The acute effects of periosteal stripping and medullary reaming on regional bone blood flow. The immediate effects of surgical dissection on regional bone blood flow were studied using the hydrogen washout technique and the results were compared in mature and immature rabbits. Epiphyseal circulation in young animals was eliminated by stripping the epiphyseal periosteum, and even in mature rabbits epiphyseal blood flow was markedly reduced by periosteal stripping. This suggests that after skeletal maturity blood supply crossing from the metaphysis into the epiphysis is limited. The blood flow rate was not altered by wide reaming of the epiphyseal center in either young or old animals. The rates of bone blood flow in the metaphysis and diaphysis were not altered by separate periosteal stripping or medullary reaming in either age group. Combined reaming and stripping eliminated blood flow in the diaphyseal cortical bone, but in the metaphysis fairly rapid blood flow remained even after reaming and periosteal stripping were done. These findings suggest that arterial supply and venous drainage traverse both endosteal and periosteal surfaces, and either system is capable of sustaining adequate bone tissue circulation.


Effect of repetitive impulsive loading on the knee joints of rabbits. To simulate the forces from hopping, the right foot of adult rabbits was subjected to 1 1/2 the animal's body weight 40 times a minute for 20-40 minutes per day. During these brief periods of repetitive impulsive loading the legs were held in short-leg splints to eliminate the natural shock-absorbing mechanism associated with ankle dorsiflexion and calve muscle stretching. Under these conditions subchondral bone stiffening occurred and was associated with the earliest metabolic changes of cartilage damage. When bone stiffening returned to normal the effect on the cartilage did not completely disappear, although these effects diminished. The results suggested that subchondral bone stiffening accompanies the earliest metabolic changes in osteoarthrosic chondrocytes and suggests that trabecular microfracture may occur very early in this sequence of events.


Microstructural organization of human and bovine cruciate ligaments. Human and bovine anterior cruciate ligaments studied with the SEM demonstrate fascicular bundle and connective tissue sheath components. In the human, collagen fibers of the connective tissue sheath, although approximately the same diameter as the fascicular fibers, have an orientation suggestive of a binding rather than a tensile function. While both elements have tensile properties, it is hypothesized that the contribution from the sheath component is minimal and, consequently, detailed studies of the tensile properties of ligaments will produce meaningful data when related to the appropriate cross-sectional areas. In direct contrast to the human counterpart, the SEM appearance of bovine cruciate ligaments is tendon-like, characterized by very dense subfasciculi surrounded by very thin connective tissue sheaths.


Upper extremity surgery in stroke patients. Surgical procedures are performed on the nonfunctional upper extremity following stroke to correct spastic flexion contractures that cause pain or prevent adequate hygiene. In the upper extremity surgical procedures are most commonly performed to improve extension at the wrist, fingers or thumb. If the deformity is primarily due to spasticity rather than fixed myostatic contracture, anesthetic block of the median and/or ulnar nerve preoperatively enables the surgeon to determine that extension will be improved after the appropriate flexor tendons are lengthened. Careful presurgical evaluation of motor sensory function enables the surgeon to predictably select those patients who will benefit from surgery.


Pathologic femoral shaft fractures comparing fixation techniques using cement. To determine the most stable mode of internal fixation for the pathologic femoral shaft fracture with extensive cortical destruction, 2 fixation techniques incorporating methylmethacrylate were compared. Osteotomies through standardized cortical defects were created in intact embalmed femora to simulate a standard pathologic fracture. Fixation obtained with either intramedullary Schneider rods or 28-hold ASIF plates, both using bone cement, was compared in torsion and bending. In torsion, plate-fixed femora failed at a mean load of 71.2 newton-meters compared to 26.8 newton-meters for the Schneider rod counterparts. In bending, plate-fixed bones at a mean load of 8133.9 newtons compared to 1921.4 newtons for rod-fixed femora. Fixation with double plates and methylmethacrylate was clearly more stable and allowed for immediate pain-free ambulation.


Biological reaction to carbon fiber implants: the formation and structure of a carbon-induced "neotendon". In 43 young rabbits, the tendo Achilles and flexor digitorum longus tendon were excised and replaced by filamentous carbon fiber. Tendo-Achilles in controls was repaired by silk or nylon sutures or left without replacement. Concurrent excision of the posterior tibial nerve was performed in one group of the carbon-replacing tendo-Achilles operations. When fully functioning, carbon-induced "neotendon" rapidly developed from young fibroblastic tissue outgrowths of the loose mesenchymal tissue of the perineurium and adventitia of the blood vessels in the adjacent neurovascular bundle. Silk or nylon replacement of the excised Achilles tendon did not lead to successful production of a new substitute. Carbon fibers were unsatisfactory for replacement implants for the flexor digitorum longus tendons.


Load-bearing in the knee joint.

Load-bearing in the knee joint. The surfaces of the knee--anomalous to most animal joints through apparent gross incongruity--would appear more congruous if the menisci bore load. A simple system is used to show how the menisci can bear load. The strong tibial fixation and structure of the menisci, and the geometry of the femoral condyles indicate that the menisci bear load throughout flexion and extension. Confirmatory experimental results show that in partially degenerate human and healthy pigs' knees the menisci bear at least 45 and 75% respectively of the total joint load. The knee joint is similar in this respect to other synovial joints.


The value of delayed (24-hour) bone scintigraphy. Delayed 24-hour scintigraphy was performed in 23 patients. It was found to be useful in enhancing abnormal uptake, enabling better anatomic localization and verifying doubtful uptakes in the 4-hour study. The underlying causes of these observations are probably a better lesion-to-blood ratio and a slow uptake in certain lesions.


67Ga scintigraphy in lymphomas with special reference to cardiac apical mass. The cardiac apical mass of Hodgkin's disease, an infrequent presentation of lymphomas, can be selectively labeled with 67Ga-citrate. Three cases are presented illustrating the value of 67Ga scintigraphy in the differential diagnosis of pericardial masses, as well as its role in the management and assessment of therapy.


Electromyographic analysis of equinovarus following stroke. The pattern of muscle activity was determined in 40 hemiplegic stroke patients with equinus, equinovarus or varus deformities. Although the exact pattern of muscle activity varied with each patient, the following general conclusions are possible. Premature firing of the triceps surae due to release of primitive locomotor control mechanisms and a hyperactive stretch response during limb loading are important causes of equinus. Prolonged firing of the tibialis anterior during stance and inactivity of the peroneus brevis are the principal factors responsible for varus.


Definitive diagnosis of choledochal cyst by 99mTc-pyridoxylideneglutamate sequential scintiphotography. Sequential supine scintiphotography of the abdomen was performed after intravenous administration of 99mTc-pyridoxylideneglutamate (99mTc-PG) to verify the presence of choledochal cyst in an 18-month-old boy who presented with a mass in the right upper quadrant of the abdomen. The total body radioactivity effect, which is similar to the total body opacification during intravenous cholangiography or urography, was clearly demonstrated as a cold area corresponding to the cyst and assisted in the diagnosis. The specific finding was sequential filling of the gallbladder and cyst. In view of the relatively low radiation dose and good physical characteristics of 99mTc for imaging, 99mTc-PG sequential scintiphotography is useful for the definitive preoperative diagnosis of choledochal cyst in infants and children.


Surgical correction of gait abnormalities following stroke. Lower extremity abnormalities in stroke patients can be reliably improved by surgery. Surgical treatment is most frequently recommended for patients with: equinovarus; toe curling; excessive hip and knee flexion; limb scissoring. Unless the patient's disability is so severe he cannot walk, the operation is performed not before 6 and preferably not until 9 months after sroke.


Right subhepatic abscesses detected by technetium liver scans. A focal defect at the inferior margin of the right lobe of the liver was found in two patients with subhepatic abscesses. This defect must be differentiated from the porta hepatis and the gallbladder fossa. When technetium liver scans are obtained in patients with usspect abdominal abscesses, the inferior margin of the right lobe of the liver should be carefully scrutinized so that right subhepatic abscesses will not be overlooked.


New approaches to the nursing care of the stroke patient. Prevention and maintenance constitute a large part of the nurse's role in caring for the stroke patient during the acute stage of his illness. The nurse must have knowledge of both the subjective and objective effects of a stroke to formulate an effective Nursing Care Plan. Consistency is vital in providing an environment in which a stroke patient can relearn fundamental activities. Confusion, and thus the diminished ability to learn, is often relieved by familiarity and predictability of surroundings, persons, and routines. Nursing's participation in positioning, range of motion exercises, bowel and bladder retraining and providing appropriate sensory input is essential. The nurse must assume the role of coordinator and evaluator of the patient's rehabilitation, using 24 hour-a-day observation coupled with educational background and experience, to determine obs-acles and assess the patient's ability to resume living in his previous environment.


Rehabilitation of the communicatively impaired stroke patient. The stroke patient who has lost the ability to communicate has lost more than the ability to talk. To one degree or another, he has lost the ability to understand his environment, the ability to structure his thought process internally in a logical and meaningful order, and the ability to formulate language in a logical and meaningful order. The ability to structure one's thoughts and ideas internally, as well as the ability to communicate them to others, are intrinsic factors in an individual's ability to motivate himself to establish a goal and to pursue the acquisition of that goal. Therefore, the successful physical rehabilitation of the stroke patient with a communication disorder rests heavily upon an understanding and a resolution of his communication problem.


The jugular venous reflux.

The jugular venous reflux. Attention is drawn to the various patterns with which the jugular venous reflux may occur in cerebral dynamic studies. The importance of identifying this phenomenon is stressed.


Benign chondroblastoma of talus demonstrated by skeletal scanning. A patient with a benign condroblastoma of the talus bone is described. A review of the pathogenesis and more common sites of predilection of this unusual tumor is presented. This is the first case, to our knowlege, shown by labeled phosphate scanning.


Radionuclide angiocardiography: use in the detection of myocardial rhabdomyoma. A neonate with a large rhabdomyoma of the heart was evaluated with radionuclide angiocardiography. The images revealed a "cold" area on the inferior surface of the heart which displaced the left ventricle. The findings were correlated with radiographic angiocardiography and were verified at surgery and autopsy. The value of this noninvasive technique in the evaluation of a seriously ill neonate is stressed.


