Pregnancy does not adversely affect renal transplant function.

Women with functioning transplanted kidneys often become fertile again. Indeed, renal function, endocrine status and libido rapidly improve after renal transplantation, and 1:50 women of childbearing age become pregnant. However, there is concern regarding the haemodynamic changes of pregnancy, which could lead to a decline in graft function (temporary or permanent). We examined obstetric data and renal parameters in 29 patients and 33 pregnancies. Mean serum creatinine and creatinine clearance remained stable throughout pregnancy and 1 year postpartum. However, there was a significant increase in proteinuria from a mean of 0.45 g/24 h around the time of conception to 1.11 g/24 h at delivery (p<0.05). The proteinuria resolved to baseline levels at 3 months postpartum. We highlight certain parameters to be considered before conception to allow a good obstetric outcome and prolong stable renal function: serum creatinine <150 micromol/l, proteinuria <1 g/day, absence of histological evidence of chronic allograft rejection, controlled blood pressure (140/90) and stability of maintenance immunosuppression.     

Valdecoxib does not impair platelet function

The platelet effects of a supratherapeutic dose of the new cyclooxygenase (COX)-2 specific inhibitor, valdecoxib (40 mg twice a day), naproxen 500 mg twice a day, diclofenac 75 mg twice a day, and placebo were compared in 62 healthy adult subjects in this 7(1/2) day single-center, randomized, placebo-controlled trial. Platelet aggregation responses (to arachidonate [AA], collagen, and adenosine diphosphate [ADP]), bleeding time, and serum thromboxane B(2) (TxB(2)) concentrations were measured at baseline and at regular intervals on days 1 and 8. Valdecoxib had no effect on platelet function. Naproxen and diclofenac significantly reduced the platelet aggregation response to AA and to a lesser extent collagen and ADP at most assessments compared with placebo. Naproxen significantly lowered serum TxB(2) levels. In contrast to standard doses of 2 nonsteroidal antiinflammatory drugs (NSAIDs), a supratherapeutic valdecoxib dosage does not impair platelet function (COX-1). Valdecoxib may be a safer analgesic option than conventional NSAIDs in patients for whom bleeding complications are a concern. (Am J Emerg Med 2002;20:275-281.     

Jugular bulb catheterization does not increase intracranial pressure

Cerebral venous monitoring through jugular bulb catheterization (JBC) allows assessment of global oxygen delivery adequacy. Because of concern that venous obstruction by catheterization may cause or exacerbate intracranial hypertension, physicians are reluctant to puncture this vessel in brain-injured patients. We evaluated the impact of JBC on intracranial pressure (ICP). 37 consecutive pediatric patients with jugular bulb catheters and ICP monitoring were studied. ICP was monitored in 28 patients during JBC. Also immediately after JBC and daily thereafter the contralateral, ipsilateral, and bilateral jugular veins were compressed in all 37 patients to assess patency of these vessels. Change in ICP was noted. If ICP increased more than 5 torr, compression was stopped. Preinsertion ICP was 17.3±5.1 and postinsertion 17.2±5.1 torr. The maximum rise in ICP was 2 torr in a single patient while 6 others had a decrease in ICP. 120 compression tests were performed. Compression ipsilateral to the catheter caused the ICP to rise from 16.0±4.3 to 18.4±4.4 torr, and in contralateral compression 15.9±4.2 to 17.0±4.4. Neither the duration of catheterization nor the precompression ICP correlated with the rise in ICP. These data revealed no evidence of jugular venous obstruction in the catheterized vessel. We conclude that JBC can be performed in patients without aggravating and elevated ICP.This study was made possible by a generous grant from the Christopher C. Tackett, Jr. Memorial Research fund     

Methylphenidate does not improve cognitive function in healthy sleep-deprived young adults.

BACKGROUND: Abuse of methylphenidate, a treatment of attention-deficit/hyperactivity disorder, is reported to be increasing among students for the purpose of improving cognition. METHODS: A single capsule, containing methylphenidate (20 mg) or placebo, was administered to healthy young adults orally following 24 hours of sleep deprivation. Measurements included percent change in score from sleep-deprived baseline on four standardized tests of cognitive function: Hopkins Verbal Learning, Digit Span, Modified Stroop, and Trail Making tests. Measurements also included percent changes in blood pressure and heart rate from sleep-deprived baseline and plasma methylphenidate concentration. RESULTS: Differences in cognitive test performance were not observed between intervention groups. In subjects receiving methylphenidate, mean percent changes from baseline for systolic blood pressure and heart rate were increased relative to placebo between 90 and 210 minutes following capsule administration (maximum increases of 9.45% and 11.03%, respectively). The timing of peak differences in physiologic measures did not correlate with peak serum methylphenidate concentrations. Exit questionnaire ratings of "capsule effect" and perceived performance on the postcapsule administration of the most challenging cognitive test were both higher (p = .044 and p = .009, respectively) for the methylphenidate group than for the placebo group. CONCLUSIONS: Cognitive improvement among sleep-deprived young adults was not observed following methylphenidate administration. Benefits perceived by abusers may relate to increased confidence and sense of well-being, as well as to sympathetic nervous system stimulation. Moreover, methylphenidate administration results in physiologic effects that could be harmful to certain individuals.     

