Jones v. Murray.
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Blood Specimen Collection↗
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Allowing new technology to erode constitutional protections: a Fourth Amendment challenge to non-consensual DNA testing of prisoners.
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Blood Specimen Collection↗
The renal handling of insulin and thyroid hormones in normal man.
1. The renal extraction of insulin and thyroid hormones T3 and T4 was studied in man by right renal vein catheterization. 2. The mean renal extraction of insulin was 0-46, suggesting that the right renal vein should be utilized in comparable studies. 3. No renal extraction of thyroid hormones was detected.
Adult↗
Regulation of dextranase synthesis by Streptococcus mutans.
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Dextranase↗
The capability of accident and emergency departments to safely decontaminate victims of chemical incidents.
OBJECTIVES: To evaluate the capability of accident and emergency (A&E) departments in six health regions of England to safely decontaminate casualties exposed to hazardous chemicals. METHODS: In January 1999 a postal questionnaire was sent to the clinical director of all A&E departments in Trent, North and South Thames, South and West, North West and, Anglia and Oxford Health Regions. The questionnaire inquired about characteristics of the department, decontamination facilities and equipment, and staff training. Nonresponders were sent a second questionnaire and contacted by telephone if they failed to respond to the second mailing. RESULTS: 308 of 326 departments identified (94%) returned a questionnaire. There was no significant difference in response rate by region (p = 0.99). Analysis was restricted to 154 major departments seeing more than 20000 new attendances per year. Of these 154 departments, 109 (71%) had a written chemical incident plan but only 55 (36%) maintained a list of nearby industrial chemical sites. Fifty nine departments (38%) stated that members of staff had received training in the management of chemically contaminated casualties in the preceding year. Eighteen departments (12%) possessed the level of personal protective equipment (PPE) recommended for decontamination by the Ambulance Services Association. Ninety six departments (62%) had a designated decontamination room but only seven (7%) of them incorporated all the features generally considered necessary for safe decontamination. Forty one units (27%) had the capability to decontaminate casualties outside of the department either with warm water from a shower attachment or with a mobile decontamination unit. Thirty six departments (23%) had neither a decontamination room nor the ability to decontaminate casualties outside the department. Only 16 units (10%) had both adequate PPE and either a decontamination room or the capability to decontaminate outside the department. CONCLUSIONS: This study has identified deficiencies in the current NHS capability to respond to chemical incidents. To resolve this, nationally recognised standards for decontamination facilities, equipment and training should be formulated, agreed and implemented.
Chi-Square Distribution↗
Contamination of flexible fiberoptic bronchoscopes with Mycobacterium chelonae linked to an automated bronchoscope disinfection machine.
Between December 5, 1989, and September 25, 1990, Mycobacterium chelonae was isolated from endoscopic or bronchial washings in 14 patients on a single clinical service. A phenotypically unique strain of M. chelonae subspecies abscessus that was highly resistant to cefoxitin (MIC greater than 256 micrograms/ml) and different from 13 control isolates of M. chelonae recovered elsewhere in the hospital was identified in all these patients and the rinse water from the bronchoscope disinfecting machine. None of the outbreak patients had evidence of invasive M. chelonae disease. Aggressive infection control measures on the disinfecting machine, including use of sterile water in the wash and rinse cycles, increasing the 2% alkaline glutaraldehyde exposure time, frequent replacement of the glutaraldehyde, and disinfection of the machine, failed to eradicate the M. chelonae, presumably because of the presence of a biofilm inside the machine. Rinsing the scopes with 70% alcohol after automated disinfection eliminated the outbreak strain. This study demonstrates that automated bronchoscope disinfecting machines may become heavily contaminated with mycobacteria that resist usual disinfection, resulting in a source of bronchoscope contamination.
Bronchoscopes↗
Bulky extramedullary plasmacytomata: rare mode of relapse in myelomatosis.
