Evolution of the differential regulation of duplicate genes after polyploidization. In the 50 million years since the polyploidization event that gave rise to the catostomid family of fishes the duplicate genes encoding isozymes have undergone different fates. Ample opportunity has been available for regulatory evolution of these duplicate genes. Approximately half the duplicate genes have lost their expressions during this time. Of the duplicate genes remaining, the majority have diverged to different extents in their expression within and among adult tissues. The pattern of divergence of duplicate gene expression is consistent with the accumulation of mutations at regulatory genes. The absence of a correlation of extent of divergence of gene expression with the level of genetic variability for isozymes at these loci is consistent with the view that the rates of regulatory gene and structural gene evolution are uncoupled. The magnitude of divergence of duplicate gene expressions varies among tissues, enzymes, and species. Little correlation was found with the extent of divergence of duplicate gene expression within a species and its degree of morphological "conservatism", although species pairs which are increasingly taxonomically distant are less likely to share specific patterns of differential gene expression. Probable phylogenetic times of origin of several patterns of differential gene expression have been proposed. Some patterns of differential gene expression have evolved in recent evolutionary times and are specific to one or a few species, whereas at least one pattern of differential gene expression is present in nearly all species and probably arose soon after the polyploidization event. Multilocus isozymes, formed by polyploidization, provide a useful model system for studying the forces responsible for the maintenance of duplicate genes and the evolution of these once identical genes to new spatially and temporally specific patterns of regulation.


Effect of changes in population size on the correlation between mutation rate and heterozygosity. The effect of changes in population size on the correlation between mutation rate and heterozygosity was studied by using two models: sudden change in population size and gradual change. It was shown that the results for the two models are close to each other, unless the rate of change for the latter is exceedingly slow. Thus, in many cases, the former model, which is much simpler than the latter, can be used to treat the present problem. Numerical computations showed that the correlation in a population that is expanding or has expanded in the recent past is stronger while the correlation in a population that is decreasing or has experienced a population reduction or bottleneck in the recent past is weaker than that for an equilibrium population with the same mean heterozygosity. However, regardless of whether the population is at equilibrium or not, the proportion of variation in heterozygosity that is attributable to variation in molecular weight over loci is rather small if the mean heterozygosity of the population is low, say of the order 0.05 or smaller.


Energetics of peptide bond formation at elevated temperatures. The free energies of formation of the peptide bond between carbobenzoxy-glycine and L-phenylalanine amide in aqueous solution at temperatures up to 60 degree C were calculated from experimentally determined equilibrium constants. The reaction was catalyzed by a thermophylic enzyme. The thermodynamic energy barrier to peptide bond formation was found to decrease with increasing temperature: the standard free energy of peptide bond formation did appear to become negative in the region of 60 degrees C. The possible significance of these results for peptide bond formation under prebiotic conditions is discussed.


The molecular heterogeneity and diversity of reptilian keratins. Reptile keratins produce complex electrophoretic patterns, contain a number of size classes, and contain protein fractions analogous to the fractions found in other keratins. Thus, reptile keratins are similar to the heterogenous keratins of birds and mammals, and quite different from amphibian epidermal keratins. This heterogeneity may be related to the multiple functions performed by the epidermis of these organisms. The chemical diversity of reptile keratins seems to depend on the morphological differences between the tissues in which they occur. This situation is also found among these proteins in mammals and birds suggesting that keratin diversity is related to the morphological and presumably functional differentiation of epidermal tissues. The distribution of the keratin fractions in each tissue contributes to this diversity but the significance of these fractional differences is uncertain. A comparison of the half-cystine and glycine content of vertebrate alpha and ø keratins suggests that the alpha and ø proteins of reptiles may be related to the soft alpha keratins of mammals and amphibians. Mammalian hard keratins probably represent a uniquely derived group of proteins which are unlike the other vertebrate keratins. The presence of a "high sulphur" matrix component in both hard mammalian alpha and reptilian ø keratins may represent some form of molecular convergence which provides these distantly related proteins with similar physical or organizational properties.


The catalysis of nucleotide polymerization by compounds of divalent lead. Soluble lead salts and a number of lead-containing minerals catalyze the formation of oligonucleotides from nucleoside 5'-phosphorimidazolides. The effectiveness of lead compounds correlates strongly with their solubility. Under optimal conditions we were able to obtain 18% of pentamer and higher oligomers from ImpA. Reactions involving ImpU gave smaller yields.


Surgical immunology: a historical review of its role in the armamentarium of the surgical oncologist. Immunology is taking its place in multimodality therapy of malignant diseases-currently an adjuvant role. Historical development of this role and definition of terms and principles are herein presented in brief fashion.


Surgical management of radiation enteritis. In the great majority of patients treated with radiation, only transitory injury to the bowel occurs, but in five percent of patients, permanent damage to the small bowel or rectum is seen. Symptoms of radiation enteropathy may begin four to six months after the treatment is completed or may not present until several years later. Most often, the patient presents with abdominal pain, diarrhea, hematochezia, and signs of malnutrition. Others may present, initially, with intestinal obstruction, perforation, or fistulization. It is important to differentiate this clinical syndrome from recurrent cancer by appropriate radiological studies and biopsies.This paper presents four patients who were treated with radiation for invasive carcinoma of the cervix and subsequently developed radiation enteritis. All were treated surgically and are surviving.


Surgical management in sicklemia.

Surgical management in sicklemia. A review of the history and pathophysiology of sickle cell disease is given. The clinical types (crises) are discussed along with their relationship to surgical occurrences, both elective and emergency. Specifics of perioperative management are discussed and the cardinal features of importance are enumerated. A retrospective study of sickle cell disease in a community hospital is presented, outlining the surgical experience over a ten-year period.


Traumatic diaphragmatic hernias: analysis of six cases. During three years, from January 1975 through December 1977, the authors saw six cases of traumatic left diaphragmatic hernias, all of whom survived. All were males aged 17 to 56 years, with an average age of 30 years. Four (67 percent) of the cases resulted from blunt abdominal trauma while two (33 percent) were due to stab wounds of the left lower chest. Admitting chest x-ray findings were diagnostic for all acute hernias due to blunt trauma and for all hernias presenting with a delayed interval. Digital exploration of all penetrating lower chest wounds is recommended by some authors if exploratory laparotomy is not contemplated. Our preferred approach for the repair of the hernias includes (1) laparotomy for all acute cases, (2) thoracotomy for delayed cases, and (3) separate abdominal thoracic incisions whenever a combined approach is considered necessary. The repair should be carried out in two layers with nonabsorbable sutures.


Rupture of cervical esophagus from blunt trauma with concomitant fracture dislocation of C4-C5 vertebrae. A patient is presented who had sustained a high posterior cervical esophageal laceration (secondary to an automobile accident) with concomitant fracture of the C(4) - C(5) spine. It was treated by Gulbrandson conversional method. To the author's knowledge, this represents the first recorded rupture of the cervical esophagus associated with high cord lesions as a result of blunt trauma to the neck.


Moyamoya disease in black adults.

Moyamoya disease in black adults. A 40-year-old hypertensive black female, who suddenly developed aphasia, lethargy, and a right hemiparesis, and a 42-year-old non-hypertensive black male, who suddenly developed intractable headache, drowsiness, and vomiting, were found by angiography to have moyamoya disease. This condition is characterized by a decreased caliber of the internal carotid arteries and bilateral occlusion of the anterior and middle cerebral arteries with visualization of an extensive collateral network of tortuous blood vessels of the rete mirabile type at the base of the brain.


Colorectal carcinoma: a review of the experiences at Hubbard Hospital. The records of 112 patients treated for carcinoma of the colon at Hubbard Hospital between 1956 and 1971 were reviewed. The mean age was 64.4 years and 64.9 percent were females. Only 27 percent presented with Duke's A lesions. The delay in seeking medical therapy averaged 4.48 months from onset of symptoms. Most patients presented with complications of their disease and the majority had other concurrent diseases which contributed significantly to the poor overall five-year survival figures.


Management of tuberculous pneumothorax in Nigeria. Forty-eight patients with tuberculous pneumothorax treated at the University College Hospital in Ibadan, Nigeria, over a 40-month period were reviewed. This represents 90 percent of all patients admitted with nontraumatic "spontaneous" pneumothorax during the period of survey. This finding shows that pulmonary tuberculosis (still endemic in Nigeria) is the most common cause of spontaneous pneumothorax in Ibadan.Because of delay in presentation, over 70 percent of the patients presented with hydropneumothorax or pyopneumothorax, which tend to prolong the length of intubation days and the period of hospitalization. The most significant factors affecting prognosis are nutritional status of the patient, extent of parenchymal damage, severity of the bronchopleural fistula, and presence of empyema.The goal of therapy had been directed toward prompt intercostal tube drainage, complete evacuation of fluid and pus, improvement in the nutritional status of the patient, and effective chemotherapy. With this approach, open thoracotomy was rarely indicated and decortication was only necessary in five patients. Our results with intercostal tube drainage and chemotherapy alone have been very encouraging.


Transitional cloacogenic carcinoma of the anus and rectum: report of three cases. Transitional cloacogenic carcinoma of the anus is one of the rarest tumors of the alimentary tract. It represents less than two percent of all anorectal cancers. Three cases are presented from the surgical files of George W. Hubbard Hospital, Meharry Medical College, which were collected during a period of 15 years.


