Beauty is pain: pediatric burns resulting from hair curling and flat irons.

Ceramic and metal hair straightening and curling irons are common household items which reach up to 450°F in as little as five seconds. Of particular concern is the threat these devices pose to children. Our objective is to characterize and bring attention to this preventable injury in the pediatric population. Retrospective records from a high-volume level I trauma center and regional burn center from 2011-2015 were analyzed. Inclusion criteria were defined as patients <11 years of age, as those presenting with burns above this age were more likely to be utilizing the tools for hair styling. A total of 59 patients were identified with an average age of 2.4 years. The average burn size was 0.30%, with an average 0.24% 2nd degree TBSA. The etiology of the burns included touching a hair iron that was within reach (61%), pulling a hair iron's power cord (15%), stepping/rolling/jumping onto a hair iron left on the ground (17%), and hair irons falling (7%). The majority of households were comprised of unemployed (64%), single (60%) parents. CPS consult was required for 20% of patients. Grafting and excision was necessary for 20% of patients The pediatric population is at risk for accidental burns with household hair irons. These burns typically have a small TBSA, but may require excision and grafting and extended follow-up.

Les lisseurs et fers à friser, en céramique ou en métal, sont des objets courants au domicile. Leur température peut monter à plus de 230°C en quelques secondes. Le risque qu'encourent les enfants est préoccupant. Nous avons explorés ces brûlures afin de déterminer des stratégies de prévention. Nous avons analysé rétrospectivement les données d'un CTB régional, recueillies entre 2011 et 2015. Nous n'avons retenu que les brûlures atteignant les enfants de 11 ans au maximum (59 cas, âge moyen 2,4 ans), les enfants plus âgés étant susceptibles d'utiliser ces instruments à leur propre bénéfice. La surface brûlée était de 0,3 % dont 0,24 % de 2ème degré. La brûlure était consécutive au toucher d'un ustensile atteignable (61%), à la traction sur le cordon d'alimentation (15%), à la marche dessus (17%), à la chute de l'objet (7%). Les familles concernées étaient en majorité monoparentales (60%) sans emploi (64%). Les services de protection de l'enfance ont été sollicités dans 20% des cas. Les enfants sont particulièrement à risque de brûlures lors d'accidents domestiques, pouvant impliquer des fers à friser et des lisseurs. Ces brûlures sont typiquement peu étendues mais peuvent être profondes, nécessiter une greffe et un suivi prolongé.

Quetiapine in overdosage: a clinical and pharmacokinetic analysis of 14 cases.

Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported to and screened by the toxicological laboratory of the Central Hospital Pharmacy The Hague between January 1999 and December 2003. Cases with known suggested amount of intake and medical outcome were included. From the patient's medical record and from the toxicological laboratory findings, patient demographic characteristics (gender, age), details of quetiapine intoxication (estimated time of ingestion, estimated amount of ingestion, and coingested drugs) and clinical parameters were obtained. Severity of intoxication was graded by the Poisoning Severity Score (PSS). Individual pharmacokinetic parameter values were calculated using a one-compartment open model and a Bayesian fitting procedure. Out of a total of 21 intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to 8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood sampling at the emergency ward. The most frequent findings were somnolence and tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%), and severe in 3 patients (21%). Severity of intoxication was not associated with a higher amount of quetiapine intake. The authors found no correlation between the serum concentration of quetiapine and the amount ingested. Elimination t(1/2) was not prolonged. It can be concluded that quetiapine intoxications appear to proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our case series. No fatalities occurred. The severity of clinical symptoms was not associated with either a high serum concentration or the suggested amount ingested of quetiapine.

Chemical and posttranslational modification of Escherichia coli acyl carrier protein for preparation of dansyl-acyl carrier proteins.

