Piperacillin kinetics.

Piperacillin kinetics. Piperacillin was administered to normal, healthy volunteers by an intravenous infusion over 30 min at dosage regimens of 12 gm daily (4 gm every 8 hr) and 24 gm daily (6 gm every 6 hr) for 5 consecutive days. Mean peak serum level after 12 gm daily was 244 +/- 24 (SE) microgram/ml and after 24 gm daily, 353 +/- 7 microgram/ml. After infusion the serum level declined monoexponentially in most subjects. On the 12-gm daily dosage mean values were 60 min for half-life (t1/2), 16 1 for volume of distribution, 188 ml/min for body clearance, and 139 ml/min for renal clearance. The same values on day 4 were 47 min, 12 1, 181 ml/min, and 125 ml/min; the volume of distribution was lower than on day 1. On the 24-gm daily dosage regimen, t1/2 was 60 min; volume of distribution, 16 1; body clearance, 183 ml/min; and renal clearance, 101 ml/min on day 1 compared to 68 min, 15 1, 148 ml/min, and 71 ml/min on day 4, the last 2 being significantly lower than on day 1. High renal clearance values were observed at low serum concentrations and vice versa, suggesting saturation of the tubular secretion process at high piperacillin concentrations in serum.


Cephalothin kinetics: before, during, and after cardiopulmonary bypass surgery. Cephalothin kinetics was studied in 5 patients the day before (PREOP), during (SURG), and the day after (POSTOP) cardiopulmonary bypass surgery. The PREOP (114 ml/min) and SURG (94 ml/min) renal clearances were of the same order but both were less than POSTOP renal clearance (248 ml/min). Cephalothin total body clearance during operation was lower (p less than 0.01) than PREOP or POSTOP clearance, with decreased metabolic clearance the primary cause. There was reduction in cephalothin elimination throughout the surgical procedure, not only in the period of extracorporeal circulation, indicating that general anesthesia had a significant influence on drug disposition. The metabolite deacetylcephalothin was rapidly formed on all 3 days and its kinetic behavior paralleled that of the parent drug.


Presence of 2,4-diamino-N10-methylpteroic acid after high-dose methotrexate. Assay of plasma methotrexate has been established as important to its safe use. We have investigated the specificity of 2 assay procedures for methotrexate: the competitive dihydrofolate reductase binding assay (CRBA) and the radioimmunoassay (RIA). The RIA of plasma methotrexate resulted in consistently higher values than the CRBA, with greater differences at later measurement times. A compound that strongly cross-reacts in the RIA, but not the CRBA, has been identified in plasma and urine of patients on high-dose methotrexate therapy, and appears to be the carboxypeptidase cleavage product (2,4-diamino-N10-methylpteroic acid) on the basis of chromatographic and ultraviolet spectral properties. Although this compound is present as a minor contaminant in commercial methotrexate preparations, quantitative assessment of urinary excretion suggests that in man a major portion of the compound is derived from methotrexate metabolism.


Kinetics of intravenous melphalan.

Kinetics of intravenous melphalan. We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High-pressure liquid chromatography and 14C-melphalan were used to assay drug concentration in plasma and urine. Composite plasma t1/2alpha was 7.7 +/- 3.3 and t1/2beta was 108 +/- 20.8 min for 8 of the patients. The mean 24-hr urinary excretion of melphalan was 13.0 +/- 5.4% of the administered dose. In 2 patients, 80% to 100% of the measured 14C counts in plasma and urine samples at each study interval, up to 24 hr after drug administration, could be accounted for by the sum of parent compound, monohydroxy and dihydroxy products, and methanol nonextractable radioactivity (i.e., protein-bound activity). These data and evidence of rapid disappearance from plasma at 37 degrees in vitro suggest that spontaneous degradation, and not enzymatic metabolism, is the major determinant of the t1/2 of melphalan in vivo.


Identification and quantitation of hydrazine in the urine of patients treated with hydralazine. Hydrazine has been identified by gas chromatography-mass spectrometry in the 0- to 24-hr urine of patients administered hydralazine. With a specific gas chromatographic assay procedure, the amount of hydrazine in the 0- to 24-hr urine was determined in patients treated with various doses of hydralazine. The amount of hydrazine detected in the urine was greater in the slow acetylator phenotype than in the rapid acetylator phenotype. Studies indicated that hydrazine was not produced by chemical breakdown of hydralazine or its known metabolites in urine and therefore was unlikely to be a urinary artefact formed by chemical decomposition in the urine.


Metabolic responses to plasma concentrations of theophylline. We investigated the effect of intravenous infusions of aminophylline on plasma glucose, insulin (IRI), glucagon (IRG), growth hormone (HGH), cortisol, and free fatty acid (FFA) levels in healthy young subjects. Six received an intravenous loading dose of aminophylline (6.0 mg/kg over 20 min) followed by a maintenance dose (0.9 mg/kg/hr) for 100 min. Another 7 subjects initially received smaller loading (3.0 mg/kg) and maintenance (0.45 mg/kg/hr) doses, and after 60 min they received a second loading dose (3.0 mg/kg) followed by a larger maintenance dose (0.9 mg/kg/hr) over 120 min. In these fasting volunteers, infusion of aminophylline, which produced theophylline levels in the usual therapeutic range (10 to 20 microgram/ml) caused small increases in plasma glucose levels without changing IRI, IRG, HGH, or cortisol. There were rapid, pronounced, and prolonged rises in FFA associated with the aminophylline infusion. Increases in FFA paralleled the rise in theophylline levels. It is concluded that routine therapeutic doses of theophylline, i.e., doses that achieve serum levels normally encountered in treatment for bronchial asthma, cause a marked rise in FFA and a slight rise in glucose (8 +/- 3 mg/dl) without changing levels of IRI, IRG, HGH, or cortisol.


A critical viewpoint by a general surgeon toward reconstructive surgery after mastectomy. Reconstructive breast surgery is accompanied by hazards, both known and unknown, which may endanger the life of the patient. On the other hand, the benefits are largely a modest gesture toward the physical and emotional adjustment. It is the duty of the physician to present all aspects of the contemplated procedure and let the patient decide whether her emotional needs justify the risks entailed.


Effects of radiation therapy on wound healing after mastectomy. There is increasing use of various forms of reconstructive surgery. This will mean that more patients with previously irradiated tissue will be subjected to these procedures. It is imperative that the surgeon and the radiation therapist collaborate in the management of these patients in order to avoid unneccessary injuries.


Chemotherapy and wound healing.

Chemotherapy and wound healing. Only patients with carcinoma of the breast who have a good prognosis after curative surgery are the best candidates for reconstructive surgery. On the other hand, patients who have a poor prognosis should not be considered for reconstructive breast surgery. Patients with guarded and intermediate prognoses who are candidates for adjuvant chemotherapy programs may be considered for reconstruction after completion of their programs and not prior to or during the programs. They should be evaluated at the end of such program, which ranges from one to two years, to assure absence of occult metastases and to assure complete bone marrow recovery. Even then, if metastases develop at a later date (after insertion of the prosthesis), tissue sloughing may occur at the site of the implant that may delay therapy or cause overwhelming infection.


Breast reconstruction following mastectomy for malignant disease: a surgical oncologist's point of view. The various factors that enter into the decision and recommendation for breast reconstruction after mastectomy must include the time and number of procedures which may be required and the probability of recurrent cancer, but most of all, the degree of enthusiasm of the woman herself for the procedure. Only a small percentage of women who initially express interest in reconstruction actually carry it through to completion, for many reasons. What may have been considered initially as a "must" may lose its attractiveness with the passage of time and the realization that mutilation need not be an absolute synonym for mastectomy. Since there is no perfect reconstruction yet available, there cannot be any arbitrary and dogmatic rules established to separate the "should's" from the "should not's". We must await more technical advances from innovative surgeons and biomedical scientists before that millennium arrives. Concurrently, we must endeavor to find techniques of earlier and earlier detection, in the ultimate hope that the diagnosis of breast cancer may be made at a time early enough in its natural history that mastectomy would no longer be required and cure would be guaranteed!


Sulfonylurea drugs and insulin-independent diabetes mellitus. Insulin-independent diabetes is a disease characterized by insulin resistance and the patient's concomitant inability to compensate by exaggerated insulin secretion. A primary abnormality in the plasma membrane of the afflicted cells may cause both of these phenomena. Recent studies investigating the mechanism of action of sulfonylurea drugs show that these agents probably exert their antidiabetic action by increasing insulin sensitivity and ameliorating the insulin resistance, rather than by increasing insulin secretion. Dietary treatment alone, though effective in lowering the FPG level, does not ameliorate the insulin resistance of insulin-independent diabetes mellitus. Thus, sulfonylurea drugs appear to be rational therapeutic agents for the treatment of this form of diabetes. Clinical studies confirm the beneficial effects of these drugs in controlling the hyperglycemia of insulin-independent diabetes. Major unresolved questions are (1) Why do primary and secondary failures occur? (2) Is the underlying membrane abnormality progressive? (3) How long are sulfonylureas effective? (4) What is the mechanism of the membrane disturbance and how do sulfonylureas ameliorate it? (5) Do sulfonylureas drugs cause cardiovascular toxicity? The answers to these questions will provide further insight into our understanding of insulin-independent diabetes and will lead to the development of better drugs for its treatment. In the meantime, sulfonylureas are rational agents for the therapy for this disorder, if they are used appropriately.


The effects of psychotropic drugs and diuretics on blood glucose levels in diabetes mellitus. It has been clearly established that most diuretics and most tranquilizers can raise blood glucose levels in diabetics, while antidepressants can lower them. The extent of these effects is variable but can be highly significant clinically. Chlorpromazine has very likely been responsible for a considerable increase in the prevalence of diabetes in hospitalized psychotics, while antidepressants can produce useful improvement of diabetic control, especially in brittle diabetics.


Hemispheric efficiency in middle and later adulthood. Right and left hemisphere efficiency, as measured by dichotic memory for numbers, was assessed in a sample of older adults in Experiment I. Right hemisphere efficiency dropped off sharply with age, while left hemisphere efficiency did not show a significant decline. A second group of subjects was tested on a musical note recognition task in Experiment II. Regression analyses revealed significant age decrements in performance, regardless of ear/hemisphere involved. The writers suggested that the reported decline with age in spatial ability may result from an age related decline in right hemispheric functioning, even on tasks that are right hemisphere dominant. The lack of decline reported for verbal ability may be a consequence of the lack of decline in left hemisphere efficiency with regard to left hemisphere dominant tasks.