Cystadenoma and cystadenocarcinoma of the pancreas. Cystadenomas and cystadenocarcinomas of the pancreas are rare, with few cases encountered by any one surgeon or institution. Cystadenomas account for less than ten percent of all cystic lesions of the pancreas with less than 300 examples reported in the literature. Cystadenocarcinomas represent one percent of all pancreatic cancers with very few cases reported.This report is a presentation of a 48-year-old black female who was treated at Meharry Medical College for cystadenocarcinoma of the pancreas, and is followed by a review of the world literature.


Retained surgical sponge simulating a pancreatic mass. An abdominal mass evaluated angiographically suggested either a carcinoma or a pseudocyst of the pancreas. Exploratory laparotomy revealed a cystic mass containing a surgical sponge left in the patient's abdomen during a surgical procedure 12 years previously. A review of the literature is included and complications caused by surgical foreign bodies and means of avoiding such complications are discussed.


Duodenum inversum.

Duodenum inversum. Duodenum inversum is usually associated with chronic abdominal pain which is of unknown etiology. Incomplete rotation of the bowel may be associated with this anomaly. An unusually high incidence of pancreatitis, elevated bilirubin, and hypoalbuminemia was noted in this series of nine patients.


Cardiopulmonary parameters and prognosis after severe multiple trauma. Comprehensive cardiopulmonary and metabolic monitoring of severely traumatized patients for 7 days from the time of injury has allowed us to determine parematers which correlate with survival and nonsurvival. The earliest and most persistent change is an increased pulmonary vascular resistance which results in right heart overload and failure. Left heart "failure" which has been previously described with acute respiratory failure and shock is shown to be a mathematical artifact caused by dilatation of the right heart and encroachment on left ventricular filling volume. Causes of death in most patients were not directly referable to right heart dysfunction but we postulate that hypercoagulability and microembolism could independently produce the observed pulmonary vascular changes as well as the multiple organ failure which usually was responsible for death. Resolution of this question will require more sophisticated hematologic evaluation.


Selective hepatic artery ligation: limitations and failures. The hospital records of 540 consecutive patients with hepatic trauma were reviewed. Persistent arterial bleeding from hepatic wounds was encountered in approximately 10% of severe liver injuries. Compression of the porta hepatis will result in cessation of bleeding in such patients and subsequent ligature of the appropriate lobar artery will provide permanent, safe control of bleeding. Failures of selective hepatic artery ligation commonly result from incomplete diagnosis of the extent of injury to portal veins and hepatic veins.


Recurrent themes in ambulance critique review sessions over eight years. For 8 years biweekly ambulance critique review sessions have evaluated performance and discussed management of cases brought to our hospital by ambulance. Over 500 cases reviewed have centered primarily on evaluation and care at the scene and its possible relation to outcome. Problems which have recurred on the scene include whether the patient would have benefited from less time in stabilization and immobilization; manipulation of deformed fractures for splinting; use of tourniquets; techniques of airway maintenance; and management of infrequently seen problems such as hypothermia and drowning. Interaction problems with physicians on the scene and in the Emergency Room (ER) come from questioning physician authority even without specific knowledge of the appropriate techniques of emergency care. A related problem is lack of ER staff familiarity with Emergency Medical Technician (EMT) procedures and ambulance equipment. The value of critique review sessions has been seen in improved rapport and interaction among ER staff and ambulance personnel. Improved outcome needs to be assessed in a carefully controlled study. The enthusiasm and attendance of ER staff and ambulance personnel has grown and endured over 8 years. The review sessions have spread to other area hospitals with some success.


Value of "inconclusive lavage" in abdominal trauma management. Peritoneal lavage is an invaluable adjunct in the evaluation of abdominal trauma. Of 780 abdominal trauma patients in a prospective study, 685 underwent percutaneous peritoneal lavage. RBC counts in the effluent above 50,000/mm3 corresponded well with findings at exploration; however, two thirds of the patients having counts between 20,000--50,000/mm3 had serious injury at celiotomy. The data suggest the need for a reappraisal of lavage criteria for operation.


Management of duodenal wounds.

Management of duodenal wounds. A 30-year experience with 321 wounds of the duodenum was reviewed. Of the total, 302 had some form of perforation; 19 had intramural hematomas. All patients underwent laparotomy shortly after admission except six cases of radiographically diagnosed submucosal hematoma. Occasional dehiscence of the duodenal suture line and its life-threatening complications (six of 52 cases, or 12%) led to a policy of routine duodenal decompression by gastrostomy plus twin jejunostomies in 1962. Following use of the latter technique in 237 patients, only one leak occurred. By contrast, failure to decompress had an 8% leak rate; direct drainage of the suture line gave an even greater incidence of dehiscence or fistula, 23%. Associated pancreatic injuries were treated as separate wounds by sump drainage of distal pancreatectomy. None of three patients subjected to pancraticoduodenectomy for massive combined pancreatic and duodenal trauma survived. A long-armed T-tube was always inserted for recognized as well as suspected common duct wounds. Although most of the 41 deaths were due to major vascular trauma and sequelae of hemorrhagic shock, duodenal complications did contribute to significant morbidity and five mortalities during the earlier years of review.


Combined pancreatoduodenal injuries.

Combined pancreatoduodenal injuries. Operative management of combined pancreatic and duodenal injuries has been a controversial subject in recent years. Methods advocated include resection, duodenal diversion, and simple repair and drainage. Excellent results have been reported with each of these, but most reported series are small, preventing definitive conclusions concerning the value of any treatment modality. During an 8-year period ending December 1976, 308 pancreatic injuries and 175 duodenal injuries were treated. Sixty-eight of the patients had combined pancreatic and duodenal injuries and constitute the basis for this report. Fifty-five patients sustained penetrating injuries and 13 had blunt injuries. Eighteen underwent repair and drainage. The remaining 50 required more extensive procedures which included duodenal diversion and pyloric exclusion in 32, pancreatoduodenectomy in six, and a variety of procedures in the remainder. The operative mortality rate was 26.4%, including five patients who died intraoperatively. In the entire series only one death was directly attributable to the pancreatoduodenal injury. We conclude that no single procedure is uniformly applicable to these injuries. Surgeons treating trauma of this severity should be familiar with a variety of techniques for repair, and treatment should be individualized. Preservation of tissue should be accomplished when possible.


Brainstem auditory evoked responses in patients comatose as a result of blunt head trauma. The brainstem auditory evoked response (BAER) was evaluated as an aid in the early diagnosis and prognosis of 17 comatose blunt head-injury patients. Click stimuli (60 dBSL, 10/sec) were presented monaurally through headphones. BAER's were recorded between Cz and ipsilateral mastoid; contralateral mastoid ground. No BAER waves occurred in three "brain-dead" patients. Two patients with initially abnormal BAER's did not show improvement in followup recordings, and died of their brain injuries. Recovery occurred in 12 patients with normal followup BAER's, regardless of whether initial BAER's had been abnormal (three patients) or normal (nine patients). Apparently, initial BAER's (mean, 31 hours postinjury) can be abnormal as the result of reversible damage. Followup BAER's (3 to 6  days postinjury) did correspond with patient outcome at a time when clinical prognoses were often uncertain. BAER's aided diagnostically in determining the extent of brainstem damage and the effectiveness of treatment.


A review of the complications of burns, their origin and importance for illness and death. Complications are the major causes of illness and death after burning and most of them stem from the burn wound. Their origin and importance are reviewed with emphasis on problems and growing points in knowledge. Fluid leakage from the circulation into the burn is the cause of hypovolemic shock, but the underlying permeability changes in the burn are only partly understood. Other nonbacterial complications include acute cardiac failure, acute anemia, hemolytic jaundice, renal failure, encephalopathy, complex hypermetabolic effects including pseudodiabetes, gastric and duodenal ulceration, deep vein thrombosis and pulmonary embolism, pulmonary and glomerular microthrombosis, hepatic jaundice, and arterial thrombosis. Involvement of the airway in conflagrations carries special hazards like glottic edema and inhalation of irritant fumes. Nowadays, bacterial causes are dominant and these remain the main challenge. Bacterial infection and invasion of the burn are usually responsible for septicemia, bronchopneumonia, and pyelonephritis although other sources also contribute. Indirect manifestations of septicemia include paralytic ileus, acute gastric dilatation, toxic myocarditis, and some cases of renal failure. Therapeutic complications like agranulocytosis, thrombocytopenia, and colitis occur at times. High concentrations of oxygen given therapeutically can produce fatal aseptic hypoxic pneumonitis.


Cranio-orbito-facial injuries: technical suggestions. Eight per cent of 387 acutely head-injured patients had concomitant orbitofacial injuries. Irrespective of the magnitude of brain injury, the main surgical goals in such cases treated were closure of CSF fistulas, maximizing recovery of eye movement, visual and masticatory function, and esthetic reconstruction. The strictly neurosurgical lesions should be dealt with at once because of the risk of intracranial infection. Antibiotic acrylic and antibiotic wax are valuable in such intervention. In most cases it is advantageous to treat lesions of the upper two thirds of the facial complex in the same operative session. For this reason neurosurgeons who do not have ready access to a maxillofacial specialist should be prepared to cope with the problems presented by orbitofacial injuries.


