Utility of initial bolus insulin in the treatment of diabetic ketoacidosis.

Current guidelines for treatment of diabetic ketoacidosis (DKA) recommend administration of an intravenous bolus dose of insulin followed by a continuous infusion. This study was designed to investigate whether the initial bolus dose is of significant benefit to adult patients with DKA and if it is associated with increased complications. This was a non-concurrent, prospective observational cohort study of adult patients who presented with DKA in a 12-month period. Charts were divided into two groups depending on whether they received an initial bolus dose of insulin. Data on glucose levels, anion gap (AG), intravenous fluid administration (IVF), and length of stay (LOS) were collected. Primary outcome was hypoglycemia (need for administration of 50% dextrose). Of 157 charts, 78 received a bolus of insulin and were designated the treatment group, the remaining 79 formed the control group. Groups were similar at baseline and received equivalent IVF and insulin drips. There were no statistically significant differences in the incidence of hypoglycemia (6% vs. 1%, respectively, p = 0.12), rate of change of glucose (60 vs. 56 mg/dL/h, respectively, p = 0.54) or AG (1.9 vs. 1.9 mEq/L/h, respectively, p = 0.66), LOS in the Emergency Department (8 vs. 7 h, respectively, p = 0.37) or hospital (5.6 vs. 5.9 days, p = 0.81). Equivalence testing revealed no clinically relevant differences in IVF change, rate of change of glucose, or AG. Administration of an initial bolus dose of insulin was not associated with significant benefit to patients with DKA and demonstrated equivalent changes in clinically relevant endpoints when compared to patients not administered the bolus.

A randomized, double-blind, prospective study comparing the efficacy of continuous versus pulsed radiofrequency in the treatment of lumbar facet syndrome.

STUDY OBJECTIVES: To compare the efficacy of continuous radiofrequency (CRF) thermocoagulation with pulsed radiofrequency (PRF) in the treatment of lumbar facet syndrome. DESIGN: Prospective, randomized, double-blinded study. SETTING: Ambulatory pain clinic at a level-I trauma center and teaching institution. PATIENTS: 50 ASA physical status I, II, and III patients, at least 18 years of age, scheduled to undergo CRF or PRF for lumbar back pain. INTERVENTIONS: Target facet joints were identified with oblique radiographic views. Continuous radiofrequency thermocoagulation was delivered at 80 degrees C for 75 seconds, while PRF was delivered at 42 degrees C with a pulse duration of 20 ms and pulse rate of two Hz for 120 seconds. MEASUREMENTS: Visual analog scale (VAS) pain assessment and Oswestry Low Back Pain and Disability Questionnaire (OSW) were administered at baseline and then at three months. Comparisons between groups and within groups were made of the relative percentage improvement in VAS and OSW scores. MAIN RESULTS: No significant differences in the relative percentage improvement were noted between groups in either VAS (P = 0.46) or OSW scores (P = 0.35). Within the PRF group, comparisons of the relative change over time for both VAS (P = 0.21) and OSW scores (P = 0.61) were not significant. However, within the CRF group, VAS (P = 0.02) and OSW scores (P = 0.03) showed significant improvement. CONCLUSIONS: Although there was no significant difference between CRF and PRF therapy in long-term outcome in the treatment of lumbar facet syndrome, there was a greater improvement over time noted within the CRF group.

Effective lactate clearance is associated with improved outcome in post-cardiac arrest patients.

