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Dahl salt-sensitive rats develop hypovitaminosis D and hyperparathyroidism when fed a standard diet.

The Dahl salt-sensitive rat (S), a model for salt-sensitive hypertension, excretes protein-bound 25-hydroxyvitamin D (25-OHD) into urine when fed a low salt diet. Urinary 25-OHD increases during high salt intake. We tested the hypothesis that continuous loss of 25-OHD into urine would result in low plasma 25-OHD concentration in mature S rats raised on a standard diet. Dahl S and salt-resistant (R) male rats were raised to maturity (12-month-old) on a commercial rat diet (1% salt) and switched to 0.3% (low) or 2% (high) salt diets 3 weeks before euthanasia. Urine (24 h) was collected at the end of the dietary treatments. Urinary 25-OHD and urinary 25-OHD binding activity of S rats were three times that of R rats, resulting in lower plasma 25-OHD and 24,25-dihydroxyvitamin D concentrations in S rats than in R rats (P < 0.001). Plasma parathyroid hormone concentrations of S rats were twice that of R rats. S rats fed 2% salt had higher plasma 1,25-dihydroxyvitamin D concentrations than those fed 0.3% salt (P = 0.002). S rats excreted more calcium into urine than R rats (P < 0.001) and did not exhibit the expected calciuric response to salt. Proteinuria of the S rats was three times that of the R rats, suggesting kidney damage in the S rats. Low plasma 25-OHD and 24,25-dihydroxyvitamin D and high plasma 1,25-dihydroxyvitamin D and PTH concentrations seen in the mature S rats have also been reported for elderly patients with low-renin (salt-induced) hypertension. An implication of this study is that low vitamin D status may occur with age in salt-sensitive individuals, even when salt intake is normal.

Animals↗

Do race, gender, and source of payment impact on anesthetic technique for inguinal hernia repair?

STUDY OBJECTIVE: To evaluate the potential differences in the type of anesthesia provided to patients of different race, gender, and source of payment undergoing inguinal hernia repair (IHR). DESIGN: Retrospective cohort study. SETTING: Ambulatory surgical centers/National Survey of Ambulatory Surgery. PATIENTS: 5810 patients older than 14 years who underwent IHR in an ambulatory surgical center. INTERVENTIONS: Inguinal hernia repair under different types of anesthesia. MEASUREMENTS: The association of race, gender, and source of payment with different types of anesthesia for IHR as determined by multivariate regression analysis. RESULTS: Significant discrepancies in the use of various anesthetics between patients of different race, gender, and source of payment were found. Patients identified as black and those of other minority groups were significantly more likely to receive general anesthesia compared with those identified as white (odds ratio [OR] 2.76, confidence interval [CI] 1.96-3.88 and OR 1.66, CI 1.14-2.42, respectively). Those identified as black were less likely to receive epidural anesthesia compared with their white counterparts (OR 0.36, CI 0.14-0.95). Women were less likely than men to undergo IHR with epidural anesthesia (OR 0.5, 95% CI 0.3-0.85). CONCLUSION: Significant discrepancies in the use of various anesthetics for IHR between patients of different race, gender, and insurance status were found. Despite limitations inherent to secondary data analysis, the findings raise the possibility that nonmedical factors may influence anesthetic management.

Adolescent↗

Intensity-modulated radiotherapy improves target coverage, spinal cord sparing and allows dose escalation in patients with locally advanced cancer of the larynx.

BACKGROUND AND PURPOSE: An investigation has been carried out into the potential of intensity-modulated radiotherapy (IMRT) to improve the coverage of the targets and the sparing of the spinal cord (SC) in radiotherapy treatment of the larynx and bilateral cervical lymph nodes, in patients with advanced larynx cancer. PATIENTS AND METHODS: Conventional radiotherapy (CRT) and IMRT plans were produced for six patients to treat the larynx (PTV1) and lymph nodes (PTV2) to 50 Gy (phase 1). A second plan was created to treat the PTV1 to 65 Gy and PTV2 to 50 Gy (phases 1 and 2). The potential to escalate the dose to both the larynx (to 67 Gy) and the nodes (to 56 Gy) was investigated for the IMRT plans. RESULTS: The phase 1 treatment gave average minimum doses (dose received by 99% volume) of 38.1 (+/-8.2) and 48.5 (+/-0.2)Gy for PTV1, treated by CRT and IMRT, respectively, and 35.9 (+/-2.9) and 46.2 (+/-1.8)Gy for PTV2. For the two phase treatment the average minimum doses to PTV1 were 51.6 (+/-8.2) (CRT) and 62.1 (+/-0.7)Gy (IMRT) (p=0.028) and for PTV2 were 36.2 (+/-2.9) (CRT) and 46.8 (+/-0.5)Gy (IMRT) (P=0.0004). The average maximum doses (dose received by 1% volume) to the SC were 42.5 (+/-1.9) (CRT) and 37.9 (+/-1.4)Gy (IMRT) (P=0.01). For the dose escalated IMRT plans the minimum dose to PTV1 was 64.6 (+/-0.5) and 50.8 (+/-1.8)Gy to PTV2. The average SC maximum was 41.5 (+/-1.6)Gy. CONCLUSIONS: IMRT offers improved target homogeneity and reduces irradiation of the SC. This sparing of normal tissue structures is sufficient that significant dose escalation of both the larynx and lymph nodes may be possible.