Exploration of low-velocity gunshot wounds of the neck. Review of 68 consecutive patients seen between 1966 and 1976 with low-velocity gunshot wounds of the neck is reported. Treatment and results are compared. Comparison of preoperative evaluation and operative findings shows that the initial evaluation may miss serious injuries. Associated severe injuries are common. Morbidity following exploration is low. Exploration of all low-velocity gunshot wounds to the neck is recommended.


Arthrography as a method of diagnosing soft-tissue injuries of the wrist. Wrist arthrography was performed in 30 patients suffering from post-traumatic wrist sprain, or whom 15 sustained fractures. A longstanding soft-tissue injury was demonstrated in 70% of the whole group and in 60% of wrist sprains not associated with fracture. Findings include radiocarpal-radionulnar communications (26.6%), radiocarpal-midcarpal communications (36.6%), midcarpal-carpometacarpal communications (30%), radiocarpal-pisotriquetral communications (60%), tendon communications (20%), and lymphatic filling (43.3%).


Routine angiographic evaluation of neck and extremity injuries. Traumatic arterial injuries are becoming more common in civilian practice. In this study arteriography was done in 91 wounds of the neck and extremities regardless of physical findings (excluding exsanguinating or trivial injuries). Physical findings suggestive of the presence or absence of arterial injury were tabulated and compared with arteriographic findings. Physical findings were often found to be unreliable, yielding a false negative result in 20% and a false positive result in 42%. It is concluded that angiography is a safe, reliable method of diagnosis and should be routinely employed in all patients with major penetrating injuries of the neck and extremities as well as in selected patients with blunt injuries.


Evaluation and treatment of penetrating cervical injuries. Because the serious nature of penetrating cervical injuries may not be readily apparent on initial evaluation, and since delay in treatment can result in serious complications, a systematic method of evaluation and routine exploration has been employed in treating these injuries. One hundred eighty-nine patients, 49 with gunshot wounds and 140 with stab wounds, were treated in this series. Arteriography was performed in 62 patients (33%) to detect vascular injuries and to aid in the planning of the operative approach in patients with high or low neck wounds. Arteriography was 98% accurate and changed the operative approach in 29% of the positive studies. Of the 154 explorations 72 were positive (47%). There were no deaths and only four complications in the group with negative explorations. The mortality rate for the series was 2.6%. We believe that angiography in selected patients and routine exploration of wounds penetrating the platysma can minimize morbidity and mortality in these injuries.


A photoplethysmographic technique for detecting vascular compromise: a preliminary report. We have developed a photoplethysmographic technique for monitoring early signs of vascular compromise in extremities affected by direct vessel trauma, crushing trauma, or circumferential burns. The technique consists of positioning a small infrared emitter-detector array shielded from room light over a nailbed of the affected extremity and connecting the array to standard electronic monitoring equipment, thus producing a pulse tracing very similar in contour to an arterial pressure wave. In normal volunteers, simultaneous observations of the tracing and studies of muscle blood flow using Xe133 clearance showed correspondence of disappearance of the plethysmographic signal with limb-threatening levels of ischemia produced by inflation of a blood-pressure cuff. Studies comparing this technique to compartment pressures and arterial flow determined by ultrasound Doppler measurement are continuing. Clinically, we have used this monitoring technique on 29 trauma patients thus far, including 18 with circumferential full-thickness burns of at least one extremity. We believe that these preliminary studies suggest that photoplethysmography is a valuable continuous monitor of vascular status following trauma and a reliable indicator of nutritional blood flow.


The use of Technetium-99m stannous pyrophosphate scintigraphy to identify muscle damage in acute electric burns. High-voltage electric burns are often associated with deep muscle damage in addition to a limited cutaneous burn. Technetium-99m stannous pyrophosphate (99mTc-PYP) scintigrams were evaluated as a diagnostic tool to detect and localize both large and focal areas of skeletal muscle necrosis. Scintigrams were performed in 14 patients between the first and fifth postinjury days and imaging was done over areas of suspected and clinically apparent muscle injury. Muscle damage was identified by an increased cellular uptake of the tagged material. All 14 patients had gross and histologic evidence of muscle necrosis. Muscle necrosis was identified as early as 24 hours and as late as 6 days postinjury. The location and extent of muscle injury was correctly ascertained preoperatively in all patients.


The etiology of post-traumatic empyema and the role of decortication. Decortication post-traumatic empyema (PTE) was performed in 27 patients from 1972 through 1977. All 27 patients had penetrating chest wounds and were refractory to antibiotics and tube thoracostomy. Factors associated with PTE included unrecognized diaphragmatic perforation, large hemothorax greater than 500 ml, pulmonary contusion, extrathoracic extension of hematoma within the chest wall, and incomplete expansion of the lung with initial tube thoracostomy. Prophylactic antibiotic usage did not prevent PTE nor lead to negative intrapleural cultures preoperatively. The timing of decortication varied with indication: two patients with infected pneumothorax had surgery within 1 week; 15 patients with infected pleural clot had surgery within 4 weeks; ten including nine who were readmitted to the hospital had surgery more than 4 weeks after injury. Prevention of PTE requires early recognition of hemo- or pneumothorax, early tube thoracostomy with complete evacuation of blood and expansion of lung, careful daily monitoring of subsequent fluid accumulation, and prompt evacuation when such fluid accumulates. Once PTE becomes well established and refractory to standard modalities, decortication with evacuation of the empyema cavity should be performed as soon as possible.


Ventilation:perfusion maldistribution secondary to the hyperdynamic cardiovascular state as the major cause of increased pulmonary shunting in human sepsis. Cardiovascular and respiratory parameters were obtained in 374 studies from 151 patients (64 septic or septic shock and 87 with nonseptic cardiogenic syndromes). Cardiac output and related measures, respiratory parameters, pulmonary blood volume (DV/m2), cardiac ejection fraction (EFx), left ventricular end-diastolic volume (LVEDV), peripheral resistance (TPR), pulmonary shunt (QS/QT), physiologic dead space (VD/VT) and mean ventilation perfusion ratios (VA/QT) were calculated. Both physiologic evaluation and multivariable statistical analyses of the data were performed. For a given level of (A-aO2 gradient/PaO2) septic patients have a higher QS/QT than cardiogenic patients. Hyperdynamic septic patients have a larger QS/QT, a greater VD/VT, and a lower VA/QT and TPR than cardiogenics. The decrease in VA/QT and the rise in VD/VT are strong functions of the increased EFx, which raises cardiac index (CI) and reduces LVEDV and the mean dispersion of pulmonary blood volume, thus causing hemodynamic redistribution of flow. QS/QT is mainly a direct function of the increase in CI which also tends to reverse the EFx-mediated rise in VD/VT. The role of the septic mediated decrease in TPR as a contributing pathologic feature and the use of volume infusion to raise LVEDV and VA/QT in high-CI septics with large QS/QT is discussed.


Affairs of the wounded heart: penetrating cardiac wounds. During the 10-year period ending 1 March 1978, 100 consecutive patients with penetrating cardiac wounds entered the Bexar County Hospital with some sign of life. The early and late mortality rate, 11%, declined to 8% during the last 4 years. Noncardiac injuries were responsible for six of the eleven deaths. Complications occurred in 17. The most frequently injured chambers were the right ventricle (46) and left ventricle (30). Sixty-nine patients had stab wounds and 26 had gunshot wounds. Pericardiocentesis was falsely positive or negative in 12 of 47 patients. Two distinct syndromes were apparent, hemorrhagic shock and cardiac tamponade. Patients with shock had immediate thoracotomy. Patients with suspected tamponade had a subxiphoid pericardial window, under local or light general anesthesia, for diagnosis and decompression before endotracheal intubation and sternotomy. Most wounds were repaired by direct suture. Cardiopulmonary bypass and thoracotomy before arrival in the operating room were rarely indicated.


Idiopathic cardiomyopathy in Botswana.

Idiopathic cardiomyopathy in Botswana. During a review of all cases of heart disease, including hypertensive cardiac failure, seen in Botswana during a period of sixteen months by one Specialist Physician observer, the importance of Idiopathic Cardiomyopathy as the commonest cause of cardiac failure clearly emerged. The aetiology of this condition and its relationship to hypertension and other factors causing an increased load on the myocardium are discussed. Viral myocarditis is presented as a separate entity, possibly playing a part in causation.


Cardiac tamponade following penetrating mediastinal injuries: improved survival with early pericardiocentesis. Cardiac tamponade was diagnosed in 197 patients admitted over 20 years (1955-1974) to the Charity Hospital of New Orleans, for emergency treatment of pentrating mediastinal injuries. Of the 197, 174 definitively treated patients followed one of three patterns of management: 96 had OR thoracotomy, 68% were unstable, and preoperative pericardiocentesis reduced mortality from 25 to 11% (p less than 0.01); 44 had emergency thoracotomy, 91% were unstable, and prethoractomy pericardiocentesis decreased mortality from 94 to 63% (p less than 0.05); 34 patients primarily with isolated stab wounds, were treated nonsurgically with pericardiocentesis and observation, only 50% were unstable and there was 15% mortality. Recurrent tamponade did not significantly increase overall or operative mortality in patients with pericardiocentesis. early, even presumptive, diagnosis of tamponade; immediate pericardial decompression via pericardiocentesis; and rapid transfer to OR for thoracotomy or sternotomy and cardiorrhaphy with continous pericardial decompression via intrapericardial catheter.