INTRODUCTION: Early, effective lactate clearance has been shown to be associated with improved mortality in patients with trauma, burns, and sepsis. We investigated whether early, high lactate clearance was associated with reduced mortality in post-cardiac arrest patients. METHODS: We performed a retrospective analysis of post-cardiac arrest patients in an urban emergency department. Inclusion criteria included pre-hospital cardiac arrest patients over the age of 18. Exclusion criteria were traumatic arrest, successful resuscitation prior to the arrival of emergency medical services, and cardiac arrest in the presence of pre-hospital providers. Primary endpoints consisted of survival to 24h and survival to hospital discharge. RESULTS: A total of 79 patients were analyzed with a mean age of 64+/-17 and mean APACHE II score of 37.7+/-5. Of the 79 patients, 27 (34%) died within 24h and 66 (84%) died during the hospital course. The mean initial lactate level for the overall group was 15+/-5.2mmol/dl with a mean lactate of 14.4+/-5.1mmol/dl in the survivors and 16+/-5.3mmol/dl in the non-survivors (p>0.05). Lactate clearance at both 6 and 12h was significantly higher for both 24-h and overall in-hospital survival (p<0.05). A multivariable analysis showed that high lactate clearance at 12h was predictive of 24-h survival (p<0.05). CONCLUSIONS: Early, effective lactate clearance is associated with decreased early and overall in-hospital mortality in post-cardiac arrest patients. These findings suggest that post-arrest tissue hypo-perfusion plays in an important role in early as well as overall mortality.

Performance verification of the Maxwell 16 Instrument and DNA IQ Reference Sample Kit for automated DNA extraction of known reference samples.

Advances in automation have been made for a number of processes conducted in the forensic DNA laboratory. However, because most robotic systems are designed for high-throughput laboratories batching large numbers of samples, smaller laboratories are left with a limited number of cost-effective options for employing automation. The Maxwell 16 Instrument and DNA IQ Reference Sample Kit marketed by Promega are designed for rapid, automated purification of DNA extracts from sample sets consisting of sixteen or fewer samples. Because the system is based on DNA capture by paramagnetic particles with maximum binding capacity, it is designed to generate extracts with yield consistency. The studies herein enabled evaluation of STR profile concordance, consistency of yield, and cross-contamination performance for the Maxwell 16 Instrument. Results indicate that the system performs suitably for streamlining the process of extracting known reference samples generally used for forensic DNA analysis and has many advantages in a small or moderate-sized laboratory environment.

Polycyclic aromatic hydrocarbon-DNA adducts in prostate cancer.

The formation of DNA adducts can lead to DNA replication errors and the potential for carcinogenesis. DNA adducts have been detected in prostate cells, but the distribution of adducts with respect to prostate cancer risk factors and histology is unknown. In a study of 130 Caucasian (n = 61) and African-American (n = 69) men with prostate cancer who underwent radical prostatectomy, we quantified polycyclic aromatic hydrocarbon (PAH)-DNA adducts in prostate tumor and adjacent nontumor cells by immunohistochemistry. A strong correlation between paired adduct levels in the two cell types was observed (r = 0.56; P < 0.0001); however, nontumor cells had a significantly higher level of adducts compared with tumor (0.30 absorbance units +/- 0.05 versus 0.17 absorbance units +/- 0.04; P < 0.0001). Variables significantly associated with PAH-DNA adduct levels in tumor cells included primary Gleason grade, tumor volume, and log-transformed prostate-specific antigen (PSA) at time of diagnosis. Tumors with a primary Gleason grade of 5 had significantly lower PAH-DNA adduct levels than tumor cells with a primary Gleason grade of 3 or 4 (P < 0.0001 for both). Tumors that involved 10% or less of the prostate gland had significantly higher PAH-DNA adduct levels than tumors that involved 15 to 20% of the prostate gland (P = 0.004). PSA levels were inversely associated with PAH-DNA adduct levels in tumor cells (P = 0.009). A similar, albeit less significant, inverse association was observed between PSA and PAH-DNA adduct levels in nontumor cells (P = 0.07). Interestingly, increasing primary Gleason grade was associated with increasing PAH-DNA adduct levels in adjacent nontumor cells (P = 0.008). Our results show that PAH-DNA adducts are present in the prostate but vary with regard to cellular histology. In prostate tumor cells, decreased cellular differentiation and increased tumor proliferation may reduce PAH-DNA adduct levels.

