Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation.

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.

Alterations in oxygen saturation and ventilation after intravenous sedation for peritoneoscopy.

The effect of intravenous sedation on oxygen saturation and ventilation was studied in 11 patients undergoing peritoneoscopy. Oxygen saturation (mean +/- SD) decreased from baseline (94.7% +/- 1.7%) to nadir (78.6% +/- 10.7%) after sedation. Respiratory depression was evident in these patients by concomitant decreases in minute ventilation and tidal volume. Baseline to nadir arterial blood gas changes in eight patients were consistent with hypoventilation and also suggested a superimposed ventilation perfusion mismatch. Mean respiratory rate did not significantly change during peritoneoscopy. Peritoneal gas insufflation stimulated increased ventilation and oxygen saturation, but no further changes in PCO2 or pH. We conclude that serious arterial oxygen desaturation and possibly some ventilation perfusion mismatch occur after sedation with intravenously administered meperidine-diazepam for peritoneoscopy with resultant hypoxemia, hypercarbia, and acidosis.

Metoclopramide kinetics in patients with impaired renal function and clearance by hemodialysis.

Metoclopramide kinetics were examined in 24 adult patients with diminished renal function and in eight healthy subjects with normal renal function. Creatinine clearance correlated with metoclopramide plasma clearance, renal clearance, nonrenal clearance, and elimination t1/2. Regardless of renal function, renal clearance accounted for less than or equal to 21% of total plasma clearance. Nonrenal clearance was reduced in patients and accounted for most of the reduction in plasma clearance. The comparatively small plasma clearances in patients imply that maintenance doses should be reduced accordingly to avoid drug cumulation. Metoclopramide clearance by hemodialysis was also assessed in four patients. Metoclopramide losses from hemodialysis were relatively small compared to estimates of total body metoclopramide stores. Compensatory dosage increases are probably unnecessary for most patients. These data also suggest that hemodialysis is not likely to be effective in metoclopramide overdose.

Passive smoking and thiocyanate concentrations in pregnant women and newborns.

Serum thiocyanate concentrations have been used as a marker of cigarette exposure in both smokers and nonsmokers. The authors used this measure to estimate passive exposure in low-risk healthy pregnant women at term. Three groups were compared: smokers, passive smokers, and nonsmokers. The mean thiocyanate concentration (95 mumol/L) was significantly higher (P less than .001) in smokers than in passive smokers (35.9 mumol/L) or nonsmokers (32.3 mumol/L). The maternal and umbilical mean cord thiocyanate concentrations were similar in the smoking group (95 versus 72 mumol/L). Although the umbilical cord levels in the infants of passive smokers and nonsmokers were similar (26 versus 23 mumol/L), both levels were significantly lower than those of smokers. Most important, there was an inverse relationship between umbilical cord thiocyanate concentration and birth weight (P less than .001). The authors found no evidence that passive cigarette smoke exposure resulted in higher maternal or umbilical cord thiocyanate concentrations than found in nonsmokers.

Comparison of sustained-release quinidines given twice daily to patients with ventricular ectopy.

To compare the steady-state kinetic profiles and ectopy-suppression rates of two sustained-release forms of quinidine with those of a conventional quinidine preparation, 18 patients with ventricular ectopy were studied in randomized crossover fashion. The drugs were conventional quinidine sulfate 300 mg q6h, sustained-release quinidine sulfate 600 mg q12h, and sustained-release quinidine gluconate 648 mg q12h. Following baseline electrocardiographic ambulatory monitoring, each drug was given for three days, with repeat ambulatory monitoring and serial plasma drug level determinations performed on the third day. There were no washout periods between treatments. Plasma quinidine levels were assayed by both enzyme multiplied immunoassay technique (EMIT) and quinidine-specific high-performance liquid chromatography (HPLC) methods. Using actual steady-state HPLC values, there were no differences in the area under the plasma concentration-time curve (AUC) among the three treatments; the dose-corrected AUC was greater for quinidine gluconate than for the other two preparations. Using EMIT values, mean plasma quinidine levels from the conventional quinidine sulfate regimen were greater during the last five hours of the 12-hour study interval. A consistently strong inverse relationship between EMIT plasma quinidine levels and hourly ectopy rates was present in only one of eight (13%) responders. Diurnal variation of quinidine kinetics was observed after two days of each treatment; trough values at midnight were slightly lower than trough values at noon. Among patients demonstrating at least 70% suppression of premature ventricular contractions (PVCs), there were no differences in ectopy rates or ectopy-suppression rates among treatments. Dosing sustained-release quinidine sulfate 600 mg or quinidine gluconate 648 mg q12h was clinically acceptable in the small number of responders studied.

The validity of transcranial radiography in diagnosing TMJ anterior disk displacement.

Two transcranial radiographic methods for determining anterior disk displacement in the TMJ were evaluated in comparison with results obtained from arthrography. Both transcranial radiographic methods could only accurately predict the presence of an anteriorly displaced disk in a range of 26% to 56% of the time (for example, the methods gave false-negative results 44% to 74% of the time). The methods were more valuable in correctly identifying joints that were free of disease, achieving this identification anywhere from 64% to 96% of the time. Although noninvasive, these two transcranial radiographic techniques produced results that lacked validity and, therefore, remain of questionable value to the clinician who is diagnosing anterior disk displacement.

Golytely lavage--is metoclopramide necessary?