The use of indium-111-labeled leukocytes for abscess detection. A case is reported in which a labeled white cell scan was helpful in the diagnosis of a periappendiceal abscess. The method of labeling is described and the usefulness of the technique discussed.


Abnormal renal uptake in indium-111-chloride scanning. A patient with severe alcoholic liver disease, in whom there was almost complete suppression of function of the reticuloendothelial system of the liver as noted on a 99mTc-SC scan is discussed. Obstructive biliary disease was suggested on 131I-rose bengal imaging. The depressed RES function was confirmed on 111In-chloride scan, showing abnormal uptake in the kidneys which could be secondary to inflammatory infiltration in the renal parenchyma from urinary tract infection with gamma enterococci.


Hypertrophic Riedel's lobe of the liver. Riedel's lobe, noted on 99mTc-sulfur colloid liver scintigraphy, was present in 86 (3.3%) of 2604 patients reviewed. Hypertrophied Riedel's lobe was found in 30 cases of which 25 (83%) were females and 5 (17%) were males. Liver scintigraphy will detect the presence of a hypertrophied Riedel's lobe and is recommended in all cases of right sided abdominal masses.


Doughnut phenomenon in bone scintigraphy. A doughnut phenomenon was observed in bone scintigraphy in three cases of metastatic thyroid carcinoma to the skull. Additional dynamic and static studies were performed to evaluate the relative roles of vascularity, vessel permeability and new bone formation in producing this phenomenon. This was accomplished through the use of 99mTc-diphosphonate, 99mTc-labeled red blood cells and 99mTc-pertechnetate. The important factor was found to be a new  bone formation. Late uptake of diphosphonate was shown only in the periphery of the lesion, where formation of new bone takes place. This occurred even in the presence of increased vascularity and vessel permeability in the lesion as a whole.


Bone scan in sickle cell crisis.

Bone scan in sickle cell crisis. 99mTc-diphosphonate bone scans of 13 patients in acute sickle crisis were analyzed. Twelve of the 13 patients had abnormal scans, with increased activity in joints and skull being a common finding. One patient with splenic calcification and two patients without splenic calcification had splenic uptake of diphosphonate. Most of the abnormal scans showed hot areas, with cold areas seen only in four cases. There was no correlation between the site of pain clinically and the abnormal areas on scanning. The pathophysiology of the abnormal uptake of radioactivity and the role of bone scanning on sickle cell disease are discussed.


Is the anterior bone scan necessary in the diagnosis of osseous metastases? Bone imaging studies of 1650 patients with known or strongly suspected extraosseous malignancies were reviewed to determine whether a completely negative posterior view was sufficient to exclude metastatic disease. Of 708 negative posterior images, 27 (3.4%) were positive for metastasis on anterior views. All of the anterior lesions were in the sternium, sternoclavicular joints and first four ribs. When the posterior view is positive, further views may be unnecessary. Negative or equivocal posterior images necessitate anterior views of the thoracic cage.


Intracoronary myocardial perfusion imaging: patterns in patients with coronary artery disease. Myocardial imaging following the intracoronary injection of radiolabeled particles is used to identify transmural scars in patients being evaluated for coronary atherosclerosis. Selective imaging of the microcirculation derived from each major coronary vessel is accomplished using a dual radionuclide technique. This report illustrates the various normal and abnormal imaging patterns encountered in patients with coronary artery disease. The regional myocardial nomenclature proposed by the American Heart Association Council on Cardiovascular Surgery is used. Correlation of the nuclear study with the contrast arteriogram and ventriculogram is essential for identifying both transmural scars and regions of collateral circulation. The procedure is safe and can be performed during routine coronary angiography.


The role of 67Ga in an unusual form of American Burkitt's lymphoma. An uncommon primary site for an American Burkitt's lymphoma in the nasopharyngeal region was demonstrated by radiogallium imaging in a 14-year-old white boy. Fifth cranial nerve involvement and cerebrospinal fluid cytology for Burkitt's responded initially to four drug chemotherapy with objective reduction in the tumor radiogallium uptake. Clinical relapse and recurrence of the tumor radiogallium uptake in less than three weeks following the completion of therapy was observed. Local irradiation and chemotherapy successfully reduced the symptoms and eliminated the radiogallium tumor uptake. Radiogallium imaging is advocated as a principal method for staging and monitoring the course of Burkitt's lymphoma.


Abnormal gallium scan in regional enteritis. Regional enteritis in a 41-year-old woman was localized on a 67Ga-citrate scan, appearing as a well-circumscribed abnormality in the pelvis simulating an abscess or a malignant neoplasm. Gallium-67-citrate scintigraphy is useful in localizing granulomatous inflammations including regional enteritis, and its use may be beneficial in evaluating the extent and the state of disease process.


"Lunch syndrome," a bone-scanning artifact: case report. After a photon-deficient area in the region of the stomach under the ribs on the left side was noted in some bone-scanning patients, a successful attempt was made to produce the artifact by having a cooperative patient eat a large lunch. The comparison of the scans before and after lunch showed the presence of a postprandial artifact in the area in question. It is important not to confuse this artifact with a space-occupying avascular mass in that part of the abdomen.


Demonstration of superior vena caval obstruction and "hot spot" on liver scan in a case of non-Hodgkin's lymphoma. A case of total superior vena cava obstruction and "hot spot" in the liver demonstrated by a radiocolloid liver scan in a case of non-Hodgkin's lymphoma of the anterior mediastinum, is presented. The study showed total obstruction of the superior vena cava and the presence of collateral circulation. The patient received radiation therapy, and a subsequent radiocolloid study showed relief of the obstruction and disappearance of the "hot spot."


The validity of 99mTc-pyridoxylideneglutamate (P.G.) cholescintigraphy as a diagnostic test for cholecystitis. The purpose of this investigation was to determine the diagnostic value (validity) of technetium-99m-pyridoxylideneglutamate cholescintigraphy (99mTc-PGC) in patients with and without cholecystitis and to compare its validity to those of oral cholecystography (OC) and ultrasonography (US). 99mTc-PGC was applied to 50 patients with acute, subacute, and/or chronic cholecystitis with cystic duct obstruction proven histologically and operatively, and also to 27 non-diseased volunteers and 43 patients with right upper quadrant abdominal pain who subsequently were proven free of gallbladder disease. In addition, 38 patients had OC, and 31 had US performed. The results shows that the sensitivity and specificity of 99mTc-PGC were 100%. Whereas for OC the sensitivity was 87%, specificity was 100%. For US the sensitivity was 70%, and specificity was 93%. The repeatability of 99mTc-PGC, OC, and US were 100%, 97% and 81% respectively. These data show that 99mTc-pyridoxylideneglutamate cholescintigraphy is a valid diagnostic tool in the evaluation of patients with cholecystitis, and is also safe and simple.


Thyroid scintigram in familial medullary carcinoma of the thyroid gland. Findings on thyroid scintigram were compared with results of thyroid palpation and size and location of C-cell disease in 68 thyroid lobes of 35 patients with familial medullary thyroid carcinoma (MTC) and high basal or stimulated plasma calcitonin values. Rectilinear scans showed cold nodules in 24 (35%) of 68 lobes. In three lobes, the cold nodules did not coincide with MTC (2 macrofollicular adenomas, 1 colloid goiter). Thus, the true positive rate for rectilinear scans was 31%. Palpation identified nodules in 20 lobes (29%), but the true positive rate was only 26%. Patients with MTC have high basal or stimulated calcitonin values long before the tumor is detectable by scan or even later by palpation. When the tumors were large enough to be seen on thyroid scans, the most frequently encountered single pattern was that of symmetrically located cold nodules in the middle of otherwise normal thyroid lobes. This pattern, if encountered in a thyroid scan, should raise the suspicion of MTC.


Ferrokinetics: methods and interpretation. The measurement of erythroid activity is based on the study of plasma iron kinetics. The radioiron injected should be bound specifically to transferrin, and the measurement of plasma 59Fe activity should be corrected for variation in plasma iron concentration. In addition, 59Fe-transferrin activity should be measured free of 59Fe-haemoglobin contamination. Analysis of the plasma 59Fe clearance curve over 14 days can give measures of total, effective and ineffective erythropoiesis, together with the red cell lifespan. Simpler ferrokinetic studies cannot be reliably used to assess erythropoiesis.


Children with psychogenic abdominal pain and their families. Management during hospitalization. Children hospitalized with psychogenic abdominal pain and the children's families are discussed from the perspective of a child psychiatrist working within the pediatric hospital. Psychosocial and emotional difficulties for the child and parents are noted as families use somatic symptoms to deal with psychic distress. Principles for management are emphasized, utilizing a comprehensive team approach by physicians, nurses, and other health professionals. Through constructive use of hospitalization and informed follow-up, these children and their parents can be helped toward symptomatic improvement and a more meaningful understanding and resolution of their underlying emotional difficulties.


Pharmacokinetics of lithium: elimination half-time, renal clearance and apparent volume of distribution in schizophrenia. The elimination half-time and renal clearance of lithium was measured in 12 schizophrenic patients. Minimum plasma lithium concentrations during alternate dosage intervals in 5 patients increased rapidly during the first 2 to 3 days of treatment and reached a steady state level after 5 to 6 days. After the establishment of the remaining 7 patients on lithium the decline in plasma lithium concentration when treatment was stopped was monoexponential. Elimination half-times ranged from 19.3 to 41.3 hours (mean +/- SD = 28.9 +/- 7.9h) and were significantly correlated with renal creatinine clearance (p less than 0.01). Renal lithium clearances ranged from 13.5 to 36.8 ml/min (mean +/- SD = 24.4 +/- 8.0 ml/min) and the apparent volumes of distribution ranged from 0.39 to 1.39 L/kg (mean +/- SD = 0.79 +/- 0.34 L/kg). There was no evidence that the elimination parameters of lithium in schizophrenic patients were significantly different from those in healthy individuals or manic-depressive patients.