Is screening for urine infection in well infants with prolonged jaundice required? Local review and meta-analysis of existing data.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) neonatal jaundice guidance recommends a urine culture for investigation of babies with prolonged jaundice. However, the evidence cited for this guidance is limited. We aimed to review local data and the existing literature to identify evidence to either support or refute this guidance. METHOD: We retrospectively reviewed 3 years of urine cultures from our outpatient prolonged jaundice clinic. We then conducted literature review with meta-analysis of studies presenting original data on urine tract infection (UTI) rates in jaundiced and prolonged jaundiced babies. RESULTS: From our local data, none of the 279 patients met our unit clinical criteria for UTI. Literature review revealed considerable differences worldwide in UTI rates in both jaundiced and prolonged jaundiced cases. Using pooled data from our literature review and our local population, the incidence of UTI in prolonged jaundiced babies is 0.21% (95% CI 0.0% to 0.73%) in the UK. This is significantly lower than the figure indicated from the data from elsewhere in the world, 8.21% (95% CI 4.36% to 13.0%). CONCLUSIONS: The findings both from our local data and the current literature do not support the practice of routine screening for urine infection in well babies with prolonged jaundice. In view of the above, we no longer include urine culture in screening of well infants with prolonged jaundice. We hope that NICE will re-examine the evidence and recommend changes to their guidance on the role of routine screening for urine infection in babies with prolonged jaundice.

Role of angiotensin II type 2 receptors and kinins in the cardioprotective effect of angiotensin II type 1 receptor antagonists in rats with heart failure.

OBJECTIVES: We studied the role of angiotensin II type 2 (AT(2)) receptors and kinins in the cardioprotective effect of angiotensin II type 1 antagonists (AT(1)-ant) in rats with heart failure (HF) after myocardial infarction. BACKGROUND: The AT(1)-ant is as effective as angiotensin-converting enzyme inhibitors in treating HF, but the mechanisms whereby AT(1)-ant exert their benefits on HF in vivo are more complex than previously understood. METHODS: Brown Norway Katholiek rats (BNK), which are deficient in kinins because of a mutation in the kininogen gene, and their wild-type control (Brown Norway [BN]) underwent myocardial infarction. Two months later, they were treated for two months with: 1) vehicle; 2) AT(1)-ant (L158809, Merck, Rahway, New Jersey); 3) AT(1)-ant + AT(2)-ant (PD-123319, Parke Davis, Ann Arbor, Michigan); or 4) AT(1)-ant + kinin B(2) receptor antagonist (B(2)-ant) (icatibant) (only BN). We measured left ventricular weight (LVW) gravimetrically, myocyte cross-sectional area (MCSA) and interstitial collagen fraction (ICF) histologically, and ejection fraction by ventriculography. RESULTS: Development of HF was comparable in BN and BNK rats. The AT(1)-ant reduced LVW and MCSA and the AT(2)-ant blocked these effects in BN rats, but the B(2)-ant did not. The AT(1)-ant reduced LVW and MCSA in BNK rats, and this effect was reversed by the AT(2)-ant. In BN rats, ICF was reduced and LVEF increased by AT(1)-ant, and both AT(2)-ant and B(2)-ant reversed these effects. In BNK rats, the AT(1)-ant failed to reduce ICF, and its therapeutic effect on LVEF was significantly blunted. CONCLUSIONS: In HF, the AT(2) receptor plays an important role in the therapeutic effects of AT(1)-ant, and this effect may be mediated partly through kinins; however, kinins appear to play a lesser role in the antihypertrophic effect of AT(1)-ant.

SPARC affects glioma cell growth differently when grown on brain ECM proteins in vitro under standard versus reduced-serum stress conditions.

