Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease.

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) has historically been managed with oxygen, antibiotics, and blood transfusions. Recently high-dose corticosteroid therapy was shown to reduce the duration of hospitalization in children with SCD and vaso-occlusive crisis. Therefore, we chose to assess the use of glucocorticoids in ACS. We conducted a randomized, double-blind placebo-controlled trial to evaluate the efficacy and toxicity of intravenous dexamethasone (0.3 mg/kg every 12 hours x 4 doses) in children with SCD hospitalized with mild to moderately severe ACS. Forty-three evaluable episodes of ACS occurred in 38 children (median age, 6.7 years). Twenty-two patients received dexamethasone and 21 patients received placebo. There were no statistically significant differences in demographic, clinical, or laboratory characteristics between the two groups. Mean hospital stay was shorter in the dexamethasone-treated group (47 hours v 80 hours; P = .005). Dexamethasone therapy prevented clinical deterioration and reduced the need for blood transfusions (P < .001 and = .013, respectively). Mean duration of oxygen and analgesic therapy, number of opioid doses, and the duration of fever was also significantly reduced in the dexamethasone-treated patients. Of seven patients readmitted within 72 hours after discharge (six after dexamethasone; P = .095), only one had respiratory complications (P = 1.00). No side effects clearly related to dexamethasone were observed. In a stepwise multiple linear regression analysis, gender and previous episodes of ACS were the only variables that appeared to predict response to dexamethasone, as measured by lengh of hospital stay. Intravenous dexamethasone has a beneficial effect in children with SCD hospitalized with mild to moderately severe acute chest syndrome. Further study of this therapeutic modality is indicated.

Magnetic resonance imaging of muscle in amyotrophic lateral sclerosis.

OBJECTIVE: To characterize leg muscle abnormalities in patients with ALS using MRI, and to correlate MRI with standard neurologic measures of motor neuron dysfunction. METHODS: Eleven ALS patients were studied twice (once at baseline and again after 4 months) and compared with eight normal control subjects. MRI data of the lower extremities were compared with tibialis anterior compound muscle action potential amplitude (CMAPa) and foot dorsiflexion maximal voluntary isometric contraction (MVIC). RESULTS: Muscle MRI was abnormal by visual inspection in six of 11 patients. The mean muscle T1 time and muscle volume were not different in patients compared with normal control subjects (p > 0.1). However, the mean T2 times were increased in the patients compared with normal control subjects (p = 0.009). T1 times did not correlate with CMAPa or MVIC. Muscle volume correlated with MVIC (r = 0.73 to 0.78, p < 0.02) but not with CMAPa (p > 0.05). There was a strong negative correlation (r < -0.8, p < or = 0.01) between muscle T2 time and MVIC and CMAPa. Also, the change in T2 relaxation time correlated with the change in CMAPa as the disease progressed (r = -0.63, p = 0.037). CONCLUSION: Of the MRI characteristics studied, T2 relaxation time was the best indicator of motor neuron dysfunction and may have a role in objective evaluation of motor neuron dysfunction.

Proposed cutoff values to define bladder outlet obstruction in women.

OBJECTIVES: There is no accepted urodynamic definition of outlet obstruction in women. Currently, the diagnosis is made on the basis of history and radiographic and endoscopic findings. The goal of this study is to design a pressure-flow nomogram (PdetQmax/Qmax) and define cut-off values for obstruction. METHODS: Two groups were studied prospectively in an open study: 124 control and 35 clinically obstructed patients. All had a complete history, physical examination, normal neurologic evaluation, cystoscopy, voiding cystography, and urodynamics-with-pressure-flow study. Pressure-flow plot and receiver operator characteristic curves (ROCs) were constructed to determine optimal cut-off values to predict obstruction for peak flow rate (Qmax) and detrusor pressure at maximal flow (PdetQmax). RESULTS: The etiology of obstruction was previous anti-incontinence surgery (n = 13), large cystocele (n = 11), urethral stricture (n = 6), and other (n = 5). On the basis of ROC curves, using cut-off values of Qmax of 15 mL/s or less and 12 mL/s or less, sensitivity was 85.7% and 71.4%, and specificity 78.2% and 90.3%, respectively. Using cut-off values of PdetQmax of more than 25 and more than 30 cm H2O, sensitivity was 74.3% and 71.4%, and specificity 79.8% and 88.7%, respectively. Using a combined cut-off value of Qmax of 1 5 mL/s or less and PdetQmax of more than 20 cm H2O, sensitivity was 74.3% and specificity was 91.1%. CONCLUSIONS: Based on this prospective, controlled study, preliminary cut-off values were obtained for refining the definition of outlet obstruction in women.