Intravesicular pressure monitoring does not cause urinary tract infection

Objective To determine whether intravesicular pressure monitoring using a closed system increases the risk of nosocomial urinary tract infection.Design Retrospective chart and database review.Setting Surgical/trauma intensive care units of a regional level-I trauma center.Patients 3108 critically ill patients of which 122 patients underwent intravesicular pressure monitoring.Interventions Severity-adjusted urinary tract infection rates were compared among patients with and without intravesicular pressure monitoring.Measurements and results Over a 24-month period, 122 consecutive patients had 2202 intravesicular pressure measurements performed. During 1448 urinary catheter days, 15 patients who required intravesicular pressure monitoring developed a urinary tract infection with a severity-adjusted device-related infection rate of 7.9 infections per 1000 catheter days. Of the 2986 patients who did not require such monitoring, 98 patients developed a urinary tract infection with an infection rate of 6.5 infections per 1000 catheter days (p = 0.56).Conclusions Intravesicular pressure monitoring using the closed transducer technique is safe and does not increase the risk of urinary tract infection.     

Granulocyte concentrate splitting does not affect phenotype and function

Background

More granulocyte concentrates (GCs) could be produced for more patients from the same donor if apheresis bags were split and stored for longer periods of time. Hence, we tested the hypothesis that splitting and extension of storage of GCs do not impair granulocyte function or viability.

Study Design and Methods

Granulocyte apheresis concentrates were produced using modified fluid gelatin as a separation enhancer, split into two portions, and stored for 24 and 48 h. Granulocyte function, represented by cell migration, reactive oxygen species (ROS) production, and neutrophil extracellular trap formation (NETosis), was measured by live-cell imaging. ROS production, adhesive surface protein expression, and viability were measured by flow cytometry.

Results

Splitting had no effect on any of the tested parameters. After 24 h of storage, live-cell imaging showed no significant difference in migration, time to maximum ROS production, time to half-maximum NETosis, viability, or CD11b expression, but ROS production induced by phorbol 12-myristate 13-acetate (PMA) decreased from an initial median fluorescence intensity of 1775–590 artificial units. After 48 h, PMA-induced ROS production, viability, and migration declined, as reflected by decreases in median total distance (119 vs. 63.5 μm) and median Euclidean distance (30.75 vs. 14.3 μm).

Conclusion

Splitting GC products has no effect on granulocyte viability or function, but extended storage >24 h does compromise granulocyte function. The findings confirm that GCs should be transfused within 24 h of collection. Longer storage cannot be recommended.     

Hypercholesterolemia does not alter endothelial function in spontaneously hypertensive rats

In humans, hypercholesterolemia and hypertension are associated with endothelial dysfunction. Here, we assess whether hypercholesterolemia induces endothelial dysfunction in rats with pre-existing hypertension. Spontaneously hypertensive rats (SHR) and normotensive controls (WKY) were fed with a high-cholesterol diet for 12 weeks, and endothelial function was assessed in isolated thoracic aortic rings. In SHR and WKY rats, the hypercholesterolemic diet resulted in the elevation of total cholesterol and low-density lipoprotein levels by approximately 2.5- and 4.5-fold, respectively. However, in aorta, the basal nitric oxide (NO) production--as assessed by the magnitude of L-NG-nitroarginine methyl ester-induced vasoconstriction as well as the NO-dependent relaxation induced by acetylcholine or histamine--were not diminished either in SHR or in WKY rats fed with the hypercholesterolemic diet. Interestingly, prostacyclin (PGI2) production in aortic rings from SHR rats was higher than in the aorta from WKY rats. However, the hypercholesterolemic diet had no further effects on PGI2 production in the aorta either of SHR or WKY rats. The monocyte chemoattractant protein 1 level in plasma was slightly elevated in SHR and WKY rats fed with the hypercholesterolemic diet compared with their normocholesterolemic counterparts. In summary, even in the presence of pre-existing hypertension, hypercholesterolemia fails to modify NO-dependent and PGI2-dependent endothelial function in SHR rats; it also does not induce a robust inflammatory response. Both are prerequisites for the development of atherosclerosis.     