Secreted protein acidic and rich in cysteine (SPARC) has a suppressive effect on U87 glioma cell proliferation when assessed in vitro and in vivo using parental U87T2 and U87T2-derived SPARC-transfected clones. Since SPARCinteracts with extracellular matrix (ECM) proteins, we examined the effect of SPARC secretion on proliferation, morphology, and cell density of glioma cells grown in vitro, in the absence and presence of ECM proteins under standard (10% fetal bovine serum [FBSI) and reduced (0.1% FBS) serum stress conditions. Under standard conditions, MTT (3-(4,5-cimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide) growth curves, morphology, and Western blot analyses demonstrated that SPARC had a suppressive and biphasic effect on growth that was not grossly modulated by the ECMs. The SPARC-induced changes in morphology observed at 24 h were not altered by the presence of ECMs. Under reduced-serum stress conditions, Western blot, morphological, and flow cytometric analyses indicated that the SPARC-induced suppressive growth effects were eliminated when the cells were grown on plastic. However, ECM-specific changes in growth were observed, some of which correlated with secreted SPARC levels. These results indicate that the differential effects of SPARC and ECMs on proliferation are dependent on culture conditions. Since the results obtained under standard conditions agree with our in vivo observations, we conclude that the ability of SPARC to suppress proliferation is regulated to a greater degree by the level of SPARC and that this suppressive effect is not influenced by the presence of any of the ECMs examined.

Short-term outcome after mesh or shouldice herniorrhaphy: a randomized, prospective study.

BACKGROUND: Retrospective analyses have shown that long-term recurrence rates after Lichtenstein mesh and Shouldice herniorrhaphies are low. Therefore differences in short-term outcome may be important determinants of one's choice of repair. Although proponents of the mesh repair claim that their methods is less morbid, to our knowledge no prospective comparative studies of short-term morbidity have been reported. METHODS: One hundred five adult patients were randomized to undergo either a mesh or Shouldice inguinal hernia repair. Postoperative pain, narcotic use, and time to resumption of usual activities and employment were recorded. Patients were blinded to the type of repair received until all data were collected. RESULTS: There was no difference between the herniorrhaphy methods with respect to postoperative pain, duration of narcotic use, and time to resumption of usual activity and employment. Recovery was rapid for both groups of patients. By 3 days after operation, 50% of patients rated their pain as very mild or less and no longer required narcotic analgesics. Patients in both groups returned to usual activity and work by a median of 9 days after operation. CONCLUSION: Both of these well-established methods can be used to repair inguinal hernias with local anesthetics in an outpatient setting with minimal morbidity. Despite the "tension-free" design of the mesh repair, short-term outcomes of mesh and Shouldice repairs of inguinal hernias do not differ.

Use of cellulose powder for the treatment of seasonal allergic rhinitis.

This study was designed to determine whether a unique cellulose powder extract could prevent the classic hay fever attack from occurring among volunteers who have suffered for some years. Nasaleze enhances nasal mucus, which allows the filtration of allergens, to ensure that only clean air reaches the lungs. One hundred two volunteers were recruited and, using a simple 5-point scoring system to grade their general well-being and severity of any hay fever attacks, the overall average score was 3.85, indicating that Nasaleze was able to control hay fever very well. Rapid relief of symptoms was also demonstrated, sometimes within minutes after inhalation. Overall, 77% of volunteers reported a significant reduction in the number of challenges throughout the study period and most graded Nasaleze as more effective and reported fewer side effects than with a wide range of chemical treatments.

Glomerular cytochrome P-450 and cyclooxygenase metabolites regulate efferent arteriole resistance.