Recent advances in the treatment of cystinosis.

Cysteamine bitartrate capsules (Cystagon) have been approved by the US Food and Drug Administration for use in patients with nephropathic cystinosis. Plasma cysteamine concentrations were virtually identical at various times following ingestion of either cysteamine hydrochloride or Cystagon capsules in 24 normal control subjects. A transfer study was done with eight cystinosis patients who had been receiving either cysteamine hydrochloride or phosphocysteamine for many years. The plasma cysteamine concentration was significantly higher 2h after Cystagon and the leukocyte cystine content was significantly lower at all times after Cystagon compared to older forms of the drug. These differences are probably the result of greater patient compliance in taking the capsules compared to the older, liquid forms of the drug. A new method for following the course of renal glomerular deterioration in diseases such as cystinosis has been published recently. This method was used to re-analyse data on the efficacy of cysteamine treatment and to re-analyse new data on treating cystinosis patients with either of two doses of cysteamine (1.30 g/m2 per day and 1.95 g/m2 per day). This new method agrees well with other methods and shows that both doses of drug are equally effective in maintaining glomerular function.

Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.

OBJECTIVE: To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications. DESIGN: A placebo-controlled, randomized trial. SETTING: Outpatient setting of specialty clinics in Dallas and Temple, Texas. INTERVENTIONS: Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously. PATIENTS: 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis. MEASUREMENTS: Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry. RESULTS: In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia. CONCLUSIONS: Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.

Prognostic indicators in children with IgA nephropathy--report of the Southwest Pediatric Nephrology Study Group.

Investigators in 13 pediatric nephrology centers reviewed clinical and pathological features in 218 children and adolescents with IgA nephropathy (IgAN), with particular emphasis on 80 patients who had follow-up periods of at least 4 years. Potential prognostic markers in the 80 children were compared between 12 (15%) who developed end-stage renal disease (ESRD) versus 68 who did not. The relationship between clinical and pathological features and the subsequent development of ESRD was examined using stepwise linear discriminant analysis in addition to standard univariate analysis. Seven variables were found to be predictive of ESRD: the presence of glomerular sclerotic changes, especially when this was associated with proliferation or sclerosis in 20% or more of the glomeruli; black race; hypertension at biopsy; proteinuria at biopsy; age at presentation; crescents; male sex. Using the resulting discriminant function, development of ESRD could be correctly predicted in 95% of the subjects. We conclude that ESRD is more common in American children with IgAN than was realized previously. Risk factors previously documented in adult studies have been confirmed, especially the presence of glomerular sclerosis, proteinuria, and hypertension.

Dietary protein and growth in infants with chronic renal insufficiency: a report from the Southwest Pediatric Nephrology Study Group and the University of California, San Francisco.