In two cases of myelomatosis relapse was accompanied by the development of bulky extramedullary plasma cell tumours, which created serious management problems. In both cases the histology was of a poorly differentiated plasmacytoid tumour with frequent mitoses. In one case paraprotein had completely disappeared from the serum and urine after six months' treatment with melphalan alone but did not correlate with improved survival. It is concluded that extramedullary spread of myelomatosis in the form of bulky tumour deposits is a rare and ominous mode of tumour progression or relapse. Rises in serum and urinary paraprotein concentrations are not the inevitable signs of relapse.
Cecal Neoplasms↗
Possible mechanism of the synergistic effect of heparin and dihydroergotamine.
A combination of heparin and dihydroergotamine mesylate (Heparin-Dihydergot) has been shown to be more effective than either of these drugs alone in preventing postoperative venous thromboembolism. The possible mechanism for the synergistic effect of heparin and dihydroergotamine was assessed. Phlebograms obtained after administration of 0.5 mg of dihydroergotamine showed marked constriction of the tibial and soleal veins with a significant reduction in the mean diameter of the femoral vein. The effect on the coagulation mechanism was assessed in 28 patients. Blood samples were withdrawn from the femoral vein during varicose vein operations. A significant difference was observed in antithrombin III activity, kaolin-cephalin clotting time, beta-thromboglobulin, and fibrino-peptide levels between the control, dihydroergotamine, heparin, and the combination groups.
Antithrombin III↗
Use of molecular and reference susceptibility testing methods in a multicenter evaluation of MicroScan dried overnight gram-positive MIC panels for detection of vancomycin and high-level aminoglycoside resistances in enterococci.
Modified MicroScan gram-positive MIC no. 8 panels (PM-8) were analyzed for their improved ability to detect vancomycin resistance (VR) and high-level aminoglycoside resistance (HLAR) in enterococci. A validation study design that utilized selected challenge strains, recent clinical isolates, and reproducibility experiments in a multicenter format was selected. Three independent medical centers compared the commercial panels to reference broth microdilution panels (RBM) and Synergy Quad Agar (QA). Resistance was verified by demonstration of VR and HLAR genes by PCR tests. The study was conducted in three phases. (i) In the challenge phase (CP), two well-characterized sets of enterococci were obtained from the Centers for Disease Control and Prevention; one set contained 50 isolates for VR testing and one contained 48 isolates for HLAR testing. In addition, a set of 47 well-characterized isolates representing diverse geographic areas, obtained from earlier national surveillance studies, was tested at the University of Iowa College of Medicine (UICM). (ii) In the efficacy phase (EP), each laboratory tested 50 recent, unique clinical isolates by all methods. (iii) In the reproducibility Phase (RP), each laboratory tested the same 10 strains by all methods in triplicate on three separate days. All isolates from the EP were sent to the UICM for molecular characterization of vanA, -B, -C1, -C2-3, and HLAR genes. In the CP, the ranking of test methods by error rates (in parentheses; very major and major errors combined, versus PCR results) were as follows: for high-level streptomycin resistance (HLSR), QA (12.0%) > PM-8 (5.2%) > RBM (1.6%); for high-level gentamicin resistance (HLGR), RBM (3.7%) > PM-8 (3.1%) > QA (2.6%); and for VR, RBM = QA (3.0%) > PM-8 (1.2%). In the EP, agreement between all methods and the reference PCR result was 98.0% for HLSR, 99.3% for HLGR, and 98. 6% for VR. In the RP, the percentages of results +/- 1 log2 dilution of the all-participant mode were as follows: for VR, 100% (PM-8), 98.9% (QA), and 90.0% (RBM); for HLSR, 99.6% (RBM), 98.5% (PM-8), and 82.2% (QA); and for HLGR, 99.6% (RBM), 99.3% (PM-8), and 98.1% (QA). The ability of the PM-8 to detect VR and HLAR in enterococci was comparable to those for reference susceptibility and molecular PCR methods and was considered acceptable for routine clinical laboratory use.
Anti-Bacterial Agents↗
Single-dose pharmacokinetics of sodium ferric gluconate complex in iron-deficient subjects.
