Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.

Transcranial Doppler assessment of cerebral perfusion reserve in patients with carotid occlusive disease and no evidence of cerebral infarction.

Using transcranial Doppler ultrasound (TCD), we measured bilateral middle cerebral artery mean blood flow velocities (MCAVs) before and 10 minutes after intravenous infusion of 1 gram of acetazolamide in 20 patients without cerebral infarction. Seven patients had normal carotid arteries (group 1), seven had unilateral internal carotid artery (ICA) stenosis > or = 75% (group 2), and six had unilateral ICA occlusion (group 3). Before acetazolamide infusion, side-to-side differences in MCAV were 0.06 cm/sec in group 1 (p = 0.98), 4.3 cm/sec in group 2 (p = 0.36), and 15.0 cm/sec in group 3 (p = 0.02). Bilateral MCAV increased in all three groups after acetazolamide infusion, and the side-to-side differences in MCAV were 3.2 cm/sec in group 1 (p = 0.40), 11.4 cm/sec in group 2 (p = 0.04), and 27.6 cm/sec in group 3 (p = 0.03). Patients with carotid stenosis or occlusion and ipsilateral transient ischemic attacks (TIAs) had higher side-to-side differences in MCAV before (p = 0.03) and after (p = 0.01) acetazolamide than did asymptomatic patients with carotid disease. The association of impaired cerebral perfusion reserve and TIAs suggests that the TCD-acetazolamide test may enable identification of a subgroup of patients with carotid occlusive disease who are at higher risk for stroke.

Gd-DTPA-enhanced 3D MR imaging of cervical degenerative disk disease: initial experience.

PURPOSE: To assess whether a single enhanced T1-weighted gradient echo volume sequence, with the appropriate reformatted images, could be equivalent to a more conventional 2D set of MR sequences for the evaluation of cervical extradural degenerative disk disease (bony canal and foraminal stenosis; disk herniation). MATERIALS AND METHODS: Sixty-one patients evaluated for extradural degenerative disease by MR were imaged with a "standard" MR examination (Sagittal T1-weighted spin echo, axial low flip angle gradient echo), were then given 0.1 mmol/kg Gd-DTPA intravenously, and reimaged with either a 3D FLASH (fast low angle shot), TR 40/TE 7/1 excitation), 40 degree flip angle, acquired as 64, 2-mm sagittal partitions, or a 3D turbo FLASH (MP RAGE-magnetization prepared rapid acquisition gradient echo) (10/4/1), 10 degree flip angle acquired as 128, 2-mm coronal partitions. The volume sequences were reconstructed in the axial plane, and right and left 45 degree oblique coronal planes. The two sets of examinations (standard vs volume) were prospectively interpreted by two neuroradiologists for quality of examination, and location, type, and severity of extradural degenerative disease in a random, blinded, independent fashion. RESULTS: There was no significant difference between the standard examination and the 3D MP RAGE for central extradural disease. The 3D FLASH examination was significantly worse than the standard examination in identification of central extradural disease, with an average of 21 herniations not identified, or underestimated in size. Neither the 3D FLASH, nor the 3D MP RAGE examinations showed any significant improvement compared to the routine 2D examination for the location and severity of foraminal disease. CONCLUSION: If extradural degenerative disk disease is being evaluated, then a single enhanced 3D T1-weighted imaging sequence taking 6 minutes can be equivalent to a routine set of mixed 2D spin echo and low flip angle gradient echo sequences.

Factors predisposing to clinical disability in patients with cavernous malformations of the brain.

The factors predisposing to an aggressive clinical course in cavernous malformations of the brain are not known. Disabilities from neurological deficits and from seizures were assessed and graded in 84 patients harboring 100 cavernous malformations and were correlated with patient sex and age, lesion size, lesion location, lesion multiplicity, and previous overt hemorrhage. Univariate analysis showed that female sex, infratentorial lesion location, and previous gross hemorrhage were significantly associated with subsequent neurological disability. Logistic regression analysis showed that infratentorial lesion location and previous gross hemorrhage were independent factors simultaneously and significantly associated with neurological disability. Age less than 40 was the only significant factor predisposing to seizure disability (in both univariate and multivariate analyses). Lesion size, multiplicity, and other factors did not influence clinical disability. This information should assist in management decisions regarding cavernous malformations.

Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy.