Escherichia coli acyl carrier protein (ACP) contains a single tyrosine residue at position 71. The combined o-nitration of apo-ACP Y71 by tetranitromethane and reduction to 3-aminotyrosyl-apo-ACP were performed to introduce a specific site for attachment of a dansyl fluorescent label. Conditions for purification and characterization of dansylaminotyrosyl-apo-ACP are reported. Dansylaminotyrosyl-apo-ACP was enzymatically phosphopantetheinylated and acylated in vitro with an overall approximately 30% yield of purified stearoyl-dansylaminotyrosyl-ACP starting from unmodified apo-ACP. The steady-state kinetic parameters k(cat) = 22 min(-1) and K(M) = 2.7 microM were determined for reaction of stearoyl-dansylaminotyrosyl-ACP with stearoyl-ACP Delta(9)-desaturase. These results show that dansylaminotyrosyl-ACP will function well for studying binding interactions with the Delta(9)-desaturase and suggest similar possibilities for other ACP-dependent enzymes. The efficient in vivo phosphopantetheinylation of E. coli apo-ACP by coexpression with holo-ACP synthase in E. coli BL21(DE3) using fructose as the carbon source is also reported.

Incidence and onset of critical illness polyneuropathy in patients with septic shock.

BACKGROUND: To estimate the incidence and onset of critical illness polyneuropathy (CIP) in patients in septic shock. METHODS: Prospective, observational study, no interventions, in a general 9-bed ICU of a large teaching hospital. Twenty-five patients consecutively admitted to the ICU for treatment of septic shock were studied. Within 72 h of admission to the ICU a complete neurological examination and electromyografic studies were done. Studies were repeated weekly until discharge of ICU or death or CIP confirmed. RESULTS: Nineteen patients developed CIP (76%), with a majority (80%) within 72 h after onset of septic shock. All twenty-two patients with multi organ dysfunction syndrome (MODS) had CIP. The three patients without MODS did not have CIP (P<0.01). CONCLUSIONS: In a group of patients suffering from septic shock the incidence of CIP is high (76%). The onset is early, within 72 h after onset of septic shock. CIP is an early feature of MODS, developing after septic shock.

Probing the photoreaction mechanism of phytochrome through analysis of resonance Raman vibrational spectra of recombinant analogues.

Resonance Raman spectra of native and recombinant analogues of oat phytochrome have been obtained and analyzed in conjunction with normal mode calculations. On the basis of frequency shifts observed upon methine bridge deuteration and vinyl and C(15)-methine bridge saturation of the chromophore, intense Raman lines at 805 and 814 cm(-)(1) in P(r) and P(fr), respectively, are assigned as C(15)-hydrogen out-of-plane (HOOP) wags, lines at 665 cm(-)(1) in P(r) and at 672 and 654 cm(-)(1) in P(fr) are assigned as coupled C=C and C-C torsions and in-plane ring twisting modes, and modes at approximately 1300 cm(-)(1) in P(r) are coupled N-H and C-H rocking modes. The empirical assignments and normal mode calculations support proposals that the chromophore structures in P(r) and P(fr) are C(15)-Z,syn and C(15)-E,anti, respectively. The intensities of the C(15)-hydrogen out-of-plane, C=C and C-C torsional, and in-plane ring modes in both P(r) and P(fr) suggest that the initial photochemistry involves simultaneous bond rotations at the C(15)-methine bridge coupled to C(15)-H wagging and D-ring rotation. The strong nonbonded interactions of the C- and D-ring methyl groups in the C(15)-E,anti P(fr) chromophore structure indicated by the intense 814 cm(-1) C(15) HOOP mode suggest that the excited state of P(fr) and its photoproduct states are strongly coupled.

Systemic hemodynamics and renal function in hemorrhaged dogs resuscitated with cross-linked hemoglobin.

