for Jensen's model of enzyme recruitment as the basis for the evolution of different biosynthetic pathways.
Renal Failure in Patients with Neurogenic Lower Urinary Tract Dysfunction

People with multiple sclerosis, paraplegia and neural tube defects typically have neurogenic lower urinary tract dysfunction (NLUTD). This encompasses detrusor hyperreflexia with or without detrusor sphincter dyssynergia and hypo- or acontractility. Their effects undermine safe, effective and controlled storage and voiding of urine and predispose to reflux nephropathy. Therefore, patients in these diagnostic groups with NLUTD would be expected to have increased risk of renal failure. The aim of this study was to quantify this risk using the General Practice Research Database (GPRD). All patients registered in the database between 1994 and 1997 and aged 10–69 were included in the study. The prevalence and incidence of renal failure and renal replacement therapy in the general population was ascertained, as was the prevalence of multiple sclerosis, paraplegia and neural tube defects. The prevalence of renal failure in each of the special populations was then compared with the prevalence in the unaffected general population. The age-standardised prevalence of renal failure in the GPRD population aged 10–69 years was 14 per 10,000. The rate ratio of renal failure compared with the general population in each of the years 1994–1997 for neural tube defects ranged between males (M) 6.8–9.0 and females (F) 9.2–11.5, for paraplegia M 4.1–9.0, F 4.0–7.0, and for multiple sclerosis M 0.4–1.3, F 0.5–2.2. As expected, people with paraplegia or neural tube defects were found to have a substantially increased risk of renal failure compared with the general population. We could not demonstrate an increased risk of renal failure in people with multiple sclerosis. We believe this finding requires further study, but may reflect a problem in the recognition of renal failure in this group of patients. We recommend that all three patient groups should be regularly screened so that renal impairment may be detected prior to the development of renal failure.
Na/H antiporter mRNA expression in single nephron segments of rat kidney cortex.

Renal cortical tubules consist of polarized epithelial cells where Na/H antiport activity has been demonstrated on the apical and/or basolateral membrane. Apical Na/H antiport activity plays an important role in transcellular bicarbonate (HCO3-) reabsorption, whereas basolateral Na/H antiport activity could be involved in transcellular HCO3- secretion as well as cell volume and pH control. To determine whether this heterogeneity in both localization and function is due to the existence of more than one Na/H antiporter, we studied the tissue distribution of Na/H antiporter mRNA by use of reverse transcription (RT) and polymerase chain reaction (PCR) in isolated nephron segments from rat renal cortex. The primers used were directed against the rat renal cortical Na/H antiporter cDNA which is homologous to the human growth factor-activatable Na/H antiporter. RT/PCR of beta-actin mRNA were performed as positive controls. Na/H antiporter mRNA expression in the proximal tubule was not detectable in S1 and S2 segments from superficial and most midcortical nephrons, which exhibit exclusively luminal Na/H antiport activity. It was expressed in S1 and S2 segments from juxtamedullary nephrons which have also basolateral Na/H antiport activity. Beta-actin mRNA was expressed uniformly in all segments of the proximal tubule. Na/H antiporter mRNA was also expressed in cortical thick ascending limb and cortical collecting duct, segments with basolateral Na/H antiport activity as well as in the glomeruli. In conclusion, at least two different Na/H antiporters exist in the renal cortex, i.e., the proximal tubule. The close correlation between functional localization of basolateral Na/H antiport activity and mRNA expression suggests that the rat kidney Na/H antiporter DNA homologous to the human growth factor activatable Na/H antiporter encodes a basolateral exchanger. The observed expression in a minority of midcortical proximal tubules could reflect a certain heterogeneity in these nephron segments.
Examination of Lesions in the Urinary Bladder and Kidney of Dogs Induced by Nefiracetam, a New Nootropic Agent

Toxic lesions induced by nefiracetam, a nootropic drug, in the urinary bladder and kidney were examined by repeated oral administration of 300 mg/kg/day for 1, 2, 3, 4, or 11 wk to male and female beagle dogs. Each dog was sacrificed after each treatment period, and urinalysis and serum biochemistry were performed for surviving dogs at several time points. One male and 2 females died during week 10 or 11. Degeneration and desquamation of epithelial cells and edema and hemorrhage in the lamina propria were observed in the urinary bladder after 1 wk of treatment. These changes became severe as time progressed and were reflected in the clinical abnormalities of hematuria and increased protein excretion in urine. However, epithelial regeneration and hyperplasia were seen thereafter, and almost no change was seen in the urinary bladder after treatment for 11 wk. Instead of recovery as in the urinary bladder, the kidney showed epithelial degeneration and hyperplasia in the papilla and collecting duct and interstitial congestion and hemorrhage after treatment for 11 wk. Extensive hemorrhage and papillary necrosis were seen in animals that died during week 10 or 11 of dosing. These kidney changes were associated with increased urinary volume and decreased osmotic pressure. The lesions are thought to have a common etiopathogenesis and to be initiated by the epithelial damage with a time lag between expression of injury in the urinary bladder and the kidney.
Reduced cerebral glucose metabolism and increased brain capillary permeability following high‐dose methotrexate chemotherapy: A positron emission tomographic study