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent, 27 patients, ages 3-10 years, were randomized to receive 10, 20, or 30 micrograms.kg-1 (Groups A, B, and C, respectively) of preservative-free morphine administered intrathecally by the surgeon after dural closure. Postoperatively, vital signs, pulse oximetry, and pain intensity scores were recorded hourly for 24 hr. Supplemental intravenous morphine was administered postoperatively according to a predetermined schedule based on pain scores. There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose. Time to first supplemental morphine dose was not different between groups. When compared to Groups A and B, cumulative 6-hr supplemental morphine dose was significantly lower in Group C (38.6 +/- 47 micrograms versus 79.1 +/- 74 and 189.6 +/- 126 for Groups A and B, respectively). By 12 hr, cumulative supplemental morphine dose was similar in Groups A and C. Group B consistently had a higher supplemental dose requirement than Groups A and C at 6, 12, and 18 hr. By 24 hr, there was no difference in cumulative dose among groups. Postoperative pain scores and the incidence of respiratory events, nausea, vomiting and pruritus were comparable among groups. These data suggest that intrathecal morphine at 30 micrograms.kg-1 provides the most intense analgesia at 6 hr following selective dorsal root rhizotomy, but was otherwise comparable to the 10 micrograms.kg-1 dose.

Fascial closure in the management of infected pancreatic necrosis.

Reports have focused on the perceived benefit of a new method of managing pancreatic necrosis and sepsis: leaving the abdomen packed open after debridement, the "marsupialization" technique. We have continued to treat infected pancreatic necrosis with aggressive pancreatic debridement and drainage, closure of the abdomen, and prompt reoperation as often as necessary if further sepsis is identified. We report 52 consecutive patients with infected pancreatic necrosis operated upon between July, 1972 and March, 1990. Postoperative organ failure and APACHE II scoring correlated with survival. Patients with APACHE II scores less than 15 had an operative mortality rate of 4 per cent, whereas patients with scores greater than 15 had a 44 per cent mortality rate. We recognize that no two retrospective series are truly comparable, but in comparison to published reports on the open technique, fascial closure after pancreatic debridement appeared to produce fewer wound complications (only one dehiscence and one incisional hernia) and fewer trips to the operating room.

Azathioprine vs cyclosporine in recipients of HLA-identical renal allografts.

BACKGROUND: Siblings with identical human leukocyte antigens (HLA) are preferred transplant donors. OBJECTIVE: To compare the outcomes in azathioprine-treated and cyclosporine-treated recipients of renal transplants from HLA-identical siblings. METHODS: Retrospective review. RESULTS: From August 1980 to June 1989, 53 consecutive patients received renal transplants from HLA-identical donors. These patients received prednisone and either azathioprine (n = 26) or cyclosporine (n = 27). A mean of 8.4 years elapsed since transplantation in the azathioprine-treated patients and 4.7 years elapsed in the cyclosporine-treated patients. The 5-year patient and graft survival rates were 100% and 92%, respectively, for azathioprine-treated patients and 96% and 83%, respectively, for cyclosporine-treated patients (P = .379 for comparison of graft survival). There was no difference between the two groups in the number of rejections or the time to the first rejection episode. At 5 years after transplantation, cyclosporine-treated patients had a significantly higher median serum creatinine concentration (1.7 mg/dL) than did azathioprine-treated patients (1.3 mg/dL, P = .018). Maintenance steroid therapy was successfully withdrawn in six azathioprine-treated patients and seven cyclosporine-treated patients. CONCLUSIONS: Azathioprine and cyclosporine produce equally satisfactory outcomes in this immunologically favored group. The need for continued steroid therapy in these patients requires further study.

Etiology of motor or sensory stroke: a prospective study of the predictive value of clinical and radiological features.

The diagnostic utility of clinical and radiological features for distinguishing penetrating artery disease from other causes of stroke has been questioned. To address this issue, we prospectively evaluated more than 40 features in 85 patients with pure motor, sensorimotor, or pure sensory syndromes. Nonischemic causes were present in 4 patients. The causes of ischemic stroke in the other 81 patients were penetrating artery disease (32 patients), large artery occlusive disease (17), cardioembolism (12), other causes (8), and undetermined (12). Of the features evaluated, frequent transient ischemic attacks (greater than or equal to 1/day), transient ischemic attacks occurring only within 1 week of stroke, pure motor hemiparesis (similar involvement of face, arm, and leg), pure sensory stroke, and round or oval infarction were associated (p less than 0.05) with penetrating artery disease. However, only pure sensory stroke involving two or more regions of the body and pure motor hemiparesis associated with subcortical infarction of less than 1.5 cm had positive predictive values exceeding 90% for penetrating artery disease. Carotid bruit ipsilateral to an anterior circulation infarction, monoparesis, and striatocapsular infarction had positive predictive values exceeding 90% for causes other than penetrating artery disease; however, half of the striatocapsular infarctions were of undetermined cause. These data suggest that certain clinical and radiological features are useful for distinguishing penetrating artery disease from other causes of stroke.