"Transcortical" features of aphasia following left thalamic hemorrhage. In a series of 14 thalamic hemorrhage documented by Computerized Axial Tomography (CT) scans, aphasia was present in seven out of eight patients with left lesions while it was absent in the six patients with right lesions. In three cases where detailed language testing was performed, aphasia was characterized by reduction of spontaneous speech with semantic paraphasias, preserved repetition and partially defective auditory verbal comprehension. The language disturbance was persistent in two patients, while it recovered spontaneously within four weeks in one patient. The clinical picture in these patients is similar to the classical "transcortical" aphasias, which are usually due to damage of the marginal language areas. It is suggested that the left thalamus contributes to the semantic level of verbal behavior, which is possibly subserved by these areas.


Memory retraining in brain-damaged patients: the airplane list. Recall failures can be traced to inadequate encoding and unfocussed retrieval search. A method is given for encouraging deep and elaborate encoding of a list of words, and two brain-damaged patients who were unable to recall the list at first, were shown to retrieve many of the words when retrieval cues were given by the examiner.


Rehabilitation of alexia: a case study.

Rehabilitation of alexia: a case study. This case study described the success of a technique labeled Multiple Oral Rereading (MOR) in the remediation of a case of acquired alexia in an adult male. Unusually slow visual-verbal processing characteristic of this patient is sometimes noted in dyslexic children. The possibility that MOR might prove effective for other selected cases of acquired alexia and "developmental" dyslexia is considered.


Signal detection theory and the effects of severe head injury upon recognition memory. Previous reports by Brooks (1974a, 1974b) employed the techniques of signal detection theory to analyse the effects of severe head injury upon recognition memory. The arguments contained in these papers are criticized with specific reference to the validity of the parameters of signal detection theory as indices of sensitivity and response bias. It is suggested that, when the theory is applied in an appropriate manner, severe head injury is shown to produce an impairment of recognition sensitivity with no concurrent change in response bias. The use of theory neutral procedures for evaluating sensitivity and response bias leads to the same conclusion.


Time on target meter.

Time on target meter. The design and construction of an inexpensive time-on-target meter are presented with a logic diagram. This meter has been found to facilitate the recording of proprioceptive feedback performance by automatically recording the cumulative percent of time that the subject's manual tracking is within a specified range on a given trial.


Visual scanning and matching dysfunction in brain-damaged patients with drawing impairment. Visual matching and visual exploration were examined in 7 normal subjects and 20 brain-damaged patients with drawing impairment measured by the Bender Gestalt Visual-Motor Test. Right brain-damaged patients made significantly more errors of rotation and integration than left brain-damaged patients. Selecteded Bender figures were also used as stimuli for both visual matching and visual exploration tests. The ability to match Bender figures was found to be impaired in right but not left brain-damaged patients. All patients showed eye movement and fixation patterns different from those normals. Patients essentially had more fixations and shorter fixation durations. Significant intercorrelations were found between the total Bender Gestalt score and visual matching and visual exploration scores. These findings indicate that visual matching and visual exploration measures can be used to evaluate perceptual impairment in individuals who do not have adequate motor responses or where impaired motor responses may confound interpretations about visual cognitive impairment.


Presentation-time limits on memory retrieval. An experiment which varied presentation-time of a list of 20 sentences relating pairs of words was done. The subjects were 94 undergraduates. Processing variations included for some groups instructions to use visual imagery, and retrieval variations included recall and matching recognition. The results indicate that variations in presentation-time are strongly related to memory retrieval. Several experiments are reviewed, and the importance of specifying presentation-time in studies of memory-retraining in brain-damaged patients is emphasized.


Performance by split-brain humans on lateralized vigilance tasks. Studies are described of the vigilance performance of the cerebral hemispheres of split-brain man. Investigations of visual, auditory and tactual performance are reported for six total commissurotomy patients. The vigilance tasks were lateralized to test the functions of the two hemispheres and make comparison between them. The right hemisphere emerges the superior in its vigilance performance in every case. The results support the association of sustained attention with the functions of the right hemisphere and they suggest that there are different mental mechanisms for selective and sustained attention.


The effect of concurrent activity on hemispheric asymmetries. Two experiments were performed to test Kinsbourne's (1970) contention that perceptual laterality effects are affected by the nature of concurrent activity. In the first, subjects listened to verbal or nonverbal dichotic material while holding verbal or spatial material in memory. In the second, subjects localized dots while remembering a list of abstract words. In neither experiment did the concurrent activity alter the laterality effect in the manner suggested by Kinsbourne's model. This model therefore cannot provide a general explanation for perceptual laterality effects.


Material specific serial memory deficit in adolescent dyslexics. The present experiment was concerned with an assessment of possible serial, as opposed to general, memory deficit in dyslexia. Previous studies had consistently confounded general and serial memory assessments. Fifteen specifically dyslexic adolescents and 15 normal-reading controls were administered four separate memory tasks. In the general memory for verbal material task they were shown 20 words, each for three seconds, and were then given a deck of 40 word cards and required to pick out the 20 words just seen. In the serial memory version of the verbal task they were again shown 20 words and subsequently required to reproduce the order in which they had been shown. Two comparable (general and serial) procedures were also administered using faces as the to-be-remembered materials. Results showed comparable performances of the dyslexics and controls on both versions of the face memory task and on the general memory version of the words task. On the serial reproduction version of the verbal task, however, dyslexics were found to be significantly impaired relative to controls. Thus, adolescent dyslexics appear to have a memory impairment which is specific for both type of material (verbal) and type of memory (serial). The results are compatible with Orton's (1937) speculation regarding "sequecing" and "memory" in dyslexia and with the view that the defect resides within the neuropsychological processes of the language-dominant hemisphere.


Recovery of memory and learning functions following traumatic brain injury. Twenty-four traumatically brain-injured males, of whom eight had sustained right-sided, eight left-sided, and eight bilateral or diffuse closed head injuries, took a battery of neuropsychological tests within the first six months, the second six months, the second year and the third year post injury. Performances on WAIS Digits Forward and Backward and Rey's Auditory-Verbal Learning Test were classified as within or below normal range. Comparisons were made (1) between time periods and tests and (2) between subgroups formed by severity, site of lesion, and age. The findings give an overall picture of wide performance variability with consistent improvement in immediate memory span and learning. Recovery varied with the specific nature of the tested function, task complexity, and severity of injury. Neither age, site of injury, not recency were associated with improvement.


Hemisphere functioning in autistic children. Recent research in childhood autism has provided support for the hypothesis that a central cognitive deficit involving severe language impairment underlies this disorder. In this study a group of autistic children were tested for handedness and for lateralization of speech function using a dichotic listening task. Contrary to earlier reports there were no left-handed children in the group although a number showed mixed preference. In the dischotic listening task using pairs of single syllable words the autistic group performed similarly to a matched group of normal children in terms of numbers of correct responses but over all did not show the right ear advantage characteristic of the normal children. There was a significant excess of right hemisphere dominance for verbal stimuli amongst the autistic children suggesting that for some at least, language functions had developed in the right hemisphere. Lateralization was shown to be related to presence or absence of speech before the age of 5 years and to IQ level.


Is hemispheric specialization important to scholastic achievement? Scholastic achievement in both reading and mathematics were examined as a function of hemispheric specialization for visually presented words and pictures. Two groups of subjects (mean ages = 8.8 and 13.3) were included so that hemispheric specialization at an early and later phase of reading sophistication could be monitored. The results indicated that a lack of specialization for words is associated with higher reading achievement in both age groups and that right hemispheric specialization for words is likely to be accompanied by less reading skill. The results were discussed in terms of developmental changes in hemispheric processing and the need to investigate a variety of hemispheric specialization patterns and a variety of acquired skills (music, mathematics, art).


Correlation of changes in body weight and pulmonary vascular pressures with lung water accumulation during fluid overload. The accumulation of excess lung water is a major concern after the infusion of large amounts of crystalloid solution. The parameters used to monitor total body and lung water balance include changes in body weight, and the measurement of pulmonary vascular and plasma colloid osmotic pressures. We studied the reliability of these parameters in predicting lung water during severe fluid overload in nephrectomized sheep. We found that the normal lung appeared resistant to excess fluid accumulation, particularly when compared to the splanchnic circulation. Body weight change was an unreliable index of lung water with a correlation coefficient of 0.43. Pulmonary vascular pressures were the best index (r = 0.83) with lung water accumulating rapidly after capillary pressure exceeded 30 cm H2O. The difference between pulmonary capillary pressure and plasma colloid osmotic pressure was not as reliable (r = 0.72) as was capillary pressure alone.


Studies in shock and resuscitation, I: use of a hypertonic, albumin-containing, fluid demand regimen (HALFD) in resuscitation. We have reevaluated and clinically tested the current concepts of shock and resuscitation on a logical, physiological, and physical basis. We have considered the currently accepted resuscitation paradigm which is based upon the thesis that early rapid resuscitation of "lost" fluid volume is mandatory and that adequacy of resuscitation can be evaluated by central venous pressure, PAP, PAWP, pulse rate, blood pressure, and/or urine volume. Such methods also accept as natural concomitants that capillary beds are "damaged by injury"; that they "leak" salt, fluid, and albumin; and that these are expected occurrences which are injury-related. We have also examined and clinically evaluated the thesis that MAP is a primary reflector of the relationships between volume and the size of the currently available functional vascular space. (Currently available functional vascular space is mediated through the baroreceptor (stretch receptor)/neuroendocrine mechanisms.) Under this hypothesis, fluid resuscitation comprises infusion of a volume per unit time given so as to replete currently measurable fluid losses and to normalize and/or sustain MAP and the normal osmolar and oncotic relationships at the capillary/tissue interface while holding hydrostatic pressure at normal. Using burn injury as a model, we compared statistically homogeneous, randomly selected groups of burn patients who were resuscitated using a hypotonic fluid (130 mOsm/liter) alone (group R: 7 patients), hypertonic fluid (240 mOsm/liter) alone group H: 5 patients), or the hypertonic fluid containing albumin (12.5 g/liter) (group A: 7 patients). The results indicate that significantly smaller volumes of fluid were needed to resuscitate the patients in group A with a significantly more rapid normalization of physical, physiological, and biochemical parameters. We conclude that the physically and physiologically appropriate method of resuscitation, demonstrated in burn injury, comprises the use of a fluid given at a rate: (1) to maintain mean arterial and hydrostatic pressures within normal range; (2) that delivers a volume per unit time which does not exceed the capacity of the currently available functional vascular space; (3) that replaces concurrent measurable fluid losses; (4) that is hypertonic (to normalize capillary/tissue osmotic gradients); and (5) that contains colloid (to normalize capillary/tissue osmotic gradients); and (5) that contains colloid (to normalize capillary/tissue oncotic gradients). We further conclude that salt, fluid, and colloid loss into the interstitium during resuscitation frequently is due to the rate delivered and/or the physical nature of the fluid used and not to capillary bed damage outside the zone of injury.