Pharmacokinetics of oral acetylcysteine: absorption, binding and metabolism in patients with respiratory disorders. The fate of an oral 100 mg dose of 35S-acetylcysteine, a mucolytic agent, was studied in 10 patients with respiratory disorders, 5 of whom underwent pneumonectomy or lobectomy a few hours after administration of the drug. In the 5 nonoperated patients, plasma radioactivity concentrations were maximal after 2 to 3 hours and remained high after 24 hours; about 22% of radioactivity was excreted in urine after 24 hours. In the 5 operated patients, plasma radioactivity concentrations were comparable with those in the nonoperated patients. Lung tissue radioactivity concentrations after 5 hours were comparable with those in plasma, while the presence of small amounts of radioactivity in the bronchial secretions indicates that acetylcysteine passes into the mucus. Total radioactivity after 5 hours consisted of free, unchanged drug and metabolites (about 22% of total in plasma, 48% in lung tissue), unchanged drug bound to protein by means of labile disulphide bridges (about 14% in plasma, 47% in lung tissue), and drug firmly bound to protein (about 64% in plasma, 5% in lung tissue). Oral acetylcysteine is rapidly absorbed and slowly excreted and is available in the lung in an active form for at least 5 hours at high concentrations.


Congenital lobar emphysema.

Congenital lobar emphysema. Congenital lobar emphysema is an uncommon but potentially life-threatening cause of respiratory distress in the newborn. The clinical picture and radiologic findings are diagnostic. Lobectomy in the distressed neonate is curative. In infants with onset of symptoms between one and four months of age surgery may not be necessary. Etiology and pathology of congenital lobar emphysema are not clear at present and require further elucidation.


Intestinal atresia.

Intestinal atresia. Forty-five patients with intestinal atresia, including 20 with duodenal, 21 with jejunoileal, and 3 with colonic obstruction, were encountered at the Yale-New Haven Hospital between 1970 and 1976. The  overall survival rate in the 43 operated cases was 93 per cent. The major reasons for the excellent operative survival with this malformation include: (1) the care received in a regional neonatal center; (2) the early recognition and appropriate case selection, denying operation unless mandated in babies with duodenal atresia and trisomy 21; (3) primary repair using modern surgical techniques which minimize anastomotic complications and the "blind-loop" and "short gut syndrome"; and (4) the use of uncomplicated long-term total parenteral nutrition in approximately one-half of operated cases.


Congenital diaphragmatic hernia: hypoplastic lung and pulmonary vasoconstriction. The abnormal pulmonary vasculature of the infant with congenital diaphragmatic hernia combined with a single expanded lung creates persistent pulmonary hypertension. Survival depends on the ability of the myocardium to withstand this increased work load until the second lung expands and pulmonary hypertension ceases.


Biliary excretion of vincristine.

Biliary excretion of vincristine. A patient with pancreatic carcinoma and a choledochal T tube was given tritiated vincristine sulfate ([3H]-VCR) intravenously. Peak biliary excretion occurred in 2 to 4 hr and this sample contained 9.7% of the injected radioactivity. The first 24-hr bile sample contained 21.7% of the dose and 76.4% of the cumulative 72-hr biliary excretion. During a 3-day period of observation, 4.2%, 45.6%, and 49.6% of the excreted radiolabel was present in the feces, urine, and bile, respectively. Products of VCR metabolism and decomposition appeared in the bile rapidly; only 46.5% of the drug was present in the parent form in the 2-hr collection. Since significant amounts of these products were also identified in control specimens of bile, blood, plasma, and buffer alone after brief periods of incubation, the origin and nature of the species appearing in the bile remain unclear. Observing the fecal route to be the major source of elimination of radiolabel following intravenous injection of [3H]-VCR in our patients previously, we now conclude the biliary system to be the principal route of excretion of VCR and its products. Hepatic dysfunction might therefore alter elimination kinetics and increase the exposure to VCR and its products which might augment toxicity and require dose modification.


Kinetics of mezlocillin and carbenicillin. The kinetics of mezlocillin, a semisynthetic acylureido penicillin, more active than carbenicillin against many gram-negative bacteria, were compared with those of carbenicillin. Following an intravenous infusion of 4 gm in 5 min to 8 normal men there was an average serum level of 294 microgram/ml for mezlocillin and 365 microgram/ml for carbenicillin. The t1/2 for mezlocillin was 47 min and that for carbencillin was 70 min. The apparent volume of distribution was 13.4 L for mezlocillin and 14.4 L for carbenicillin. The mean urinary recovery of mezlocillin was 72% and that for carbenicillin was 92%. Constant infusion of 5 mg of mezlocillin over 2 hr gave steady-state levels of 234 microgram/ml. Half-life, apparent volume of distribution, and serum and renal clearance of mezlocillin after constant infusion were in the same range as those after rapid infusion.


Oral clonidine loading for rapid control of hypertension. In order to determine the efficacy and safety of oral clonidine loading to control hypertension rapidly, 15 patients received 0.1 or 0.2 mg clonidine initially followed by hourly doses of 0.1 mg until the blood pressure was substantially reduced or until a total of 0.5 mg had been given. Twelve (80%) responded with a reduction in mean blood pressure of 33 +/- 3 (SE) mm Hg in an average time of 2.25 hr. Side effects were minimal. Four of the 5 patients hospitalized solely for purposes of blood pressure control responded to clonidine loading and were discharged the next day. Clonidine loading proved to be safe and effective for rapid control of hypertension and may be preferred to intravenous antihypertensives for some indications.


Automated monitoring of drug-test interactions. A computer-based file of the effects of drugs on clinical laboratory tests was used in a university hospital to generate reports of all potential interactions between the drugs administered to a patient and the laboratory tests ordered on his body fluids. More than 13,000 patient days were monitored in four different nursing units. The physician users of the system indicated that automatic reporting of possible drug-test interactions had both educational and clinical value. A critical review of patient charts suggested that automatic reporting of drug-test interactions caused physicians to alter therapy in about 0.1% of instances in which a report was generated. The users themselves indicated that they altered treatment as a result of the reports in a substantially greater number of cases.


Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function. The concentrations of quinidine, (3S)-3-hydroxyquinidine (3-OH), and 2'-oxoquinidinone (2'-OXO) in serum samples from 25 patients on long-term quinidine therapy were determined by a high-pressure liquid chromatography assay. Large individual variation in the levels of each of the compounds measured was observed. After correcting for differences in protein binding, the ratio of 3-OH/quinidine in serum water is 0.61 +/- 0.31 (SD) and the ratio of 2'-OXO/quinidine is 0.39 +/- 0.44. Seven of the 25 patients had serum water levels of one of these metabolites similar to or greater than that of quinidine. The quinidine levels, after normalizing for dose, are significantly higher in hemodialysis patients (about twice) than in nonazotemic patients; azotemic patients have mean values intermediate between them. Quinidine, 3-OH, and 2'-OXO are equally potent antiarrhythmic drugs (ED50 = 0.18, 0.17, and 0.21 mmoles/kg, respectively) when tested against chloroform- and hypoxia-induced ventricular fibrillation in mice. O-Desmethylquinidine, a new metabolite detected in urine of quinidine-treated patients, is less active. Quinidine and 2'-OXO are equally potent (ED50 = 0.010 mmoles/kg), while 3-OH seems less potent and more toxic when tested against BaCl2-induced ventricular arrhythmias in rabbits. Thus, these metabolites appear to contribute to the effects of quinidine and may make a significant contribution in some cases.


Effect of smoking on caffeine clearance. The elimination of caffeine from saliva was compared in groups of healthy smokers (n = 13) and nonsmokers (n = 13). Mean caffeine t1/2 in smokers (3.5 hr) was shorter than that in the nonsmokers (6.0 hr). The body clearance of caffeine in the smokers (155 +/- 16 ml . kg-1 . hr-1) was greater than that in the nonsmokers (94 +/- 18 ml . kg-1 . hr-1) (p less than 0.05). No significant difference was noted in the apparent volume of distribution in smokers (720 +/- 67 ml . kg-1) and nonsmokers (610 +/- 80 ml . kg-1). These differences probably reflect the induction of hepatic aryl hydrocarbon hydroxylase (AHH) activity in smokers. The increased clearance of caffeine by smokers may contribute to the higher consumption of coffee reported to occur in this group.


Is phenytoin metabolism dose-dependent by enzyme saturation or by feedback inhibition? The suggestion from animal experiments that phenytoin metabolism may be dose-dependent in man due to feedback inhibition by the major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, was examined in 3 normal subjects by measuring phenytoin clearance during an intravenous infusion of the metabolite and during a control infusion of solvent. Clearance was measured using both carbon-labeled and unlabeled phenytoin. The infusion of metabolite did not produce any consistent change of phenytoin clearance, suggesting that feedback inhibition does not occur in man.


Kinetics of intravenous and intramuscular morphine. The disposition of parenteral morphine was assessed in two pharmacokinetic studies. In Study 1, 10 mg of morphine sulfate was administered by intravenous (IV) infusion, intramuscular (IM) injection, or both, to 8 healthy young adult male volunteers. Plasma morphine concentrations were determined by radioimmunoassay in multiple blood samples drawn after each dose. Mean (+/-SE) kinetic parameters following IV morphine were: volume of distribution (Vd), 3.2 (+/- 0.3) L/kg; elimination half-life (t1/2beta), 2.9 (+/- 0.5) hr; clearance, 14.7 (+/- 0.9) ml/min/kg; extraction ratio, 0.70 (+/- 0.04). After IM morphine, peak plasma levels ranged from 51 to 62 ng/ml and were reached within 20 min of injection. The absorption half-life averaged 7.7 (+/- 1.6) min. Systemic availability was 100% complete. In study 2, 4 elderly male patients (61 to 80 yr of age) received 45 to 80 mg of morphine sulfate IV prior to operative repair of an abdominal aortic aneurysm. Morphine pharmacokinetics were determined as described above. Kinetic variables were Vd, 4.7 (+/- 0.2) L/kg; t1/2beta, 4.5 (+/- 0.3) hr; clearance, 12.4 (+/- 1.2) ml/min/kg; extraction ratio, 0.59 (+/- 0.05). Both studies demonstrate that morphine distribution is rapid and extensive and its t1/2beta relatively short. IM morphine is rapidly and completely absorbed.