Dose Fractionation, Radiation↗

Treatment accuracy of fractionated stereotactic radiotherapy.

BACKGROUND AND PURPOSE: To assess the geometric accuracy of the delivery of fractionated stereotactic radiotherapy (FSRT) for brain tumours using the Gill-Thomas-Cosman (GTC) relocatable frame. Accuracy of treatment delivery was measured via portal images acquired with an amorphous silicon based electronic portal imager (EPI). Results were used to assess the existing verification process and to review the current margins used for the expansion of clinical target volume (CTV) to planning target volume (PTV). PATIENTS AND METHODS: Patients were immobilized in a GTC frame. Target volume definition was performed on localization CT and MRI scans and a CTV to PTV margin of 5mm (based on initial experience) was introduced in 3D. A Brown-Roberts-Wells (BRW) fiducial system was used for stereotactic coordinate definition. The existing verification process consisted of an intercomparison of the coordinates of the isocentres and anatomy between the localization and verification CT scans. Treatment was delivered with 6 MV photons using four fixed non-coplanar conformal fields using a multi-leaf collimator. Portal imaging verification consisted of the acquisition of orthogonal images centred through the treatment isocentre. Digitally reconstructed radiographs (DRRs) created from the CT localization scans were used as reference images. Semi-automated matching software was used to quantify set up deviations (displacements and rotations) between reference and portal images. RESULTS: One hundred and twenty six anterior and 123 lateral portal images were available for analysis for set up deviations. For displacements, the total errors in the cranial/caudal direction were shown to have the largest SD's of 1.2 mm, while systematic and random errors reached SD's of 1.0 and 0.7 mm, respectively, in the cranial/caudal direction. The corresponding data for rotational errors (the largest deviation was found in the sagittal plane) was 0.7 degrees SD (total error), 0.5 degrees (systematic) and 0.5 degrees (random). The total 3D displacement was 1.8 mm (mean), 0.8 mm (SD) with a range of 0.3-3.9 mm. CONCLUSIONS: Portal imaging has shown that the existing verification and treatment delivery techniques currently in use result in highly reproducible setups. Random and systematic errors in the treatment planning and delivery chain will always occur, but monitoring and minimising them is an essential component of quality control. Portal imaging provides fast and accurate facility for monitoring patients on treatment and the results of this study have shown that a reduction in CTV to PTV margin from 5 to 4 mm (resulting in a considerable increase in the volume of normal tissue sparing) could be made.

Adenoma↗

Postinjury thromboxane receptor blockade ameliorates acute lung injury.

BACKGROUND: Acute lung injury is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Thromboxane A2 has been found to be a central mediator in the development of septic and oleic acid (OA)-induced acute lung injury. Our previous study demonstrated a beneficial effect of preinjury thromboxane A2 receptor blockade. The current study examines the efficacy of postinjury receptor blockade on oxygenation capacity and pulmonary hemodynamics in an isolated lung model of OA-induced acute lung injury. METHODS: Four groups of rabbit heart-lung preparations were studied for 60 minutes in an ex vivo perfusion-ventilation system. Saline control lungs received saline solution during the first 20 minutes of study. Injury control lungs received an OA-ethanol solution during the first 20 minutes. Two treatment groups were used: T10, in which the thromboxane receptor antagonist, SQ30741, was infused 10 minutes after the initiation of OA infusion; and T30, in which the thromboxane receptor antagonist was infused 30 minutes after OA infusion. RESULTS: Significant differences were found in oxygenation (oxygen tension in T10 = 62.6 +/- 11.7 mm Hg, T30 = 68.2 +/- 21.2 mm Hg; injury control = 40.2 +/- 9.0 mm Hg, saline control = 123.5 +/- 16.01 mm Hg; p < 0.001) and percentile change in pulmonary artery pressure (T10 = 1.1% +/- 19.4% increase, T30 = 11.2% +/- 7.3% increase; injury control = 47.6% +/- 20.5%, saline control = 4.2% +/- 6.81%; p < 0.001). CONCLUSIONS: This study demonstrates that blockade of the thromboxane A2 receptor, even after the initiation of acute lung injury, eliminates pulmonary hypertension and improves oxygenation.