A preliminary report on the treatment of intestinal schistosomiasis with oxamniquine. Oxamniquine proved to be an efficient drug for the treatment of Schistosoma mansoni in adults. The cure rate obtained with a single oral dose of 15 mg/kg was 81.3 per cent. With 15 mg given b.d. for a single day the cure rate was 90 per cent. Post-treatment reduction of egg count was 93.7 and 95 per cent respectively within three months follow-up period. The drug, given by the oral route, was well tolerated, non-toxic, and side-effects were evanescent. Further studies are needed to indicate its use for mass treatment and control of schistosomiasis.


Primate retroviruses: intracistronic mapping of type D viral gag gene by use of nonconditional replication mutants. Nonconditional replication mutants of squirrel monkey retrovirus (SMRV), an endogenous type D virus of primates, are shown to be defective in post-translational processing of nonglycosylated virus-coded structural proteins. Utilizing such mutants, in combination with sensitive radioimmunological assays, we demonstrate the existence of a 72,000-molecular-weight precursor polyprotein (Pr72gag) encoded by a region of the SMRV genome designated gag. Post-translational cleavage of this precursor polyprotein gives rise to virion structural proteins of 35,000 (p35), 16,000 (p16), 12,000 (p12), and 9,000 (p9) molecular weight. Three of these viral proteins, p35, p16, and p9, are shown to be phosphorylated. Analysis of viral antigen expression in cell lines nonproductively infected with either of two replication-defective SMRV mutants or mink cells productively infected with wild-type SMRV resulted in the detection of several SMRV Pr72gag intermediate cleavage products. Adjacent proteins within such intermediates are identified by use of specific competition immunoassays, and the intracistropic order of individual structural proteins with SMRV Pr72gag was tentatively deduced as NH2-p16-p12-p35-p9-COOH.


Transforming region of group A, B, and C adenoviruses: DNA homology studies with twenty-nine human adenovirus serotypes. The 31 human adenovirus (Ad) serotypes form five groups based upon DNA genome homologies: group A (Ad12, 18, 31), group B (Ad3, 7, 11, 14, 16, 21), group C (Ad1, 2, 5, 6), group D (Ad8, 9, 10, 13, 15, 17, 19, 20, 22-30), and group E (Ad4) (M. Green, J. Mackey, W. Wold, and P. Rigden, Virology, in press). Group A Ads are highly oncogenic in newborn hamsters, group B Ads are weakly oncogenic, and other Ads are nononcogenic. However, most or all Ads transform cultured cells. We have studied the homology of Ad5, Ad7, and Ad12 transforming restriction endonuclease DNA fragments with DNAs of 29 Ad types. Ad5 HindIII-G (map position 0-7.3), Ad7 XhoI-C (map position 0-10.8), and Ad12 (strain Huie) EcoRI-C (map position 0-16) and SalI-C (map position 0-10.6) fragments were purified, labeled in vitro (nick translation), and annealed with DNAs of Ad1 to Ad16, Ad18 to Ad24, and Ad26 to Ad31. Hybrids were assayed by using hydroxylapatite. Ad5 HindIII-G hybridized 98 to 100% with DNAs of group C Ads, but only 1 to 15% with DNAs of other types. Ad7 XhoI-C fragment hybridized 85 to 99% with DNAs of group B Ads, but only 6 to 21% with DNAs of other types. Ad12 (Huie) EcoRI-C hybridized 53 to 68% with DNAs of five other Ad12 strains, 53% with Ad18 DNA, 56% with Ad31 DNA, but only 3 to 13% with DNAs of other types. In vitro-labeled Ad12 (Huie) SalI-C hybridized 35 to 71% with DNAs of 6 other Ad12 strains, 44% with Ad18 DNA, 52% with Ad31 DNA, but only 2 to 7% with DNAs Ad7, Ad2, Ad26, or Ad4. When assayed using S-1 nuclease, SalI-C annealed 17 to 44% with DNAs of group A Ads. The melting temperatures of the hybrids of Ad5 HindIII-G with all group C Ad DNAs were 84 degrees C in 0.12 M sodium phosphate (pH 6.8). The melting temperature of the Ad12 (Huie) EcoRI-C hybrid with Ad12 (Huie) DNA was 83 degrees C, but was only 71 to 77 degrees C with DNAs of other group A Ads. Thus, group C and group B Ads both have very homologous transforming regions that are not represented in DNAs of non-group C Ads or non-group B Ads, respectively. Similarily, group A Ads have unique but less homologous transforming regions. These different transforming nucleotide sequences may be reflected in the different oncogenic properties of group A, B, and C Ads.


Characterization of measles virus-specific proteins synthesized in vivo and in vitro from acutely and persistently infected cells. Measles virus protein synthesis has been analyzed in acutely and persistently infected cells. To assess the role of measles in subacute sclerosing panencephalitis (SSPE), measles viral proteins synthesized in vivo or in vitro were tested for reactivity with serum from a guinea pig(s) immunized with measles virus and sera from patients with SSPE. Guinea pig antimeasles virus serum immunoprecipitates the viral polypeptides of 78,000 molecular weight (glycosylated [G]), 70,000 molecular weight (phosphorylated [P]), 60,000 molecular weight (nucleocapsid [N]), and 35,000 molecular weight (matrix [M]) from cells acutely infected with measles virus as well as from chronically infected cells, but in the latter case, immunoprecipitated M protein has a reduced electrophoretic migration. Sera of SSPE patients immunoprecipitated all but the G protein in acutely infected cells and only the P and N proteins from chronically infected cells. In immunoprecipitates of viral polypeptides synthesized in a reticulocyte cell-free translation system, in response to mRNA from acutely or persistently infected cells, the 78,000-molecular-weight form of the G protein was not detected among the cell-free products of either mRNA. Guinea pig antimeasles virus serum immunoprecipitated P, N, and M polypeptides from the products of either form of mRNA, whereas SSPE serum immunoprecipitated the P and N polypeptides but not the M polypeptide. The differences in immunoreactivity of the antimeasles virus antiserum and the SSPE serum are discussed in terms of possible modifications of measles virus proteins in SSPE.


Origin of small RNA in von Magnus particles of influenza virus. A clone of recombinant virus obtained from the cross between WSN and Hong Kong strains of influenza virus gave rise to progeny containing predominantly von Magnus particles. In the electropherogram of virus RNA, the P3 gene was markedly diminished, and a new species of RNA (extra RNA) was present in addition to eight gene segments. The origin of the extra RNA was studied by two-dimensional gel electrophoresis of T1 RNase-generated oligonucleotides. Four out of five large oligonucleotide spots present in the extra RNA matched to those contained by the P3 gene. It was concluded that the extra RNA was derived from the P3 gene probably by deletion. The possible origin of the spot which was present in the extra RNA but not in eight gene segments including P3 was discussed.


Two small virus-specific polypeptides are produced during infection with Sindbis virus. We have identified and characterized two small virus-specific polypeptides which are produced during infection of cells with Sindbis virus, but which are not incorporated into the mature virion. The larger of these is a glycoprotein with an approximate molecular weight of 9,800 and is found predominantly in the medium of infected cells. Three independent lines of evidence demonstrate conclusively that this 9,800-dalton glycoprotein is produced during the proteolytic conversion of the precursor polypeptide, PE2, to the virion glycoprotein E2. This small glycoprotein is therefore analogous to the virion glycoprotein E3 of the very closely related alphavirus, Semliki Forest virus. The 9,800-dalton glycoprotein of Sindbis virus, unlike the E3 glycoprotein of Semliki Forest virus, is not, however, present in the viral particle. The other virus-specific polypeptide is 4,200 daltons in size, does not appear to be a glycoprotein, and is neither incorporated into the mature virus nor released into the culture medium. The gene for this small polypeptide is present in the viral 26S mRNA (the mRNA which encodes all the viral structural polypeptides) and appears to be located in the portion of the mRNA which encodes the two viral glycoproteins. The possibility that this 4,200-dalton polypeptide functions as a signal peptide during the synthesis of the viral membrane glycoproteins is discussed.


Nucleosome-like structural subunits of intranuclear parental adenovirus type 2 DNA. The intranuclear structure of parental adenovirus 2 DNA was studied using digestion with micrococcal nuclease as a probe. When cultures were infected with 32P-labeled virions, at a multiplicity of 3,000 particles per cell, 14 to 21% of parental DNA penetrated the cell and reached the nucleus. Of this parental DNA, 60% could be solubilized by extensive digestion with micrococcal nuclease. The nuclease-resistant fraction contained viral deoxyribonucleoprotein monomers and oligomers. These nucleosome-like structures contained DNA fragments which are integral multiples of a unit-length DNA of approximately 185 base pairs. The monomeric DNA is similar in length to the unit-length DNA contained in cellular nucleosomes. However, the viral oligomers are slightly smaller than their cellular counterparts. DNA-DNA hybridization demonstrated that all segments of the viral genome, including those expressed as mRNA only at late times, are represented in the nucleosomal viral DNA. The amount of early intranuclear viral chromatin was proportional to multiplicity of infection up to multiplicities of 4,000 particles per cell. However, viral transcriptional activity did not increase in direct proportion to the amount of viral chromatin. Maximum accumulation of intranuclear viral chromatin was achieved by 3 h after infection. The intranuclear parental viral chromatin remained resistant to nuclease digestion even at late times in infection, after viral DNA replication had begun.