Cross-linked hemoglobin (XL-Hb) infused into dogs increases mean arterial pressure (MAP) but decreases blood flow to the renal (RBF), mesenteric (MBF), and iliac (IBF) circulations. These actions differ markedly from dextran infusion (which increases RBF, MBF, and IBF without altering MAP) and may be due to scavenging of nitric oxide by XL-Hb. However, because the hormonal milieu regulating regional circulation is altered during hemorrhage (when XL-Hb may be used), we studied whether systemic hemodynamics, RBF, MBF, IBF, and renal excretory function in hemorrhaged dogs was altered when resuscitated with XL-Hb compared with dextran (n = 6 each). Hemorrhage decreased MAP by 25% due to a 75% decline in cardiac output. RBF, MBF, and IBF all fell by 33, 64, and 72%, respectively (P<0.05 each). There was also a fall in glomerular filtration rate (GFR), urinary flow, and sodium excretion (P<0.05 each). After resuscitation, MAP, cardiac output, RBF, MBF, IBF, and GFR all recovered to basal values with either XL-Hb or dextran. Urinary flow and sodium excretion increased to above basal levels with dextran (both by 3.5-fold; P<0.05) or XL-Hb (by 7.5- and 10-fold, respectively; P<0.05). We conclude that resuscitation with XL-Hb after hemorrhage not only increases MAP, but also restores RBF, MBF, IBF, GFR, and urinary sodium and volume excretion analogously to dextran. The results contrast with those in normal dogs and suggest that nitric oxide inhibition does not impair hemodynamic and renal function recovery during hemorrhage.

Low-dose angiotensin II increases free isoprostane levels in plasma.

Chronic intravenous infusion of subpressor doses of angiotensin II causes blood pressure to increase progressively over the course of several days. The mechanisms underlying this response, however, are poorly understood. Because high-dose angiotensin II increases oxidative stress, and some compounds that result from the increased oxidative stress (eg, isoprostanes) produce vasoconstriction and antinatriuresis, we tested the hypothesis that a subpressor dose of angiotensin II also increases oxidative stress, as measured by 8-epi-prostaglandin F(2alpha) (isoprostanes), which may contribute to the slow pressor response to angiotensin II. To test this hypothesis, we infused angiotensin II (10 ng/kg per minute for 28 days via an osmotic pump) into 6 conscious normotensive female pigs (30 to 35 kg). We recorded mean arterial pressure continuously with a telemetry system and measured plasma isoprostanes before starting the angiotensin II infusion (baseline) and again after 28 days with an enzyme immunoassay. Angiotensin II infusion significantly increased mean arterial pressure from 121+/-4 to 153+/-7 mm Hg (P<0. 05) without altering total plasma isoprostane levels (180.0+/-24.3 versus 147.0+/-29.2 pg/mL; P=NS). However, the plasma concentrations of free isoprostanes increased significantly, from 38.3+/-5.8 to 54.7+/-10.4 pg/mL (P<0.05). These results suggest that subpressor doses of angiotensin II increase oxidative stress, as implied by the increased concentration of free isoprostanes, which accompany the elevation in mean arterial pressure elevation. Thus, isoprostane-induced vasoconstriction and antinatriuresis may contribute to the hypertension induced by the slow pressor responses of angiotensin II.

Role of hydrophobic partitioning in substrate selectivity and turnover of the ricinus communis stearoyl acyl carrier protein delta(9) desaturase.