STUDY OBJECTIVES: To determine the single-dose pharmacokinetics of intravenous sodium ferric gluconate complex in sucrose injection (SFGC) in iron-deficient human volunteers, and to assess iron transport. DESIGN: Open-label, randomized study. SETTING: Clinical research facility. SUBJECTS: Fourteen iron-deficient men and women. INTERVENTIONS: Subjects were randomized to receive a single intravenous dose of either SFGC 62.5 mg administered over 30 minutes or SFGC 125 mg over 60 minutes. Five days later, the same subjects were rerandomized to receive a second intravenous dose of SFGC, either 62.5 mg administered over 4 minutes or 125 mg over 7 minutes. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected at predefined times before, during, and up to 72 hours after the infusion to determine the single-dose pharmacokinetics of SFGC. Assays were performed for both total iron and transferrin-bound iron, from which drug-bound iron could be calculated. Urine was collected over 24 hours before dosing and for 24 hours after the start of infusion to determine the renal elimination of iron. Clearance of SFGC from serum was rapid and far exceeded rates reported for iron dextran. Pharmacokinetic parameters were unaffected by dose or infusion rate. Serum iron derived from SFGC did not exceed the binding capacity of transferrin. Serum iron from SFGC became rapidly available (< 24 hrs) as transferrin-bound iron, but only after passage through another compartment, presumably the reticuloendothelial system (RES). At least 80% of the administered iron was transported to bone marrow within 24 hours after infusion. CONCLUSIONS: Iron derived from SFGC appears to be rapidly transferred to a bioavailable iron compartment as transferrin-bound iron after digestion in the RES. At the doses administered in this study, liberation of potentially toxic, free iron was not detectable.
Adult↗
Mercury contamination incident.
BACKGROUND: The aim of this paper is to describe an incident where elemental mercury led to widespread contamination and the exposure of 225 individuals and confirmed toxicity in 19 individuals. The paper describes the incident and difficulties found in trying to assess the risk to individuals and to identify and decontaminate the residences involved. METHODS: All individuals exposed to elemental mercury in the incident were followed up for 15 months. RESULTS: Thirty-seven individuals were found to be 'at risk' and 13 were symptomatic of mercury poisoning. Five patients required chelation therapy. The incident was closed when the risk of poisoning and re-exposure was minimized. CONCLUSION: Incident management depends on early effective communication and collaboration between all agencies involved.
Adolescent↗
A prospective randomized trial comparing manual and automated endoscope disinfection methods.
OBJECTIVE: To compare the efficacy of endoscope disinfection using automated and manual systems. DESIGN: Prospective randomized trial. SETTING: A 1,000-bed tertiary care referral center. METHODS: All endoscopes underwent a three-stage decontamination process including brushing and cleaning with water and detergent, manual or automated disinfection with 2% glutaraldehyde, and 70% alcohol rinse with forced air drying. Cultures were obtained from endoscopes from both groups before and after alcohol rinse and then after overnight storage. RESULTS: Cultures from 8/30 (27%) automated and 11/30 (37%) manually disinfected (P = 0.58) endoscopes grew gram-negative bacteria and/or nontuberculous mycobacteria before the alcohol rinse. After alcohol rinse, 3 (10%) of 30 automated and 8 (27%) of 30 manually disinfected endoscopes remained contaminated (P = 0.28). Manually disinfected endoscopes were contaminated more frequently with coliform bacteria, whereas endoscopes undergoing automated disinfection were more frequently contaminated with nontuberculous mycobacteria, but the differences were not statistically significant. After alcohol rinse and forced air drying, there was no difference in contamination rates between freshly disinfected endoscopes and those stored overnight (7/30 (23%) versus 4/30 (13%), P = 0.50). Colonoscopes and duodenoscopes were contaminated more often than gastroscopes (P = 0.00001). CONCLUSION: The persistent endoscope contamination after manual and automated disinfection indicates the importance of developing more reliable and effective disinfection methods.
Automation↗
Analysis of two translocation breakpoints and identification of a negative regulatory element in patients with Rieger's syndrome.
