Determinants of lung bacterial clearance in normal mice.

The determinants of the lung clearance of Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus were studied in normal mice after exposure to an aerosol of viable bacteria and 99mTc-labeled dead bacteria. The fraction of bacteria in lungs that remained viable 4 h after exposure were: S. pneumoniae, 7.3%; K. pneumoniae, 121%; E. coli, 88.5%; S. aureus, 27.6%. The rate of physical removal of bacterial particles (Kmc) was determined from the change in lung 99mTc counts with time: Kmc ranged between 7 and 12%/h and and was similar in all species. The rate of mucociliary clearance and of intrapulmonary bacterial killing (Kk + Kmc) was calculated from the change in bacterial counts with time in animals that had received tetracycline to inhibit bacterial multiplication. Kk, the rate of intrapulmonary killing, was obtained by subtraction of Kmc from (Kk + Kmc). The calculated values for Kk were: S. pneumoniae, - 87%/h; K. pneumoniae, - 17%/h; E. coli, - 18%/h; S. aureus, - 22%/h. The rate of intrapulmonary bacterial multiplication (Kg) was estimated from the relationship of bacterial counts in tetracycline and nontetracycline-treated animals, assuming that tetracycline altered only Kg. Kg, expressed as the doubling time, was: S. pneumoniae, 310 min; K. pneumoniae, 217 min; E.coli, 212 min; S. aureus, infinity (no multiplication). The data indicate that the marked differences in the clearance of these species from the normal mouse lung result from the interaction of differing rates of in vivo bacterial multiplication and killing.

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.

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.

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.

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.

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.

Clinical measures of gestational age in normal pregnancies.

Obstetric findings in 89 healthy women were evaluated prospectively by one obstetrician unaware of menstrual history. With weekly examinations, fetal heart tones were audible by fetoscope at 17.1 +/- 1.1 weeks' gestation (mean +/- SD) and the fundus reached the umbilicus at 16.6 +/- 0.9 weeks. At 20 to 31 weeks, fundal height in centimeters equaled weeks' gestation (confidence interval: +/- 3 weeks). The accuracy of predicting delivery date from combined findings (SD: 11.4 days) approached that from reliable menstrual history (SD: 10.2 days). Gestational age at delivery minus the pediatric Dubowitz estimate was 0.4 +/- 1.7 weeks. Gestational age may be overestimated by up to six weeks by assuming that the fundus reaches the umbilicus or that fetal heart tones appear at 20 weeks. However, carefully derived obstetric estimates potentially may be more reliable than pediatric estimates.

A paired controlled study of vaginal and abdominal delivery of the low birth weight breech fetus.

In a paired, controlled, retrospective study, 44 low birth weight breech fetuses delivered vaginally were compared with 44 breech fetuses delivered by cesarean section. Seven deaths occurred in the vaginal delivery group, compared with only 1 in the abdominal delivery group. Asphyxia, trauma, and intracranial hemorrhage were also found more frequently among vaginally delivered fetuses. The authors conclude that for the low birth weight breech fetus, delivery by cesarean section is preferable.

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.

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.

Effects of medial meniscectomy in patients older than forty years.

Forty-nine of the sixty-five consecutive patients who were more than forty years old when medial meniscectomy was performed returned for follow-up evaluation one to twelve years postoperatively. Pain was present in 62.2 per cent of the patients with so-called degenerative tears and in 75 per cent of those with so-called traumatic tears. The medial joint space was significantly thinner in the patients with degenerative tears than in those with traumatic tears. The roentgenographic findings of osteoarthritis were significantly more severe on the side operated on. The femorotibial angle was always in relatively more varus angulation on the involved side (mean, 5.3 degrees) than on the uninvolved side.

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).

Educator perceptions of accreditation.

A 25-item survey was developed to collect data for a paper delineating educators' concerns for accreditation. Distributed randomly in the instrument were statements relating to the constructive aspects of accreditation, the constraints on the effectiveness of accreditation, and the logistical short-comings of the accreditation process. Responses were separated into four categories of institutions and were subjected to computer analysis. Results clearly demonstrated different perceptions of relative importance among the various institutional categories. Of possibly greater significance was the demonstration that the great majority of respondents expressed far more concern over the processes of accreditation than they did over the principles.

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.

Long-term survival after resection for bronchogenic carcinoma.

Of 915 resections for bronchogenic carcinoma over a 25-year period (1945-1969), 249 patients survived over 5 years; 127 of the patients eligible survived over 10 years, 61 over 15 years, and 22 over 20 years. The case material was divided into three time periods: 1945-49, 1950-59 and 1960-69, as well as by extent of resection. Lobectomy became the operation of choice, pneumonectomy being reserved for the more extensive lesions. Observed survival rates at 5, 10 and 15 years for 561 patients in the lobetomy series were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19% in the 1960-69 period. Observed rates for 354 patients having pneumonectomies were similar for three time periods, being 16, 8 and 6% at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10 and 15 years rose from 33, 28 and 26%, repectively, in the 1950-59 period to 50, 39 and 35% in the last time period, becoming a near horizontal curve segment after 5 years. Dominant factors in survival were extent of the lesion and stage of nodal involvement, histologic type and location being less significant.

Sonar fetal cephalometry: comparison of bistable with gray scale and real-time techniques.

The fetal biparietal diameter was measured simultaneously with B-scan bistable and gray scale techniques and subsequently with real-time ultrasonography. Measurements were made from outer table to outer table with the bistable technique, which has been proven to be accurate and reliable. With the gray scale and real-time modalities, distances were measured between several landmarks from the same image. Off all measurements taken from gray scale and realtime images, those between the centers of each band outlining the fetal skull showed the best correlation and the closest values to measurements using the standard bistable technique. Discrepancies exceeded 2 mm in only 5% with the gray scale and in 2% with the real-time technique. Using the measurement between outer and inner aspects of the cephalic band, the percentages of discrepancies exceeding 2 mm were 7% with gray scale and 6% with real time.

Linear growth of the thoracic spine in chest roentgenograms from birth to 16 years.

The length of the thoracic spine was measured in chest roentgenograms of 331 children from birth to 16 years and standards for thoracic spine length in this age group were obtained.