Stearoyl acyl carrier protein Delta(9) desaturase (Delta9D) uses a diiron center to catalyze the NADPH- and O(2)-dependent desaturation of stearoyl acyl carrier protein (ACP) to form oleoyl-ACP. The reaction of recombinant Ricinus communis Delta9D with natural and nonnatural chain length acyl-ACPs was used to examine the coupling of the reconstituted enzyme complex, the specificity for position of double-bond insertion, the kinetic parameters for the desaturation reaction, and the selectivity for acyl chain length. The coupling of NADPH and O(2) consumption and olefin production was found to be maximal for 18:0-ACP, and the loss of coupling observed for the more slowly desaturated acyl-ACPs was attributed to autoxidation of the electron-transfer chain. Analysis of steady-state kinetic parameters for desaturation of acyl-ACPs having various acyl chain lengths revealed that the K(M) values were similar ( approximately 2.5-fold difference) for 15:0-18:0-ACP, while the k(cat) values increased by approximately 26-fold for the same range of acyl chain lengths. A linear increase in log (k(cat)/K(M)) was observed upon lengthening of the acyl chain from 15:0- to 18:0-ACP, while no further increase was observed for 19:0-ACP. The similarity of the k(cat)/K(M) values for 18:0- and 19:0-ACPs and the retained preference for double-bond insertion at the Delta(9) position with 19:0-ACP (>98% desaturation at the Delta(9) position) suggest that the active-site channel past the diiron center can accommodate at least one more methylene group than is found in the natural substrate. The DeltaDeltaG(binding) estimated from the change in k(cat)/K(M) for increasing substrate acyl-chain length was -3 kJ/mol per methylene group, similar to the value of -3.5 kJ/mol estimated for the hydrophobic partition of long-chain fatty acids (C-7 to C-21) from water to heptane [Smith, R. , and Tanford, C. (1973) Proc. Natl. Acad. Sci. U.S.A. 70, 289-293]. Since the K(M) values are overall similar for all acyl-ACPs tested, the progressive increase in hydrophobic binding energy available from increased chain length is apparently utilized to enhance catalytic steps, which thus provides the underlying physical mechanism for acyl chain selectivity observed with Delta9D.

An analysis of age and family history on outcome after breast-conservation treatment: the University of Pennsylvania experience.

PURPOSE: The present study reports the effects of patient age and family history on outcome after breast-conservation treatment. In addition, the interaction of age and family history is examined to determine outcome for younger patients with a positive family history of breast cancer (i.e., at a higher risk of having the BRCA1 or BRCA2 gene) after breast-conservation treatment. PATIENTS AND METHODS: From 1977 to 1992, 1021 women underwent breast-conservation treatment for American Joint Committee on Cancer stage I and II breast cancer at the Hospital of the University of Pennsylvania. In all patients, breast-conservation treatment included complete gross excision of the primary tumor and axillary lymph node dissection, followed by definitive breast irradiation. When indicated, radiation to the regional lymphatics, adjuvant chemotherapy, and/or adjuvant hormones were given. Patients were divided for analysis into three age groups (< or = 40 years, 41 to 50 years, and > or = 51 years) as well as three family history groups (first-degree relative positive for breast cancer, other family history positive for breast cancer, and negative family history for breast cancer). Median follow-up after treatment was 6.1 years. RESULTS: The 10-year actuarial overall survival rates were 74% for women aged < or = 40 years, 82% for women aged 41 to 50 years, and 82% for women aged > or = 51 years (P = 0.12). For the younger women, aged < or = 40 years, there was a higher 10-year rate of deaths from breast cancer (P = 0.007) but a lower rate of deaths from other causes (P = 0.08) than in the older two age groups. The younger women had a higher rate of local failure at 10 years compared with the two older age groups (22%, 18%, and 12%, respectively), but this difference was not statistically significant (P = 0.10). No significant differences were found between the three family history groups (first-degree relative positive for breast cancer, other family history positive for breast cancer, and negative family history for breast cancer) for survival, freedom from distant metastases, or local failure (all P > or = 0.25). For younger women, aged < or = 40 years, the 5-year outcomes for survival, freedom from distant metastases, and local failure were not different according to family history status (all P > or = 0.18). Similarly, the 5-year outcomes were not different according to family history status for women aged 41 to 50 years (all P > or = 0.46) and for women aged > or = 51 years (all P > or = 0.54). DISCUSSION: The present study has confirmed that breast-conservation treatment is suitable for appropriately selected younger patients or patients with a positive family history of breast cancer. Further, a positive family history of breast cancer in younger women does not represent a contraindication to breast-conservation treatment. In summary, younger age, positive family history of breast cancer, or younger age plus a positive family history of breast cancer should not preclude the use of breast-conservation treatment for appropriately selected patients.

