Use of complementary markers in assessing glycaemic control in people with diabetic kidney disease undergoing iron or erythropoietin treatment.

AIMS: HbA(1c) values are unreliable in patients with diabetes who have chronic kidney disease who receive iron and/or erythropoiesis stimulating agents. The study aimed to evaluate the utility of the complementary glycaemic markers glycated albumin, fructosamine and 1,5 anhydroglucitol in this group of patients. METHODS: A prospective study of patients with Type 2 diabetes and chronic kidney disease stage IIIB/IV undergoing intravenous iron or erythropoiesis-stimulating agent therapy. Glycaemic control was monitored using HbA(1c), seven-point daily glucose thrice weekly, continuous glucose monitoring, glycated albumin, fructosamine and 1,5 anhydroglucitol. RESULTS: Fifteen patients [9 men; median age 72 years (interquartile range 68-74), follow-up period (16.4 ± 3.7 weeks)] received parenteral iron; 15 patients [11 men; 70 years (interquartile range 62-75), (17.3 ± 3.3 weeks)] received erythropoiesis-stimulating agent. HbA(1c) fell following treatment with both iron [57 mmol/mol (7.4%) to 53 mmol/mol (7.0%), P < 0.001] and erythropoiesis-stimulating agent [56 mmol/mol (7.3%) to 49 mmol/mol (6.6%), P = 0.01] despite mean blood glucose remaining unchanged (iron: 9.55 to 9.71 mmol/l, P = 0.07; erythropoiesis-stimulating agent: 8.72 to 8.78 mmol/l, P = 0.89). Unlike HbA1c , the glycated albumin, fructosamine and 1,5 anhydroglucitol levels did not change following iron [glycated albumin (16.8 to 16.3%, P = 0.10); fructosamine (259.5 to 256 µmol/l, P = 0.89); 1,5 anhydroglucitol (54.2 to 50.9 µmol/l, P = 0.89)] or erythropoiesis-stimulating agent [glycated albumin (17.9 to 17.5%, P = 0.29), fructosamine (324.3 to 306.0 µmol/l, P = 0.52), 1,5 anhydroglucitol (58.2 to 46.7 µmol/l, P = 0.35)]. Despite this, HbA(1c) was consistently the marker most closely related to mean blood glucose before and after each treatment (R range 0.7-0.88). CONCLUSIONS: These data indicate that HbA(1c) was statistically most closely related to mean blood glucose, but clinical trends in glycaemia in patients undergoing iron or erythropoiesis-stimulating agent therapy are likely best assessed by including one of these additional glycaemic markers.

Two cases of self-limiting nephropathies secondary to dengue haemorrhagic fever.

We report two cases of dengue haemorrhagic fever which developed self-limiting gross nephrotic-range proteinuria. One patient was a 32-year-old Bangladeshi and the other a 42-year-old Chinese national. Both patients did not have manifestations of renal damage, such as increase in serum creatinine, haematuria or urinary casts. Gross nephrotic-range proteinuria, which was self-limiting due to dengue haemorrhagic fever, has not been previously reported in Singapore. We postulate that this nephrotic-range proteinuria is a manifestation of increased glomerular leakage of protein, due to glomerulonephritis associated with dengue haemorrhagic fever.

Problems related to epidural analgesia for postoperative pain control.