Plasma codeine and morphine concentrations after therapeutic oral doses of codeine-containing analgesics. Plasma concentrations of codeine and morphine were determined by specific radioimmunoassays in healthy human subjects at various times following oral administration of analgesic preparations containing therapeutic doses of codeine phosphate. Following administration of codeine phosphate (60 mg) in combination with aspirin (650 mg) or acetaminophen (600 mg) to two separate groups, mean peak codeine plasma concentrations and beta-phase elimination half-lives were 159 ng/ml and 2.9 hr or 138 ng/ml and 2.4 hr, respectively. Mean maximum concentrations of metabolically produced morphine were 6.8 ng/ml (aspirin-codeine phosphate administration) and 7.4 ng/ml (acetaminophen-codeine phosphate). Following drug administration, the mean ratio of the areas under the respective plasma concentration-time curves for morphine and codeine was 0.095 for the aspirin-codeine phosphate study and 0.12 for the acetaminophen-codeine phosphate study. Thus, free morphine represented about 10% of the free codeine area in each case. These results support the hypothesis that metabolically produced morphine may influence or be responsible for the analgesic efficacy of codeine.


Effect of cimetidine on renal function in normal man. To evaluate the effect of acute histamine H2-receptor blockade on renal function, renal function studies were performed in a control state and after cimetidine. Studies included acid excretion in response to acid loading, bicarbonate reabsorption during bicarbonate infusion, and urinary concentrating ability. Cimetidine produced no significant effect on any of these functions. During bicarbonate infusion, inulin clearance remained constant while creatinine clearance fell, possibly because of an effect on tubular creatinine secretion.


Long-term oral bronchodilator therapy of asthma with pirbuterol. We studied the effects of an oral beta2 selective bronchodilator, pirbuterol, in 12 male asthmatic patients over periods ranging from 6 to 23 months (mean, 13.8). Each patient was evaluated initially by physical examination, urinalysis, blood analysis, and pulmonary function tests. Patients were examined at regular intervals thereafter. Patients remained off all bronchodilator therapy for 12 hr before each visit. Blood analysis, urinalysis, and pulmonary function tests were performed and the pulmonary function tests were repeated approximately 2 hr after an oral dose of pirbuterol. We found no significant changes in the baseline resistance or in the bronchodilator response to pirbuterol during the course of the study, but there was a significant decrease in the functional residual capacity (FRC). The reduction in FRC could be due to the prolonged reduction in airways resistance with continuous therapy. We found no increase in the bronchodilator response to pirbuterol during oral prednisone therapy. There were no significant changes in serum potassium. Side effects attributable to pirbuterol, nervousness and tremor, occurred in only 2 patients and were easily controlled.


Pharmacokinetic considerations in exchange transfusion in neonates. Neonates undergoing blood exchange often receive concomitant therapy. Questions may be raised whether dosage regimen alterations are necessary to replace drug lost as a result of the exchange procedure. Our study reports the changes in plasma concentration of kanamycin during an exchange transfusion and a pharmacokinetic analysis of the effect of the exchange on drug elimination. The relationships of the volumes of distribution, elimination rate constant, and time after dosing on the fraction of the dose eliminated in the blood exchange are developed on the basis of a one-compartment body model. Computer simulations using the equations developed were used to estimate the fraction of a dose that might be removed as a result of an exchange transfusion. As the disposition rate constant or the apparent volume of distribution increase, i.e., the clearance of the drug increases, the fraction of the dose removed by the exchange process decreases. Thus, significant amounts of drug removal may occur in an exchange transfusion for drugs with low clearance when the exchange is initiated early in the drug dosing interval. In our study, only 3% of the kanamycin dose was removed as a result of the exchange process, and dosing adjustment would not be required. This was in part due to initiation of the exchange late in the dosing interval, although the maximum calculated percentage of the dose which could have been removed under the exchange conditions employed was only 10%.


Effect of intravenous thiamine on pralidoxime kinetics. Subjects were given pralidoxime chloride (5 mg/kg, intravenously) alone and again while they were receiving an infusion of thiamine hydrochloride. After the addition of thiamine: (1) overall, the urinary excretion of oxime was the same but the amount excreted in the first three hours was smaller; (2) the plasma half-life of oxime lengthened; (3) the plasma concentrations of oxime rose; and (4) the intercompartmental clearances and rate constant for elimination for oxime fell. These changes suggest that thiamine and oxime compete for a common renal secretory mechanism or that thiamine alters the membrane transport of oxime.


Purine biosynthesis de novo by lymphocytes in gout. 1. A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [14C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. 2. Synthesis of 14C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. 3. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values obtained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. 4. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [14C]glycine incorporation into urinary uric acid.


Natriuretic effect of propranolol on dogs with chronic bile-duct ligation. 1. Chronic ligation of the bile duct in dogs is associated with salt retention and a blunted natriuretic response to extracellular volume expansion. The mechanism of this phenomenon has not been clarified. 2. We have examined the influence of chronic beta-adrenergic blockade on sodium excretion in dogs with bile-duct ligation during extracellular hypotonic volume expansion. 3. Urinary excretion of sodium and fractional excretion of sodium rose significantly after 5 days of oral DL-propranolol administration to dogs with bile-duct ligation. 4. The antinatriuresis after bile-duct ligation was not followed by a significant alteration in the mean peripheral plasma renin activity as compared with control values. 5. It is suggested that propranolol can partially reverse the antinatriuresis of chronic bile-duct ligation, and that this is mediated by an extrarenal effect of the beta-adrenergic blockade.


Central and peripheral fatigue in sustained maximum voluntary contractions of human quadriceps muscle. 1. The fatigue of force that occurs during the first 60 s of a maximum voluntary contraction of the human quadriceps has been examined by comparing the voluntary force with that obtained by brief tetanic stimulation at 50 Hz in nine healthy subjects. In three subjects the voluntary force declined in parallel with the tetanic force whereas in the remainder it fell more rapidly, suggesting that central fatigue was present. 2. For those subjects who showed little or no central fatigue, surface electromyograph (EMG) activity remained approximately constant while the force declined by about 60%. In the others, EMG activity and force declined in parallel but when an extra effort was made the subjects could briefly increase their force and this was accompanied by a proportionately greater increase in EMG activity (generally up to the original value). 3. It is concluded that in sustained maximum voluntary contractions of the quadriceps (a) central fatigue may account for an appreciable proportion of the force loss, (b) surface EMG recordings provide no evidence that neuromuscular junction failure is the limiting factor determining the loss of force in this muscle.


Effects of airway anaesthesia on the ability to detect added inspiratory resistive loads. 1. The effects of airway anaesthesia on the ability to detect added inspiratory resistive loads were studied in normal subjects. A 4% solution of lignocaine hydrochloride was used for anaesthesia of the airways. 2. After anaesthesia of the mouth and upper airways to the level of the vocal cords there was a significant deterioration in the detection ability expressed in terms of the absolute added resistance (deltaR), with a concomitant increase in pulmonary resistance (Rint.). However, there was no significant change in the detection ability expressed in terms of the ratio of deltaR to the sum of Rint. and the minimal resistance of the apparatus (deltaR/Ro). 3. After combined anaesthesia of the upper and lower airways there was no significant change in pulmonary resistance or in the detection ability expressed either as deltaR or as deltaR/Ro. 4. We conclude that, in normal subjects, the main site of detection of added inspiratory resistive loads does not lie in the upper or lower airways. Our results and those of previous studies suggest that the diaphragm is the most likely site of detection of added resistive loads.


Effect of blood transfusion on the carbon monoxide transfer factor of the lung in man. 1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion. 2. The mean haemoglobin concentration increased from 7.7 to 11.1 g/dl. 3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations. TLCO (standardized) = TLCO (observed). (10.2 + Hb)/1.7 Hb, where haemoglobin (Hb) is expressed as g/dl. 4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.


Effect of administration of Sar1-Ala8-angiotensin II during the development and maintenance of renal hypertension in the rat. 1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin-angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.


Effect of arterial pressure and inheritance on the sodium excretory capacity of normal young men. 1. In normal young adult sons of normotensive parents the rate of renal sodium excretion is highly correlated with mean arterial pressure after a large intravenous isotonic fluid load. The correlation appeared to strengthen with time and was improved when the rate of sodium excretion was corrected for variations in the rate of glomerular filtration. 2. There was no such correlation in normal, age-matched sons of hypertensive parents. 3. In eight of the 20 normotensive sons of hypertensive parents studied, the rate of renal sodium excretion per unit of mean arterial pressure was significantly higher than in the sons of normotensive parents. 4. Because the sons of hypertensive parents are much more likely to become hypertensive than those of normotensive parents, we suggest that an abnormality of renal sodium handling precedes the development of demonstrable hypertension.


Induction of lysinuria in the rat by two para-substituted guanidinophenylalanines. 1. p-Guanidino- and p-guanidinomethyl-phenylalanine increase the renal excretion of lysine especially and, to some extent, cystine in the phenylalanine-loaded rat. The methyl derivative is the more effective. 2. The lysinuria is dose-dependent, reversible, pronounced when the intravenous infusion of analogue exceeds 10 mumol min-1 kg-1 and does not appear to be secondary to changes in urine flow or sodium excretion. 3. A mechanism for induced basic amino-aciduria conditions is suggested.


The use of the human erythrocyte as a model for studying the action of diuretics on sodium and chloride transport. 1. The Na+ and Cl- transport systems of human erythrocytes have been compared for their sensitivities to diuretics known to act in the ascending limb of Henle's loop. In addition, chemical analogues of 'loop' compounds and also diuretics which act in other areas of the nephron have been examined. 2. The Na+ transport system lacks specificity with respect to inhibition by 'loop' diuretics and also a related chemical analogue studied at equivalent concentrations. 3. The Cl- transport system is inhibited, at low concentrations, by diuretics known to act in the ascending limb of Henle's loop. 4. Erythrocyte Cl- transport offers a useful model with which to study the biochemical action of diuretics.