Lower esophageal sphincter pressure and serum motilin levels.

The gastrointestinal hormone motilin has recently been proposed as having a physiological role in the determination of lower esophageal sphincter (LES) strength. The present study was performed to evaluate the effect of gastric alkalinization of LES pressure and serum motilin levels. Instillation of 0.1N NaHCO3 into the stomach resulted in a significant increase in LES pressure (P less than 0.01) without affecting serum motilin levels. No correlation was found between fasting serum motilin levels and resting LES pressure (r = -0.31). These observations do not support the theory that LES pressure increases during gastric alkalinization are mediated through motilin release.     

Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function.

OBJECTIVE: To assess whether fluvoxamine alters the pharmacokinetics of alcohol or potentiates alcohol-related impairment of cognitive function. METHODS: The study design required partially "blinded" balanced crossover studies, each involving 12 healthy male volunteers who each received a 40 gm dose of intravenous or oral alcohol after single and multiple doses of 50 mg fluvoxamine. Main outcome measures for pharmacokinetics were venous blood alcohol and plasma fluvoxamine. Main outcome measures for pharmacodynamics were word recall, simple and choice reaction time, number vigilance, memory scanning, and word recognition. RESULTS: The pharmacokinetics of intravenous alcohol were not affected by concomitant administration of fluvoxamine. Compared with placebo-alcohol, alcohol slightly increased the rate of fluvoxamine absorption, but the area under the plasma concentration-time curve from 0 to 12 hours at steady state was unchanged. As expected, alcohol significantly impaired cognitive function in volunteers. However, fluvoxamine did not potentiate the effects of alcohol and in some instances appeared to reverse the effects or reduce their duration. Fluvoxamine was well tolerated: only mild adverse effects were reported, and none of those required intervention. CONCLUSION: Fluvoxamine does not interact significantly with alcohol or potentiate alcohol-related impairment of cognitive function.     

Hemodilution does not alter the aortic-to-femoral arterial pressure difference in dogs

Introduction.Distal arterial pressure normally differs from aorticpressure. This difference is modified by changes of vascular resistance.Hemodilution, due to decreased viscosity, decreases vascular resistance.Therefore, the difference between aortic and distal arterial pressures couldbe altered as well. We investigated whether acute hemodilution affected thisdifference in dogs. Methods.Eleven mongrel dogs weighing 16.6 ±4.4 kg were anesthetized with pentobarbital and sufentanyl and mechanicallyventilated. Arterial presssure was recorded using Millar catheter-tippedpressure transducers in the proximal aorta and in the distal femoral artery.An electromagnetic flowmeter probe was placed around the aorta. Effectivedownstream pressure was estimated by extrapolation of exponential arterialpressure decay during 3-second occlusion of the proximal aorta. Hemodilutionwas effected by removal of 30 ml/kg of blood and replacement with 60 ml/kg ofwarmed saline. In addition, the effects of 1 µg/kg phenylephrine and 4µg/kg of sodium nitroprusside were measured before and afterhemodilution. Results.Hemodilution decreased hematocrit from 39± 11.2% to 25.6 ± 4.95%. Systolic and mean pressures wereunchanged but aortic diastolic pressure decreased significantly, from 86± 17 to 79 ± 15 mmHg (p < 0.005). Peak systolicpressure was 13.5 ± 7.2 mmHg higher in the femoral artery than in theaorta before, and 16 ± 8.7 mmHg after, hemodilution (p >0.05). Nitroprusside decreased the femoral to aortic peak systolic pressuredifference from 14.3 ± 6.3 to 7.7 ± 15.3 mmHg, p = 0.05before hemodilution and from 14.3 ± 8.8 to 2.5 ± 11 mmHg,p < 0.005 afterwards. Hemodilution significantly decreased theeffective downstream pressure, from 44 ± 9 to 36 ± 6.8 mmHg inthe aorta (p< 0.05), and from 51 ± 2 to 37 ± 3.1mmHg in the distal femoral artery (p< 0.05). Conclusion.Acute hemodilution did not alter the aortic-to-distal arterial pressuredifference in dogs.     

Postcholecystectomy syndrome. How to determine if the sphincter of Oddi is the cause.

Recurrence of pain after cholecystectomy is common. This postcholecystectomy syndrome, defined as pain that is unexplained by upper abdominal radiologic and/or endoscopic studies, including endoscopic retrograde cholangiopancreatography, often results from sphincter of Oddi dysfunction. Endoscopic demonstration of elevated sphincter of Oddi pressures is required for diagnosis. The treatment of choice is usually endoscopic sphincterotomy, which yields long-term relief in most patients. Surgical sphincteroplasty or use of calcium channel blockers or long-acting nitrates may be effective if endoscopic sphincterotomy is not suitable.     