INTRODUCTION: Epidural analgesia provides excellent analgesia after major surgery but it is not without adverse effects. This retrospective study aims to evaluate the efficacy of analgesia and the problems commonly encountered postoperatively. MATERIALS AND METHODS: Elective surgical patients who had epidural catheters inserted perioperatively intended for postoperative analgesia over a 1-year period were studied. Anaesthetic charts and daily records of patient evaluation by the Acute Pain Service (APS) for pain relief, side effects and their subsequent management were analysed. RESULTS: A total of 471 patients had epidural catheters inserted for postoperative analgesia. Ninety per cent of patients received continuous local anaesthetic infusion (75% ropivacaine and 15% bupivacaine) and 10% received intermittent morphine boluses. There were few serious complications but 60% of patients required one or more interventions by the APS, mainly for inadequate analgesia. One-third of patients had their epidural analgesia terminated prematurely due to inadequate analgesia (14.2%), shortage of beds in the high-dependency unit (14%) and other complications. Only 19% of patients had no reported adverse effects. CONCLUSION: Although the incidence of serious complications was low, there was a high incidence of minor adverse effects especially during the first 48 hours. This emphasises the importance of close monitoring during the early postoperative period and the APS in the management of side effects, especially inadequate analgesia.

Microfluidic arrays of fluid-fluid diffusional contacts as detection elements and combinatorial tools.

This paper describes microfluidic systems that can be used to investigate multiple chemical or biochemical interactions in a parallel format. These three-dimensional systems are generated by crossing two sets of microfluidic channels, fabricated in two different layers, at right angles. Solutions of the reagents are placed in the channels; in different modes of operation, these solutions can be either flowing or stationary-the latter is important when one set of channels is filled with viscous gels with immobilized reagents. At every crossing, the channels are separated either by a single membrane or by a composite separator comprising a membrane, a microwell, and a second membrane. These components allow diffusive mass transport and minimize convective transport through the crossing. Polycarbonate membranes with 0.1-1-microm vertical pores were used to fabricate the devices. Each crossing of parallel channels serves as an element in which chemical or biochemical interactions can take place; interactions can be detected by monitoring changes in fluorescence and absorbance. These all-organic systems are straightforward to fabricate and to operate and may find applications as portable microanalytical systems and as tools in combinatorial research.

Patient-controlled sedation with propofol for colonoscopy.

BACKGROUND: Patient-controlled sedation (PCS) allows the patient to titrate the dosage of sedative drugs according to need. METHODS: To compare the efficacy of PCS by using propofol with anesthetist-administered midazolam during colonoscopy, 88 patients were randomized to receive either intravenous midazolam 0.05 mg/kg bolus (1 mg increments as required) or propofol PCS (0.3 mg/kg bolus, zero lockout). Heart and respiratory rates, blood pressure, and oxygen saturation were monitored. Patient cooperation, endoscopist satisfaction, and level of sedation were scored. Patient satisfaction was assessed by questionnaire. To correct for multiple testing of data, statistical significance was asserted only for individually stated p values with p < 0.01. RESULTS: Oxygen saturation and hemodynamics were stable in both groups. Better patient cooperation (good vs. minimal; p = 0.008) and higher endoscopist satisfaction (very good vs. good; p = 0.001) were achieved with PCS. Although more sedated intraoperatively (sedation score 4 vs. 2; p = 0.03 for a single test of hypothesis; correction for multiple testing of data removes this significance), patients in the propofol PCS group were more alert by 30 minutes and discharged earlier (mean and SD times were 43.3 [12.1] min compared with 61.0 [29.7] min; p = 0.001.) More patients in the PCS group (86 vs. 6l%; p < 0.001) were satisfied with their overall level of comfort. CONCLUSION: PCS with propofol is effective and results in high patient satisfaction and faster discharge.

Inhaling nitrous oxide reduces the induction dose requirements of propofol.

Inhaling nitrous oxide (N(2)O) before propofol induction appears to decrease propofol usage. To investigate the efficacy of N(2)O as a component of the drugs used to induce anesthesia, the effect of inhaling a N(2)O:oxygen (O(2)) mixture on the dose of propofol required to induce anesthesia was determined in a double-blinded manner. We randomized 117 unpremedicated patients scheduled for elective surgery into three groups. Group FN received 1 microg/kg fentanyl and breathed 4 L/min N(2)O + 2 L/min O(2). Group PN received placebo and breathed 4 L/min N(2)O + 2 L/min O(2). Group FO received 1 microg/kg fentanyl and breathed 6 L/min O(2). Propofol was infused at 20 mg/min after 1 min of gas mixture inhalation, and the infusion stopped when there was loss of response to verbal command. The mean (SD) propofol dose was 0.75 (0.30), 0.84 (0.26), and 1.33 (0.51) mg/kg, and the induction time 133 (57), 142 (47), and 226 (78) s for Groups FN, PN, and FO, respectively. We conclude that inhalation of 66% N(2)O in O(2) 1 min before the IV induction of anesthesia with propofol at 20 mg/min, reduces the induction dose of propofol by 44% and decreases the time required for the induction of anesthesia (P < 0.001).