One year's experience in a regional poison control center: The Intermountain Regional Poison Control Center. The Intermountain Regional Poison Control Center in Salt Lake City, Utah, has served as a regional poison center since 1971. Between 1972 and 1976 the call load has more than tripled, with the highest frequency of calls per population coming from counties most proximate to the center. Two-thirds of the cases involve children age five or less, with 18 or over being the next large group. Adolescents and school-age children comprised the smallest group of cases. Two predominant types of poisonings were encountered: accidental ingestions of toxic substances in children and intentional self-poisonings in adults, but the poison center handled almost every conceivable type of poisoning or toxic situation. A detailed analysis of the center's overall experience as well as these two major categories is presented.


Regionalization of poison centers--a rational role model. The Rocky Mountain Poison Center is a model system for regionalization. Minimal cost is achieved by concentrating expensive equipment and information materials in the main center. Access to information is rapid because each subregional center has a POISINDEX and thus the capacity to provide standardized initial therapy as soon as contact is made. Full integration of professional activities from training to education is accomplished within the framework of Emergency Medical Services. Public education is uniform throughout the region so that medical interaction is consistent and the public receives maximum reinforcement. Funding is found through many sources and includes a cost-sharing program in which 18 Colorado hospitals participate. Institutions with similar regionalized programs, integrated with Emergency Medical Services and drug consultation, will provide cost effective programs well-tailored to the unique characteristics of each region.


Hemlock water dropwort poisoning--a review. Hemlock water dropwort (Oenanthe crocata) is probably the most poisonous plant in the British Isles. The roots are the most toxic part of the plant and have been eaten in mistake for the roots of several other plant species with often fatal results. A recent nonfatal case of poisoning is reported and previous cases reviewed. Present evidence suggests that barbiturates, particularly short-acting agents are life saving and are the drugs of choice in the treatment of the convulsions.


Five cases of intentional ingestion of 25 percent diazinon with treatment and recovery. The use of atropine to block the effects of acetylcholine and pralidoxime chloride to restore cholinesterase in the blood, along with supportative therapy, intravenous fluids, and oxygen, prevented death in five cases of intentional ingestion of 25% diazinon. Treatment of such cases must be tailored to the condition of the patient, and all residual poison in the stomach must be removed as rapidly as possible with gastric lavage to prevent absorption of the poison.


Detection and assay of organophosphate pesticides in human blood by gas chromatography. Gas chromatography was used in blood samples for determining human exposure to organophosphate insecticides. The identification is difficult beyond 48 hr after exposure because of the high reactivity of these compounds.


Recognition and management of drug abuse emergencies. As with any medical emergency, the initial approach to the management of the drug abuse emergency is to attend to the potential threat to life. Establish and maintain an adequate airway, with respiratory support if necessary: secure a reliable intravenous route: administer appropriate drugs and antidotes; and perform the necessary diagnostic procedures to identify the cause of the problem. Always make an assessment of the psychological threat of self-destruction before discharging a patient who has taken an overdose. Be suspicious of drug overdose ina comatose or oddly-behaving patient. Consider the possibility of multiple drug abuse. Finally, always consider the possibility that causes other than drugs may be producing these symptoms.


Allergic contact dermatitis to radiotherapy dye. Allergic contact dermatitis to resorcin in Castellani's paint used to mark radiotherapy ports is reported.


Contact dermatitis from an ostomy deodorant. Two patients with contact dermatitis from an ostomy agent are described. Detailed patch testing revealed contact allergic dermatitis to one of the twelve groups of ingredients which largely comprised citronella oil. The problem of dermatitis is discussed in relation to the perfume ingredients of the ostomy agent.


Solubility of cobalt in cement.

Solubility of cobalt in cement. Unlike chromate, cobalt occurring as cobalt oxides in cement is not water-soluble in a detectable amount. Cobalt oxides are to some extent soluble in the presence of amino acids with which cobalt forms complexes. Such complexes can elicit patch test reactions. It is postulated that cobalt is more readily dissolved by forming complexes in eczematous skin than in normal skin. This may explain why cobalt sensitization in cement eczemas is secondary to chromate sensitivity.


Photoepicutaneous testing. UV-induced protection against photoxic reactions in normal and vitiliginous skin: a clinical and histological study. The effect of erythemic UV irradiation on the phototoxic reactions caused by topical methoxsalen + UVA exposure was studied on normal skin, normal-looking skin of vitiligo patients, and vitiliginous skin. Although only slight histological changes were detectable 9 days after irradiation with 5 MED of erythemic UV, this pre-irradiation did induce protection against photoxic reactions in all skin types. This protection was clinically equal in all skin types; the slight differences were not statistically significant. Histological evaluation, however, showed a most conspicuous protective effect on vitiliginous skin. In all skin types the influence of UV pre-irradiation was confined to epidermal protection; the dermal phototoxic changes were unaffected.


Cross allergy between paranitro compounds with special reference to DNCB and chloramphenicol. Cross allergy between paranitro compounds including DNCB and chloramphenicol, was studied in 42 patients. A total of 27 had been primarily sensitized to DNCB, and 15 patients with eczema exhibited a delayed-type reaction to chloramphenicol, showing a positive patch test. All 15 patients with chloramphenicol allergy cross reacted with chloramphenicol succinate and chloramphenicol palmitate. Three of them cross reacted with paranitrobenzoic acid, and two of these also with paradinitrobenzene. None of the 15 patients cross reacted with DNCB in acetone or DNCB in petrolatum, and none reacted to picric acid, paranitrophenol or dinitroorthocresol. The 27 patients primarily sensitized to DNCB did not cross react with any of the paranitro compounds studied, in particular not with chloramphenicol or its salts. Thus, the study confirms the specificity of the DNCB sensitivity.


Reactions to peroral propylene glycol.

Reactions to peroral propylene glycol. A peroral challenge test with 2--15 ml of propylene glycol (PG) was made in 38 patients with allergic-type epicutaneous test reactions to PG. Eight of 10 patients with a positive epicutaneous reaction to 2 % PG and seven of the other 28 patients with a positive epicutaneous reaction to 100-100 % PG developed an exanthem 3--16 h after ingestion of the drug. In all but one case the rash disappeared within 24--48 h without any medication. In one case the exanthem was treated with prednisone for 4 days, and the symptoms disappeared gradually in 6 days. None of the 20 control patients had skin symptoms. Nausea, vertigo and a curious sensation were recorded in four PG-sensitive patients and in three control patients. These symptoms were apparently due to the general pharmacodynamic effects of PG and they were regarded as non-allergic in nature. It was concluded that PG is a potential allergen and it must be added to the list of causes of drug exanthems.


The AaDO2 and venous admixture at varying inspired oxygen concentrations in chronic obstructive pulmonary disease. The alveolar to arterial oxygen pressure difference (AaDO2) and pulmonary venous admixture (Qs/Qt) were measured in 32 patients with chronic obstructive pulmonary disease during right heart catheterization at inspired oxygen concentrations (FIO2) of 21, 24, 28, 35, and 40%. Patients without chronic hypercapnia (PaCO2 is less than 45 torr, group A) had Qs/Qt less than 25% while breathing room air; their AaDO2 rose at a rate of 3 torr for each percent increase in FIO2. In those with chronic hypercapnia (PaCO2 greater than 44 torr., (group B), THE Qs/Qt was always greater than 24% during air breathing and the AaDO2 rose at a rate of 5 torr for each percentage increase in FIO2. These changes should be considered in the interpretation of the AaDO2 in patients with COPD in whom the FIO2 is changed during the course of therapy. The Qs/Qt fell curvilinearly with increasing FIO2 but the rates of fall were quantitatively different in groups A and B. A physiological explanation for the changes in Qs/Qt and ADO2 which result from changes in FIO2 is presented.


Immediate and long-term outcome of infants less than 1000 grams. In order to assess the immediate and long-term outcome of very low birth weight infants, a retrospective analysis of clinical and biochemical parameters of 100 consecutive newborns with birth weights less than 1000 g was carried out. Overall neonatal mortality for this group was 69%. For infants between 751 to 1000 g, the mortality rate was 52%. Of the 23 infants who were discharged, neurodevelopmental assessment was performed in 16. Twelve of the 16 were neurologically normal. The data indicate a favorable prognosis for infants with birth weight less than 1000 g.


Changes in cardiac rhythm in children treated with dopamine. We reviewed the charts of 31 children receiving dopamine to document possible changes in cardiac rhythm associated with dopamine infusion. Six of these developed a dysrhythmia while on dopamine. All six were receiving dosages greater than 10 microgram/kg/min; in five of the six patients the infusion rate varied from 10-20 microgram/kg/min. Of the remaining 25 patients, 14 had preexisting dysrhythmias of nonventricular origin. Two of these 14 patients converted to sinus rhythm while on dopamine. Eleven patients who were in preexisting sinus rhythm had no rhythm changes on dopamine. Based on the results of this study, we recommend that dopamine should be used cautiously in children in the dosage range between 10-20 microgram/kg/min.


Method for continuously measured oxygen consumption and cardiac output for use in critically ill patients. A method for continous measurements of oxygen consumption (VO2) and cardiac output is described. This relatively inexpensive system was found to be practical for monitoring critically ill patients over the past 5 years. Clinical studies illustrating its usefulness are presented.


Comparison of right atrial and pulmonary capillary wedge pressures. The right atrial pressure (Pra) was compared to the pulmonary capillary wedge pressure (Pcw) in 54 patients. In patients with heart disease, the correlation of Pra with Pcw was poor. However, in patients without clinical heart disease, Pra approximated Pcw, in both absolute number and change. This finding was independent of disease process or the presence of controlled mechanical ventilation.


Sigma SR, a new method of measuring erythrocyte sedimentation rate. Its value in studying the action and interactions of non-steroidal anti-inflammatory agents. Sigma SR is a new method of measuring erythrocyte sedimentation rate (ESR) and is characterized by an unvarying haematocrit, routinely corrected to 35%, and the sum of 4 sedimentation levels at 20, 30, 40, and 50 minutes. Two studies were carried out in patients with inflammatory arthritic disorders; the first in 25 patients treated with 1800 mg ibuprofen daily for 7 days, and the second in 31 patients treated either with indomethacin alone (150 mg/day) or combined with aspirin (1500 mg/day) for 5 days. In addition to the assessment of clinical parameters, the ESR was measured using the classical Westergren and the sigma SR methods. The results showed that there were little or no changes from baseline values in the ESR using the Westergren method. With the sigma SR method, however, statistically significant changes were recorded after treatment and these correlated with the clinical findings which demonstrated the anti-inflammatory action of ibuprofen and the reduction in activity of indomethacin by aspirin.