BACKGROUND: Rieger's syndrome is an autosomal dominant disorder characterized by eye, tooth, and umbilical anomalies. A gene responsible for Rieger's syndrome, PITX2, has previously been cloned using two patients with balanced translocations, t(4;16) and t(4;11), with breakpoints that lie near the gene, but which do not interrupt it. METHODS: We sequenced both breakpoint regions on chromosome 4 and screened this area for novel genes. Fluorescence in situ hybridization (FISH) was used to determine if PITX2 was still present on the 4:16 chromosome. Both the chromosome 16 and chromosome 11 breakpoints were cloned and sequenced using panhandle polymerase chain reaction (PHPCR). Transient transfection studies were performed to compare effects on a reporter gene between native chromosome 4 sequence and chromosome 11 sequence. RESULTS: The region surrounding PITX2 on chromosome 4 is rich in repetitive elements, but no novel genes were identified. FISH demonstrated that PITX2 was intact on the 4:16 translocation chromosome. The PHPCR experiments demonstrated that the translocated regions of chromosomes 16 and 11 were repeat-rich, and transfection studies revealed a slight enhancer effect with the chromosome 4 sequence, and a strong silencer effect when the chromosome 11 sequence was present. CONCLUSIONS: Given the lack of any novel genes near either breakpoint, changes in potential regulatory elements may be the best model to explain the loss of PITX2 expression in these patients and hence the Rieger's syndrome phenotype.
Abnormalities, Multiple↗
The neutron therapy clinical programme at the National Accelerator Centre (NAC).
A total of 721 patients were treated in the neutron therapy programme at NAC from February 1989-March 1995 with a p(66)/Be isocentric unit. The preliminary results showed: 3-year local control and survival probabilities of 57 and 79% respectively for advanced salivary gland tumours; increased local control for twice-daily neutron therapy for advanced head and neck cancer compared with photon therapy; local control rates of 68 and 83% for locally advanced breast cancer treated with 17 and 19 Gy respectively; complete response rates of 67% for macroscopic residual soft tissue sarcomas and those with irresectable disease of less than 10 cm; complete response rate of 56% for macroscopic residual uterine sarcoma with a median follow up of 38 months; 2-year local control rate and survival of 44 and 38% respectively for advanced squamous carcinoma of the maxillary antrum; complete response rate of 38% for advanced osteosarcomas and chondrosarcomas.
Breast Neoplasms↗
Diagnostic and phylogenetic perspectives of the 2023 Murray Valley encephalitis virus outbreak in Australia: an observational study.
BACKGROUND: An outbreak of Murray Valley encephalitis virus (MVEV), the largest since 1974, was observed in Australia between Jan 1 and July 31, 2023. This study aims to characterise the utility of diagnostic platforms, testing algorithms, and genomic characteristics of MVEV to facilitate a comprehensive framework for MVEV testing and surveillance in the outbreak setting. METHODS: In this observational study, we assessed flavivirus diagnostics for all patients with suspected Murray Valley encephalitis in Australia from Jan 1 to July 31, 2023. We included all patients with confirmed Murray Valley encephalitis, probable Murray Valley encephalitis, or acute unspecified flavivirus infection using the Communicable Diseases Network Australia case definition. Cases were excluded if an alternative diagnosis was identified. We collected blood, serum, cerebrospinal fluid, brain tissue, urine, or a combination of these samples, as appropriate and at the discretion of the treating clinician. We conducted multimodal diagnostic testing, which included flavivirus-specific serological and nucleic acid amplification testing. Metagenomic next-generation sequencing, including next-generation deep sequencing, target-enrichment, and targeted amplification, was conducted on human and representative mosquito-derived samples obtained from established mosquito population surveillance programmes for phylogenetic analysis. FINDINGS: 27 patients with encephalitis were assessed for MVEV between Jan 1, 2023, and July 31, 2023, 23 (85%) of whom fulfilled national case definitions for confirmed Murray Valley encephalitis. Patient ages ranged from 6 weeks to 83 years (median 