Highly inducible cell lines derived from mice genetically transmitting the Moloney murine leukemia virus genome. Permanent, non-virus-producing cell lines have been established from a mouse embryo carrying an endogenous, genetically transmitted Moloney murine leukemia virus (M-MuLV) genome. These cells carry the M-MuLV genome, as demonstrated by hybridization of cellular DNA to M-MuLV complementary DNA, but do not express it at the levels of virus production, accumulation of intracellular viral p30, or M-MuLV-specific RNA. Treatment with bromodeoxyuridine (50 microgram/ml for 24 h) resulted in induction of XC-positive NB-tropic virus, although only a small fraction of the cells released virus (less than 0.1% after 48 h). Immunofluorescent staining and flow microfluorometry indicated that a wave of p30 accumulation occurs in the induced cells, with a maximum at 24 to 48 h after the addition of bromodeoxyuridine. Furthermore, most, if not all, cells were induced to produce p30 protein. Similar kinetics were found for the accumulation of M-MuLV-specific RNA in the cytoplasm of induced cells. This rapid induction of virus expression in a majority of cells was dependent on the presence of the M-MuLV genome and probably represents primarily the expression of this endogenous virus since induction was not observed in cells similarly derived from a sibling embryo lacking the M-MuLV genome.


Reevaluation of the proteins in rabies virus particles. Protein content and localization of individual proteins of rabies virus have been studied. Four major proteins (estimated molecular weights, about 65,000, 54,000, 37,000 and 21,000), one minor component (molecular weight, about 200,000), and one intermediate (as regards its molar concentration) component (molecular weight, about 43,000) were revealed in rabies virus particles. In subviral particles accumulating in virus-infected cells, the 200,000-, 54,000-, and 37,000-dalton components were revealed. Some properties of the subviral particles allow them to be considered as viral nucleocapsids and the proteins composing them as analogs of L, N, and NS proteins of other rhabdoviruses. Thus, the protein composition of the rabies virus strain studied does not differ from that of other rhabdoviruses.


Magical thinking and imipramine poisoning in two school-age children. Two young school-aged boys took an overdose of imipramine hydrochloride to help their enuresis. One child died, and the other required resuscitation. An office survey found that one third of school-aged children did not realize the potentially hazadous consequences of taking extra amounts of prescription medications. Physicians might be able to prevent similar needless tragedies by warning both the child and the parents of the unusual lethality of imipramine and other dangerous prescription drugs.


Purification and characterization of an early glycoprotein from adenovirus type 2-infected cells. An adenovirus type 2 early glycoprotein with an apparent molecular weight of 19,000 (E19K) in sodium dodecyl sulfate-polyacrylamide gels has been extensively purified. Purification involved detergent solubilization of membrane fractions from infected cells, followed by affinity chromatography on a lectin column and DEAE-Sephadex chromatography. The purified material contained three polypeptides (E40K, E19K, E17.5K), with approximately 90% of the material in the E19K moiety. All three polypeptides yielded identical tryptic peptide maps. The E19K polypeptide contained glucosamine as revealed by [3H]glucosamine labeling of infected cells and amino acid analysis of the purified protein. Immunoprecipitation with a monospecific antiserum showed that the E19K polypeptide started to be synthesized at 2 h, with a maximal rate at 4 h after infection. It was also synthesized at a low rate late in the infectious cycle (12 to 24 h postinfection). Immunoprecipitation from three adenovirus type 2-transformed hamster embryo cell lines and two adenovirus type 2-transformed rat cell lines revealed that one of the hamster cell lines (ad2HE4) and one of the rat cell lines (A2T2C4) expressed this protein.


Carbohydrate components of influenza C virions. The carbohydrate components of influenza C virions grown in chicken kidney (CK) cells were analyzed by gel filtration following exhaustive digestion with Pronase. The [(3)H]glucosamine-labeled glycopeptides were larger and more heterogeneous than those of influenza A/WSN virions; three major size classes (G(1), G(2), and G(3)) were resolved. Treatment with Vibrio cholerae neuraminidase caused a decrease in size of G(1) and G(2), along with release of about 16% of the (3)H label. The released sugar components were identified as N-acetylneuraminic acid by thin-layer chromatography. Peak G(3) was highly labeled with [(3)H]mannose, whereas G(1) and G(2) contained lower levels of mannose. The three major viral glycoproteins gp88, gp65, and gp30 were isolated from sodium dodecyl sulfate-polyacrylamide gels, and their glycopeptide components were analyzed after Pronase digestion. The three size classes of glycopeptides were obtained from any of the three glycoproteins; however, the relative amounts of the three components varied among the glycoproteins. Host cell-derived components, which appear to be mucopolysaccharides and glycoproteins, were found associated with influenza C virions grown in CK cells. These components contained glycopeptides that were mainly of sizes similar to peak G(2) from influenza C virions. Previous studies have shown that influenza A/WSN virus grown in several cell types contained only two size classes of glycopeptides. Two size classes comparable to peaks G(2) and G(3) from influenza C virions were also observed in influenza A/WSN grown in CK cells. Thus the large G(1) glycopeptides appear to be characteristic of influenza C virions.


Autologous transfusions. Experience in a community blood center. Review of the clinical records of 103 patients participating in a community-blood-bank-sponsored autologous transfusion program confirmed the safety of autologous blood and the practically of such a community-centered program. There were no transfusion reactions, increased morbidity, or reports of hepatitis among the autologous donor-patients. A previously unobserved phenomenon was that surgeons tended to transfuse less blood to patients who had autologous blood available, rarely exceeding the number donated, although this varied from one to three units for similar surgery. Only eight of the 103 patients  intentionally received a transfusion with homologous blood in addition to their autologously donated blood. Patients, their physicians, and the blood bank can all benefit substantially from such a program.


Mittelschmerz. Sonographic demonstration. Ultrasonography of the pelvis at mid-menstrual cycle in normal women has demonstrated small quantities of free fluid in 40% of cycles. Two thirds of the cycles associated with pain had ultrasonically demonstrated fluid at ovulation. These sonographic findings at Mittelschmerz confirm the physiological trauma of ovulation.


Reversible acute renal failure induced by indomethacin. Acute renal failure occurred during indomethacin therapy in a patient with chronic pyelonephritis. Urinary prostaglandin E2 levels were diminished but returned to normal after discontinuation of drug therapy and recovery of renal function. Prostaglandins may be critical for the integrity of renal function, and the use of prostaglandin inhibitors such as indomethacin and other nonsteroidal anti-inflammatory drugs may be deleterious in patients with underlying renal disease.


The fat embolism syndrome.

The fat embolism syndrome. The fat embolism syndrome is a symptom complex of acute respiratory failure after long-bone fractures. It is thought to be caused by deposition of embolic fat within the pulmonary capillaries, resulting in a capillary leak within the lung. The source of the embolic fat appears to be marrow fat. Alterations in circulating free fatty acids, increases in fibrin split products, and increases in platelet adhesiveness have been observed to occur in this syndrome and probably play an important part in the production of the pulmonary lesion. The signs and symptoms of the syndrome are hypoxemia, tachypnea, petechiae, fever, altered sensorium, and chest roentgenograms similar to signs of the adult respiratory distress syndrome (ARDS). Early recognition is facilitated by monitoring of arterial blood gas levels for hypoxemia. Treatment is directed at ARDS using graduated oxygen therapy and steroids.


Chest wall syndrome. A common cause of unexplained cardiac pain. Twelve patients with severe, often incapacitating chest pain initially believed to be cardiac in origin were shown on subsequent evaluation to have chest wall syndrome. Diagnosis was suspected by the atypical nature of pain in 11 of 12 patients and confirmed by chest wall tenderness simulating the spontaneously occurring pain in all. Seven patients had chest wall syndrome in conjunction with other associated cardiac conditions. Five patients had isolated chest wall syndrome. All five had normal ejection fractions and no regional wall abnormalities on radionuclide cineangiographic studies performed during symptom-limited supine exercise, findings observed in few patients with coronary artery disease. Chest wall syndrome should be considered in all patients with chest pain, as its recognition can greatly aid in patient care.


Continuous monitoring for ventricular arrhythmias during exercise tests. Exercise stress testing is being increasingly used to verify exercise-induced arrhythmia and to aid in assessing antiarrhythmic drug efficacy. The true prevalence of ventricular arrhythmia during exercise testing is underestimated by means other than continuous monitoring. We compared the yield of ventricular premature beats (VPBs) between a continuous recording system ("trendscription") and intermittent monitoring among 39 patients undergoing a total of 50 consecutive exercise studies. By intermittent monitoring, 22 (44%) of 50 of the exercise tests demonstrated VPBs; with trendscription, 31 (62%) exhibited such arrhythmia. Most striking, however, was a sixfold increase in the disclosure of complex and repetitive forms of VPBs (56 vs nine episodes). Thus, this form of monitoring presents a cost-efficient, on-line method that allows concentration on the patient during exercise as well as clear recording of all arrhythmic events.


Surveillance of nosocomial infections by antibiotic monitoring. Records of all patients receiving intravenous gentamicin sulfate during a 92-day interval were reviewed to detect nosocomial infections that had been missed by routine surveillance. Only 46 of 48 of the 99 treatment courses had been detected. In 96% of cases not detected by routine surveillance, use of gentamicin was considered justified. Of the patients missed by surveillance, 83% were in oncology wards, and 46% had severe neutropenia and fever of unknown origin. Antibiotic surveillance proved a useful adjunct in estimating the incidence of nosocomial infections in such patients.