Bradykinin dilates efferent arterioles via release of efferent arteriole epoxyeicosatrienoic acids when perfused retrograde (no glomerular autacoids). However, when efferent arterioles are perfused orthograde through the glomerulus, bradykinin-induced dilatation is caused by a balance between: (1) the glomerular vasoconstrictor 20-hydroxyeicosatetraenoic acid and vasodilator prostaglandins, and (2) epoxyeicosatrienoic acids from the efferent arteriole and possibly the glomerulus. However, the role of 20-hydroxyeicosatetraenoic acid has only been studied with a cyclooxygenase inhibitor, which may artificially enhance its production by shunting arachidonic acid into the cytochrome P450 pathway. We hypothesized that in the absence of cyclooxygenase inhibition, bradykinin induces release of 20-hydroxyeicosatetraenoic acid from the glomerulus, which blunts the vasodilator effect of bradykinin; and that prostaglandins released from glomeruli in response to bradykinin are generated by cyclooxygenase-1. Rabbit efferent arterioles preconstricted with norepinephrine were perfused orthograde from the end of the afferent arteriole. Bradykinin was added to the perfusate with or without a 20-hydroxyeicosatetraenoic acid antagonist (20-HEDE), epoxyeicosatrienoic acid synthesis inhibitor (MS-PPOH), and/or cyclooxygenase-1 (SC-58560) or cyclooxygenase-2 inhibitor (NS-398). Bradykinin-dependent dilatation was enhanced by 20-HEDE but blunted by MS-PPOH. When the inhibitors were present, bradykinin-induced dilatation was abolished by blockade of cyclooxygenase-1 but not cyclooxygenase-2. We concluded that: (1) in the absence of cyclooxygenase inhibitors, bradykinin causes the release of a glomerular vasoconstrictor (20-hydroxyeicosatetraenoic acid) that antagonizes the vasodilator effect of epoxyeicosatrienoic acids released from the efferent arteriole and perhaps from the glomerulus, and (2) bradykinin-induced vasodilatation is caused by the release of epoxyeicosatrienoic acids from the efferent arteriole and glomerular metabolites of cyclooxygenase-1.

Inhibition of p38 mitogen-activated protein kinase protects the heart against cardiac remodeling in mice with heart failure resulting from myocardial infarction.

BACKGROUND: Mitogen-activated protein kinases (MAPKs) have emerged as an important pathophysiologic regulator during the development of heart failure (HF). p38 MAPK activity is elevated in cardiac hypertrophy and HF. We used a mouse model of myocardial infarction (MI) to test the hypotheses that (1) inhibition of p38 MAPK activity may improve cardiac function and remodeling after myocardial infarction (MI) and (2) coadministration of a p38 inhibitor (p38i) and an angiotensin-converting enzyme inhibitor (ACEI) may provide only limited further cardioprotection in this model. METHODS AND RESULTS: MI was induced in C57BL/6J mice by ligating the left anterior descending coronary artery and then either left untreated or treated with a p38i (SC-409, 30 mg/kg/day in chow), ACEI (enalapril, 20 mg/kg in drinking water), or p38i plus ACEI for 12 weeks. Echocardiography was performed and systolic blood pressure measured before MI and weekly thereafter. At the end of the study, interstitial collagen fraction (ICF) and myocyte cross-sectional area (MCSA) were examined histologically. We found that p38i significantly increased left ventricular ejection fraction and cardiac output and decreased left ventricular area at diastole, ICF, and MCSA. ACEi and p38i each had similar beneficial effects in this mouse model of HF produced by a large MI. Coadministration of p38i and ACEi did not provide any additional benefit. CONCLUSION: Our data suggest that inhibition of p38 MAPK provides significant cardioprotection in mice with HF post-MI.

Counseling on contraceptives: an unfilled need.

PIP: The dictum that pharmacists have a fundamental responsibility to provide health care information for their patients includes the need to furnish complete and accurate information on all of the contraceptive products that currently are on the market. To help accomplish this, many different resources are available that provide guidance for comprehensive patient education on all the different products and devices. If one agrees to the principle that an individual's sexuality is an accepted element of his or her life, then promoting sexual well-being should be an important part of health care. Yet, it seems that pharmacists and other health care professionals in general have not been particularly liberated about talking about and making objective assessments on sexual matters. Health care professionals seem to need more education to enable them to provide accurate information, to augment their own knowledge bases, and to reduce their inhibitions and possible misconceptions about sexual matters. Pharmacists do not want to appear as if they are encouraging or promoting sexual activity, but, given the consequences of nonuse of contraception, socially responsible pharmacists need to disseminate basic information about the use of contraceptive products. At some level, too, objective guidelines should be established to help pharmacists in handling contraceptive information. Pharmacists can play a key role in counseling on both prescription and nonprescription methods. In fact, pharmacists may be the only health care professionals with whom a sexually active person can speak about nonprescription contraceptive methods. Some pharmacists have been reluctant to provide patient information because of the risk of possible liability. But this attitude seems to be changing. The recent emphasis on clinical functions in pharmacy practice has led to speculation that, as pharmacists come to assume new roles, they may become liable for not providing some of this information. At present, at least 22 states already have guidelines or regulations requiring pharmacists to counsel patients. To provide the most effective learning experience, active participation is the key ingredient. It is necessary to elicit active participation in the counseling process. It is not possible to give complete guidance on the subject of contraceptives to every patient that comes in the store. Nor is every person going to be receptive, at least initially, to the idea of talking about contraception with a pharmacist. Yet, the role of the pharmacist takes on greater significance now because of the controversy that continues to surround some of the safety and efficacy issues of oral contraceptives and IUDs. Brochures and other materials are available to help pharmacists counsel patients on all of the different contraceptive methods.^ieng