A study on tissue concentrations of cephradine achieved in patients with peripheral vascular disease. The levels of cephradine were measured in serum, voluntary muscle and subcutaneous fat samples collected from 30 patients during surgical operations for peripheral vascular disease. Cephradine 2 g was administered in two equal doses by intramuscular and intravenous routes before each operation. The mean levels found in the serum and muscle were well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens, in contrast to the relatively low mean level found in subcutaneous fat.


On the technique of external cardiac compression. ECG, arterial flow and pressure were recorded during external cardiac compression (ECC) in a patient whose heart had ceased beating. The patient was a 68-year-old female who remained comatose for 2 weeks after an emergency laparotomy for perforated diverticulitis of the colon. She developed sepsis, renal failure, and cardiopulmonary failure. During ECC, the pressure on the sternum was maintained for about 0.5 sec (sustained pressure technique), flow and mean arterial pressure were improved by 32 and 20%, respectively, as compared with flow and pressure obtained with a quick and more jerky compression. During spontaneous heart activity with a low blood pressure, a superimposed ECC improved both flow and mean arterial pressure. Calcium chloride and adrenaline injected into the right atrium increased the tone and contractile power of the heart and greatly improved flow and pressure when the heart was subsequently compressed during asystole.


The effect of salicylate infusion on the alveolar epithelial membrane in the isolated perfused lung. We observed two patients with aspirin (ASA) ingestion (blood levels of 87 and 56.5 mg/100 ml) who presented with noncardiogenic pulmonary edema (adult respiratory distress syndrome. To determine if ASA had a direct effect on the alveolar epithelial membrane, we established an in vitro isolated lung model and perfused it with platelet free plasma. T1/2 (in minutes), the time for 50% equilibration between the plasma and the saline filled lung, was determined before and after 500 mg salicylate infusion for various molecular weight dextrans. T1/2 decreased significantly (p less than 0.05) as follows: 3000 MW dextran, 2273 +/- 932 to 961 +/- 375; 40,000 MW dextran, 4059 +/- 1550 to 733 +/- 275; 70,000 MW dextran, 11,730 +/- 2750 to 7700 +/- 2230. Histamine levels in plasma and lung liquid did not change significantly with ASA infusion. We conclude that ASA directly increases alveolar epithelial permeability to dextrans less than 70,000 MW.


The contraceptive effects of a new low-dose combination type oral contraceptive. A study was carried out in 9 women volunteers to investigate the centron of 0.75 mg lynestrenol plus 0.0375 mg ethinyl oestradiol given for 22 days per cycle over a period of 6 cycles. The results of assessments of a number of hormonal, vaginal and cervical parameters showed that this combination has a two-fold effect: a central effect on the pituitary and a peripheral effect on the ovaries and on endometrial development. The findings of an effect on cervical mucus, as with higher dose combinations, were not sufficiently consistent to warrant a claim for a cervical barrier. The preparation appeared to be well tolerated but there was a high incidence of irregular bleeding in the first treatment cycle. In most of the women, however, this had corrected itself by the second cycle.


The use of salsalate for control of long-term musculo-skeletal pain: an open, non-comparative assessment. An open study was carried out in general practice to assess the analgesic effectiveness, tolerance and side-effects of salsalate when given at a dosage of 3 g per day for 6 weeks. Sixty-six patients who were known long-term analgesic users were treated: they included 16 with active inflammatory disease of rheumatoid type, 20 with degenerative joint disease, and 27 with other musculo-skeletal conditions. Three patients were withdrawn during the study because of gastro-intestinal upset. Assessments, using rating scale scores, were made pre-trial and at 2-weekly intervals of joint pain, other musculo-skeletal pain, and duration of morning stiffness. The results showed that there was marked improvement in joint pain and morning stiffness, particularly in those patients with inflammatory joint disease. Improvement in musculo-skeletal discomfort was less evident. Side-effects were reported on 24 occasions, the most frequent being dyspepsia. Faecal occult blood tests showed that there were 7 patients with probable blood loss during treatment, 4 of them, however, had no other clinical signs or symptoms of gastrointestinal intolerance.


The effectiveness of temazepam as a hypnotic: an open, multi-centre assessment in 804 patients with sleep disorders. An open, multi-centre study was carried out in 804 patients complaining of sleep disorders to assess the effectiveness and acceptance of temazepam as a hypnotic. Patients received between 10 mg and 30 mg (mean 16.4 mg) temazepam each night for a week. Subjective assessments using a self-administered questionnaire were made daily of the quality and quantity of sleep. The results showed that sleep induction was rapid and most patients enjoyed a relatively uninterrupted night's sleep, and awakened feeling refreshed. Patient acceptance was good and there was a low incidence of residual or other adverse effects of treatment.


Dysmorphology: an approach to a child with structural defects. An approach to children with structural defects has been presented. The ultimate goal of this approach is a specific overall diagnosis. In such cases appropriate genetic counseling for the parents, accurate prognostication relative to the child's future development and an appropriate plan to help the child reach his potential usually are possible. When an overall diagnosis is lacking, the most that can be expected is a better understanding of the nature and onset of the problem. That in itself can often be helpful to patients and to all others dealing with children having structural defects.


Sarcoidosis.

Sarcoidosis. Sarcoidosis is a disease of unknown etiology with protean manifestations. Its history is revealed in its many eponymic syndromes. The histologic features are nonspecific, as are most of the clinical manifestations. The diagnosis is made by exclusion. The immunologic abnormalities are fascinating, with features of both hyperactivity and depression. Therapy is nonspecific and generally symptomatic.


Psoriasis and arthritis.

Psoriasis and arthritis. The relationship of psoriasis and arthritis is controversial. It has been reported that 7 percent of patients with psoriasis have arthritis. In approximately half of these cases, it is a sero-negative inflammatory polyarthritis, two-thirds of which clinically resemble rheumatoid arthritis. A distinctive peripheral arthropathy is displayed by 1 percent of psoriatics. One-fifth of this group, or less than 0.2 percent of psoriatics, suffer deforming arthritis multilans. The epidemiologic, clinical, radiologic, serologic, and genetic evidence for and against psoriatic arthropathy as a unique entity are reviewed. The prognosis of psoriatic arthritis appears to be better than previously suggested. Therapeutic measures are also reviewed.


Xanthomas and lipoproteins.

Xanthomas and lipoproteins. Xanthomas and lipoprotein abnormalities are important to all physicians. Many factors affect the synthesis and degradation of cholesterol and triglyceride, the lipids of major importance in these disorders. Lipids travel in serum bound to protein moieties, forming lipoproteins. Hyperlipoproteinemias may be either primary or secondary to other diseases. Primary hyperlipoproteinemias recently have been reclassified, based on genetic studies. The four types of xanthomas include tendinous, tuberous, eruptive, and planar. Since xanthomas are usually not diagnostic of a specific disease entity, history, physical, and laboratory data are required for appropriate classification and treatment.


Erythema nodosum. A review.

Erythema nodosum. A review. Erythema nodosum is not an uncommon dermatologic entity. Sarcoidosis and streptococcal infection have become the two most common causes, while tuberculosis was the predominant etiology prior to the use of isoniazid. Histoplasmosis and coccidioidomycosis are two important geographic considerations. Laboratory tests should include a PPD test, chest x-ray, throat culture for beta-streptococcus, and ASO titer determination as a minimum. Symptomatic treatment remains unsatisfactory in many cases, although recent success has been reported with oral potassium iodide.


Purpura fulminans.

Purpura fulminans. Purpura fulminans is the cutaneous manifestation of acute activation of the clotting mechanism resulting in massive hemorrhage due to an intravascular consumption coagulopathy. Peripheral necrotizing purpura is a warning signal, and early recognition of the clinical situation and heparin therapy may be lifesaving. Clinical manifestations and histologic features of this condition, along with its pathogenesis, treatment, and differential diagnosis are discussed.


Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum. Pseudoxanthoma elasticum (PXE) is a genetic disorder of connective tissue with multi-systemic manifestations. Although the skin changes are striking, the eye and cardiovascular lesions can be most devastating to the patient. A review of the clinical and pathologic findings and recent therapeutic approaches is presented. Recent investigations on the pathogenesis and genetics of PXE are also discussed.


Differential diagnosis of sclerodermoid skin changes. Sclerotic changes in the skin are most frequently caused by scleroderma. In those cases in which scleroderma is not implicated, careful historical, physical, histologic, and laboratory evaluation will allow an appropriate diagnosis to be made. In this way, appropriate therapy and prognostication can be given.


Cutaneous manifestations of gastrointestinal disease. Numerous diseases affect the skin and gut simultaneously. The early recognition and treatment of both components is often essential to decrease morbidity and even prevent death precipitated by gastrointestinal crises. A number of the diseases affecting both the skin and gut are discussed, with particular emphasis on recent developments.


Pruritus as a manifestation of systemic disorders. A significant internal disorder is present in only a limited number of patients with essential pruritus. The mechanisms for the production of pruritus in these disorders are poorly understood and frequently are unrelated to liberation of histamine. Proteolytic enzymes in lymphoproliferative disorders, bile acids in obstructive hepatobiliary disease, parathyroid hormone in chronic renal failure, and prostaglandins and kinins are but a few of the chemicals that may ultimately be responsible for the development of pruritus in these and other purely cutaneous disorders. Patients with essential pruritus should have a comprehensive physical and laboratory evaluation, but psychologic, environmental, and other factors must be considered when thorough clinical evaluation is unrewarding. Treatment should be directed towards elimination of the underlying alteration, control of the additional factors, and alleviation of the symptom.


Differential frequency of human X and Y chromatin as related to cell density in vitro. The relationship between cell density in vitro and the frequency of fluorescent X chromatin and/or Y chromatin-positive interphase nuclei was studied in cultured cells from three human male and female subjects. It was found that altough the frequency of fluorescent X chromatin-positive cells was proportional to cell density, the frequency of fluorescent Y chromatin-postitive cells was independent of cell density. Our results are compared with those of other investigators.