Animals↗

Nitric oxide potentiates acute lung injury in an isolated rabbit lung model.

BACKGROUND: The effect of inhaled nitric oxide (NO) treatment on pulmonary function in the setting of adult respiratory distress syndrome is controversial. We examined the effect of inhaled NO on pulmonary function in an isolated rabbit lung model of oleic acid (OA)-induced acute lung injury. We hypothesized that NO would decrease pulmonary artery pressure and improve oxygenation. METHODS: Rabbit heart-lung blocks were isolated, flushed in vivo, harvested, and immediately perfused with whole blood and ventilated with 50% oxygen (O2). Pulmonary artery pressure was determined every 15 seconds for 60 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, and 60 minutes after initiation of OA infusion. Rabbits were randomized into four study groups: saline control; OA control, which received a 20-minute infusion of 50% OA/ethanol solution; NO treatment (20 ppm NO inhaled before OA infusion); and NO control, which underwent NO (20 ppm) pretreatment, followed by saline infusion. Pulmonary artery pressure, oxygenation (arteriovenous O2 difference), compliance, and wet/dry lung weight were determined. RESULTS: Pretreatment with NO caused significant increases in pulmonary artery pressure (NO treatment versus NO control and saline control; no significant difference between NO treatment group and OA control group), and did not improve oxygenation in our model. CONCLUSIONS: Contrary to our hypothesis, pretreatment with NO potentiates acute lung injury in our isolated lung model. There was significant exacerbation of pulmonary hypertension and no improvement in oxygenation. Further investigation of the possible deleterious effects of NO in acute lung injury are needed, especially in the early acute phases of this process.

Animals↗

Sodium nitroprusside mitigates oleic acid-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI) is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Oleic acid (OA) creates a significant ALI that physiologically mimics human adult respiratory distress syndrome (ARDS). It has been hypothesized that pulmonary vasodilatation may improve ALI. Studies in our laboratory using this model and nitric oxide (NO) have shown that NO inhalation is detrimental and worsens the effects of OA. We studied the effect of pretreatment with a potent vasodilator, sodium nitroprusside (SNP), on ALI induced by OA in an isolated lung model. We hypothesized that pretreatment with SNP will worsen pulmonary hypertension and oxygenation in OA-induced ALI, similar to the effects seen with inhaled NO in this model. METHODS: Rabbit heart lung blocks were isolated, flushed in vivo, harvested, immediately perfused with whole blood, and ventilated with 50% oxygen. Pulmonary artery pressure was determined every 15 seconds for 90 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, 60, and 90 minutes after initiation of OA infusion. Four groups were studied: saline control (SC), oleic acid control (OAC; 20-minute infusion of 50% OA/ethanol into pulmonary circulation), SNP control (NPC; 10 microg/ kg/min SNP infused without subsequent OA infusion), and SNP treatment (NPRx); 10 microg/kg/min SNP infused before OA/ethanol. Pulmonary artery pressure (PAP), oxygenation (arterio-venous oxygen difference [AVO2], compliance (CPL), and wet/dry lung weight were determined. RESULTS: No significant differences were found between the NPRx group and SC. Pretreatment with SNP eliminated the detrimental effects of OA infusion. CONCLUSIONS: Contrary to our hypothesis, pretreatment with SNP eliminates the decrease in oxygenation and increase in lung weight, and ameliorates pulmonary hypertension in our isolated lung model of OA-induced ALI.

Animals↗

A case series of low-dose fenoldopam in seventy cardiac surgical patients at increased risk of renal dysfunction.