Isolation and characterization of cDNA clones corresponding with mRNAs that accumulate during auxin-induced lateral root formation.

Lateral root formation in root cultures of Arabidopsis thaliana can be initiated by exogenous addition of auxin. In order to find cDNA clones of which the corresponding mRNAs accumulate during this process, a cDNA library was constructed from root cultures treated with the active auxin 1-naphthaleneacetic acid (1-NAA). Differential screening of this library with cDNA probes derived from mRNA populations isolated from root cultures treated with 1-NAA and the inactive analogue 2-naphthaleneacetic acid (2-NAA) led to the isolation of four cDNA clones, designated AIR1, AIR3, AIR9 and AIR12. Accumulation of the mRNAs starts between 4 and 8 h and continues till at least 24 h after addition of an active auxin. Sequence analysis revealed that AIR1 encodes a protein that is related to a large family of proteins that consist of a proline-rich or glycine-rich N-terminus and a hydrophobic, possibly membrane spanning C-terminus. The putative function of these proteins is coupling of the cell wall to the plasma membrane. Surprisingly, AIR1 lacks the proline-rich or glycine-rich N-terminus which is thought to be important for interaction with the cell wall. AIR3 encodes a subtilisin-like serine protease which is believed to be active outside the plant cell. Although AIR9 and AIR12 do not show any significant homology to sequences in the database, they are also predicted to function outside the cell. Our screening thus indicates that a variety of genes encoding extracellular proteins are activated during auxin-induced lateral root formation.

Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair.

The XPC-HR23B complex is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). Its function is unknown. Using a novel DNA damage recognition-competition assay, we identified XPC-HR23B as the earliest damage detector to initiate NER: it acts before the known damage-binding protein XPA. Coimmunoprecipitation and DNase I footprinting show that XPC-HR23B binds to a variety of NER lesions. These results resolve the function of XPC-HR23B, define the first NER stages, and suggest a two-step mechanism of damage recognition involving damage detection by XPC-HR23B followed by damage verification by XPA. This provides a plausible explanation for the extreme damage specificity exhibited by global genome repair. In analogy, in the transcription-coupled NER subpathway, RNA polymerase II may take the role of XPC. After this subpathway-specific initial lesion detection, XPA may function as a common damage verifier and adaptor to the core of the NER apparatus.

Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity.

XPC-hHR23B protein complex is specifically involved in nucleotide excision repair (NER) of DNA lesions on transcriptionally inactive sequences as well as the nontranscribed strand of active genes. Here we demonstrate that not only highly purified recombinant hHR23B (rhHR23B) but also a second human homolog of the Saccharomyces cerevisiae Rad23 repair protein, hHR23A, stimulates the in vitro repair activity of recombinant human XPC (rhXPC), revealing functional redundancy between these human Rad23 homologs. Coprecipitation experiments with His-tagged rhHR23 as well as sedimentation velocity analysis showed that both rhHR23 proteins in vitro reconstitute a physical complex with rhXPC. Both complexes were more active than free rhXPC, indicating that complex assembly is required for the stimulation. rhHR23B was shown to stimulate an early stage of NER at or prior to incision. Furthermore, both rhHR23 proteins function in a defined NER system reconstituted with purified proteins, indicating direct involvement of hHR23 proteins in the DNA repair reaction via interaction with XPC.