Pulmonary hypertension secondary to minor pulmonary embolism. The response of pulmonary arterial pressure to minor degrees of pulmonary embolism was examined in 18 patients with embolic occlusion of less than 25% of the pulmonary vascular bed. Patients with pulmonary embolism were compared to normal controls matched for age and sex and to patients with a variety of acute pulmonary disorders without pulmonary embolism. Patients with pulmonary embolism and patients with other acute pulmonary diseases had significantly higher pulmonary arterial pressures and significantly lower values for arterial oxygen tension (PaO2) than did normal subjects. The degree of pulmonary hypertension correlated with the PaO2. Pulmonary hypertension occurring after minor degrees of pulmonary embolism may be a response to mild arterial hypoxemia.


A prospective cooperative study of complications following flexible fiberoptic bronchoscopy. The frequency of complications following flexible fiber-optic bronchoscopic procedures was studied prospectively in 908 patients from 13 cooperating hospitals. Major complications (respiratory arrest, pneumonia, pneumothorax, and obstruction of airways) occurred in 1.7 per cent (15) of the procedures. There was one death, yielding a mortality of 0.1%. Minor complications, including vasovagal reactions, fever, cardiac arrhythmias, bleeding, obstruction of airways, nausea and vomiting, pneumothorax, psychotic reaction, and aphonia, occurred in 6.5% of the procedures. Pneumothorax occurred after 5% (four) of 85 transbronchial biopsies. Although serious complications occur more frequently than previously reported from retrospective studies, complications after fiberoptic bronchoscopic procedures are still quite infrequent. The relative risks and benefits must always be carefully weighed in patients being considered for a fiberoptic bronchoscopic procedure.


The value of fiberoptic bronchoscopy in the management of pulmonary collapse. Nineteen fiberoptic bronchoscopic procedures were performed on ten patients for the treatment of pulmonary collapse. All but two patients were being treated for severe, life-threatening nonpulmonary diseases. Thick, tenacious, and, at times, purulent mucous plugs were successfully aspirated from the bronchial passages. Complete to partial radiologic reexpansion of the collapsed pulmonary region was observed following all but one procedure. Significant improvement in blood gas levels was also noticed immediately after the procedure. Bronchoscopic examination in these seriously ill patients did not cause any complications. The therapeutic value of fiberoptic bronchoscopic procedures in patients developing pulmonary collapse due to thick secretions and mucous plugs was demonstrated.


The effect of fiberoptic bronchoscopy on cardiac rhythm. Cardiac rhythm was monitored in 70 patients prior to, during, and following fiberoptic bronchoscopic procedures. Minor abnormalities in rhythm were frequent. Major cardiac arrhythmias occurred in 11% (8/70) of the patients during the bronchoscopic procedure. All arrhythmias were self-limited and had no hemodynamic consequence. Patients with evidence of coronary arterial disease, chronic obstructive pulmonary disease, or previously known premature ventricular contractions were at no higher risk for developing major arrhythmias. Hypoxemia (arterial oxygen pressure less than 60 mm Hg) at the end of the procedure correlated significantly with the development of new major arrhythmias.


Miconazole for treatment of disseminated coccidioidomycosis. Unfavorable experience. Miconazole at dosages up to 30 mg/kg/day was given intravenously to seven patients with complicated courses of disseminated coccidioidomycosis. Six had received treatment with amphotericin B previously and five of these patients could be evaluated for the efficacy of the treatment. In three patients the condition failed to respond to therapy, another patient required intratracheal administration of amphotericin B later, and the fifth patient had an equivocal response to treatment. Severe phlebitis, pruritus, nausea, vomiting, hyperlipidemia, and thrombocytosis were frequent side effects. These limited unfavorable results indicate that until controlled studies demonstrate its safety and efficacy, therapy with miconazole should be reserved for highly selected patients with disseminated coccidioidomycosis who cannot receive amphotericin B.


Mechanical stimulation of the heart: its therapeutic value in tachyarrhythmias. This report presents the experience obtained with the use of mechanical stimulation of the heart by external ("chest thump") and internal (stimulation via catheter) means in the treatment of tachyarrhythmias. The chest thump was used primarily for termination of ventricular tachyarrhythmias. Endocardial stimulation of the right and left ventricles and right atrium via catheters was used for both ventricular and supraventricular arrhythmias. The experience reported includes 68 patients, 19 of whom were treated successfully with mechanical stimulation and 49 of whom required other types of treatment. Of the 32 patients with 33 episodes of atrial tachycardia, eight episodes (24%) were treated successfully (three episodes by right atiral stimulation and five by right ventricular stimulation). Of the four patients with five episodes of junctional tachycardia, three episodes (60%) were treated successfully (one episode by right atrial stimulation and two by right ventricular stimulation). Of the 32 patients with ventricular tachycardia who experienced 37 episodes, 15 episodes (41%) were treated successfully (three by right ventricular stimulation, two by left ventricular stimulation, and ten by chest thump). In two of these patients, the thump was applied to an area of paradoxical pulsation.


The association between atrial septal defect and prolapse of the tricuspid valve. An echocardiographic study. The echocardiograms of 52 patients with atrial septal defects were reviewed. Six patients were noted to have prolapse of the tricuspid valve. Three of these subjects had associated prolapse of the mitral valve. The diagnosis of tricuspid valvular prolapse was confirmed by angiograms in one patient. Four patients had midsystolic tricuspid valvular prolapse, and holosystolic prolapse of the tricuspid valve was observed in two. In one patient a striking increase in the degree of tricuspid valvular prolapse was noted after closure of the atrial septal defect. A concomitant increase in the degree of tricuspid regurgitation was noted after surgery. Aggravation of tricuspid valvular prolapse should be considered as one of the causes of clinical and hemodynamic deterioration in the condition of a patient following repair of an atrial septal defect.


Allergic bronchopulmonary aspergillosis associated with smoking moldy marihuana. A 27-year-old man who habitually smoked marihuana developed clinical, laboratory, and radiologic findings consistent with allergic bronchopulmonary aspergillosis. Culture of the marihuana obtained from the patient's source yielded heavy mixed growths of Aspergillus. Treatment with corticosteroids was effective.


Cerebral dye embolus: a complication of selective bronchography following transbronchial biopsy. Cerebral embolization of an aqueous solution of propyliodone (Dionosil) occurred during selective bronchographic studies following a fiberoptic bronchoscopic procedure with transbronchial biopsy in a patient undergoing investigation of a pulmonary lesion. The embolization resulted in a grand mal seizure and transient neurologic deficits. This potential complication has not been previously reported. We suggest that selective bronchographic studies be avoided when the transbronchial biopsy is associated with endobronchial bleeding.


Propranolol-induced dysfunction of the sinus node in Wolff-Parkinson-White syndrome. We report the findings in a patients with the Wolff-Parkinson-White syndrome (type A) who initially had recurrent fainting episodes. It appeared that they were caused by prolonged posttachycardiac depression of the sinus node, which was induced by treatment with propranolol. The possibility of covert dysfunction of the sinus node in patients with Wolff-Parkinson-White syndrome should be considered before commencing therapy with beta-adrenergic blocking agents.


Rhabdomyolysis and renal failure following status asthmaticus. Acute renal failure developed in a 25-year-old man following status asthmaticus. He was found to have myoglobinuria. Vigorous contraction of the respiratory muscles and hypoxia were considered to be responsible for the development of myoglobinuria. Associated dehydration, in the presence of myoglobinuria, also contributed to the development of acute renal failure.


Pharmacokinetics of cephalosporin antibiotics: protein-binding considerations. The therapeutic activity of antibiotics depends on several factors including absorption, elimination kinetics, distribution in the body, minimal inhibitory concentrations (MIC), stability against enzymes, and plasma-protein binding. Some of these factors are interrelated, for example, the extent of protein binding of an antibiotic influences its elimination kinetics, distribution into tissues, MIC, and antibacterial activity. To evaluate the potential efficacy of an antibiotic, it is important to know the extent of its binding to plasma proteins especially since the protein-bound fraction of the antibiotic is devoid of antibacterial activity. Cephalosporins are a new class of broad-spectrum antibiotics that bind to plasma proteins in different degrees. Reported values for protein binding range from 6% for cephradine to 92% for cefazolin. The effects of protein binding of some of the commonly used cephalosporins on antibacterial activity and several pharmacokinetic parameters are discussed in this communication.


Comparative in vitro activity of five nitrofurans. Five nitrofurans- nitrofurantoin, nifuratel, nitrofurazone, furazolidone and and SQ 18,506--have been tested against 201 microbial strains. Escherichia coli, Streptococcus faecalis, micrococci and Staphylococcus epidermidis were sensitive to all five compounds; furazolidone and SQ 18,506 were the most active against these species. Klebsiella aerogenes was less sensitive, and Proteus spp., Providencia stuartii and Pseudomonas aeruginosa strains were resistant. Nifuratel was inhibitory for some Candida albicans strains, and SQ 18,506 was highly active against this species. Nifuratel was judged overall to have superior in vitro antimicrobial properties to nitrofurantoin.


Amikacin therapy of serious gram-negative bacillary infections in chronic hemodialysis patients. Amikacin was used to treat 7 serious gram-negative bacillary infections in patients undergoing chronic hemodialysis. 4 were caused by pathogens resistant to gentamicin. 5 infections were cured; 1 was improved and another failed to respond. Mean 1-hour peak serum levels of amikacin ranged from 25.8 to 44.3 microgram/ml. Mean serum levels of amikacin after 6 h of hemodialysis were 61.5% of predialysis levels. Amikacin is highly effective but doses must be reduced in patients requiring hemodialysis and serum levels monitored to avoid ototoxicity.


Clinical experience with bacteraemia in patients with leukaemia and allied neoplastic diseases. 134 bacteraemic episodes in 112 patients with leukaemia and allied disorders over a 5-year period were reviewed. The patients were divided, with respect to neoplastic disease, into 3 prognostic groups according to estimated periods of survival of years (group 1), months (group II) or weeks (group III). High mortality was correlated to group III, gram-negative rod bacteraemia and septic shock. Low leucocyte levels and intensive antineoplastic treatment did not adversely influence the prognosis of the bacteraemic patients. Appropriate antibiotic therapy was correlated with a significantly lower mortality, and it is concluded that aggressive antibiotic therapy is indicated when bacteraemia is suspected from clinical judgement.