Concurrent chemotherapy and radiation for breast conservation treatment of early-stage breast cancer.

PURPOSE: The optimal sequencing of chemotherapy and radiation therapy in patients with early-stage breast cancer undergoing breast-conservation treatment remains controversial. The purpose of this study is to evaluate the outcome of patients treated with one specific sequence of concurrent chemoradiation followed by additional chemotherapy. METHODS: Between 1977 and 1992, 210 patients with stage I and II breast cancer underwent lumpectomy and axillary lymph node dissection followed by treatment with concurrent chemotherapy and radiation therapy, followed by further chemotherapy. Chemotherapy consisted of two 28-day cycles of CF (oral cyclophosphamide, 100 mg/m2 day 1 to 14, and intravenous 5-fluorouracil, 600 mg/m2 days 1 and 8) during radiation therapy, followed in general by six cycles of CMF (CF doses as above plus intravenous methotrexate 40 mg/m2 days 1 and 8) after the completion of radiation therapy. Fifty patients also received hormonal therapy, predominantly tamoxifen. One hundred ten patients had clinical T1 lesions, and 100 had T2 lesions. Fifty-three patients were pathologic N0, and 157 patients were pathologic N1 (123 patients had one to three positive nodes, and 34 patients had four or more positive nodes). Median follow-up for node-negative patients (5.2 years) is shorter than for node-positive patients (7.6 years). Therefore, outcome is reported at 5 and 10 years for node-positive patients but only at 5 years for node-negative patients. RESULTS: For node-positive patients, outcomes at 5 and 10 years, respectively, were 86% and 70% for overall survival, 78% and 67% for no evidence of disease survival, and 82% and 69% for freedom from distant metastases. For node-negative patients, outcomes at 5 years were 94% for overall survival, 94% for no evidence of disease survival, and 94% for freedom from distant metastases. Pathologic nodal status was predictive of outcome after treatment. Local failure in the treated breast was 5% at 5 years and 13% at 10 years for all patients. CONCLUSIONS: Concurrent CF with radiation therapy followed by six cycles of CMF after radiation therapy results in excellent survival, freedom from distant metastases, and local control for both node-negative and node-positive patients. This regimen of concurrent chemotherapy and radiation therapy is one option for sequencing, and it avoids the delays in administration of either modality that are associated with other sequencing regimens.

Effect of meclofenamate or ketoconazole on the natriuretic response to increased pressure.

Increases in renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion (DRIVE) decrease proximal sodium reabsorption and increase urinary fractional sodium excretion (FENa). This natriuretic response is blunted by inhibition of the cyclooxygenase pathway. However, complicating the interpretation of the effects of cyclooxygenase inhibition on sodium excretion are the following: (1) products of the other pathways of arachidonic acid metabolism, such as the cytochrome P-450 metabolites, may be attenuated when cyclooxygenase activity is reduced; (2) the proximal tubule has a high biosynthetic capacity for cytochrome P-450 metabolites of arachidonic acid. Therefore, the purpose of the present study was to compare blockade of the epoxygenase products of the cytochrome P-450 pathway with ketoconazole to blockade of the cyclooxygenase pathway with meclofenamate on the natriuretic response to increased RIHP during DRIVE. RIHP, fractional excretion of lithium (FELi), FENa and glomerular filtration rate (GFR) were measured before and after DRIVE in control (n = 6), meclofenamate-treated (n = 6), and ketoconazole-treated (n = 5) rats. DRIVE was achieved by infusing 100 microL of 2.5% albumin solution directly into the renal interstitium. In control animals, DRIVE significantly increased RIHP (delta 2.8 +/- 0.6 mm Hg), FELi (delta 13.4% +/- 5.2%), and FENa (delta 1.29% +/- 0.31%). In the ketoconazole-treated group, RIHP (delta 3.9 +/- 0.8 mm Hg), FELi (delta 19.3% +/- 2.0%), and FENa (delta 1.73% +/- 0.43%) also significantly increased. However, the natriuretic response to DRIVE was blunted during cyclooxygenase blockade with meclofenamate when compared with control or ketoconazole-treated animals (FELi (delta 2.5% +/- 1.4%, not significant) and FENa (delta 0.07% +/- 0.18%, not significant), even though the response of RIHP was intact (delta 4.5 +/- 0.4 mm Hg, p < 0.001). These results suggest that the natriuretic response to increased RIHP is dependent on the presence of, but not necessarily the increased synthesis of, products of cyclooxygenase rather than the cytochrome P-450 epoxygenase pathway for arachidonic acid metabolism.