Experimental evaluation of 2F transthoracic thermodilution cardiac outputs in small animals. Cardiac output can be measured with a computer using a 2F transthoracic catheter placed during surgery. When injections are made into a central venous catheter, this technique allows for cardiac output measurements to be made in children with complex congenital heart disease not appropriate for placement of a transvenous pulmonary artery catheter. Using rabbits similar in size to the infants most likely to need this technique, 26 experimental comparisons of thermodilution and indocyanine green dye cardiac outputs were made with cardiac outputs as low as 0.2-0.4 liter/min. The relationship between green dye and thermodilution was statistically significant (p less than 0.001) and almost linear (r = 0.92). This documents the validity of both the 2F transthoracic catheter technique in the low range of cardiac outputs appropriate for infants and children.


Tetanus: a review.

Tetanus: a review. Tetanus is caused by the organism Clostridium tetani, which produces tetanospasmin, a neurotoxin responsible for the clinical manifestations of muscle rigidity and reflex spasms. The majority of cases follow an anaerobic wound infection associated with trauma. Incubation period is usually 3 days to 3 weeks. 75% of patients present with trismus. Reflex spasms are seen in 70% of patients and characterize the severity of the disease. Treatment involves removal of the offending organism, neutralization of free neurotoxin, controlling rigidity and reflex spasm, and minimizing complications. Diazepam may be used alone in mild cases. Severe cases require the addition of nondepolarizing neuromuscular blocking agents and mechanical ventilation. Respiratory complications occur early and require aggressive airway management. A serious, late complication is the syndrome of sympathetic nervous system overactivity that is treated with alpha and beta blockade. High mortality rates seen in the United States may be due to delays in diagnosis and lack of familiarity with treatment. The disease is preventable with adequate immunization.


Impact of cardiopulmonary resuscitation training on resuscitation. Restoration of adequate spontaneous circulation after "arrest" and cardiopulmonary resuscitation (CPR) of 546 patients before and 460 patients after initiation of a CPR training course in a 500-bed city hospital is reported. Between January 1972 and June 1976, adequate circulation after CPR was present in 38.6% of patients before and 50.4% after training ICU nurses and house physicians in modern resuscitation techniques. Factors crucial to resumption of adequate circulation are: (1) CPR training of all hospital personnel so that effective CPR can be started immediately after recognition of an arrest situation, (2) production of a palpable pulse with closed chest cardiac massage, and (3) prompt effective therapy so that the time interval between arrest and resumption of adequate spontaneous circulation is short.


Renal failure in the respiratory intensive care unit. The development of renal failure during respiratory failure is of grave prognostic significance. In 686 patients with respiratory failure, 74 developed renal failure; these had a mortality of 80%. The leading predisposing factors are: 1) gastrointestinal bleeding with hypovolemic shock; 2) sepsis with shock; 3) drug induced nephrotoxicity; and 4) hypotension. With antacid gastric neutralization, judicious use of nephrotoxic antibiotics, the incidence of renal failure can be reduced. Once renal failure occurs, early dialysis may increase the chances of recovery in these critically ill patients.


Stability of the arterial/alveolar oxygen partial pressure ratio. Effects of low ventilation/perfusion regions. The alveolar-arterial oxygen partial pressure difference (AaDO2) and the arterial/alveolar oxygen partial pressure ratio (a/APO2) were compared for stability when inspired oxygen concentration (FIO2) changed. The analysis was based on a three-compartment lung model and experimental results in 10 patients with respiratory failure receiving assisted ventilation. It was found that a/APO2 was more stable than AaDO2 and more useful for: (1) comparing gas exchange in patients receiving different levels of FIO2, (2) following gas exchange in the same patient as FIO2 is changed, and (3) estimating the PaO2 expected at a given level of FIO2 if blood gas data are available at another level. However, areas with low ventilation/perfusion (V/Q) ratios may cause sudden changes in a/PO2 at certain critical values of PAO2. Most stable is a/APO2 and, therefore, most useful at FIO2 levels greater than 0.3, and PaO2 levels less than 100 torr.


Effect of dopamine on intrapulmonary shunt fraction and oxygen transport in severe sepsis with circulatory and respiratory failure. The hemodynamic response to a dopamine HCl infusion (10 microgram/kg per min) was measured in 25 adult patients with severe sepsis: there were 6 patients with circulatory hyperdynamic states, 9 patients with myocardial failure, and 10 with hypovolemia. Each patient also had acute respiratory failure. Changes of intrapulmonary shunt fraction (Qs/Qt), arterial and mixed venous oxygen tension (PaO2 and PvO2), oxygen transport, and oxygen consumption (VO2) were evaluated before and after dopamine infusion. Dopamine infusion produced clinical improvement and increased cardiac output. The hemodynamic response seemed to differ slightly according to the pattern of circulatory failure: chronotropic effect appeared to be predominant in hyperdynamic states, whereas inotropic effect appeared to be predominant in myocardial failure or hypovolemia. Moreover, in hypovolemic patients we noted a rise in pulmonary capillary wedge pressure suggesting an additional increase in venous return. During this treatment, we also noted a worsening of the Qs/Qt despite the increase in pulmonary blood flow; this worsening did not prevent significant improvements in VO2, but the improvement in PVO2 was offset by increased Qs/Qt and PaO2 remained unchanged.


Bedside determination of bicarbonate and base excess, blood oxygen saturation and content, VD/VT, and P50 using a programmable calculator. Assessing and modifying oxygen transport are major parts of ICU patient management. Determination of base excess, blood oxygen saturation and content, dead space ventilation, and P50 helps in this management. A program is described for determining these variables using a T1 59 programmable calculator and PC 100A printer. Each variable can be independently calculated without running the whole program. The calculator-printer's small size, low cost, and hard copy printout make it a valuable and versatile tool for calculating physiological variables. The program is easily entered by an stored on magnetic card, and prompts the user to enter the appropriate variables, making is easy to run by untrained personnel.


An improved program to calculate intrapulmonary shunting. A computer program was developed to calculate intrapulmonary venous admixture on a Texas Instruments TI 59 programmable calculator. The program incorporates the following characteristics: 1) a correction for saturated water vapor pressure which varies with body temperature; 2) a mathematical model of the standard oxyhemoglobin dissociation curve; and 3) correction factors for shifts of the dissociation curve due to variations in pH and carbon dioxide tension. It also corrects oxygen tensions obtained at electrode temperature to those at patient temperature, and calculates variations of the Bunsen solubility coefficient of oxygen in blood with body temperature.


Management of acute epiglottitis.

Management of acute epiglottitis. Airway obstruction secondary to acute epiglottitis is a dramatic, life-threatening emergency. Early diagnosis and provision of an adequate artificial airway are critical in the management of these patients. Tracheostomy has been the traditional method of securing the airway in acute epiglottitis, but more recently, endotracheal intubation has been advocated. Whichever method of airway management is preferred, it is imperative that every hospital have a protocol for the management of acute epiglottitis so that immediate action can be taken.


Experimental approach to the correlation of hemodynamic changes with increases in urinary lactate dehydrogenase as a new parameter reflecting serious renal tissue damages. From previous investigations with nephroptotic patients increased urinary LDH was assumed to be a reliable marker indicating a renal tissue defect due to the organs descent in erect position. Animal experiments now allowed correlation of this enzymatic activity with controlled changes of anatomical and physiological parameters. Changes of the renal hemodynamics or urinary flow induced in acute experiments in dogs simulated kidney displacement in nephroptotic patients. Both ureters were cannulated for separate urine collection and one kidney was manipulated. The renal arterial or venous flow was reduced or the ureter was occluded under electromagnetic blood-flow control. Arterial constriction alone (30%/15 min) selectively caused a drastic decrease (approximately 80%) of Xenon wash-out (= nutrient-flow) in the renal cortex. Under the same conditions radio-labeled microspheres injected intracardially showed a centralization of the renal capillary blood flow from the outer cortex to the juxtamedullary zone. Urinary LDH activities increased up to 800% immediately after arterial constriction. In accordance with total LDH activity the percentage distribution of isoenzymes changed: LDH-I increased and the LDH-V decreased. Neither constriction of the renal vein nor ureteral occlusion had similar effects. In long-term experiments backward fixation of one kidney in rats would reflect the effects of kidney displacement over years in nephroptotic patients: animals were unilaterally nephrectomized and the remaining kidney was dislocated backwards (approximately 2,5 vertebrae) and fixed to the lateral pelvic wall. "Ptotic" rats showed during the following examinations a constant increase of urinary LDH up to 50% by 26 weeks postoperatively. In accordance with increased LDH the isotope nephrogram was pathological and arteriographies showed a stretched and narrowed renal artery. In a number of rats "ptotic" fixation was not effective enough. All these animals showed normal LDH, isotope nephrograms and arteriographies. Both animal experiments documented that reduced flow/hypoxia is essentially responsible for the tissue damage in the kidney manifested by increased release of urinary LDH.