62·0 years [IQR 31·0-67·5]) and patients were mostly male (21 [78%] male patients and six [22%] female patients). Incidence varied widely by geographical region and was highest in the Northern Territory (32·0 per 1 000 000 population). Diagnostic specimen collection generally occurred promptly (median 6·0 days [IQR 4·0-14·5] from symptom onset to diagnostic specimen collection). In seven patients, case assignation relied on convalescent serum samples to assess for seroconversion or an appropriate rise in antibody titre (to four times the initial value or greater), or both. MVEV-specific IgM was detectable in serum samples of 17 (81%) of 21 patients tested by day 7 and MVEV IgG or total antibody (TAb) were detected in 18 (100%) of 18 patients tested by day 30. MVEV-specific IgM (or TAb) and MVEV RNA were detected in cerebrospinal fluid collected within 14 days of symptom onset in nine (39%) of 23 patients and seven (28%) of 25 patients, respectively. Phylogenetic analysis revealed two circulating MVEV genotypes, G1A and G2, in mosquitoes and humans in 2023. In southeast Australia, only G1A was detected and probably introduced from enzootic foci in northern Australia. INTERPRETATION: This study provides a comprehensive overview of the diagnostic workflows and phylogenetic evaluations used during the 2023 MVEV outbreak in Australia, emphasising the importance of a multimodal approach for accurate and timely confirmation of flavivirus infection. Further One Health surveillance for MVEV and other zoonotic flaviviruses is key, given potential expanded ecological niches in the context of episodic climatic events. FUNDING: None.
Humans↗
Modification of glucocorticoid-induced changes in myofibrillar protein turnover in rats by protein and energy deficiency as assessed by urinary excretion of Ntau-methylhistidine.
The effects of differing degrees of experimental protein-energy malnutrition on the response of myofibrillar protein turnover rates to administration of corticosteroid has been studied in two experiments on rats. The basal control diet, offered ad lib. in each case, contained 40 g protein/kg, and other groups received diets containing 62 X 5, 95 or 220 g protein/kg at 0 X 67, 1 or 1 X 5 times the level of the control energy intake. Daily administration of 25 or 30 mg corticosterone/kg body-weight after 18 d pre-feeding caused an increase in plasma protein, glucose and insulin concentrations, but a decrease in the corticosterone: insulin values. Liver size and protein content increased, as did the fractional excretion of dietary nitrogen as urea-N in all treated groups. However, whereas a fall in food intake and body-weight occurred in one experiment the reverse occurred in the other. Ntau -Methylhistidine excretion was 12% lower for rats receiving 40 v. 220 g protein/kg diet and excretion was increased by only 57 v. 90% respectively, when the two groups of rats were given 30 mg corticosterone/kg per d. Rats which received 25 mg corticosterone/kg per d and up to 95 g protein/kg diet increased excretion of Ntau -methylhistidine by an average 35%. The fractional degradation rate of myofibrillar protein (kd) was reduced by about 10% by the low-protein diet from 3 X 1 to 2 X 8%/d. During corticosterone treatment the increment in kd for rats on this diet was only 60% of that for rats receiving the 220 g protein/kg diet, i.e. an increase of 1 X 8 v. 3 X 0%/d. Energy restriction further reduced kd during low-protein intake but did not affect the response to the corticosterone. Variations in dietary protein from 40 to 95 g/kg had little effect on the increase in kd during steroid treatment. The effect of corticosterone on calculated synthesis rates (ks) differed markedly between experiments. While ks fell by 50-65% in rats which lost weight on treatment, it rose by up to 60% in rats where carcass non-collagen-protein accretion remained unchanged or increased, despite an increase in kd. Protein deficiency decreases the catabolic response to glucocorticoid, but the net metabolic response appears crucially dependent on changes in food intake or the stage of growth of the rat or both. A net anabolic response with increased fractional rates of myofibrillar protein breakdown, synthesis and accretion was observed in growing rats fed on relatively-low-protein diets and given 25 mg corticosterone/kg per d.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