Estrogen and testosterone have opposing effects on chronic cardiac remodeling and function in mice with myocardial infarction.

Premenopausal women are much less prone to develop cardiovascular disease than men of similar age, but this advantage no longer applies after menopause. We previously found that male mice have a significantly higher rate of cardiac rupture than females during the acute phase of myocardial infarction (MI); however, the effects of sexual hormones on chronic remodeling are unknown. We hypothesized that estrogen (E) may protect the heart from chronic remodeling and deterioration of function post-MI, whereas testosterone (T) may have adverse effects. Mice (4 wk old) of both genders were divided into four groups: female groups consisted of 1) sham ovariectomy (S-Ovx) + placebo (P) (S-Ovx + P), 2) S-Ovx + T, 3) Ovx + P, and 4) Ovx + T; and male groups consisted of 1) sham castration (S-Cas)+ P (S-Cas + P), 2) S-Cas + 17beta-estradiol (E), 3) Cas + P, and 4) Cas + E. MI was induced 6 wk later. Echocardiography was performed to assess cardiac function and left ventricular dimensions (LVD). Myocyte cross-sectional area (MCSA) was measured at the end of the study. In females, both testosterone and ovariectomy decreased ejection fraction (EF) and increased LVD, and when combined they aggravated cardiac function and remodeling further. Testosterone significantly increased MCSA. In males, castration or estrogen increased EF and reduced LVD, whereas castration significantly reduced MCSA. Our data suggest that estrogen prevents deterioration of cardiac function and remodeling after MI, but testosterone worsens cardiac dysfunction and remodeling and has a pronounced effect when estrogen levels are reduced.

Ratios of charged antiparticles-to-particles near mid-rapidity in Au + Au collisions at sqrt[s(NN)]=130 GeV.

We have measured the ratios of antiparticles to particles for charged pions, kaons, and protons near mid-rapidity in central Au+Au collisions at sqrt[s(NN)] = 130 GeV. We observe / = 1.00+/-0.01(stat)+/-0.02(syst), / = 0.91+/-0.07(stat)+/-0.06(syst), and

/

= 0.60+/-0.04(stat)+/-0.06(syst). The / and

/

ratios give a consistent estimate of the baryo-chemical potential mu(B) of 45 MeV, a factor of 5-6 smaller than in central Pb+Pb collisions at sqrt[s(NN)] = 17.2 GeV.

Charged-particle pseudorapidity density distributions from Au+Au collisions at sqrt[s(NN)]=130 GeV.

The charged-particle pseudorapidity density dN(ch)/d eta has been measured for Au+Au collisions at sqrt[s(NN)] = 130 GeV at RHIC, using the PHOBOS apparatus. The total number of charged particles produced for the 3% most-central Au+Au collisions for /eta/

Pseudorapidity and centrality dependence of the collective flow of charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV.

This paper describes the measurement of collective flow for charged particles in Au+Au collisions at sqrt[s(NN)]=130 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). The measured azimuthal hit anisotropy is presented over a wide range of pseudorapidity (-5.0