Urinary N-acetyl-beta-D-glucosaminidase (NAG) as an indicator of renal disease. The automated fluorimetric assay of N-acetyl-beta-D-glucosaminidase (NAG) has proved to be of value in the detection of rejection in transplant patients and in monitoring the course of renal disease. The urine can be diluted prior to assay, due to the sensitivity of the fluorimetric method and this reduces the effect of endogenous inhibitors. Time consuming dialysis or gel filtration steps are therefore unnecessary. Results are available to the physician within hours of the collection of the urine sample, since factoring the enzyme activity by the creatinine concentration avoids the necessity of collecting twenty-four hour or timed urine samples. Over one hundred samples can be assayed in a day using the automated procedure. The excretion of NAG in normal individuals varies with age and the activity found in pathological samples should always be compared with age-matched controls. The development of a new series of colorimetric substrates has allowed the production of a simple 'Dipstick' which should be of value in the screening of at-risk populations for renal disease. The diagnostic potential of the estimation of urinary NAG activity is enhanced by the separation of its isoenzymic forms by ion-exchange chromatography on DEAE-cellulose.


Comparative nephrotoxicity of gentamicin and netilmicin: functional and morphological correlations with urinary enzyme activities. An increase in urinary enzyme activities reflected biopsy confirmed aminoglycoside nephrotoxicity (proximal tubular injury) before changes in blood urea nitrogen, serum creatinine, urinary osmolality and urinary protein excretion. Netilmicin, a semisynthetic derivative of gentamicin, was less nephrotoxic than gentamicin.


Tubular-toxic effects of aminoglycosides and their combinations with cephalosporins. Cephalosporins have a distinctly different effect from that of aminoglycosides on membranes of the proximal tubule of the human kidney as measured by urinary AAP concentrations. Except for a slight influence by cephacetrile, cephalosporins showed no effect on the proximal tubule. In contrast, after three days of administration, the aminoglycosides caused a cumulative increase in membrane proteins of the proximal tubule to be excreted in the urine. Tobramycin appears to have the least and amikacin the greatest effect on the brush border membranes of the proximal tubule of the normal human kidney. The combination of cephalosporins with aminoglycosides increases the potential toxic effect on the proximal tubule.


Clinical relevance of different electrophoretic methods for the analysis of urinary proteins. Three electrophoretic techniques are usually available in the clinical laboratories for the qualitative investigation of urinary protein patterns: 1) acetate cellulose, 2) immuno-electrophoresis; and 3) SDS-polyacrylamide gel electrophoresis. Proteinuria (the excretion of proteins in excess of 150 mg/day or 100 microgram/min) usually signifies either increased permeability of the glomerular-capillary membrane of diminished tubular reabsorption. Since glomerular disease is associated with an increased clearance of albumin and higher molecular weight proteins, whereas tubular damage is associated with the predominant excretion of proteins of lower molecular weight than albumin, it seems logical to establish a classification of proteinuria according to the molecular weight of its constituents. One can thus basically distinguish 5 types of proteinurias: 1) physiological; 2) tubular; 3) selective glomerular; 4) non selective glomerular; and 5) mixed proteinurias. Additionally one must distinguish "myeloma proteinurias" where monoclonal complete or incomplete gamma-globulins are found in the urine. Clinically it may be useful to determine the qualitatively normal or pathologic character of a quantitatively normal proteinuria, especially in the following conditions: 1) for early diagnosis of nephropathy in patients, such as diabetics, which are particularly prone to suffer from renal complications; 2) to confirm the clinical cure or to predict the recurrence of renal diseases; and 3) in such situations as orthostatic, or myeloma proteinuria, or any elevation of the urinary protein output of unknown etiology.


Preparation of urine for enzyme determinations by gel filtration. The activities of several enzymes in urine are masked by the presence of interfering substances in native urine. From several methods proposed for the removal of low molecular mass interferences dilution, dialysis, gel filtration, and ultrafiltration have been successfully applied. Gel filtration seems to be of these most suitable. I is effective, accurate, precise and economical. Scale-down procedures provide for acceptable speed. By this method the complete separation of lactate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, arylsulphatase A, alpha-glucosidase, beta-galactosidase, trehalase, N-acetyl-beta-glucosaminidase, beta-glucuronidase and leucine arylamidase from low molecular mass substances, e.g. a heat-stable, competitive inhibitor of N-acetyl-beta-glucosaminidase was possible. The preparation and determination of urinary enzymes should be thoroughly standardized and controlled. Acceptable precision (coefficient of variation less than 10% between-day) can be achieved with manual spectrophotometric methods.


Diagnostic significance of SDS-PAA-electrophoresis of urinary proteins: different forms of proteinuria and their correlation to renal diseases. Different types of urinary protein excretion may be recognized by determination of the proteins molecular weight. Beside chromatography different electrophoretic procedures have been applied to urinary proteins to study the underlying renal disease. The various zone electrophoreses separate merely by surface charge, proteins however covered by sodium dodecyl sulfate (SDS) migrate according to their molecular radius. So by SDS-polyacrylamide electrophoresis (SDS-PAe) macromolecular proteinurias (Mr 60,000- greater than 300,000 daltons) due to glomerular damage may be distinguished from micromolecular forms (Mr 10,000-70,000 d) due to tubular dysfunction. By densitometric quantitation of the separated Ig and transferrin an index of the glomerular selectivity is obtained, i.e. the capacity of the glomerular system, to retain serum proteins of a Mr above 150,000 d. By this procedure proliferative and degenerative glomerulopathies may be distinguished from minimal change disease, focal glomerular sclerosis and early membranous nephropathy; serial determinations of this selectivity index in the latter two disease entities show a gradual deterioration of glomerular protein handling with time. A glomerular proteinuria of even "physiological" quantity has been proved as early sign of renal involvment in systemic diseases; it may be detected earlier as for example the retinopathy in juvenile diabetics. Micromolecular proteinurias also occur at least in two forms: the typical tubular proteinuria (MW 10,000-70,000 d) is associated with acute or chronic severe tubular dysfunction as in interstitial nephritis and acute kidney failure; rejection episodes of kidney transplants lead to transient tubular proteinurias, too. The second form of micromolecular proteinuria (Mr 40,000-70,000 d) has been found frequently in association with a glomerular in diabetic and hypertensive glomerulosclerosis. By measuring clearances of the microproteins, the proteinuria with this pattern could be established as form independant from glomerular and tubular proteinurias. The constancy of the two micromolecular proteinurias led to the hypothesis of at least two selective mechanism of tubular protein resorption. SDS-PAe additionally allows the differentiation of extrarenal proteinurias, as caused by overflow, paraproteins, postrenal Ig-secretion or bleeding etc. In comparing clinical and in part histological data of about 2,000 patients suffering from kidney diseases the analysis of urinary proteins by this method has been proved as valuable non-invasive tool for diagnosis and follow-up.


Urinary hydroxyproline in healthy patients and in prostate patients with and without bone metastases. An essential part of the classification of prostate carcinoma is the diagnosis of bone metastases. This was done with 70 patients using x-ray analysis, scintography, determination of the acid and alkaline phosphatase, and pelvic crest biopsy, as well as aspiration of the pelvic and sternal bone marrow. In addition, the hydroxyproline concentration was determined in the 24-hour-urine. The study, which was initially undertaken on a sample group (n = 145), yielded a high correlation between age and sex and hydroxyproline values. Women before menopause show significantly lower values than do men of the same age. The data on patients with prostata cancer (n = 70) showed that patients with and without bone metastases, who had been treated with estrogens, had a significantly lower quantity of hydroxyproline than did patients who had not received estrogen therapy. Patients with skeletal metastases (n = 24) showed significantly higher hydroxyproline excretion in the urine than did those with prostate cancer without metastases, or healthy men of the same age (n = 35). Comparison of the results of hydroxyproline determination with the other diagnostic methods for demonstrating bone metastases showed that hydroxyproline determination was diagnostically on par with the scintigram. Pelvic crest biopsy, pelvic and sternal marrow aspiration can be considered valuable supplementary diagnostic procedures.


Nephrotoxicity of low molecular weight serum proteins: physicochemical interactions between myoglobin, hemoglobin, bence-jones proteins and tamm-horsfall mucoprotein. Three types of low molecular weight serum proteins, myoglobin, hemoglobin and BENCE-JONES proteins, are associated clinically with acute renal failure. All have isoelectric points which render them anionic at blood pH but cationic in the distal nephron under conditions of aciduria. Experiments in which these proteins were mixed with TAMM-HORSFALL mucoprotein in vitro and the pH lowered with lN HCl showed co-precipitation of proteins at pH levels of 5.5 and below. In vivo experiments in which 11 different BENCE-JONES proteins of pl ranging from 5.2 to 6.6 were injected into aciduric, hydropenic rats showed an acute rise in serum urea nitrogen and creatinine concentrations with BENCE-JONES proteins of pl greater than 5.7 compared with little change in rats injected with BENCE-JONES proteins of pl less than 5.7. These data suggest that protein pl and urine pH are important in determining nephrotoxicity; a mechanism by which these low molecular weight serum proteins and TAMM-HORSFALL proteins interact in the distal nephron to initiate acute renal failure in postulated.


Uromucoid excretion in normal individuals and stone formers. A quantitative immunological determination of uromucoid according to Laurell's method has been established. The average excretion rate of this glycoprotein in normal individuals was found to be 51.1 +/- 5 mg/24 hours. The uromucoid excretion in patients with calcium-oxalate, calcium-phosphate and cystine stones showed no significant change. In patients with urate stones and those with renal tubular acidosis a significant decrease in uromucoid excretion was found. Localization of uromucoid was found to be in the cells of the distal tubular section and the collecting tubules which was verified by immunincubation with FITC conjugated antihumanuromucoid globuline.


Immunotitration of alkaline phosphatase isozymes in normal and pathological urine. Isoenzyme patterns of alkaline phosphatase are determined quantitatively in extracts of human kidney as well as in human urine by means of immunotitration technique. Both media contain two types of AP isoenzymes: liver and intestinal like AP. Intestinal AP is located as a minor component of total AP activity (1-4%) in particle-free fraction of the kidney. Urinary AP activity is found after high speed centrifugation in supernatant (100,000 Xg) as well as in the 100,000 Xg sediment and can only be made soluble from the latter by n-butanol treatment. Intestinal AP in urine is concentrated in the supernatant while in sediment the isoenzyme pattern resembles to that of kidney. Urine of normal persons contains most of AP activity in the sediment and consists mainly of liver type AP. Urinary AP of patients with renal diseases or after application of cytotoxins contains little sedimentable activity, mainly intestinal AP.