This report describes growth and nutrition data from the feasibility phase of a clinical trial that was designed to evaluate the effect of diet protein modification in infants with chronic renal insufficiency (CRI). The purpose of the proposed trial was to compare the safety (effect on growth in length) and efficacy [effect on glomerular filtration rate (GFR)] of a diet with a low protein: energy (P:E) ratio versus a control diet in such patients. Twenty-four infants with GFRs less than 55 ml/min per 1.73 m2 were randomly assigned at 8 months of age to receive either a low-protein (P:E ratio 5.6%) or control protein (P:E ratio 10.4%) formula, which resulted in average protein intakes of 1.4 and 2.4 g/kg per day in the low and control groups, respectively. Overall energy intakes over a 10-month period of study averaged 92% +/- 12% recommended dietary allowance (RDA) for length in the low-protein group and 92 +/- 15% RDA in the control group. Weight for age standard deviation scores (SDS) were comparably low in both groups at the time of randomization (low-protein--2.0 +/- 1.3, control -1.9 +/- 1.1) and at the end of the study (low -1.9 +/- 1.2, control -1.7 +/- 0.9). Length for age SDS at entry tended to be lower in the low-protein group but were not significantly different in the two groups (low -2.2 +/- 1.4 vs. control -1.7 +/- 1.4). However, at 18 months the low-protein group had a significantly lower SDS for length (-2.6 +/- 1.2 vs. -1.7 +/- 1.4).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of etomidate on cerebral metabolism and blood flow in a canine model for hypoperfusion.

The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on cerebral metabolism and blood flow were studied in 29 dogs during cerebral hypoperfusion. Three groups of animals were studied during a 45-minute normotensive and a 30-minute hypotensive period: 10 control animals without etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals receiving doses of etomidate sufficient to suppress electroencephalographic bursts (high-dose group). The mean arterial pressure fell to similar levels (p less than 0.05) during hypotension in all three groups (40 +/- 5, 38 +/- 3, and 27 +/- 6 mm Hg, respectively). The mean cerebral oxygen extraction fraction rose (p less than 0.05) from 0.23 +/- 0.02 to 0.55 +/- 0.08 in the five control animals tested and from 0.33 +/- 0.02 to 0.53 +/- 0.02 in the seven animals tested in the low-dose group, but did not increase (p greater than 0.05) in the four animals tested in the high-dose group (0.24 +/- 0.03 to 0.23 +/- 0.05). Mean cerebral blood flow levels decreased in all groups during hypotension (p less than 0.05): 42 +/- 3 to 21 +/- 4 ml/100 gm/min (52% +/- 12% decrease) in the five animals tested in the control group, 60 +/- 8 to 24 +/- 6 ml/100 gm/min (56% +/- 13% decrease) in the four animals tested in the low-dose group, and 55 +/- 8 to 22 +/- 3 ml/100 gm/min (60% +/- 4% decrease) in the four animals tested in the high-dose group. In summary, the cerebral oxygen extraction fraction increased in the control animals and low-dose recipients during hypotension, suggesting the presence of threatened cerebral tissue. In contrast, the cerebral oxygen extraction did not change during hypotension when high-dose etomidate was administered. It is concluded that high-dose etomidate may preserve the cerebral metabolic state during hypotension in the present model.

Ringer's lactate with or without 3% dextran-60 as volume expanders during abdominal aortic surgery.

OBJECTIVE: To compare a solution of 3% dextran-60 (D60) in Ringer's lactate (RL) with RL alone as maintenance fluids for abdominal aortic surgery. DESIGN: Randomized control trial of 20 consecutive patients undergoing elective aortic reconstructive surgery. SETTING: A surgical ICU in a university hospital. PATIENTS: Consecutive patients, mean age 64 yr. Five patients had abdominal aneurysm, 12 had aortic obstruction disease, and three had aortic renal bypass surgery. These patients were followed for 1 month. INTERVENTIONS: Pulmonary artery occlusion pressure of at least 10 mm Hg and a urine output greater than 30 mL/h were used to guide the intraoperative fluid infusion rates, which were 36 and 104 mL/kg of D60 and RL, respectively (ratio 1:2.9). MEASUREMENTS AND MAIN RESULTS: Body weight at 24 hr had increased more with RL (7.8 kg) than with D60 (3.2 kg) infusion (p less than .01), despite intraoperative urine volumes of 151 and 92 mg/kg with RL and D60, respectively. Total intravascular albumin decreased from 0.7 g/kg (1.4 to 0.7 g/kg) in both groups, corresponding to a plasma volume (PV) loss of 13 mg/kg without fluid infusions. A total intravascular dextran of 0.5 g/kg resulted in a PV expansion at 1 hr of 4.4 mL/kg above preoperative level, in sharp contrast to 7.0 mL/kg decrease in PV with RL. Of the intraoperative 3% D60 and RL infused, an estimated 51% D60 and 6% RL remained as PV expansion at 1 hr. CONCLUSIONS: A diluted colloid solution in Ringer's lactate is of significant value in maintaining intravascular volumes and hemodynamics during and after major operative procedures.