Regional glucose metabolic rate constants and blood‐to‐brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high‐dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug‐induced alteration in blood–brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.
Genetic–morphologic association study: association between the low density lipoprotein‐receptor related protein (LRP) and cerebral amyloid angiopathy

Accumulating evidence suggests that genetic factors such as apolipoprotein E (APOE), can act in different ways in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). The role of the low‐density lipoprotein‐receptor related protein (LRP), the major cerebral APOE receptor, in AD has been discussed controversially depending on data from different populations and methodological approaches. We examined the influence of LRP polymorphisms on CAA in 125 post‐mortem cases genotyped for APOE and classified according to the neurofibrillary Braak and Braak staging of AD (indicating neurodegeneration grade). CAA was assessed separately for leptomeningeal (CAAlep.), noncapillary cortical (CAAcort.) and capillary cortical (CAAcap.) vessels in β‐amyloid stained sections. Our results suggest: (i) the 87 bp allele of LRP5′ polymorphism (LRP5′) is an independent predictive factor for CAAcort. and CAAlep. ; (ii) the C/C genotype (C allele) of the LRP exon 3 polymorphism is positively associated with the severity of CAAlep. and CAAcort. , implicating a younger age of CAA onset and/or faster CAA progression; (iii) as CAAcort. and CAAlep. showed different genetic associations in contrast to CAAcap. , we can underscore the hypothesis that different molecular mechanisms are involved in CAA pathogenesis of noncapillary and capillary cerebral vessels. Our results lead us to postulate that the LRP5′87 bp and the LRP exon 3 C alleles of the LRP gene (or another locus that might be in linkage disequilibrium with these LRP polymorphic sites) could modify cerebrovascular LRP function or expression in noncapillary cerebral vessels, leading to an increased cerebrovascular amyloid deposition.
Excess winter mortality: Method of calculating mortality attributed to influenza is disputed

EDITOR—We challenge the method that Donaldson and Keatinge used to calculate mortality due to influenza.1 Data covering the period 1970-99 were used, but the authors state that the regression analysis started on 1 January 1990. On the basis of the 10 year analysis, they estimate an average of 1265 per million excess winter deaths from all causes, equivalent to 67 000 nationally in England and Wales. They say that 2.4% of this excess (equivalent to a national average of 1620 deaths per year) is attributable to influenza. This estimate contrasts with those obtained by other groups: Tillett et al estimated an annual average of 12 000 deaths (1968-9 to1977-8)2, Nicholson 13 800 (1975-6 to1989-90)3, and Fleming 12 500 (1989-90 to 1998-9). 4 The estimate of 12 500 is equivalent to 19% of the 67 000 total excess winter deaths, rather than 2.4%. Donaldson and Keatinge estimated total deaths attributable …
Change in length of relaxed muscle fascicles and tendons with knee and ankle movement in humans

Ultrasonography was used to measure changes in length of muscle fascicles in relaxed human tibialis anterior and gastrocnemius during passively imposed changes in joint angle. Changes in the length of muscle fascicles were compared to changes in the length of the whole muscle‐tendon units calculated from joint angles and anthropometric data. Relaxed muscle fascicles underwent much smaller changes in length than their muscle‐tendon units. On average, muscle fascicles in tibialis anterior [saw] 55 ± 13 % (mean ±s.d.) of the total change in muscle‐tendon length. This indicates nearly half of the total change in muscle‐tendon length was taken up by stretch of tendon. In gastrocnemius, which has relatively long tendons, only 27 ± 9 % of the total change in muscle‐tendon length was transmitted to muscle fascicles. Thus, the tendency for passive movement to be taken up by the tendon was greater for gastrocnemius than tibialis anterior (P = 0.002). For these muscles, the relatively large changes in tendon length across much of the physiological range of muscle‐tendon lengths could not wholly be explained by tendon slackness, changes in fibre pennation, or stretch or contraction history of the muscle. Our data confirm that when joints are moved passively, length changes [seen] by muscle fascicles can be much less than changes in the distance between muscle origin and insertion. This occurs because tendons undergo significant changes in length, even at very low forces.
Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway

Aim: We analysed the effect of physiological doses of androgens following orchidectomy on skeletal muscle and bone of male rats, as well as the relationships between muscle performance, hypertrophy and the Akt/mammalian target of rapamycin (mTOR) signalling pathway involved in the control of anabolic and catabolic muscle metabolism.
A comparative study of caudal bupivacaine and midazolam-bupivacaine mixture for post-operative analgesia in children undergoing genitourinary surgery.