The effects of sequence and type of chemotherapy and radiation therapy on cosmesis and complications after breast conservation therapy.

PURPOSE: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy. METHODS AND MATERIALS: The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy +/- hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate (CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up. RESULTS: The use of chemotherapy had an adverse effect on cosmetic outcome compared to no chemotherapy, which was of borderline significance at 3 years (92% excellent or good cosmetic outcome vs. 96% respectively, p = 0.057); however, cosmesis was not different at 5 years (91 vs. 93% respectively, p = 0.67). Cosmesis was not significantly different between patients treated sequentially and those treated concurrently (3 year: 87 vs. 93% respectively, p = 0.33), nor was it different between patients who received CMF vs. CAF (3 year: 92 vs. 93% respectively, p = 0.89). Hormonal therapy did not influence cosmetic outcome (p = 0.78). The incidence of Grade 4 or 5 arm edema (> or = 2 cm difference in arm circumference) was 2% without chemotherapy vs. 8% with chemotherapy (p = 0.00002). However, the incidence of arm edema was not affected by sequencing or type of chemotherapy (all p > or = 0.52). Patients treated sequentially had a 10% incidence of Grade 4 or 5 arm edema vs. 7% in the patients treated concurrently (p = 0.52). The incidence was 7 vs. 9% in patients treated with CMF vs. CAF (p = 0.73). The incidence of clinical pneumonitis and rib fracture was not influenced by use of chemotherapy, sequence of chemotherapy or use of hormonal therapy (all p > or = 0.06). CONCLUSIONS: Chemotherapy can be given concurrently with radiation therapy in the treatment of Stage I and II breast cancer with breast-conserving therapy without seriously compromising cosmetic outcome or incidence of complications compared to patients receiving other sequences of chemotherapy. Hormonal therapy did not affect cosmesis or complications. The chemotherapeutic regimen of cytoxan and 5-FU concurrent with radiation therapy followed by more chemotherapy is one reasonable option for breast conservation therapy in patients requiring chemotherapy.

Pattern of 72-hour intragastric acidity in a homogeneous group of intensive care unit patients.

To gain insight into the variation over time of gastric acidity in postoperative ICU patients, intragastric pH was prospectively studied in patients undergoing elective abdominal aortic reconstructive surgery during a 72-hr intra- and postoperative period. Intragastric pH was monitored continuously in 14 patients with combined glass electrodes. During the day of surgery (day 1), the median 24-hr pH for all patients was 6.25 (5.8-7.0, IQR). However, three of the 14 studied patients had a median 24-hr pH of 1.8. The median 24-hr pH throughout day 2 for all was 2.45 (1.6-4.7, P = 0.001). The median 24-hr pH on day 3 was 1.6 (1.5-2.1, P = 0.001). Median 8-hr pH values demonstrate a remarkable interpatient and intraindividual variation in the course of the postoperative period. A progressive lowering of the intragastric pH was observed in the first 40 hr. From the 40- to 48-hr interval until the end of the study, no further significant decrease was found. The intragastric pH was above 4, 74% of the time during day 1, 39% during day 2 (P = 0.006) and 16% during day 3 (P = 0.003). Percentage of time above 4 on day 2 was significantly higher than on day 3 (P = 0.04). In conclusion, since gastric acid and pepsin seem to play a role in stress ulceration, this study suggests some patients are at risk of stress ulceration from the beginning of surgery, but most patients become at risk of stress ulceration in the course of the postoperative period.