The powerful urinary procoagulant and its relation to renal diseases. Human urine and urine of various animals contains a powerful procoagulant which converts prothrombin in presence of factors V, VII, X, and phospholipids or thrombocytes into thrombin. In human beings its content of the urine is markedly reduced or totally absent in kidney diseases, but normal in hemophilic patients. Only 0.2 ml urine are required for its assessment. In experimental kidney diseases in rabbits and rats there is an inverse relationship between procoagulant and protein excretion. In the test tube 1 part of urine corrects the clotting of 5-10 parts of hemophilic plasma, even in the presence of very strong coagulation inhibitors.


Influence of human urine on phagocytosis. Human urine may inhibit or activate the phagocytosis by normal human blood of latex, zymosan and inuline. No specific difference was found between the urine of normals and patients with moderate, severe or end stage renal failure. The inhibiting effect was not due to urea or creatinine; the assumption is made that a middle molecular fraction D, which can be isolated by Sephadex G 15 columnchromatography from uraemic ultrafiltrate, is responsible for the observed inhibition. Urines of patients with significant bacteriuria were more frequently activating.


Sialidosis, a new type of inborn disease. We describe the biochemical findings concerning five different types of mucolipidosis which have been defined as sialidosis on the basis of the specific enzyme deficiency and the nature of the storage material.


Diagnostic relevance of urinary lactate dehydrogenase determination in nephroptosis and for the indication to nephropexy. Previously reported experiments with animals suggested that reduced renal arterial flow might be the actual cause for the pathogenicity of nephroptosis. Clinical studies now give evidence that measurements of urinary LDH may be a criterion equal to the isotope nephrogram (ING) in considering this disease. Patients with a "mobile" kidney verified by i.v. pyelography were examined by an ING and a 1-day test for urinary LDH. In accordance with periodic kidney displacement total urinary LDH activities were measured in a 8-h urine volume in the supine position and a 8-h urine volume in the erect position of the patients. Evaluations were all expressed as percentage increase of LDH activity of the patient in the erect versus supine position and correlated with his ING-pattern. Among 45 nephroptotic individuals 34 showed, in accordance with a pathological ING, a mean LDH increase of more than a 100%. Eleven individuals had normal INGs and less than 20% increase equal to a group of 16 normal controls. We postulated a 30% increase as the upper limit between normal and pathological urinary LDH. The percentage distribution of isoenzymes was also altered within the pathological LDH range: LDH-I, which increases in normal controls, now decreased in nephroptotic patients. LDH-IV and V, which decrease in controls, now increased. Homomeric isoenzymes obviously show reciprocal behavior. The degree of kidney descent in cm does not correlate with percentage increase of urinary LDH, i.e. it is not a criterion for pathogenicity. Biopsies taken during nephropexy revealed that from an anamnestic duration of 50 weeks onwards the kidney is significantly affected and tissue damages become evident. If patients were re-investigated after nephropexy they showed normal i.v. pyelograms and normal LDH and no longer had clinical symptoms.


Diagnosis of renal disorders: comparison of urinary enzyme patterns with corresponding tissue patterns. The goal of our study was: 1. To determine the urinary enzyme pattern from urine, taken by ureteral catheterization from the side of the renal disorder, and to compare it with the pattern from the healthy side of the same patient. 2. To compare the enzyme patterns of normal and tumor tissues with the corresponding urinary enzyme patterns.


The sensitivity of urinary enzyme measurements for detecting renal injury. The relative sensitivity of urinary enzyme measurements for detecting renal damage was determined for two nephrotoxins. Injection of a single dose of sodium phosphate (10 mmoles/kg) caused damage to the proximal tubules and led to a 15 fold increase in lactate dehydrogenase (LDH) activity excreted into the urine. In contrast to this change the serum LDH remained normal. Similar results were obtained following the injection of cephaloridine (2 g/kg) with an 18 fold increase in urinary LDH and a marginal increase in urinary glutamate dehydrogenase (GDH). By contrast the serum LDH was unchanged. Urinary enzymes are therefore more sensitive for detecting renal injury than enzymes. The four enzymes investigated are located in specific regions of the cell so that the involvement of the organelles and regions of the cell can be followed. Damage to the organelles does not appear to occur as the excretion of the lysosomal enzymes remained normal and only in the case of cephaloridine were marginal changes in the mitochondrial GDH excretion seen. The average alkaline phosphatase was also normal suggesting no gross damage to the plasma membrane although a few individual rats excreted abnormal activities of alkaline phosphatase. These rats however, also excreted high activities of LDH. This suggests that damage to the membrane causes leakage of LDH and in severe cases release of the plasma membrane enzyme alkaline phosphatase. The administration of cephaloridine at various doses showed that urinary enzyme measurements were as sensitive as histology for demonstrating renal damage and that of these enzymes, LDH was by far the most useful.


Relevance of enzyme evaluations in 24h urine to rat kidney injury caused by i.v. cephaloridine injection. Male rats were housed singly in metabolic cages, injected i.v. with cephaloridine, 24 h urine samples collected successively; then the rats were killed for obtaining the kidneys of corresponding animals. The concentrations of protein, aminopeptidase (AP), alkaline phosphatase (aPP), lactic dehydrogenase (LDH), and aldolase (ALD) were determined in urine and the percentages of injured proximal tubules counted in sections stained for aPP. The results from individual animals were: (1) After placing animals singly in metabolic cages large but not systematic changes of urinary enzyme concentrations occurred. After 6-10 days the enzymes reached steady state levels. (2) After a single injection of cephaloridine a dose dependent injury of proximal tubules was observed, the urinary LDH content correlating best with the tubular injury (r greater than 0.93) and giving up to 1,000 fold increases above normal values. (3) A circadian rhythm of the susceptibility of rat kidney for cephaloridine was observed, the smallest response was seen when the animals were injected at 7 a.m. and the largest after injection at 7 p.m. (4) In subacute toxicity studies urinary LDH was increased on day 2 above the extent after a single dose, but declined on day 3 to reach normal levels after 8 to 10 days (time of sacrifice). The kidneys revealed practically normal histology. The other enzymes studied had also returned to normal values. This indicates some adaptation mechanism.


Cytogenetics of somatic cell hybrids. I. Progression of stemlines in continuous uncloned cultures of man-mouse cell hybrids. Karyotypes of hybrid cells were studied in continuous uncloned cultures by Q- and C-bandings. Cultures were initiated by virus-mediated or spontaneous cell fusions from normal human diploid fibroblasts and mouse heteroploid RAG cells. Heterokaryons containing complete genomes of both parental cells randomly lost chromosomes from both species. The majority of cells in early growth stages, however, still possessed a nearly complete human genome. The rate of human chromosome loss in subsequent growth periods was not uniform, being gradual in some and rapid in others. The initially predominant 2n human-1s mouse (1h:1m) type was soon replaced by a less frequent 2n human-2s mouse (1h:2m) type. Over an increased period of time in mass culture, the number of stemlines decreased. One stemline, often a (1h:2m) type with a greatly reduced human complement, outgrew the others and occupied the entire culture. Therefore, the usual process of clonal isolation may confer a negative selection bias against cell hybrids retaining a large number of human chromosomes. Hybrid stemlines with stable karyotypes were established in the present HAT-agar selection system before 36 days after fusion had elapsed.


Chromosome markers in 12 inbred strains of the Norway rat, Rattus norvegicus. Morphological details of metaphase chromosomes were compared among 12 inbred strains of rats (Rattus norvegicus) by means of conventional Giemsa staining and by a sequential Q- and C-banding method. Inter-strain variations were found in seven pairs, as identified on the basis of size differences in the short arms and/or satellites of chromosomes 3 and 12 and the X chromosome and in the centromeric C-bands of chromosomes 4, 5, 7, and 9. All pairs were homomorphic in the inbred strains, while F1 hybrids between two inbred strains showed certain heteromorphic pairs expected from the parents. These chromosome markers appear to be useful for characterization of inbred strains as well as for various genetic studies, including linkage analyses.


New karyotypes and somatic and germ-cell banding in Akodon arviculoides (Rodentia, Cricetidae). Chromosomal polymorphism resulting from three autosomal pericentric inversions and a complex rearrangement involving the largest chromosome of the complement (pair 1) in Akodon arviculoides (2n= 14, 15) is reported. G- and C-banding patterns in somatic and meiotic cells allowed the precise identification of all chromosomes and rearrangements. In meiosis of male specimens with 2n = 15, a large trivalent reflecting the complex rearrangement in autosomal pair 1 was observed. Two possible explanations for it are discussed. G- and C-bands in diplotene cells in heterozygotes for the inversions showed different configurations depending on the pairing in the inverted segments. Chiasma frequency data fro three specimens are analyzed.


Colinearity in the mouse genome: a study of chromosome 2. The cytologic positions (determined by G-banding) of the breakpoints on mouse chromosome 2 of a series of ten reciprocal translocations were compared with their most probable genetic positions on the linkage map, as determined by studies on recombination with known chromosome 2 (= linkage group V) markers. The most probable proximaldistal orders of the genetic and cytologic breakpoints were found to be the same; i.e., the two sets of breakpoints were colinear. However, there was no close correspondence between these two measures of the distance apart of adjacent breakpoints, since some translocation breaks which were well separated in G-band positions seemed close together in terms of the linkage map, and vice versa. This helps to confirm LYON'S conclusion that in certain mouse chromosomes, including No. 2, the distribution of chiasmata is nonrandom.


Upper airways obstruction with bilateral vocal cord paralysis. In ten patients with bilateral vocal cord paralysis, we demonstrated variable extrathoracic airway obstruction. The ratio of forced expiratory flow at 50 percent vital capacity to forced inspiratory flow at the same lung volume (VE50/VI50) was 1.65 +/- 0.77 (mean +/- 1 SD). There was marked variability of inspiratory flow obstruction with a mean VI50 of 1.63 +/- 0.75 liters/ sec and a range from 0.9 liters/sec to 3.2 liters/sec. Nine of the ten patients required tracheostomy for symptoms of dyspnea. Follow-up flow volume loops were obtained to document the effects of surgical intervention and tracheostomy.