Low positive end-expiratory pressure does not exacerbate nebulized-acid lung injury in dogs

It is not clear if low end-expiratory pressures contribute to ventilator-induced lung injury in large animals. We sought to determine whether ventilation with a low level of positive end-expiratory pressure (PEEP) worsens preexisting permeability lung injury in dogs. Lung injury was initiated in 20 mongrel dogs by ventilating with nebulized 3N hydrochloric acid until a lower inflection point (LIP) appeared on the respiratory system pressure-volume loop. One group of 10 dogs was then ventilated for 4 hours with PEEP set below the LIP (low PEEP), whereas the remaining group of dogs was ventilated for the same time period with similar tidal volumes but with PEEP set above the LIP (high PEEP). We found histologic evidence of reduced alveolar volumes in the low-PEEP animals. However, there were no differences in neutrophil infiltration, lung lobe weights, pulmonary capillary hemorrhage or congestion, or arterial endothelin-1 concentration between the 2 protocol groups. In conclusion, we were unable to demonstrate that ventilation with PEEP set below the LIP exacerbates hydrochloric acid-induced lung injury in dogs.     

Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits

Introduction

Immobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that, compared to CMV without PEEP, the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties.

Methods

The PEEP level (8 cmH₂O) that did not induce lung overdistension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into seven groups: surgical controls and those receiving CMV, AMV or continuous positive airway pressure (CPAP) with or without PEEP for 2 days. We measured in vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase 3, insulin-like growth factor 1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger protein 1 (MuRF1) mRNA.

Results

PEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length; consequently, tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximum tetanic force (Po) production by 35% versus control (P < 0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV, with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to the fast isoform in the combined PEEP and CMV group. In both the CMV and combined PEEP and CMV groups compared to controls, IGF-1 mRNAs were suppressed, whereas Caspase-3, MAFbx and MuRF1 mRNA expression were elevated.

Conclusions

Two days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.     

Folic acid does not improve endothelial function in healthy hyperhomocysteinaemic subjects

Folic acid supplementation lowers total plasma homocysteine (tHcy) and improves endothelial function in individuals with coronary artery disease (CAD) and in those with additional CAD risk factors. In the present study, we assessed whether endothelial function is impaired in healthy subjects with hyperhomocysteinaemia but without other CAD risk factors and whether folic acid supplementation improves endothelial function in these subjects. Flow-mediated dilatation (FMD) of the brachial artery was performed on 26 healthy subjects, age 49 +/- 2 years (mean +/- S.E.M.), with high tHcy (15.6 +/- 1.5 micromol/l) and 16 healthy age-matched subjects with low tHcy (7.9 +/- 0.6 micromol/l; P < 0.001). Subjects with high tHcy were then randomized to receive 5 mg/day of folic acid or placebo for 8 weeks in a double-blind cross-over trial with a 4-week washout. FMD was not associated with tHcy and was not different between high and low tHcy groups (7.0 +/- 0.6% compared with 6.6 +/- 1.2%, P = 0.76). Treatment with folic acid decreased tHcy by 34% in hyperhomocysteinaemic subjects ( P = 0.02 compared with placebo), but had no effect on FMD (+ 0.5 +/- 0.6% compared with -0.7 +/- 0.5%; P = 0.17 compared with placebo). In healthy subjects with hyperhomocysteinaemia, but without additional cardiovascular risk, endothelial function is unimpaired and folic acid supplementation has no additional effect.     

DNR does not mean no care.

End-of-life care is a complicated topic, especially in a neurological intensive care unit. Death is a daily part of nursing care and should be treated with respect and a definite plan of care. Unfortunately, there are still hospitals that do not have protocols to deal with this outcome. The administration of opioids and appropriate sedation can be the difference between a calm serene death or one that is fraught with dyspnea, struggling, and unhappy families. Every hospital should have palliative care and hospice planning. This case study is about a dying patient that did not receive palliative care appropriately; however, through determination and personal knowledge of death and dying, a neurosurgical nurse was able to change the way a hospital dealt with do-not-resuscitate patients. Do not resuscitate does not mean no care; it means a different kind of care that can best be achieved through end-of-life protocols and education.     

Sildenafil attenuates pulmonary arterial pressure but does not improve oxygenation during ARDS

Objective  

Pulmonary hypertension is a characteristic feature of acute respiratory distress syndrome (ARDS) and contributes to mortality. Administration of sildenafil in ambulatory patients with pulmonary hypertension improves oxygenation and ameliorates pulmonary hypertension. Our aim was to determine whether sildenafil is beneficial for patients with ARDS.