Natriuretic response to renal interstitial hydrostatic pressure during angiotensin II blockade.

Increases in renal interstitial hydrostatic pressure (RIHP) increase urinary sodium excretion (UNaV). Experimentally increasing RIHP by direct renal interstitial volume expansion (DRIVE) has been shown to decrease proximal tubule sodium reabsorption. The purpose of the present study was to investigate whether the renin-angiotensin system modulates the natriuretic response to DRIVE. Unilateral nephrectomy and implantation of two polyethylene matrices were performed 3 wk before the acute experiment. Fractional sodium excretion (FENa), RIHP, and glomerular filtration rate (GFR) were measured before and after DRIVE in control rats (n = 9) and in rats receiving the angiotensin II (ANG II) receptor antagonist, losartan potassium (10 mg/kg i.v.; n = 10). DRIVE was achieved by infusing 100 microliters of 2.5% albumin solution directly into the renal interstitium. GFR remained unchanged by DRIVE in both groups. In control animals, DRIVE significantly increased both RIHP (delta 3.8 +/- 0.5 mmHg) and FENa (delta 0.92 +/- 0.19%). In the losartan-treated group, RIHP (delta 2.8 +/- 0.4 mmHg) and FENa (delta 1.93 +/- 0.41%) also significantly increased. The natriuretic response to DRIVE was significantly enhanced during ANG II receptor blockade compared with control animals (delta UNaV/delta RIHP = 2.01 +/- 0.67 vs. 0.44 +/- 0.17 mu eq.min-1 x mmHg-1, respectively; P < 0.05). These results suggest that the blockade of angiotensin enhances the natriuretic response to increased RIHP during DRIVE.

Role of renal interstitial hydrostatic pressure in natriuresis of systemic nitric oxide inhibition.

Systemic inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) increases renal perfusion pressure (RPP) and urinary sodium excretion. Increased RPP has been proposed as one of the mechanisms for the natriuresis caused by intravenous infusion of L-NMMA. We tested the hypothesis that increases in renal interstitial hydrostatic pressure (RIHP) are required for the natriuresis of L-NMMA infusion. Experiments were performed in four groups of Sprague-Dawley rats in which partial aortic clamping and/or bilateral renal decapsulation was performed to control RPP and RIHP. Infusion of L-NMMA (15 mg/kg bolus + 500 micrograms.kg-1 x min-1 continuous infusion) increased RPP (delta+ 14 +/- 1 mmHg), RIHP (delta+ 3.6 +/- 0.7 mmHg), and fractional excretion of sodium (FENa; delta 2.4 +/- 0.6%, P < 0.005). When RPP was prevented from increasing by controlling RPP with an adjustable clamp around the suprarenal aorta, RIHP and FENa did not significantly change. When only RIHP was held constant by bilateral renal decapsulation, FENa was not significantly increased (delta+ 0.68 +/- 0.36%, not significant), despite a significant rise in RPP (delta+ 18 +/- 2 mmHg, P < 0.001). Control of both RPP and RIHP prevented the increase in FENa. Thus, when renal interstitial pressure was controlled, the infusion of L-NMMA did not result in an increase in FENa. These results demonstrate that an increase in RIHP is a necessary component in the natriuresis due to systemic infusion of L-NMMA.

Intrarenal pressures during direct inhibition of sodium transport.