Echocardiographic profiles of the long-term cardiac changes in cystic fibrosis. In this echocardiographic study, assessment of the heart in children with cystic fibrosis has shown that changes occur in not only the right ventricle but also in the left ventricle and aorta, as compared with normal. Echocardiograms could be successfully performed in 34 of 37 patients. The thickness of the right ventricular anterior wall and the dimension of the right ventricular cavity  were abnormal, even in patients with mild disease (National Institutes of Health [NIH] score for severity of disease of 85 or greater). Larger, older children with lower NIH score had disproportionately larger right ventricular anterior walls and cavities. The thickness of the septal wall, the thickness of the left ventricular posterior wall, and the aortic dimensions were increased in those with severe disease. The dimensions of the left ventricular cavity for the population were slightly but significantly smaller than normal in systole and in diastole throughout the course of the disease. This study demonstrates that echocardiography is an effective noninvasive means of assessing the long-term changes in children with cystic fibrosis. These changes occur in both sides of the heart and appear to worsen as the disease progresses.


Two-dimensional echocardiographic features of bicuspid aortic valve. The two-dimensional cross-sectional echocardiographic diagnosis of bicuspid aortic valves is described and compared with results of M-mode echocardiograms. Aortic valve anatomy was determined in 19 selected patients by angiography, and confirmed in five by direct surgical visualization. Using an eccentricity index (EI) of 1.3 or greater as diagnostic of bicuspid aortic valve, M-mode correctly identified anatomy in 14 of 19 valves (74 percent), although EI varied in several patients. For two-dimensional diagnosis of bicuspid aortic valve, short axis cross section was preferred, and criteria included number of cusps seen in real time motion, irregularity of folding of cusp margins, and location of commissural insertions. Two-dimensional echocardiography correctly identified anatomy in 18 of 19 valves (95 percent). Long axis cross section disclosed valvular doming in all 8 patients in whom doming was observed angiographically, correlating with hemodynamic findings. Two-dimensional echocardiography aids in the detection of bicuspid aortic valve in a suspected population, can give an estimate of valve gradients, and explains variability in M-mode findings. As such, two-dimensional echocardiography is a valuable tool in the noninvasive diagnosis of the bicuspid aortic valve.


Short-course chemotherapy of tuberculosis with largely twice-weekly isoniazid-rifampin. Although short-course, largely twice weekly chemotherapy for treatment of tuberculosis has been shown to be effective in other countries, when given under closely controlled conditions, it has not been adopted in this country where most patients are older and are treated as outpatients. Since January, 1976, 315 patients (mean age 55.5 years) with proven pulmonary tuberculosis have been treated with rifampin (RIF) 600 mg and isoniazid (INH) 300 mg daily for one month, followed by RIF 600 mg and INH 900 mg twice-weekly for another eight months, self-administered except for a few patients. By three months, 95 percent had converted to negative culture. There were only ten failures among 185 patients in whom final results could be assessed. There has been only one relapse during 1-21 months of follow-up in 175 patients. Serious side effects were few: six instances of jaundice, two of "flu-like syndrome," and one of thrombocytopenia. This form of initial therapy for tuberculosis is safe, effective, and economical.


Two infant deaths after inhaling baby powder. The clinical course of two baby girls who died following accidental inhalation of baby powder is described. Frequent tracheobroncheal lavage was not effective therapy. An experiment using eight mice revealed that the inhalation of baby powder was fatal. Possible treatments, including tracheobroncheal lavage with saline solution and application of chelating agents, are discussed.


Steroids, hypoxemia, and oxygen transport. This study investigated the effects of administration of methylprednisolone on oxygen transport in ten stable hypoxemic (mean arterial oxygen pressure, 54 +/- 3 mm Hg) patients with chronic obstructive pulmonary disease (COPD). At 24 hours (after four injections of a bolus of 30 mg of methylprednisolone sodium succinate per kilogram of body weight, given intravenously every six hours), significant differences (P less than 0.05) were an increased cardiac index (3.0 +/- 0.2 to 4.1 +/- 0.2 L/min/sq m), a decreased peripheral vascular resistance (1,186 +/- 100 to 849 +/- 60 dynes/sec/cm-5), an increased flow of oxygen to tissue (0.90 +/- 0.07 to 1.16 +/- 0.09 L/min), a decreased arteriovenous oxygen content difference (49 +/- 3 to 43 +/- 2 ml/L), a decreased concentration of hydrogen ions in the arterial blood (38 +/- 1 to 35 +/- 1 nmol/L) and arterial carbon dioxide tension (39 +/- 2 to 32 +/- 1 mm Hg), and increased levels of lactate (1.1 +/- 0.2 to 3.7 +/- 1.0 mmol/L) and pyruvate (0.14 +/- 0.04 to 0.37 +/- 0.08 mmol/L). Fractional oxygen utilization, oxygen consumption, the partial pressure of oxygen at which hemoglobin was 50 percent saturated, and the level of 2,3-diphosphoglyceric acid remained unchanged. In vitro studies showed that these patients' red blood cells responded with a significant (more than 35 percent) increase in the level of 2.3-diphosphoglyceric acid when incubated for ten hours with concentrations of methylprednisolone that were much higher (1.0 mg/ml) than those attained in vivo (12.5 microgram/ml). These studies demonstrate that repeated infusions of high doses of steroids in a bolus in stable hypoxemic patients with COPD produce significant physiologic changes but no apparent net gain in the oxygenation of tissues.


Respiratory abnormalities among grain elevator workers. Twenty-two grain workers with respiratory symptoms and lung function abnormalities were studied. Our findings suggest that grain dust asthma probably has an allergic basis, even though skin tests and precipitin studies were negative using extracts of grain dust. Hypersensitivity pneumonitis and grain dust fever were not found in any of the subjects. We found that grain dust can cause airflow obstruction in two ways: first by inducing asthma, probably through immunologic mechanisms, and second, by causing industrial chronic bronchitis.


Effects of influenza vaccination on the peripheral airways of healthy human volunteers. Forty-two volunteers (15 of them cigarette smokers) were studied to determine the effects on the airways that might result from immunization with killed influenza virus vaccine. The forced vital capacity, the forced expiratory volume in one second, the maximal expiratory flows at 50 and 75 percnet of vital capacity, and the volume isoflow were determined before and at 24, 48, and 72 hours and one and two weeks after vaccination. For both smokers and nonsmokers, there were no significant changes in the results of these tests of pulmonary function following vaccination.


Peripheral blood flow in secundum-type atrial septal defect; preoperative and postoperative studies. The purpose of this study was to correlate intracardiac shunt and peripheral blood flow measured by a venous-occlusion plethysmograph in 30 patients with secundum-type atrial septal defects. Preoperative and postoperative blood flows in the forearm were expressed as milliliters per minute per 100 gm of tissue. Peripheral flow increased after closure of the atrial septal defect, except in seven patients whose flow decreased. A possible explanation for this decrease is discussed.


Echocardiographic findings of congenital absence of the pulmonary valve with tetralogy of Fallot. The characteristic echocardiographic findings for congenital absence of the pulmonary valve with tetralogy of Fallot were described in three patients, whose diagnoses were confirmed by operation and/or autopsy. The abnormal linear echo, which was thought to be derived from the rudimentary pulmonary valve tissue, was recorded anteriorly to the dense echo from the subpulmonary muscle mass. The echocardiographic signs of right ventricular volume overload were associated with overriding of the aorta.


Oral therapy with phentolamine in chronic congestive heart failure. Therapy with phentolamine can improve the condition of patients with congestive heart failure due to the inotropic effect of this drug, as well as its vasodilating action. The use of oral therapy with phentolamine has not been adequately investigated in patients with chronic heart failure. Therefore, nine patients with chronic heart failure due to underlying valvular disease received 50 mg of phentolamine four times a day for two weeks. Echocardiograms and measurements of systolic time intervals were obtained prior to administration of phentolamine and two weeks after the introduction of therapy with the drug. As a result of therapy with phentolamine, the ejection fraction, the percentage of change in the minor axis, and the velocity of circumferential fiber shortening significantly increased, while the left atrial dimension decreased. Therapy with phentolamine produced a significant decrease in the preejection period index, as well as the ratio of the preejection period over the left ventricular ejection time. Thus, oral therapy with phentolamine improves left ventricular function in patients with chronic heart failure.


Rapid onset of lung involvement in progressive systemic sclerosis. Lung involvement in progressive systemic sclerosis (PSS) is common but usually is of chronic onset late in the course. Skin changes usually antedate pulmonary findings. Presentation of PSS with rapid development of pulmonary interstitial fibrosis, without skin changes, has not previously been described. Such a case is discussed here and the radiologic and pathologic findings and course of pulmonary PSS are reviewed.


Human pulmonary dirofilariasis presenting as a solitary pulmonary nodule. A case of human pulmonary dirofilariasis had positive serologic testing postoperatively. Increased awareness of this entity as a cause of solitary pulmonary nodules may lead to preoperative serologic and intradermal testing, and to the possibility of arriving at a preoperative diagnosis.


Major dehiscence of a prosthetic aortic valve: detection by echocardiography. A 21-year-old man had acute aortic insufficiency three months after insertion of an aortic valve prosthesis. Chest roentgenography demonstrated abnormal orientation of the prosthesis. M-mode echocardiography showed dense, linear echoes from the prosthetic valve between the interventricular septum and the mitral valve, along with loss of normal poppet motion within the aortic root. At surgery, the prosthesis was found to be extensively disrupted, resulting in prolapse into the left ventricular outflow tract. Another valve replacement was performed with patient survival. Echocardiography appears to be a useful adjunct to established roentgenographic procedures in the diagnosis of major dehiscence of prosthetic aortic valves.


Pulmonary artery--bronchial fistula: a new complication of Swan-Ganz catheterization. A patient with a Swan-Ganz catheter developed massive hemoptysis. Injection of radiographic contrast media through the catheter revealed rapid filling of the tracheo-bronchial tree, consistent with direct pulmonary artery-bronchial communication. Development of hemoptysis in a patient with a Swan-Ganz catheter should alert the clinician to this possibility.


Peripheral pulmonary embolization from central pulmonary aneurysm. A 59-year-old man underwent successful repair of a pulmonary arterial aneurysm because of peripheral pulmonary embolization. These lesions are relatively rare; and, to out knowledge, peripheral embolization from such an aneurysm has not been previously reported.