Failure of surgery to improve outcome in hypertensive putaminal hemorrhage. A prospective randomized trial.

Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage.

Deacylated lipopolysaccharide inhibits plasminogen activator inhibitor-1, prostacyclin, and prostaglandin E2 induction by lipopolysaccharide but not by tumor necrosis factor-alpha.

Bacterial LPS and TNF induce vascular endothelial cells to express a variety of response molecules. LPS that is partially deacylated (dLPS) by a human neutrophil enzyme blocks the ability of LPS, but not TNF, to augment one of these responses, the expression of endothelial cell surface molecules that promote neutrophil adherence (J. Exp. Med. 1987; 165:1393-1402). We show that dLPS can inhibit the ability of LPS, but not TNF, to elicit the expression of plasminogen activator inhibitor-1 (PAI-1), prostacyclin, and PGE2 by human umbilical vein endothelial cells. dLPS also prevented the accumulation of specific PAI-1 mRNA in response to LPS, but not to TNF. Neither the LPS- or TNF-induced expression of PAI-1 nor the dLPS inhibition of the LPS response was mediated by prostanoids. These results indicate that dLPS can specifically block a variety of endothelial cell responses to LPS and provide support for the hypotheses 1) that dLPS and LPS may interact with a common target molecule on or in endothelial cells, and 2) that dLPS, produced by enzymatic deacylation of LPS in vivo, could inhibit endothelial cell stimulation by LPS and thereby limit the host inflammatory response to invasive gram-negative bacteria.

Aid to the evaluation of therapeutic studies.

Physicians are often faced with conflicting recommendations from therapeutic studies. An evaluation form is proposed to facilitate the evaluation of the quality of therapeutic studies and the resulting treatment or management recommendations in any area of medicine. Twelve major topics for evaluation include sample size determination, randomization, selection of control group(s), "blinding," and support for treatment recommendations. Emphasis is placed on study design and performance rather than data analysis. Thirty-four primary criteria based on accepted research standards are designated as most important, and examples from the literature are provided to illustrate their use. The form provides a comprehensive set of well-accepted standards of research in a format that encourages detailed, consistent, and thoughtful evaluation of therapeutic studies. The evaluation form is recommended as a tool for physicians who wish to develop and exercise skill in evaluating therapeutic studies.

Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis.

Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.

The effect of acetazolamide on regional cerebral blood flow in patients with Alzheimer's disease or stroke as measured by single-photon emission computed tomography.

Regional cerebral blood flow (rCBF) was assessed in 35 patients with possible or probable Alzheimer's disease (AD) and in 16 patients known to have had at least one stroke. Patients were evaluated before and after the administration of 1 g acetazolamide (ACZ) by means of a rotating four-detector single-photon emission computed tomograph (SPECT) and inhaled Xe-133. RCBF values in mL/minute/100 g were derived from eight cortical regions of interest (ROI), and from the whole transverse section as a measure of whole brain flow (WBF). ROI/WBF ratios were calculated for each ROI in paired determinations done before and 15 minutes after the administration of ACZ. Results were compared with those previously obtained in a study of 15 normal, healthy volunteer subjects. ROI/WBF ratios greater than 2 standard deviations (SD) below the mean for a given ROI in the normal group were regarded as probably abnormal, whereas ratios greater than 4 SD below the mean were considered definitely abnormal. After ACZ administration, the number of ROI greater than 2 SD below the normal mean decreased significantly in the AD group and was unchanged in the stroke patients. However, the number of ROI/WBF ratios greater than 4 SD below the normal mean fell in the AD group and rose in the stroke group, with the difference in behavior highly statistically significant. Thus, the response of low-flow areas to ACZ differs in AD and in stroke, which could be of ultimate diagnostic significance.

Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis.

The results of randomized clinical trials evaluating commonly used methods of deep vein thrombosis (DVT) prophylaxis in moderate- and high-risk general surgery patients were pooled to obtain an unbiased estimate of efficacy and risks. Low-dose heparin (LDH), dextran, heparin-dihydroergotamine (HDHE), intermittent pneumatic compression (IPC), and graded elastic stockings significantly reduced the incidence of DVT; aspirin was ineffective. In contrast to other methods, elastic stockings have not been adequately studied to determine their value in reducing DVT in high-risk patients, such as those with malignancy. Only LDH and dextran were studied in numbers of patients sufficient for demonstrating a clear reduction in pulmonary embolism (PE). In comparison studies, LDH was superior to dextran in preventing DVT, but the two agents were equivalent in protecting against PE. Although HDHE was marginally better than LDH in preventing DVT, it appeared to have no advantage in preventing PE--at least in moderate-risk patients. The incidence of major hemorrhage was not increased with any of the prophylactic agents. However, wound hematomas occurred significantly more frequently with LDH, an effect noted in the pooled data from double-blind and open trials. In comparison trials with LDH, both dextran and HDHE had significantly fewer wound hematomas. LDH administered every 8 hours appeared more effective in reducing DVT than LDH administered every 12 hours; the incidence of wound hematomas was equivalent with both regimens.

The effect of acetazolamide on regional cerebral blood flow in normal human subjects as measured by single-photon emission computed tomography.

Regional cerebral blood flow (rCBF) was evaluated in 15 normal, healthy volunteer control subjects before and after the administration of 1 g acetazolamide (ACZ) using a rotating four-detector single-photon emission computed tomograph (SPECT). ACZ, a carbonic anhydrase inhibitor, is a cerebral vasodilator. RCBF values in mL/minute/100 g were derived within eight cortical regions of interest (ROI), and from the whole slice as an expression of whole brain blood flow (WBF). ROI/WBF ratios were established for each ROI in each of the 15 subjects for both pre-ACZ and post-ACZ studies. ACZ produced a 30% +/- 17% increase in WBF. Studies were done in random order, with nine subjects undergoing the post-ACZ study first, and six the pre-ACZ, or baseline, study first. Statistical analysis showed no significant difference in any ROI that might be caused by sequence of test procedures. Ratios were then examined to determine whether rCBF elevation was proportionate in all ROI in all subjects. No significant difference was found in any ROI except for the left parietal, for which marginally significant change was identified. Subjects also were examined for possible age and sex differences in ACZ response, and no differences were found.

Haemophilus influenzae type b lipooligosaccharide induces meningeal inflammation.

We evaluated the ability of two Haemophilus influenzae type b (Hib) components, lipooligosaccharide (LOS) and capsular polysaccharide, to provoke meningeal inflammation in rabbits. Intracisternal inoculation of 2 fg-200 ng of LOS produced a dose-dependent increase in concentrations of white blood cells and protein in cerebrospinal fluid, whereas 4 micrograms of Hib capsular polysaccharide did not provoke meningeal inflammation. Preincubation of LOS with a murine monoclonal antibody to Hib LOS did not reduce the potency of the LOS. Incubation of LOS with polymyxin B (which neutralizes LOS by binding to its lipid A region) and deacylation of the LOS with acyloxyacyl hydrolase (a neutrophil enzyme that removes nonhydroxylated fatty acyl chains from lipid A) reduced meningeal inflammation. We demonstrated that purified Hib LOS induced meningeal inflammation in this model and suggest that the lipid A moiety of Hib LOS is principally responsible for this host response.