OBJECTIVE This study was designed to evaluate the analgesic efficacy of caudal midazolam-bupivacaine combination in providing post-operative pain relief in children undergoing genitourinary surgery and to study the occurrence of adverse effects. SUBJECTS AND METHODS Thirty children, aged 2 to 8 years, scheduled for genitourinary surgery were allocated randomly to receive either 0.25% bupivacaine 0.5 ml/kg (group B; n = 15) or 0.25% bupivacaine 0.5 ml/kg with 50 microg/kg midazolam (group BM; n = 15) by the caudal route immediately after induction of general anesthesia. Heart rate, arterial blood pressure and oxygen saturation were monitored throughout the study period. Postoperative pain was assessed at regular intervals for 12 hours using an objective pain score. Analgesia was supplemented whenever the pain score was > or = 4. Duration of analgesia, as well as the requirement of additional analgesics, were noted. RESULTS Lowest pain scores were observed with the addition of midazolam to caudal bupivacaine (p < 0.01). Duration of analgesia was longer in group BM (11 +/- 0.5 h) as compared to group B (7.4 +/- 2.1 hours) (p < 0.05). Fewer children (26.6%) required additional analgesia in the combination group whereas in group B, 60% of the children received analgesic supplements within 6 hours after surgery (p < 0.05). There were no significant changes in heart rate, blood pressure and oxygen saturation in both groups. We observed no untoward event in either of the groups. CONCLUSION Caudal administration of bupivacaine-midazolam mixture prolongs post-operative analgesia compared to bupivacaine alone without causing any adverse effects.
Immunity to MCA‐induced rat sarcomas: Analysis of in vivo and in vitro results

Three in vivo techniques were used to establish the specificity of tumor immunity induced after sensitization of F344 rats to syngeneic MCA‐induced sarcomas: (1) post‐excision resistance to tumor challenge, (2) passive tumor neutralization (the Winn test), and (3) concomitant immunity. In general, these assays revealed unique non‐crossreactive antigens associated with each of three sarcomas, FMF1, FMM2, and FMM3. However, spleen cells from tumor‐sensitized rats did not demonstrate cell‐mediated cytotoxicity in vitro corresponding to the specificity of tumor resistance in vivo. In the (3H)‐proline cytotoxicity assay, spleen cells from FMM3 tumor‐bearing rats or from FMM3 tumor‐immune rats were not selectively cytotoxic for cultured FMM3 target cells. Parallel analysis of spleen cells from normal or FMM3‐sensitized rats using the Winn assay and the (3H)‐proline assay revealed that (1) spleen cell cytotoxicity in vitro did not correlate with effective tumor protection in vivo; and (2) normal spleen cells were cytotoxic against cultured sarcoma target cells in vitro and inhibited tumor growth in vivo. Thus, passive tumor protection by normal spleen cells in vivo corresponded with the demonstration of natural cytotoxicity in vitro, but induced specific anti‐tumor reactivity was observed only in vivo.
ACCIDENT LITIGANTS WITH NEUROTIC SYMPTOMS

Experience gained from an examination of 750 consecutive accident litigants leads to the conclusion that the aetiology of neurotic symptoms after accidents is so complex that diagnostic labels implying single causation give a false and oversimplified picture. Terms such as "compensation neurosis", "traumatic neurosis", "Mediterranean back", "postconcussion syndrome" and many others illustrate preconceived ideas of causation which are in most cases not warranted, and it is recommended that this group of patients be considered under the general label of sufferers from "accident neurosis". The many symptoms which occur are discussed, and it is found that they present in such endless variety, and in varying severity from mild to completely disabling; they do not cluster in any consistent way to justify the delineating of discrete syndromes which are artificial and misleading; their existence confuses rather than clarifies our understanding of these unfortunate people.
High-field DNP and ENDOR with a novel multiple-frequency resonance structure.

We describe a new triply tuned (e(-), (1)H, and (13)C) resonance structure operating at an electron Larmor frequency of 139.5 GHz for dynamic nuclear polarization (DNP) and electron nuclear double-resonance (ENDOR) experiments. In contrast to conventional double-resonance structures, the body of the microwave cavity simultaneously acts as a NMR coil, allowing for increased efficiency of radiofrequency irradiation while maintaining a high quality factor for microwave irradiation. The resonator design is ideal for low-gamma-nuclei ENDOR, where sensitivity is limited by the fact that electron spin relaxation times are on the order of the RF pulse lengths. The performance is demonstrated with (2)H ENDOR on a standard perdeuterated bis-diphenylene-phenyl-allyl stable radical. In DNP experiments, we show that the use of this resonator, combined with a low microwave power setup (17 mW), leads to significantly higher (1)H signal enhancement (epsilon approximately 400 +/- 50) than previously achieved at 5-T fields. The results emphasize the importance of optimizing the microwave B(1) field by improving either the quality factor of the microwave resonator or the microwave power level.