Women physicians in medical academia. A national statistical survey. We determined the representation of women physicians on US medical school faculties by enumeration from school catalogues according to professorial rank, title series, and department affilitation. We also compiled similar data for top-level administrative posts, using periodic chronological comparisons from 1955 through 1977 and 1978. Despite a burgeoning population of women medical students, we found a pattern of underuse of women physicians characterized by limited upward mobility on the faculty (professor: median, 3.0%; range, 0% to 18.2%; assistant professor; median, 7.3%; range, 0% to 28.7%). There were no women in chief executive positions.


Severe anaphylactoid reaction to radiographic contrast media. Recurrences despites premedication with diphenhydramine and prednisone. Patients with a history of anaphylactoid reaction to radiographic contrast medium (RCM) are at increased risk for subsequent reaction. To date, 275 of these high-risk patients have been studied with use of prophylactic pretreatment with diphenhydramine hydrochloride or prednisone or both without a single severe anaphylactoid reaction on readministration of RCM. This report describes a patient who received pretreatment as described in the literature but suffered a life-threatening anaphylactoid reaction on readministration of RCM. Premedication does not eliminate the possiblity of a fatal reaction on readministration of RCM.


Aplastic anemia and agranulocytosis in patients using methazolamide for glaucoma. Carbonic anhydrase inhibitors used in the treatment of glaucoma, seizure disorders, and hypertension are rarely associated with blood dyscrasias. Several case reports of aplastic anemia with use of acetazolamide, and two cases with use of methazolamide, have appeared in the literature. This article describes two cases of aplastic anemia, at least one of which was almost certainly induced by the use of methazolamide, and one case of agranulocytosis related to the use of methazolamide.


Cefazolin vs penicillin. Treatment of uncomplicated pneumococcal pneumonia. Cefazolin sodium, 500 mg intramuscularly twice daily, was compared with penicillin G procaine, 600,000 units intramuscularly twice daily, in the treatment of 82 patients with pneumococcal pneumonia. Patients were randomly assigned except when there was a history of penicillin allergy. The patients received treatment for five days or until they were afebrile for 48 hours. No patients experienced side effects or allergic reactions. All patients recovered satisfactorily without relapses. Cefazolin in the previously described dosage is as effective as penicillin in the treatment of pneumococcal pneumonia.


Tolbutamide pharmacogenetics and the UGDP controversy. We analyzed the relationship between the pharmacogenetics of tolbutamide metabolism and the controversial University Group Diabetes Program (UGDP) study. Before the institution of that study, the extent of genetic control over the variation in the rate of tolbutamide metabolism was unknown, and all subjects included in the tolbutamide treatment group were given 1,500 mg/day of tolbutamide in a fixed dosage. We addressed the hypothesis that high accrued blood levels of tolbutamide in genetically predisposed slow inactivators might have contributed to the toxic effects reported by the UGDP study. This proposal is based on recent findings from population, twin, and family studies that tolbutamide metabolism is under monogenic control, with nearly one fourth of the population classified as slow inactivators.


Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. Tamoxifen citrate (Nolvadex [Great Britain]; no comparable US product) is a recently developed antiestrogen with significant activity against metastatic breast cancer in postmenopausal women. We investigated its usefulness in breast cancer patients after conventional endocrine therapy and combination chemotherapy had failed. Of the 50 evaluable patients, four (8%) achieved a complete remission, 14 (28%) achieved a partial remission, and ten showed a less than partial response or stabilization of their disease. Median duration of response was eight months, and the survival of responders was significantly prolonged compared to that of the nonresponders. Side effects of the treatment were mild. These results demonstrate that tamoxifen offers the best choice of therapy for patients with metastatic breast cancer after conventional endocrine therapy and combination chemotherapy have failed.


A portable medical record system for the elderly. A portable medical record system consisting of a bracelet and wallet card, was given to two groups of ambulatory, chronically ill, mentally clear, older patients. Group 1 included 23 patients discharged from a skilled nursing facility and treated in the community; group 2, 24 patients attending the outpatient department of an acute general teaching hospital. Biweekly follow-up telephone calls to patients and subsequent discussions with physicians demonstrated the usefulness of this system in predominantly nonemergency settings. Overall, the physicians noticed the bracelet during 46% of the visits and the wallet card during 28%. Group 2 physicians, however, noticed the bracelet and/or wallet card more frequently than did group 1 physicians. Reasons for the difference in recognition among the two groups and the implications for future use of a portable medical record system for the elderly are discussed.


Roentgenographic findings in infants with meconium aspiration syndrome. Aspiration of meconium produces respiratory distress of various severity and outcome. To evaluate whether the initial chest roentgenogram (0 to 8 hours of age) can be used to predict the outcome, an analysis of 80 cases with clinical and roentgenographic features of aspiration syndrome was undertaken. Infiltration was seen in 62, consolidation or atelectasis in 44, hyperinflation in 37, air leak in 25, pleural effusion in 16, and increased cardiothymic shadow in 16. Consolidation or atelectasis, most commonly associated with thick meconium aspiration, appeared to be the most significant determinant of poor outcome. Infants who had consolidation or atelectasis were more ill, had lower pH, higher fraction of inspired oxygen, higher alveolar-arterial oxygen gradients, and required longer duration of oxygen intake than those infants who had no consolidation or atelectasis. Thus, the initial chest roentgenogram can be used for predicting outcome in infants with meconium aspiration syndrome.


Burns. I. Assessment.

Burns. I. Assessment. The emergency department treatment of burn injuries requires a thorough evaluation of extent and depth of injury and an understanding of the pathophysiology involved. Fluid resuscitation must be instituted promptly and pursued vigorously. Other aspects of resuscitation demand varying priorities in different patients. Small wounds can be cared for on an outpatient basis, but patients with larger burns or those involving important functional areas should be admitted for inpatient care.


Hereditary spherocytosis with normal osmotic fragility after incubation. Is the autohemolysis test really obsolete? Two patients in two families had hereditary spherocytosis but lacked a population of RBCs with increased osmotic fragility after incubation. The diagnosis in each patient was confirmed by the presence of splenomegaly, spherocytosis, reticulocytosis, and abnormal autohemolysis corrected by glucose. Sodium flux studies showed increased sodium permeability of the RBC membrane in one patient and normal permeability in another. Hereditary spherocytosis was also present in three other family members of patient 2. The autohemolysis test is of value in confirming the diagnosis in patients with hereditary spherocytosis and normal incubated osmotic fragility.


Exertional heatstroke in novice runners. Heatstroke occurred in four apparently normal but inexperienced runners who were involved in road races of 10, 16, 32, and 42 km. Each of the runners attempted to increase his running pace by approximately 1 min/km during the last 5 km of the race. Symptoms of heatstroke occurred within five to ten minutes of the onset of increased effort. In three cases, environmental conditions (temperatures, 24 to 26 degrees C) were contributory. Specific guidelines and instructions are needed for inexperienced runners who enter distance road races.


Hypophosphatemia in hospitalized patients. Hypophosphatemia is common in hospitalized patients and occurs under a variety of circumstances other than parathyroid hormone excess. Charts of 100 inpatients with hypophosphatemia were reviewed and the patients divided into five groups on the basis of serum phosphate level: 18, 2.1 to 2.4 mg/dL; 49, 1.6 to 2.0 mg/dL; 20, 1.1 to 1.5 mg/dL; 12, 0.6 to 1.0 mg/dL; 1, 0.1 to 0.5 mg/dL. The effect of glucose ingestion on serum phosphate level was shown in one normal patient. Whenever carbohydrate was administered intravenously (45 cases), this was considered the primary cause of the hypophosphatemia. Other causes were as follows: diuretics, hyperalimentation, alcoholism, respiratory alkalosis, dialysis, insulin, corticosteroids, diabetic ketoacidosis, vomiting, phosphate-binding antacid, Gram-negative sepsis, primary hyperparathyroidism, saline, epinephrine, gastrointestinal malabsorption, and unknown. Hypophosphatemia in hospitalized patients may have multiple causes.


Selective transsphenoidal adenomectomy in women with galactorrhea-amenorrhea. Thirty women with prolactin (PRL)-secreting adenomas underwent selective adenomectomy via a transsphenoidal route. All had abnormal sella polytomes or visual fields, amenorrhea with low basal serum gonadotropin levels despite decreased serum estradiol concentrations, and elevated basal serum PRL levels with blunted PRL response to neuroendocrine stimulation tests )thyrotropin-releasing hormone, levodopa, chlorpromazine, and hypoglycemia). Of 17 patients with microadenomas, 14 (82.4%) were cured and three (17.6%) improved. None were unchanged or worse. Three (60%) of five patients with larger, but still intrasellar tumors, had normalization of PRL levels, return of menses, and resolution of galactorrhea. The patients with tumors extending out of the sella did not fare as well. Overall, 21 (70%) were cured, six (20%) improved, two (6.7%) were unchanged, and the condition of one (3.3%) became worse. All preoperative neurologic deficits resolved. Postoperative complications were minimal with no neurologic morbidity. When tumors are small, surgical results are excellent with minimal risk.