Reoperations and visual results after failed pneumatic retinopexy.

A single pneumatic retinopexy (PR) procedure failed to achieve permanent retinal reattachment in 23 (23%) of 101 cases of simple primary retinal detachment (RD). In 12 (16%) of 76 cases that were phakic or had an intact posterior capsule, a single PR failed compared with 11 (44%) of 25 cases without an intact posterior capsule. A total of 27 reoperations including eight repeat PRs (5 of which were successful) was required to achieve permanent retinal reattachment. Comparison of the final visual acuity and change from preoperative to final visual acuity between the initially failed and the successful cases demonstrated that initial failure of PR does not adversely affect the visual outcome. In all cases, the retina remained reattached at latest follow-up.

Systemic lidocaine and human somatosensory-evoked potentials during sufentanil-isoflurane anaesthesia.

The effect of systemically administered lidocaine on somatosensory evoked potentials (SSEPs) during general anaesthesia has not been widely reported. Knowledge of the influence of anaesthetic agents on evoked potentials assists in interpreting evoked potential waveforms. Accordingly, we studied the behaviour of cortical and subcortical (recorded at the second cervical vertebra) SSEPs after administration of intravenous lidocaine (3 mg.kg-1 bolus followed by infusion at 4 mg.kg-1.hr-1) during a sufentanil-based anaesthetic regimen in 16 patients undergoing abdominal or orthopaedic surgery. When compared to awake baseline recordings, the sufentanil-nitrous oxide, low-dose isoflurane anaesthetic depressed N1 amplitude by approximately 40% and prolonged latency by 10%. Fifteen minutes after establishment of this anaesthetic, the amplitude and latency of N1 were 1.13 +/- 0.56 microV and 19.81 +/- 1.63 msec, respectively. Within five minutes of adding lidocaine, amplitude decreased further to 0.84 +/- 0.39 microV (P = 0.001), while latency was extended to 20.44 +/- 1.48 msec (P = 0.01). Lidocaine did not affect cervical amplitude and prolonged latency only minimally. Despite the observed effects on amplitude and latency, SSEP waveforms were preserved and interpretable. Plasma lidocaine levels obtained at 5, 20, and 40 minutes after lidocaine were 5.17 +/- 1.33, 3.76 +/- 1.14, and 3.66 +/- 0.9 micrograms.dl-1, respectively. Our results indicate that systemically administered lidocaine at therapeutic plasma levels acts synergistically with a sufentanil-based anaesthetic to depress the amplitude and prolong the latency of SSEPs.

Evaluation of coexistent carotid and coronary disease by combined angiography.

We studied 247 patients who underwent combined coronary and carotid angiography to determine (a) the frequency of angiographic carotid stenosis (> 50%) in patients with coronary artery disease (CAD) and (b) the technical quality and safety of the combined procedure. All patients were evaluated primarily for CAD. Combined carotid angiography was performed for asymptomatic carotid bruits (115 patients, 47%), transient ischemic attacks (TIA) or stroke (66 patients, 26.5%), or inapparent/other reasons (66 patients, 26.5%). The extracranial internal carotid arteries were well visualized in 219 patients (89%); poor visualization of the internal carotid arteries was due to overlap by the vertebral or external carotid arteries. The frequency of >50% internal carotid stenosis was 36% in patients with asymptomatic carotid bruits, 42% in patients with TIA or stroke, and 8% in patients without TIA, stroke, or carotid bruits. Complication rates during combined coronary and carotid angiography in the 247 study patients were not statistically different from complication rates during coronary angiography alone in 686 control patients. These data indicate that (a) patients with CAD who have asymptomatic carotid bruits or a history of TIA or stroke have a high frequency of carotid stenosis, and (b) combined coronary and carotid angiography is a safe and technically adequate procedure.

Inotropic effects of angiotensin II on human cardiac muscle in vitro.

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.

Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients. A clinical severity score.