Acute respiratory failure and pulmonary arteritis without parenchymal involvement: demonstration in a patient with rheumatoid arthritis. A 28-year-old woman with a eight-year history of rheumatoid arthritis presented with a three-day history of dyspnea. Physical and electrocardiographic findings were consistent with pulmonary hypertension. Arterial blood gases revealed a ventilation-perfusion mismatch. Chest roentgenogram was normal. After transient improvement, she suddenly deteriorated and died. At autopsy, a necrotizing pulmonary panarteritis was found without parenchymal involvement by rheumatoid disease. The pulmonary arteries were the only vessels affected. Immunofluorescent staining revealed immunoproteins scattered throughout the vessel walls without localization to the basement membrane. The unique features of the case are discussed in relation to pulmonary hypertension and rheumatoid lung disease in which vascular lesions are usually associated with honeycomb lung. The association between the rheumatoid arthritis and pulmonary vasculitis was probably coincidental.


Intercostal artery laceration during thoracocentesis: increased risk in elderly patients. Two cases of intercostal artery laceration following thoracocentesis are reported. Subsequent analysis of 29 thoracic aortograms demonstrated a definite trend toward increasing tortuosity of intercostal arteries with advancing age. Consequently, the amount of space available for safe insertion of the thoracocentesis needle tends to decrease with advancing age. As a result, elderly patients are more prone to intercostal artery laceration during thoracocentesis, and careful attention must be paid to the proper technique for performing this examination in such patients.


Severe right ventricular outflow tract obstruction caused by an intracavitary cardiac neurilemoma: succesful surgical removal and postoperative diagnosis. A 32-year-old woman with a one-year history of progressive shortness of breath and chest pain was found to have a grade 4/6 systolic murmur at the base of the heart and left sternal border. Right ventricular enlargement was found by physical examination, ECG, and chest roentgenogram. Cardiac catheterization showed elevated right ventricular pressure, an intracavitary pressure gradient, and inability to enter the pulmonary artery. Angiography revealed a mass in the right ventricular outflow tract. Successful surgical removal of a large, well-encapsulated tumor mass was accomplished, and the tumor was interpreted as a benign neurilemoma. Postoperatively, the patient improved remarkably.


Mucor mediastinitis.

Mucor mediastinitis. A 69-year-old man with lymphocytic leukemia presented with fever, a pericardial friction rub, widening of the mediastinum, and left pleural effusion. Atrial fibrillation, refractory hypotension and acute paraplegia punctuated his hospital course. Invasion of the mediastinum, myocardium, mediastinal, coronary and spinal arteries with mucormycosis was present at post-mortem examination.


Reversible platypnea and orthodeoxia following recovery from adult respiratory distress syndrome. Platypnea nad orthodeoxia developed during an episode of adult respiratory distress syndrome in a previously healthy individual. An outstanding feature of the patient's illness was the development of numerous pneumatoceles secondary to necrotizing pneumonia. These abnormalities spontaneously improved with improvement of the underlying parenchymal lung disease.


Severe obstructive lung disease after smoke inhalation. A 26-year-old-man developed severe obstructive lung disease after inhalation of smoke from a house fire. Bronchography demonstrated changes characteristic of bronchiolitis. Despite intensive therapy with bronchodilators and corticosteroids, he continues to have severe obstructive lung disease nine months after the smoke inhalation.


Prolonged endotracheal intubation.

Prolonged endotracheal intubation. The advisability of prolonged oral or nasotracheal intubation is of continuing concern to physicians caring for patients requiring prolonged mechanical ventilatory assistance. Currently, in many health care centers, prolonged intubation is defined as being in excess of seven days. We treated a patient who required mechanical ventilatory assistance and in whom oral endotracheal intubation was maintained for two months without significant pathologic sequelae.


Loculated pericardial effusion in acute pericarditis: diagnosis by combined echocardiographic and radioisotopic techniques. A young man with a typical clinical presentation of acute pericarditis, on M-mode echocardiography, was repeatedly found to have a relatively echo-free area posterosuperior to the left ventricle, disappearing as the left ventricular apex was scanned. A radioisotopic "pericardial scan" revealed pericardial fluid lateral and inferior to the heart but not at the apex. This represents an additional type of M-mode echocardiographic presentation of loculated pericardial effusion.


Pulmonary function studies in patients with prolapse of the mitral valve. We studied the pulmonary function and chest x-ray films of 20 nonsmokers with idiopathic prolapse of the mitral valve. Forty-five percent of these patients complained of dyspnea. Of the 16 chest films reviewed, 44 percent had radiographic evidence of pectus excavatum and 25 percent thoracic scoliosis. The most common pulmonary function abnormalities were increased residual volume (63 percent) and a reduced steady state diffusing capacity (50 percent of patients). There was no relationship between the presence of dyspnea and either chest wall deformity of abnormality of pulmonary function. These pulmonary function abnormalities may reflect a pulmonary parenchymal disorder possibly secondary to a connective tissue abnormality in the lung.


Ventricular arrhythmias during exercise testing, jogging, and sedentary life: a comparative study of healthy physically active men, healthy sedentary men, and men with previous myocardial infarction. The occurrence of ventricular arrhythmias during exercise testing, jogging, and sedentary life with and without preceding exercise was studied with the aid of ambulatory electrocardiographic monitoring in healthy physically active men, healthy sedentary men, and men with previous myocardial infarction (15 men in each group). Ventricular premature beats of the same grade were found during exercise testing and jogging in ten of the 15 healthy physically active men, in ten of the 15 healthy sedentary men, and in eight of the 15 men with previous myocardial infarction. When unifocal ventricular premature beats were omitted, the corresponding figures were 14/15, 11/15, and 15/15, respectively. Healthy physically active men had less ventricular arrhythmias in all of the tested situations. The greatest number and also the highest grades of ventricular arrhythmias during the exercises were found in healthy sedentary men, whereas the men with previous myocardial infarction had ventricular arrhythmias more during sedentary life.


Fluorescence bronchoscopy for detection of lung cancer. A system using the fluorescence bronchoscope has been designed for localization of small, early bronchogenic carcinoma by the fluorescence of previously injected hematoporphyrin derivative. The system included a 200W mercury vapor lamp and primary filter, flexible fiberoptic bronchoscope with special violet-transmitting light conductor, secondary filter, and image intensifier tube. Tests indicated the system could detect a tumor only 100 micron thick at the expected concentration of hematoporphyrin derivative: 1 microgram/gm at 48 to 96 hours following intravenous injection at a dosage of 2.5 mg/kg. Examination of resected specimens (six of lung, one of esophagus) showed positive fluorescence in all cases, with fluorescence visible beyond the region visible under conventional white light examination. Fluorescence bronchoscopy has been performed on four patients thus far. Positive fluorescence was observed in all three cases where the tumor had been known to occur. Positive fluorescence was also observed in the patient with sputum positive for lung cancer, but negative x-ray film findings. However, additional examinations are required to demonstrate the smallest lesion that can be detected in vivo.


Antibacterial properties of lidocaine.

Antibacterial properties of lidocaine. The inhibitory effect of lidocaine and lidocaine plus methylparaben as a preservative was studied with 25 strains of bacteria. The tested strains were mixed with each topical anesthetic preparation, and quantitative cultures were performed on aspirates at 0, 30, 60, and 120 minutes. Results were compared to counts obtained in a lactated Ringer's solution, which were sampled at the same intervals. Lidocaine (1 percent solution) reduced quantitative counts after 120 minutes of contact by over one log for only six of the 25 strains tested. Lidocaine plus methylparaben reduced quantitative counts to a somewhat greater extent; nevertheless, all strains except Bacteroides melaninogenicus were recovered in relatively high concentrations at each sampling interval. Numerous previous studies have shown that topical anesthetic agents are toxic to bacteria. The results of this study show that this toxic effect is not sufficiently severe to prevent the recovery of most pathogens of the lower respiratory tract in bronchoscopic aspirates.


Evaluation of the single-breath diffusing capacity in asthma and cystic fibrosis. To explain why the single-breath carbon monoxide diffusing capacity (Dsb) was, on the average, elevated in 163 asthmatic subjects and 175 patients with cystic fibrosis, we simulated this elevation in ten normal subjects by having them perform the test for Dsb through an inspiratory obstruction. This resulted in an 18 percent increase in Dsb corrected for pulmonary volume. Inhalation of a bronchodilator drug was associated with relief of obstruction and a fall in the corrected Dsb in 31 asthmatic subjects but did not change either the obstruction or the corrected Dsb in 17 patients with cystic fibrosis. We suggest that elevated Dsb in asthma and cystic fibrosis is partly due to maximal inspiration against obstructed airways. This requires abnormally negative intrathoracic pressures, increasing the pulmonary capillary blood volume, and, thereby, increasing the Dsb.


Chest roentgenograms in primary pulmonary hypertension. The characteristics of 59 chest roentgenograms of patients with primary pulmonary hypertension were investigated and compared with roentgenograms of 100 healthy control subjects. The relationship with pulmonary hemodynamics was also examined. In primary pulmonary hypertension, there was remarkable protrusion of the main pulmonary artery; the DPA (T/2) and the PL/T index (see text) had high values. These indices depend mainly on pulmonary hypertension, but are partially determined physically by the size of the individual heart. The width of the descending branch of the right pulmonary artery (dPA) was about double the control value (P less than 0.001). The cardiothoracic ratio was significantly increased in primary pulmonary hypertension and there was a positive correlation between the ratio and the mean right atrial pressure (r = 0.37, P less than 0.01). However, there was no correlation with pulmonary arterial pressure or other pulmonary hemodynamic parameters. These results indicate that the increase in the cardiothoracic ratio in primary pulmonary hypertension is caused mainly by right heart failure.


Myocardial supply-demand ratio in aortic regurgitation. To analyze the relationship between the myocardial supply and demand for oxygen in patients with aortic regurgitation, the ratio of the diastolic pressure-time index (DPTI) over the systolic pressure-time index (SPTI) was derived from recordings of pressure during cardiac catheterization in 24 patients with aortic regurgitation, and this ratio was compared with that in 14 normal subjects and in ten patients with congestive cardiomyopathy (an ejection fraction less than 0.30). Patients with aortic regurgitation had a DPTI/SPTI of 0.75 +/- 0.06 (mean +/- SE), which was lower than in the normal subjects (1.24 +/- 0.06) and patients with cardiomyopathy (1.06 +/- 0.03) (P less than 0.001). Among the patients with aortic regurgitation, the 13 with a DPTI/SPTI below 0.70 had more severe aortic regurgitation than the 11 with a DPTI/SPTI above 0.70. Aortic regurgitation results in a reduced myocardial supply-demand ratio, as measured by the DPTI/SPTI, which is related to the severity of the valvular regurgitation and is not present in patients with left ventricular dysfunction secondary to congestive cardiomyopathy.