Studies of amygdalin (laetrile) toxicity in rodents. Amygdalin (laetrile), given to Fischer 344 rats in doses of 250, 500, and 750 mg/kg intraperitoneally daily for five days, caused mortalities of 30.8% 44.1%, and 56.8%, respectively. The mode of death and the elevated serum cyanide levels in the dying animals strongly suggested cyanide poisoning as the cause of death. These findings seriously question the use of amygdalin in clinical medicine under any circumstances.


Treatment of circulatory shock with dopamine. Studies on survival. Therapeutic effects of dopamine hydrochloride on the peripheral and metabolic defects of shock were investigated in 34 patients with circulatory shock associated with myocardial infarction, bacteremia, or hypovolemia. Severity of the circulatory defect characterized by hypotension, reduced cardiac output, oliguria, and notably reduced skin (toe) temperature before treatment with dopamine was not directly related to survival. However, the arterial blood concentration of lactate before treatment with dopamine indicated the likelihood of survival. Patients who ultimately survived following treatment with dopamine had normal or only mildly elevated levels of arterial blood lactate before therapy. No patients with established shock states in whom perfusion failure was associated with substantial increases in the level of arterial blood lactate survived regardless of treatment with dopamine. Increases in toe temperature during dopamine treatment also emerged as a uniquely good indicator of favorable outcome during therapy.


The aging thyroid. Increased prevalence of elevated serum thyrotropin levels in the elderly. Of 344 relatively healthy persons older than 60 years, 22 (5.9%) had a clearly elevated level of serum thyrotropin (TSH) (greater than 10 muU/mL), a finding more common in women than in men. Ten of the 22 had low values for serum thyroxine (T4) and free T4 (FT4) index, but only one had a low value for serum triiodothyronine (T3) or free T3 (FT3) index. A further 14.4% had a slightly elevated level of serum TSH (greater than 5 less than or equal to 10 muU/mL), but none had low values for serum T4 or FT4 index. Age alone has little effect on the measurements of T4; age is associated with slightly lower T3 levels, but only in men 60 years or older or in women 80 years or older. Longitudinal studies should determine if a slightly elevated serum TSH rises further with age and if there is a causal relationship between a high level of serum TSH and cardiovascular disease.


The diagnostic dilemma of isolated hyperthyroxinemia in acute illness. Eighteen patients with a variety of illnesses but no history of thyroid disease were shown to have elevated serum total and free thyroxine (T4) concentrations but low serum total triiodothyronine (T3) levels. Thyroid function tests were requested initially to excluded the possibility of hyperthyroidism in a setting of hypermetabolism. Clinical and laboratory follow-up investigations demonstrated that 15 patients were euthyroid and that hormonal alterations were transient features of the intercurrent illnesses. Three patients did, in fact, have hyperthyroidism. Retrospective analysis of diagnostic data demonstrated that of the initial thyroid function screening tests, serum total T3 concentration, the T3/TF4 ratio, and the indirectly measured free T3 (FT3) index were the most useful parameters in excluding hyperthyroidism. The FT3 index was the most helpful, being normal or low in all the euthyroid and high in each of the hyperthyroid patients.


Endometrial cancer in relation to patterns of menopausal estrogen use. Female residents of King County, Washington, in whom endometrial cancer developed between January 1975 and April 1976 were interviewed concerning prior use of menopausal estrogens. Their responses were compared with those of a random sample of women from the same population. Among current estrogen users, endometrial cancer risk was strongly related to duration of use; although only a minimal elevation of risk was present during the first two years, there was a rapid rise to a 20-fold excess after about ten to 15 years. Cessation of estrogen use led to a decline in incidence of endometrial cancer within several years, but the risk remained higher than in nonusers through the first decade after administration of the drug was stopped. Risk was elevated whether or not the regimen was cyclic and whether conjugated or other types of estrogens had been used. Dosages of less than 0.625 mg/day of conjugated estrogens produced a smaller increase in risk than did other dosages.


Thyroid function screening in psychiatric patients. Abnormalities in levels of total thyroxine and thyroxine binding capacity were common in a group of 480 newly admitted psychiatric patients. The estimated free thyroxine (EFT4) level was elevated in 43 patients (9%). In 27 of these patients, the level of EFT4 became spontaneously normal, usually within a two-week period (acute "stress hyperthyroidism"). The level of EFT4 was decreased in 42 patients (9%). In 16 of these patients, the level became spontaneously normal; the etiology of this apparent acute hypolhyroidism is unclear. The yield of new cases of primary hyperthyroidism and hypothyroidism was low, but a presumptive diagnosis of secondary hypothyroidism was made in eight patients. In addition, nine patients with known thyroid disease were taking inadequate or excessive replacement therapy. Thyroid function screening tests are of value in psychiatric patients.


Elevation of serum lactate dehydrogenase levels in renal infarction. The diagnostic value of a strikingly elevated serum lactate dehydrogenase (LDH) level in association with only small or no increases in SGOT and alkaline phosphatase levels was noted in five patients with proved renal infarction. Four had renal artery embolism and infarction in association with atrial arrhythmias; one had an acute extension of an abdominal aortic aneurysm occluding the renal artery. Other causes of a considerable isolated increase in the serum LDH level such as hemolysis and myocardial infarction can usually be easily excluded.


Hyperthyroidism due to functioning metastatic thyroid carcinoma. Precipitation of thyroid storm with therapeutic radioactive iodine. Two patients had hyperthyroidism secondary to functioning metastatic follicular thyroid carcinoma. Failure to control the thyrotoxic state with antithyroid drugs in one patient prior to treatment with radioactive iodine led to exacerbation of the thyrotoxicosis with thyroid storm and death. A second patient, in whom a euthyroid state was induced before radioactive iodine therapy, had a benign posttreatment course. Radioactive iodine therapy of functioning metastatic thyroid carcinoma should be administered with caution and only after adequate preparation of the elderly patient with cardiovascular disease.


Lithium carbonate-induced hypothyroidism. Its many faces. The correct diagnosis of hypothyroidism can be difficult, especially if it occurs in association with conditions producing similar manifestations. This point is illustrated by the presentation of three cases of lithium carbonate-induced hypothyroidism.


Cutaneous Rhizopus infection. Occurrence as a postoperative complication associated with an elasticized adhesive dressing. A 29-year-0ld woman in good health except for scoliosis suffered severe sequelae during the postoperative course for placement of a Harrington rod. A cutaneous Rhizopus infection in and about the incision site was attributed to the use of a contaminated elasticized adhesive (Elastoplast) dressing. The comtamination was established as a nosocomial problem, which is extremely difficult to control. The extent of the infection, subsequent long recovery course, and remarkable sequelae make this case unusual.


Mexiletine. Use in control of chronic drug-resistant ventricular arrhythmia. The antiarrhythmic efficacy of mexiletine hydrochloride was studied in ten selected patients with stable resistant ventricular ectopic activity in whom lidocaine, procainamide, and other antiarrhythmic agents were of no avail. Continuous Holter ECG tapes were analyzed before, during, and after mexiletine. Orally administered mexiletine was found to be very effective in treatment of drug-resistant ventricular arrhythmias, with total abolition of arrhythmia in six and satisfactory control in two additional patients. Long-term follow-up confirmed maintenance of antiarrhythmic efficacy, while biochemical and hematological screening demonstrated no abnormalities. The long therapeutic half-life of the drug allowed convenient dosage schedule and good compliance. Its efficacy, low frequency of side effects, and long half-life make it an agent of notable value in suppressing ventricular arrhythmias.


Do condom catheter collecting systems cause urinary tract infection? A study was undertaken to determine whether use of a condom catheter collection system (CCCS) is associated with urinary tract infection (UTI). No UTI developed in 79 episodes of CCCS use in patients who were cooperative or because of paralysis were unable to manipulate the collecting system (mean time per patient, 21.2 days; total number of patient days, 1,677). By contrast, in 15 patients who were identified prospectively as being uncooperative and who repeatedly manipulated the CCS, UTI developed in eight (53.3%) within a mean of 9.6 days. Urethral catheterization in cooperative patients during CCCS use was followed by development of UTI. Repeated interference with the proper use of CCCS and urethral catheterization during CCCS use are associated with an increased risk of UTI.


Diagnostic imaging procedures in acute pancreatitis. Comparison of ultrasound, intravenous cholangiography, and oral cholecystography. To evaluate the role of intravenous cholangiography (IVC), ultrasound andoral cholecystography in the diagnosis of gallstone pancreatitis, 20 patients with acute pancreatitis were studied during the first three days of an attack. The IVC successfully demonstrated the common bile duct and gallbladder in 17 (85%) 20 patients. The ultrasound studies showed the gallbladder in all 18 patients in whom the gallbladder was present. The common duct was not seen by ultrasound in any patient and the pancreas was abnormal in all patients. In the three patients with gallbladder stones these were identified on both IVC and ultrasound. Common duct stones in three patients were seen only by IVC (two of these patients had concurrent gallbladder stones and one after cholecystectomy). Oral cholecystography was of limited usefulness, although the 50% visualization rate was higher than the literature suggests.


Diazepam and drug-associated deaths. A survey in the United States and Canada. This study describes a population of deceased persons in which death was generally caused by ingestion of numerous drugs, of which diazepam was only one agent. This drug occurred with high frequency relative to the total case load at each site, but its toxicological importance was often of a low order, and its role in the fatal cases was judged as minimal.