OBJECTIVE: To relate morbidity and mortality risk to preoperative severity of illness in patients undergoing coronary artery bypass grafting. DESIGN: Retrospective analysis of 5051 patients using univariate and logistic regression to identify risk factors associated with perioperative morbidity and mortality. Prospective application of models to a subsequent 2-year validation cohort (n = 4069). SETTING: Cleveland Clinic Foundation. PATIENTS: All adult patients undergoing coronary artery bypass graft surgery between July 1, 1986, and June 30, 1988 (reference group), and July 1, 1988, and June 30, 1990 (validation group). MAIN OUTCOME MEASURES: Mortality and morbidity (myocardial infarction and use of intra-aortic balloon pump, mechanical ventilation for 3 or more days, neurological deficit, oliguric or anuric renal failure, or serious infection). MAIN RESULTS: Emergency procedure, preoperative serum creatinine levels of greater than 168 mumol/L, severe left ventricular dysfunction, preoperative hematocrit of 0.34, increasing age, chronic pulmonary disease, prior vascular surgery, reoperation, and mitral valve insufficiency were found to be predictive of mortality. In addition to these factors, diabetes mellitus, body weight of 65 kg or less [corrected], aortic stenosis, and cerebrovascular disease were predictive of morbidity. Logistic regression equations were developed, and a simple additive score for clinical use was designed by allocating each of these risk-factor values of 1 to 6 points. Both methods predict mortality. Increased morbidity was demonstrated with increases in score. CONCLUSIONS: The logistic or clinical models developed are superior to the currently available methods for comparing mortality outcome and provide previously unavailable information on morbidity based on preoperative status. The clinical scoring system is useful for preoperative estimates of morbidity and mortality risks.

3DFT MR angiography of the carotid bifurcation: potential and limitations as a screening examination.

The authors compared the three-dimensional Fourier transform (3DFT) time-of-flight magnetic resonance (MR) angiograms in 38 patients initially studied with selective intraarterial digital subtraction angiography (DSA) for suspected arteriosclerotic disease of the carotid bifurcation. MR angiograms were successfully obtained in 65 of the 75 carotid arteries (87%) visualized with DSA. DSA and MR angiographic studies were assessed for percentage area stenosis by two independent observers on two occasions. Statistical tests indicated consistency in interpretation for each observer as well as between observers. No significant difference was found between the two modalities in ability to depict changes in percentage area stenosis. For the 32 right carotid arteries in the comparison, the median for the difference between MR angiography and intraarterial DSA was 1.83% (range, -22.38% to 55.60%); for the 33 visualized left carotid arteries, it was 0.00% (range, -20.55% to 49.95%). Receiver operating characteristic analysis indicated that technically adequate MR angiography may be a sensitive screening examination for stenoses.

The hemodialysis pilot study: nutrition program and participant characteristics at baseline. The HEMO Study Group.

OBJECTIVE: Describe the nutrition program (assessments and interventions) and the participants' baseline nutritional characteristics in the Hemodialysis Pilot Study. DESIGN: Cross sectional survey in which hemodialysis patients were examined during 10 weeks of baseline (BL), before randomization study interventions (dose and flux). SETTING: Four hemodialysis centers (eight dialysis units in total). PATIENTS: Twenty-nine male (mean age, 63 years; range, 34 to 75) and 20 female (mean age, 61 years; range, 29 to 73) hemodialysis patients. INTERVENTIONS: None during BL. MAIN OUTCOME MEASURES: Feasibility of implementing the proposed nutrition program before conducting the full-scale trial, and description of baseline characteristics related to nutrition. RESULTS: A nutrition program was developed to assess nutritional status during BL and follow-up periods and to intervene in patients with weight loss or decreasing serum albumin. Methods for collecting biochemical, dietary and anthropometric data were implemented at four clinical centers. At baseline, mean protein intake estimated by single pool normalized protein catabolic rate was 0.95 +/- 0.21 gm/kg adjusted body weight (ABW) (n = 42) and by diet record assisted recalls (n = 47) 0.94 +/- 0.36 gm/kg ABW/d, respectively. Mean energy intake was 22.8 +/- 8 kcal/kg ABW/day (n = 39). Mean serum albumin concentration using the bromcresol green method was 3.8 +/- 0.4 gm/dL (n = 40). Mean body mass index was within the normal limits of 19-27 kg/m2. Mean skinfold thicknesses in females, but not males, were shifted toward the lower end of usual distributions for healthy individuals. CONCLUSIONS: The goal of designing, developing, and implementing the diet and nutrition component, and related data collection for the HEMO pilot study was accomplished at four separate clinical centers. Baseline mean protein and energy intake were low, suggesting that continuing dietary surveillance is needed. The ongoing full-scale HEMO study will provide the first prospective analysis of dietary intake, nutritional status, and outcome in maintenance hemodialysis patients as a function of dialysis dose and membrane flux.