Fiberoptic bronchoscopic nasotracheal intubation in children. A new method for nasotracheal intubation of infants and young children is described. This method offers a smooth, reliable, and rapid means of entry into these children's airways in a safe and efficient manner in a wide variety of cardiorespiratory illnesses. This technique should be reserved for well-trained physicians with adequate equipment and experience. It is an optional technique for intubation that should be available in all modern general and children's hospitals throughout the country.


Constancy of effort and variability of maximal expiratory flow rates. In 14 normal subjects and in 13 patients with obstructive pulmonary diseases, we studied the variability within an individual of values for the maximal expiratory flow rate (Vmax) recorded simultaneously vs expired pulmonary volume (at the mouth) and vs thoracic volume (measured with a body plethysmograph). We found that the variance of Vmax within an individual at 25, 50, and 75 percent of the expired vital capacity did not differ statistically whether pulmonary volume was the expired or the thoracic gas volume. In ten healthy subjects on two occasions (at an interval of 12 days, on the average), we measured the peak expiratory flow rate and Vmax at different levels of inflation, with respect to either expired or thoracic volume. There was no statistical differences in Vmax between the first and the last day. A larger variability of Vmax measured vs expired volume implies a change in the expiratory effort from one forced expiration to another and a different degree of compression of intrathoracic air. Since this was not the case, we conclude that muscular effort during repeated forced expirations is similar. The good reproducibility of effort explains in great measure the good reproducibility of Vmax.


Measurement of regional lung function by tetrapolar electrical impedance plethysmography. This study demonstrates the clinical feasibility of atraumatically measuring dynamic regional lung function with tetrapolar electrical impedance plethysmography (EIP) in the pediatric age group. A tetrapolar electrode system was used because of its ability to detect local baseline and pulsatile impedance changes, minimal electrode-tissue impedance interference, and uniform current distribution. Studies performed on 4 children 4 to 15 years old with various pulmonary diseases are presented. The information obtained on their regional ventilation and pulsatile perfusion by EIP was found to agree closely with pulmonary ventilation and perfusion scans. In one case, EIP detected pulsatile perfusion abnormalities which were not apparent in the non-pulsatile perfusion scan but were demonstrated by cineangiography. It is concluded that tetrapolar EIP can provide safe, reliable regional information about ventilation and perfusion in diseased lungs, and because of its atraumatic approach, is technically most suitable for use in children.


Selection of patients with hemoptysis for fiberoptic bronchoscopy. One hundred ten hospitalized patients with hemoptysis were reviewed to identify factors that would characterize those with malignancy and to evaluate the usefulness of fiberoptic bronchoscopy (FB) in the diagnosis of hemoptysis. Seventy patients underwent FB. This procedure was diagnostic in 22/28 (79 percent) of the carcinoma patients and in 26/42 (62 percent) of the patients with a nonmalignant cause of hemoptysis. The following three characteristics indicate a high probability of malignancy: 1) age greater than 40 years, 2) any abnormality on the chest roentgenogram, 3) hemoptysis lasting greater than one week. If any of these factors are present, FB should be done. Other factors to be considered include presence of anemia, weight loss, persistent cough, long smoking history and risk of bronchoscopic complications.


Echocardiographic analysis of systolic and diastolic left ventricular wall motion in normal man. Although the motion of the left ventricular wall has been examined by angiographic and by echocardiographic studies in both experimental animals and in man, there are no complete studies of the motion of the left ventricular posterior wall throughout the entire cardiac cycle. Because the posterior wall can be demonstrated echocardiographically in essentially all patients, it offers a potential of wide clinical application in the evaluation of left ventricular function. This study was undertaken to provide a detailed inclusive analysis of the motion of the left ventricular posterior wall. In 64 human volunteers the echocardiographic movements of the left ventricular posterior wall were identified. Using the R wave of the electrocardiogram as a reference and to identify phases of the cardiac cycle, each movement of the left ventricular posterior wall was temporally related to aortic or mitral valvular movements (or both). In a subset of 14 subjects, dual M-mode echocardiograms confirmed the validity of these temporal relationships. In three subjects, high-fidelity recordings from catheter tip micromanometers were made simultaneously with the echocardiogram to permit description of the temporal relationships between pressure and motion. Results of this study provide a base of normal data for comparison with the motion of the left ventricular posterior wall in a variety of diseases and in response to therapy.


Single-breath nitrogen washout; effects of alterations of lung volumes and elastic recoil. Strapping of the chest causes decreased lung volumes and increased elastic recoil pressure. Such strapping was used in conjunction with single-breath nitrogen washout to study the effects of changes in these factors on the dynamics of the small airways. Studies consisted of simultaneous measurements of the quasistatic lung pressure-volume curve and single-breath nitrogen washout. Strapping caused significant reductions in all lung volumes and in lung compliance at 50 percent of the total lung capacity (TLC). The volume of phase 4 was not changed; however, the ratio of closing capacity to control TLC decreased from 29.9 +/- 6 percent to 24.2 +/- 4 percent with strapping (P less than 0.02). This observation indicates that the onset of closing volumes occurred at a lower absolute lung volume during strapping, compared with control. The closing pressure of 2.1 +/- 0.8 cm H2O was not altered by strapping of the chest. The slope of phase 3 of the single-breath nitrogen-washout test and the average alveolar concentration of nitrogen were increased during strapping. A similar phenomenon occurred in three subjects who performed the single-breath nitrogen-washout test following partial vital capacities. A reduction of the onset of closure of the airways without a change in closing pressure suggests that restrictions of the chest wall caused no change in mechanical properties of the small airways. Elevation of the slope of the alveolar plateau is probably due to exaggeration of the apex-to-base nitrogen difference consequent to the strapping-associated decreased lung and alveolar compliance.


Mitral valve fluttering; an echocardiographic feature of left atrial myxoma. A patient with crescendo angina and severe three-vessel coronary disease had a left atrial myxoma found incidentally and which was removed during coronary bypass surgery. Preoperative echocardiogram revealed only coarse diastolic mitral valve fluttering without other echocardiographic features of left atrial myxoma. Postoperative echocardiogram showed disappearance of mitral valve fluttering. The isolated finding of diastolic mitral valve fluttering by echocardiography may be associated with occult left atrial myxoma.


Intoxication with ajmaline in an infant. We present a case of overdosage of ajmaline in an infant. The appearance of atactic gait and clonic tonic seizures were followed by loss of consciousness, apnea, supraventricular tachycardia, left bundle-branch block, and a prolonged Q-T interval. Cardiopulmonary resuscitation, gastric lavage, and forced diuresis were followed by complete recovery. Continuous electrocardiographic monitoring is mandatory in these cases, and the use of a cardiac pacemaker, respirator, and therapy with antiarrhythmic agents should be considered.


Hemoptysis in patients with septic pulmonary infarcts from tricuspid endocarditis. Three drug addicts with tricuspid valve endocarditis and pulmonary cavitation secondary to septic pulmonary infarcts developed massive hemoptysis. Two patients died of asphyxia and one survived. Both who died were improving clinically and had negative blood cultures when the fatal hemoptysis occurred. Therefore, however slight it may be, hemoptysis occurring in association with septic pulmonary infarcts associated with endocarditis may require prompt and aggressive measures.


Effects of 5-fluorouracil on the thiamin status of adult female rats. The effect of 5-fluorouracil on the thiamin status of normal female adult rats has been investigated. Pre-treatment of the animals with the cytotoxic drug daily for 3 successive days resulted in a significant decrease in hepatic concentrations of thiamin concomitant with a decrease in thiamin-dependent transketolase enzyme activity and an increase in thiamin-pyrophosphate-(TPP-)stimulating effect in whole blood when compared with those of pair-fed control animals. The TPP effect of transketolase enzyme activity was also increased by 5-fluorouracil in vitro. Furthermore, the treatment with 5-fluorouracil resulted in decreased liver and spleen concentrations without affecting the urinary excretory levels of thiamin in animals supplemented with large doses of the vitamin. Giving a dose comparable to a human therapeutic dose caused a similar increase in the TPP effect. These results indicate that treatment with 5-fluorouracil may be associated with thiamin deficiency by increasing either the utilization or the breakdown of thiamin.


A comparison of the in vitro activities of sulfamethoxazole and sulfadiazine combinations with trimethoprim. The sensitivity of 125 strains of 13 species or genera of bacteria to sulfamethoxazole (SMZ), sulfadiazine (SDZ), trimethoprim (TMP), SMZ + TMP and SDZ + TMP was determined by means of trays. A comparison of all combinations of the different concentrations used shows that SMZ + TMP is in 1 case and SDZ + TMP in 4 cases more effective against the 13 species or genera tested than the other combinations. SMZ and SDZ were equally effective in synergistic action (as shown by the FIC indices) against the various kinds of bacteria.


Microbiological and pharmacological evaluation, in mice and rats, of a new nitrofuran: 2-amino-4-methyl-6-(2-ethinyl-5-nitrofuryl)-pyrimidine (nifurpyrimidine). 2-Amino-4-methyl-6-(2-ethinyl-5-nitrofuryl)-pyrimidine (nifurpyrimidine) is a new furan derivative. Its spectrum of activity is wide and includes both gram-positive and gram-negative microorganisms and fungi; moreover, it inhibits the growth of multiple-drug resistant salmonellae. The minimal inhibitory concentrations ranged from 0.25 to 10 microgram/ml. Resistance was developed in vitro in a step-wise manner and was partially reversed after 7-10 passages in drug-free media. The pharmacological study of the drug was carried out in rats and mice and gave the following results: (1) no acute toxicity was demonstrable following oral administration; (2) no intestinal absorption occurred and virtually the whole dose of nifurpyrimidine administered by oral route was recovered in the intestinal content; (3) the presence of urine, plasma or feces did not modify the antibacterial activity of the compound.