OBJECTIVE: To evaluate the usefulness of low-dose fenoldopam mesylate in patients at risk of developing renal dysfunction after cardiac surgery requiring cardiopulmonary bypass. DESIGN: A prospective, single-center, observational study. SETTING: University teaching hospital. PARTICIPANTS: Seventy patients scheduled for elective cardiac surgery with one or more predefined risk factors for renal dysfunction. INTERVENTIONS: After induction of anesthesia, fenoldopam (0.03 microg/kg/min) was administered throughout surgery and into the postoperative period, until the patient was stable and weaned from all other vasoactive agents. Perioperatively, fenoldopam was also used as a second-line antihypertensive agent as required. MEASUREMENTS AND MAIN RESULTS: No patient developed renal failure that required dialysis, whereas 7.1% (5/70) developed non-dialysis-dependent renal dysfunction. Four out of these 5 patients had 2 or more risk factors (9.5%). Higher preoperative creatinine levels, a history of hypertension, myocardial infarction within 5 days of surgery, and a preoperative diagnosis of chronic renal insufficiency were all good predictors of postoperative non-dialysis-dependent renal dysfunction. Discharge serum creatinine levels were lower than preoperative levels (1.16 +/- 0.36 mg/dL v 1.26 +/- 0.34 mg/dL, p < 0.05). CONCLUSION: These findings suggest that renal function was preserved in patients at increased risk for renal dysfunction after cardiac surgery when low-dose fenoldopam was used in the perioperative period. However, a randomized, controlled trial is required to establish efficacy.

Aged↗

Speed and efficiency in the resuscitation of blunt trauma patients with multiple injuries: the advantage of diagnostic peritoneal lavage over abdominal computerized tomography.

BACKGROUND: The difference in speed, efficiency, and safety between diagnostic peritoneal lavage (DPL) and abdominal computerized tomography in the evaluation of adult blunt trauma patients with multiple injuries was investigated. METHODS: A prospective protocol was analyzed. Adult blunt trauma patients admitted to a Level I trauma center in 1994 were examined. Registry and chart data were used. Patients admitted before the institution of the protocol (January 1-June 30, 1994) were compared with those admitted afterward (July 1-December 31, 1994). Time spent in the emergency department before definitive placement or surgical intervention was studied. RESULTS: Patients in the second period, when DPL was used more frequently, spent significantly less time in the emergency department and radiology. No missed injuries were identified in either group. The percentages of nontherapeutic laparotomies were similar between the two groups. Cost was significantly lower in the group that underwent DPL. CONCLUSION: Patients with severe head injury, open fractures, or any evidence of hemodynamic instability are better served by DPL as the primary diagnostic modality. Its sensitivity and specificity are equivalent to those of computerized tomography; this facilitates evaluation and allows for simultaneous procedures and quicker initiation of definitive treatment.

Abdominal Injuries↗

Outcome and cost of trauma among the elderly: a real-life model of a single-payer reimbursement system.

BACKGROUND: As our population ages, the number of elderly trauma patients (age > or = 65 years) increases. Studies have demonstrated increased mortality and cost for a given injury severity in the elderly compared with younger patients. The financial viability of trauma centers in the United States has been an area of concern for many years. As reimbursement diminishes for privately insured patients, the ability to finance the care of the indigent is jeopardized. Medicare, the single-payer insurance plan for the elderly, reimburses at a lower rate than standard private insurance carriers. We examined the differences in outcome and cost between the elderly and younger patients and the financial burden imposed by care for elderly trauma. Our hypothesis was that elderly trauma patients would have poorer outcomes, higher cost, and generate greater financial losses than younger patients. METHODS: All patients admitted to the University of Virginia Trauma Service from July 1, 1994, to July 1, 1997 were included. Trauma registry and patients records were examined. Patients with incomplete financial data (cost, reimbursement, and payer source) were excluded. Patients were grouped by age (18-64 and > or =65 years), Injury Severity Score, and payer source. RESULTS: One thousand one hundred twenty-seven patients met the entry criteria. One hundred forty patients had incomplete financial or patient data and were excluded. Nine hundred eighty-seven patients were included in the study, of which 159 were elderly and 828 were 18 to 64 years of age. Injury Severity Scores were significantly higher in the elderly group. Only 2% of elderly patients were uninsured (76% were insured by Medicare), whereas 25% of younger patients were uninsured. Medicare reimbursement rates actually exceeded those of all other carriers (114% of costs). Elderly patients had a higher mortality rate, but the z score did not reach significance. The W score, however, indicated that there were more unexpected, negative outcomes among elderly patients. As injury severity increased, profit per case increased in the elderly and decreased in the younger group. CONCLUSION: Despite higher injury severity and lower survival probability for the elderly, the length of hospital and intensive care unit stays, as well as the percentage of admissions to the intensive care unit, were similar. The per capita cost of hospital care for the elderly was lower than for younger patients, whereas reimbursement was higher, primarily because 98% of elderly patients were insured. Medicare, the single-payer insurance plan for the elderly, adequately reimburses for elderly trauma care. This implies that universal insurance coverage for all trauma patients would be desirable, even if reimbursement rates decreased significantly. The increased mortality in the elderly requires continued study and diligence.

Adolescent↗