During Golytely cleansing for colonoscopy, two dose forms of oral metoclopramide were evaluated in separate studies for patient tolerance and adequacy of preparation. In study 1, patients were randomized to 10 mg metoclopramide (n = 21) or placebo (n = 27); in study 2, 20 mg metoclopramide (n = 21) was compared to placebo (n = 25). Ten milligrams metoclopramide was not significantly different from placebo in patient acceptance for any of the assessed symptoms. Patients taking 20 mg metoclopramide had less cramping (p = 0.02), but more nausea (p = 0.03) than placebo. Time for rectal effluent to clear was similar in all groups. The percentage of patients preferring Golytely was similar in both studies (70-79%, p = NS) and 85% of all patients were willing to repeat Golytely. Physician assessment of colon cleansing showed no difference between metoclopramide or placebo in either study, with adequate preparations in 97% and optimal cleansing in 80% of all patients. Neither 10 nor 20 mg oral metoclopramide improved adequacy of colon cleansing for colonoscopy or decreased symptoms associated with Golytely lavage.

Colon cleansing: acceptance by older patients.

The influence of age on patient acceptance and adequacy of preparation was evaluated in 557 patients from our previous colon cleansing studies for colonoscopy, barium enema, and elective colon surgery. Since study design was similar for all studies, the patients were combined and stratified to those over age 60 (old) and those 60 or younger (young). Patients were previously randomized in their respective studies to polyethylene glycol electrolyte gut lavage solution (old, 105; young, 181) or standard prep (old, 71; young, 20). Patient response data were analyzed in two fashions; distribution of response scores and minimal responses. When the distribution of scores were compared, older gut lavage patients had fewer cramps but more overall discomfort than younger patients receiving the lavage preparation. Older standard prep patients had less overall discomfort than younger standard prep subjects. Comparison of responses rated as minimal showed the older lavage patients to have fewer cramps than younger lavage patients and fewer cramps than standard preparation patients of similar age. None of the other assessed symptoms was significantly different between age groups or prep method. Most patients had minimal symptoms regardless of age or prep. Age did not influence adequacy of preparation for gut lavage or standard prep methods.

Comparison of CO2- and N2O-induced discomfort during peritoneoscopy under local anesthesia.

The most comfortable gas for peritoneoscopy has been the subject of debate. We subjected 46 patients to double-blind comparison of carbon dioxide and nitrous oxide during initial pneumoperitoneum. The discomfort from local anesthesia was similar in both patient groups. The patient's and the physician's assessment of discomfort during gas insufflation showed that carbon dioxide was more uncomfortable as perceived by the patient (p = 0.02), the physician (p = 0.0006), and objectively assessed by degree of abdominal splinting (p = 0.006). The presence of intraabdominal adhesions had no relationship to discomfort. We conclude that nitrous oxide is more comfortable for institution of pneumoperitoneum during peritoneoscopy under local anesthesia.

Bond strengths of three resin systems used with brackets and embedded wire attachments.

Orthodontic wire bonded directly to teeth with a resin adhesive system has been used to establish anchor units for procedures in orthodontics as well as for splinting teeth in other disciplines. This procedure can save the cost and time of placing a bracket. In addition, several different resin systems have been used for this procedure as well as for placing brackets. The purpose of this study was to determine the strength of three adhesive systems used to bond orthodontic wires directly to teeth and to compare these values with those found for directly bonded orthodontic brackets. Equal sample sizes of brackets or wires were attached to 240 human teeth with either Concise, Miradept, or Endur in a standardized area of etched enamel. Shear and tensile strengths were measured at 30 minutes and at 48 hours. At 30 minutes brackets were significantly stronger than embedded wires, and Concise was significantly stronger than either of the other resins. However, all significant differences between any of the three resin systems using either bonded brackets or wires disappeared at 48 hours. Whether or not this initial strength difference is clinically significant remains speculative.

Normal standards for kidney length in premature infants: determination with US. Work in progress.

In 52 healthy premature infants, 104 kidneys were sonographically examined and kidney length was measured. Kidney length was compared with four parameters: body weight, body length, body surface area, and gestational age. Scatter plots of these data demonstrated that kidney length versus body weight conformed well to a linear distribution with a high correlation coefficient. A nomogram for kidney length versus body weight in premature infants is also presented.

Ritodrine hydrochloride infusion in pregnant baboons. I. Biophysical effects.

Pulmonary edema is a potentially fatal complication of beta-sympathomimetic therapy for premature labor. Isolated case reports have supported either primary pulmonary capillary membrane injury or left ventricular failure as the cause of pulmonary edema. By simultaneously monitoring cardiac function and extravascular lung water in six control and six ritodrine hydrochloride-treated pregnant baboons, we attempted to define this pathophysiology. The pulmonary capillary wedge pressure increased in treated animals, reaching significance at 16 hours of ritodrine treatment (p less than 0.0001) concurrent with the maximum increase in cardiac index (p = 0.02). Treated animals also retained 61% of intravenously administered fluids compared with 23% in untreated control animals (p less than 0.002). There were, however, no significant differences between groups in extravascular lung water, central venous pressure, or pulmonary artery pressure. Chest radiographs and arterial blood gas analysis were also comparable between ritodrine-treated and control animals. Fluid retention and elevated hydrostatic pressure are postulated as the etiology of beta-sympathomimetic-induced pulmonary edema. There was no evidence to support a primary pulmonary capillary membrane injury by ritodrine.

Metoclopramide effect on esophageal peristalsis in normal human volunteers.

There is relatively poor documentation of the effect of metoclopramide on the human esophageal body. We, therefore, studied several parameters of esophageal function in 19 normal volunteers both before and after 20 mg intravenous metoclopramide. Contraction amplitude, wave duration, velocity, and propagation time were increased after metoclopramide. These changes were more pronounced in the distal esophagus. At the most distal manometric recording level located 2 cm above the lower esophageal sphincter, contraction amplitude increased 39% (p less than 0.01) and duration increased 22.5% (p less than 0.01) after metoclopramide. We conclude that in normal subjects metoclopramide has an effect predominant in the distal body of the esophagus.