Conservation of the hypopharyngeal mucous membrane in total laryngectomy.

Dysphagia secondary to partial pharyngeal stenosis after total laryngectomy is most likely attributable to the size of the reconstructed lumen. To reduce the incidence of this postoperative complication, we have utilized a modification of total laryngectomy that conserves the hypopharyngeal mucous membrane. The results of this surgical procedure are now reported in the context of two similar, contemporaneous groups of patients who underwent either standard wide-field laryngectomy or hypopharyngeal mucosa conservation laryngectomy. Statistical analysis showed no difference between groups in cancer control (P = .80) or survival (P = .65); whereas the group treated with hypopharyngeal conservation laryngectomy had significantly less pharyngeal stenosis as measured by dysphagia and need for dilatation (P = .011).

Dexamethasone in the treatment of experimental Haemophilus influenzae type b meningitis.

A model of experimental lapin meningitis was used to assess the effect of meningeal inflammation caused by Haemophilus influenzae type b on development of brain edema, increase in intracranial pressure, and production of brain lactate. Four treatments were assessed: dexamethasone alone, dexamethasone plus ceftriaxone, ceftriaxone alone, and no treatment. The brain water content in untreated rabbits with meningitis was 419 +/- 10 g of H2O/100g of dry weight after 29 hr of infection (vs. 405 +/- 14 in uninfected rabbits; P less than .05). In rabbits treated with dexamethasone, dexamethasone plus ceftriaxone, or ceftriaxone alone, these values were 404 +/- 12, 406 +/- 12, and 411 +/- 14 g, respectively (P greater than .05). The cerebrospinal fluid (CSF) pressure and lactate levels were significantly increased in all animals during the 24 hr of meningeal inflammation (P less than .005), and these levels were comparably reduced after 9 hr of treatment. Although the values for brain water content, CSF pressure, and lactate concentrations in infected animals treated with ceftriaxone plus dexamethasone were not significantly different from those in animals treated with ceftriaxone alone, the values were consistently lower in the former group.

Infusion volumes of Ringer's lactate and 3% albumin solution as they relate to survival after resuscitation of a lethal intestinal ischemic shock.

Previously, we have shown improved survival rate with colloid solutions of 2-4% concentration compared to 10% solutions or a colloid-free electrolyte solution, when given in volumes required to maintain the same intravascular volume expansion. This study examines the effect of increasing infusion volumes of Ringer's lactate (RL) and 3% albumin on survival time and blood volume expansion using the lethal intestinal ischemic shock model in rats. Shock was induced by exteriorization of the small intestine with added occlusion of the superior mesenteric vessels for 75 minutes. Untreated animals developed hemoconcentration to 60% in hematocrit (Hct), representing a plasma volume (PV) decrease to 57% of the preshock level. Infusion of 3% albumin increased PV linearly up to 200% above shock levels with infusion volumes of 0-45 ml/100 g bwt. RL increased PV linearly up to 80% above shock baseline level with infusion volumes up to 50 ml/100g. No further PV increase occurred despite increasing volumes of RL. No infusion volume, therefore, of RL restored PV to preshock levels. To achieve the same volume expansion up to 80% above the shock PV levels, 4.4 times larger volume of RL was needed compared to 3% albumin solution. With the same volumes infused (up to 45 ml/100 g), 4-5 times more of the 3% albumin volume infused remained in the vascular space compared to RL. Also, the excreted volume was larger with albumin than with RL, for the same volumes infused. Accordingly, the major portion of the infused RL (60-80%) was located in the extravascular space. No control animals survived 24 hours. Survival time was prolonged with both RL and 3% albumin infusions. The effect on survival time with albumin was obtained with approximately 25% of the fluid required for RL.