Renal interstitial hydrostatic pressure (RIHP) has been implicated in the regulation of sodium excretion. Studies using vasodilators and other maneuvers to increase RIHP have found a significant correlation between RIHP and sodium excretion. Since correlative studies do not prove a cause-and-effect relationship, it is not known whether the rise in sodium excretion in these studies is the result of increases in RIHP or if RIHP is elevated as a result of decreases in sodium and water reabsorption and increases in intratubular pressure. Therefore, the purpose of the present study was to determine whether elevation of intratubular hydrostatic pressures in response to direct inhibition of tubule transport with loop diuretics results in increases in RIHP in dogs and rats. Intrarenal hydrostatic pressures, renal hemodynamics, and sodium and water excretion were examined in dogs during intravenous administration of furosemide (3 mg/kg bolus followed by 0.03 mg.kg-1 x min-1) or bumetanide (60 micrograms/kg bolus followed by 1 microgram.kg-1 x min-1). Furosemide administration increased urinary flow rate (V; 0.10 +/- 0.02 to 4.6 +/- 0.97 ml/min), urinary sodium excretion (UNaV; 16 +/- 5 to 549 +/- 123 mu eq/min), and proximal tubule hydrostatic pressure (PT; 21 +/- 1 to 28 +/- 1 mmHg) but had no effect on RIHP (7.2 +/- 0.6 to 7.4 +/- 0.7 mmHg) or peritubular capillary hydrostatic pressure (14 +/- 1 to 14 +/- 1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of renal decapsulation on lithium excretion in the presence and absence of volume expansion.

The relationship between fractional sodium excretion (FENa) and fractional lithium excretion (FELi) was determined in Munich-Wistar rats with intact capsules (control, n = 16), and in rats with acute bilateral renal decapsulation (n = 16) during hydropenia and acute saline volume expansion. In response to volume expansion, the glomerular filtration rate increased significantly in both decapsulated and intact groups, but was similar in the two groups of rats at the same period. The FENa and FELi increased significantly from 0.49 +/- 0.10 and 20.09 +/- 1.76% to 1.71 +/- 0.20 and 34.14 +/- 2.82% in control rats with volume expansion. In decapsulated rats, FENa and FELi were 0.17 +/- 0.03 and 11.64 +/- 1.39% during control and increased to 1.04 +/- 0.21 and 26.23 +/- 1.17% during volume expansion. The FELi and FENa were significantly greater in control rats compared with decapsulated rats during both control and volume expansion periods. The lower FELi in bilateral renal decapsulation suggests reduced delivery of sodium from the proximal tubule.

Parlodel SRO in Parkinson's disease: a double-blind randomized comparison of Parlodel standard and Parlodel SRO.

In this study, we compared in an intent-to-treat analysis the tolerance and efficacy of Parlodel SRO with its standard galenic formulation in 34 patients with Parkinson's disease who received optimal levodopa therapy. The results suggest that Parlodel SRO was equally efficacious as Parlodel standard, but Parlodel SRO is better tolerated.

The full-length E6 protein of human papillomavirus type 16 has transforming and trans-activating activities and cooperates with E7 to immortalize keratinocytes in culture.

The wild-type E6 and E7 genes of human papillomavirus type 16 (HPV16) can cooperate to immortalize normal human keratinocytes in culture. The E6 open reading frame of HPV16 and other HPV types highly associated with cervical cancer has the potential of encoding both full-length E6 and two truncated E6* proteins, the latter being generated via splicing within the E6 open reading frame portion of the E6-E7 polycistronic transcript. Those types, such as HPV6, that are infrequently associated with cervical carcinoma lack the splice site and encode only a full-length E6. We have now found that, in addition to cooperating with E7 to immortalize keratinocytes, HPV16 E6 can induce anchorage-independent growth in NIH 3T3 cells and trans-activate the adenovirus E2 promoter. HPV6 E6 was also able to trans-activate the adenovirus E2 promoter, although it was inactive in both cell transformation assays. An HPV16 splice site mutant which expressed only the full-length HPV16 E6 was active in all three assays, indicating that the E6* proteins are not required for these activities. The plasmid which encodes the E6* proteins was inactive and did not potentiate the activity of the HPV16 splice site mutant. The mutation that prevented splicing in E6-E7 mRNA severely reduced the level of E7 protein and increased E6 protein. Taken together, the results suggest that the primary function of the splice within E6 is to facilitate the translation of E7 and reduce translation of full-length E6, rather than to generate biologically active E6* proteins.