Combined therapy in leprosy. Background and findings. This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10(4) or more bacteria. From the beginning of combination therapy with synergistic-acting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3--8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even "negativity" could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.


Why many placed children have learning difficulties. A child's normal development from infantile to adult narcissism may be disrupted by placement. The reactions and defenses may cause serious problems in school learning.


Parent/child foster placement: an alternate approach in child abuse and neglect. Placement of a single parent and child in a foster home-thus avoiding separation in certain abuse and neglect cases-permits accurate evaluation of parenting skills and judgment, important in any decision to restore the family as a safe, independent unit.


Lumbar spinal stenosis: a review article. (1) In discussing the types of lumbar spinal stenosis, emphasis has been placed on the developmental form. (2) The importance of nerve entrapment in the lateral recess has been stressed. (3) An attempt has been made to demonstrate the relationship of developmental stenosis to other lesions affecting the lumbar spine. (4) Our knowledge of the development of the lumbar spine and its patho-anatomy in children is limited. (5) Attention to minor trauma and to preventive measures during childhood will do much to prevent stenosis in later years.


Experimental hydrocephalus: cerebrospinal fluid dynamics and ventricular distensibility during early stages. Adult craniectomized cats, rendered hydrocephalic by intracisternal kaolin injection, were repeatedly studied as to parameters pertaining to cerebrospinal fluid (CSF) dynamics and ventricular size. Intraventricular pressure was up to 8-fold of normal (mean 17.1 cm H2O) initially after induction of hydrocephalus and then went gradually down after 1 month. Ventricular volumes attained their maximum volume of approximately 4.5 ml at the very earliest study. The absorptive reserve (excess of absorption over formation rate of CSF) increased with time, thereby theoretically enabling the 'arrest' of the hydrocephalic process. Ventricular distensibility also increased with time, thus even the low ventricular pressure maintains the larger ventricular volume.


Surgical treatment of spasticity in cerebral palsy. Since 1971, we have surgically treated spasticity in 109 cases of cerebral palsy with posterior rhizotomy. The best results have been obtained with functional posterior rhizotomy, an original modification of Foerster's technique, in which the selection of the roots/rootlets to be sectioned is based on functional exploration of the spinal circuits involved in the maintenance of spasticity, using intraoperative electrostimulation on dorsal roots. This method makes selective sections possible, thereby saving a larger number of normal proprioceptive afferents, with consequent reduction in negative side effects. No recurrencies have been observed in our 3-year follow-up. The main indication is Little's disease.


Extradural hemorrhage in the newborn as a result of birth trauma. During the past 18 years, 134 autopsies of intracranial hemorrhages were performed in the Department of Pathology, and 2 cases of extradural hemorrhages were discovered (2.2%). 5 cases of extradural hemorrhage (2 of our own treated surgically and 3 untreated found at autopsy) are described in detail. 1 of the 2 cases treated surgically responded favorably to surgical treatment. The mechanism of hemorrhage into extradural spaces is investigated and reconsidered following review of the literature. The necessity for right reflux brachial angiography is emphasized for early diagnosis of extradural hemorrhage.


The relation of length of institutionalization to the intellectual functioning of the profoundly retarded. The effect of institutionalization was measured in relation to performance on the Cattell Infant Intelligence Scale by 103 profoundly retarded residents with a mean CA of 20.3 years, a mean MA of 18.1 months, a mean IQ of 12.7, and a mean number of years in the institution of 10.6. After partialing out CA and MA, years in the institution was negatively correlated with success in visually directed object manipulation (Cattell items below an MA of 9 months), social imitation (9-12 months), and purposeful, constructive activities (over 20 months). The findings were compared with previous studies on retarded and nonretarded infants and children.


Developmental changes in human infant visual-evoked potentials to patterned stimuli recorded at different scalp locations. Visual-evoked potentials (VEPs) to patterned stimuli were recorded from 4 different scalp locations in 2 groups of infant subjects (ages 6 weeks and 10 weeks). Seven VEP components were identified that changed in amplitude as a function of changes in the amount of contour in the stimuli presented. Developmental shifts in these effects were interpreted to indicate a change in the physiological locus of control of infant visual preferences from a subcortical to a cortical locus over the age range examined.


A first-year follow-up of high-risk infants: formulating a cumulative risk index. Multiple developmental assessments were made at 4-month intervals over the first year of life for 2 groups of infants born at risk and 1 normal group. The groups included 46 preterm respiratory distress syndrome infants, 46 postterm postmaturity syndrome, and 59 term normal infants. The mothers were white, multiparous, middle-class, high school graduates averaging 25 years of age. Analyses of group differences revealed that the preterm respiratory distress syndrome (RDS) infants continued to exhibit delays in motor and mental development and the postmature infants in mental development. Discriminant function analyses suggesting that the most efficient predictors and accurate discriminators of continuing risk were as follows: the Parmelee obstetric and postnatal complications scores and the Brazelton interactive and motoric process scores at birth; the Denver rating, mother-infant interaction and Carey temperament ratings at 4 months; and the Bayley mental and motor scores at 8 months. On the basis of their weighted assessment scores, infants were assigned a cumulative risk index at each assessment period.


Visual acuity for single lines as a function of hue and age. 176 students in grades 2-12 were tested for visual acuity as a function of minimally resolvable red, yellow, green, and blue lines. A 3-way mixed analysis of variance revealed significant differences among the colors, with better acuity for longer wavelengths. Significant age effects as well as a sex X condition interaction were also found. Post hoc analysis revealed a significant quartic trend for age. It is argued that the differential acuity thresholds for hue and the curvilinear age trend may depend upon the coordination of the accommodation and refractive power of the eye, which are affected by differential growth rates of the lens and the axial length of the eye.


Visual and verbal processes involved in the development of picture-recognition skills. 4-5-year-old, 6-7-year-old, and 8-9-year-old children were given picture-recognition tasks in which recognition stimuli were systematically varied with respect to familiarization stimuli. Subjects were required either to verbalize or remain silent during familiarization and to identify either central figure only or whole picture recognition. Results suggested that (a) young children base recognition primarily on central figure whereas older children are more likely to utilize the entire stimulus array, and (b) younger children are more likely than older children to use spoken labels as a basis for recognition when they verbalize during familiarization.


Developmental priority of identity conservation: acceleration of identity and equivalence in normal and moderately retarded children. In an attempt to clarify the chronological relationship between identity and equivalence conservation, normal preschool-aged children (experiment 1) were exposed to brief videotape demonstrations of a model conserving identity and equivalence, identity only, equivalence only, or neither. Subsequent performances indicate that identity was easier to accelerate than equivalence, and training in both identity and equivalence appeared to be most effective in accelerating conservation. Trainable mentally retarded (TMR) children were then exposed to either the identity-equivalence-conserving or control model (experiment 2). This population, which some have argued remains at a preoperational level of functioning, was more likely to conserve identity than equivalence. In addition, conservation in the training group increased following training, though these gains were not maintained over a 3-week retention interval.


Young adolescents' beliefs concerning menstruation. In order to explore the early socialization of attitudes and expectations about menstruation, 54 young adolescent girls (both pre- and postmenarcheal) and boys responded to a questionnaire assessing evaluative attitudes toward menstruation, expected symptomatology, perceived effects on moods and activities, and sources of information for these beliefs. The results showed that even premenarcheal girls and young boys have a reasonably well-defined and mostly negative set of attitudes and expectations. Most believed that menstruation is accompanied by physical discomforts, increased emotionality, and a disruption of activities and social interactions. Although the responses of the 3 groups were remarkably similar, premenarcheal girls had a somewhat less negative evaluation of menstruation than both postmenarcheal girls and boys. Other analysis showed that symptom expectations for "girls in general" were more severe than for selves, though these 2 sets of responses were highly correlated. On the basis of these findings and the data concerning sources of information, the possible role of socialization processes in the menstrual experience is discussed.


Sex-related differences in response to practice on a visual-spatial test and generalization to a related test. 93 first graders (mean age 6.5 years) were given a pretest and posttest on half of the items from the Children's Embedded Figures Test. Half of the children were randomly assigned to a training condition and received a brief training procedure on visual-spatial disembedding prior to the administration of the posttest. Children in the control condition received no training. The performance of girls improved significantly more from pretest to posttest than the performance of boys. Boys and girls showed similar beneficial effects of training in addition to the benefit of direct practice. The tendency that was observed for boys to perform higher than girls on the pretest, p less than .10, was not evident on the posttest. Scores on the pretest predicted scores on a different measure of visual-spatial ability only for children in the control group. The results are interpreted in terms of current theories of sex differences in visual-spatial perception.


Attributional and behavioral changes following two behavior management interventions with hyperactive boys: a follow-up study. In a 6-month follow-up study of 2 interventions with hyperactive boys, different patterns of improvement were observed for an intervention which focused on self-control and 1 which employed contingent social reinforcement. Of the 2 manipulations, self-control methods produced significantly stronger long-term benefits in terms of the child's increased perception of personal control over academic outcomes; social reinforcement, on the other hand, produced significantly stronger long-term benefits in terms of teacher ratings of hyperactivity or impulsivity (Conners Teacher Rating Scale). Both interventions produced stable changes in terms of decreased behavioral impulsivity as measured by qualitative error scores on the Porteus Mazes.


[Postoperative peritonitis. A contribution on diagnosis]. Symptoms and signs of 18 patients with postoperative bacterial peritonitis were compared with the findings in uncomplicated postoperative cases. Their diagnostic values were examined: 1. Elevated temperature, hyperventilation, and somnolence are relevant, being indicative of bacterial peritonitis and already occurring before the typical findings on abdominal examination. 2. In those patients with peritonitis, hemodynamics, and metabolism are characterized by hyperdynamic circulation, premature arterial hypotension with dry warm skin, and lactate accumulation. 3. Laboratory data often reveal thrombocytemia, leucocytosis with shift to the left, and a relative and absolute hypophosphatemia.