Erythromycin for anaerobic pleuropulmonary and soft-tissue infections. Erythromycin has been reported to be active in vitro against most anaerobic bacteria. We found it effective in treating 14 of 17 patients with mild to moderately severe anaerobic or mixed aerobic/anaerobic pleuropulmonary of soft-tissue infections when adjunctive measures (eg, drainage, débridement, and the use of additional antibiotics to treat important aerobic pathogens) were employed. Erythromycin offers a reasonable therapeutic alternative to penicillin in the treatment of a penicillin-allergic patient who has a mild or moderately severe anaerobic or mixed aerobic/anaerobic infection not involving Bacteroides fragilis or fusobacteria.


Improved life expectancy for children with exstrophy of the bladder. Life-table techniques demonstrate a 98% ten-year survival, a 96% 20-year survival, and 91% 35-year survival of children with exstrophy of the bladder. These figures represent a vast improvement over the earlier figures, due in large part to technical advances that have been made in areas of surgery, anesthesia, and antibacterial and metabolic therapy.


Digoxin-prescribing. Mostly good news.

Digoxin-prescribing. Mostly good news. We examined digoxin-prescribing in 47,000 prescriptions written predominantly by physicians in a large family medicine practice. Two hundred fifty-four patients received 511 digoxin prescriptions. Dose adjustments for age (16% decrease in patients older than 64 years), for renal disease (33% decrease), and for atrial fibrillation (39% increase) followed good prescribing practices. Appropriately lower loading doses were used for digitalization. However, despite continuing concern over the bioavailability of generic digoxin tablets, less than 40% of digoxin prescriptions in this study were written for the innovator's brand-name product (Lanoxin).


Response of bladder and urethral mucosa to catheterization. Short-term urinary bladder drainage with the use of urethral Foley catheters is practiced frequently in hospitals throughout the country. We studied the urethral and bladder cellular proliferation after exposure to latex, silicone-coated latex, and 100% silicone catheters. Fifty-one male patients were studied; no differences in acute cellular reaction could be detected among the three different catheter materials. Promotion of all-silicone products in hospital use may be unwarranted.


Phototoxicity. The neglected factor.

Phototoxicity. The neglected factor. Ignorance of phototoxicity by the general biomedical community constitutes a health hazard. Certain food colorants and dyes proposed for use in angiography produce lethal effects in cells and whole organisms on light exposure but not in the dark. Yet-light-relatedness is usually neglected in toxicity studies. We urge that the specific involvement of light be considered whenever the toxicity of a light-absorbing substance is assessed.


Inflicted burns in children. Recognition and treatment. Inflicted burns are an essential part of the battered child syndrome. One hundred forty-two nonaccidental burns (16%) were found in 872 children admitted to the burn center at the Children's Hospital of Michigan during the six-year period (1972 to 1977). Of the 1,518 cases of child abuse treated during this period, 9% were caused by intentional burns. Family instability and an inability to deal with stress in crisis were important factors in the cause of these injuries.


Screening for drug and alcohol abuse in a general medical population. One hundred fifty consecutive, first-visit, general medical patients were simply and inexpensively screened by questionnaire, personal inquiry, and physical examination for drug and alcohol abuse. Seventeen (11.3%) currently used psychoactive drugs, excluding alcohol, and ten (6.7%) used drugs or alcohol on a daily basis to the point that the patient considered it an abuse problem. The majority of the drug and alcohol users recognized their problem on a short questionnaire that was part of a medical intake form. Almost all of the recognized abusers of drugs or alcohol subsequently entered treatment of their problem.


Bronchiolitis and bronchitis in connective tissue disease. A possible relationship to the use of penicillamine. Rapid onset of severe and irreversbile airflow obstruction developed in two women. One had eosinophilic fasciitis and the other had rheumatoid arthritis. Both were treated with penicillamine. In the first patient, aged 42 years, dyspnea developed after six months of therapy. Her roentgenogram showed hyperinflation. Forced vital capacity expired in one second (FEV1/FVC%) decreased from 75% to 40%, and the residual volume increased by 1 L. In the second patient, aged 54 years, cough and dyspnea developed after ten months of therapy. The FEV1/FVC% was 56%, the FEV1 was 0.9 L, and the roentgenogram was normal. Lung biopsy specimens demonstrated severe and widespread bronchiolitis. An association between obliterative bronchiolitis and rheumatoid arthritis has been reported. Penicillamine may impair healing of bronchiolitis in such patients.


Carcinomatous lung abscess. Diagnosis by bronchoscopy and cytopathology. We compared the roentgenographic, bronchoscopic, and cytopathologic findings from 26 patients with carcinomatous lung abscesses (23 of which were within the tumor) with findings from 31 patients with simple lung abscesses. Despite well-described roentgenographic characteristics of the carcinomatous abscess, differentiation from a simple abscess was frequently not possible. Direct visual findings at the time of bronchoscopy were not helpful in the absence of an endobronchial lesion. Using sputums and cytological specimens from a single fiberoptic bronchoscopy, a diagnosis was made by cytopathology on initial hospitalization in 22 (88%) of 25 patients with carcinoma. No false-positive cytological studies were reported in the nonmalignant group despite the frequent presence of inflammation and infection.


Norepinephrine-secreting tumor of the organ of Zuckerkandl. Response to propranolol alone. A 24-year-old man with diagnosed pheochromocytoma of the organ of Zukerkandl, was successfully treated with propranolol hydrochloride to lower his blood pressure. In view of the positive response to propranolol, the patient was expected to have an epinephrine-secreting tumor. However, measurement of catecholamines showed that preoperative peripheral blood, vena caval samples from the tumor, intraoperative peripheral samples, and the tumor itself contained almost exclusively norephinephrine. A response of blood pressure to propranolol in a hypertensive patient does not rule out the possibility of a pheochromocytoma, even one with the usual norephinephrine predominance.


Mucocutaneous lymph node syndrome (Kawasaki disease) in adults. Mucocutaneous lymph node syndrome has been reported to occur only in children. Three adults aged 16 to 27 years had findings compatible with this illness. Patients with fever, polymorphous skin eruption, congested conjunctiva, reddened palms and soles, red lips and oral mucous membrane, and soft-tissue swelling of the peripheral extremities and who experience membranous desquamation of fingers and toes should be suspected of having mucocutaneous lymph node syndrome. No laboratory test is currently available for confirmation of the diagnosis.


An algorithm for the operational assessment of adverse drug reactions. I. Background, description, and instructions for use. Despite widespread clinical and epidemiologic attention to adverse drug reactions (ADRs), their clinical identification has been a nonreproducible act of unspecified subjective judgment; adequate operational criteria have not been available for diagnostic decisions about the cause of an observed untoward clinical manifestation. To improve scientific precision in the diagnosis of ADRs, we have developed an algorithm that provides detailed operational criteria for ranking the probability of causation when ADR is suspected between a drug and a clinical manifestation. The algorithm provides a scoring system for six axes of decision strategy: previous general experience with the drug, alternative etiologic candidates, timing of events, drug levels and evidence of overdose, dechallenge, and rechallenge. The sum of the scores is ordinally partitioned to rate the candidate ADR as definite, probable, possible, or unlikely.


An algorithm for the operational assessment of adverse drug reactions. II. Demonstration of reproducibility and validity. The reproducibility and validity of an algorithm for diagnosis of adverse drug reactions (ADRs) were tested in a clinical spectrum of 30 suspect cases. Using a questionnaire derived from the algorithm the three algorithm developers (nonexperts) agreed on the probability of ADR in 67% of cases, with pair-wise agreement varying from 73% to 87%. The pair-wise agreement of two clinical pharmacologic experts rose from 47% without the algorithm to 63% with the algorithm, with Kw, a chance-corrected index of weighted agreement, increasing from 0.26 to 0.57. The algorithmic assessments of the three nonexperts agreed with expert consensus in 80% to 83% of cases. The ADR algorithm appears to provide a reproducible and valid method of evaluating the likelihood of ADRs in individual patients. Its use can help improve the diagnostic and epidemiologic approach to these important, complex clinical phenomena.


Measurement of plasma renin concentration using exogenous human renin substrate in normal subjects: correlation with plasma renin concentration and plasma aldosterone concentration. Measurement of plasma renin concentration (PRC) was done in normal subjects at rest and under acute stimulation of renin release under unrestricted sodium intake. Concurrent measurements of plasma renin activity (PRA) and plasma aldosterone concentration (PA) were carried out. The mean values of PRC at rest and after stimulation of renin release were 12.8 +/- 1.3 (SEM) and 21.7 +/- 4.4 (SEM) ng AT I/ml/h, respectively. These corresponded to renin contents of 3.4 +/- 0.34 (SEM) X 10(-5) Goldblatt units and 5.8 +/- 0.36 (SEM) respectively. The mean percent increase of PRC (82.1 +/- 19.3 (SEM)) %) was almost indentical to that of PA (81.5 +/- 16.4 (SEM) %), but differed from that of PRA (269 +/- 83.1 (SEM) %). A very high correlation between concurrent PRC and PA (r = 0.92, P less than 0.001) was found in normal subjects at rest and under acute stimulation of renin release. A good correlation between PRC and PRA (r = 0.85, P less than 0.001) was also observed. However, a higher correlation between percent increases of PRC and PA (r = 0.92, P less than 0.001) than that of PRA and PA (r = 0.80, 0.01 less than P less than 0.005) was found. Results show that PRA is a good index of the renin content in plasma in normal subjects at rest and PRC reflects actual renin concentration in plasma at rest as well as under stimulation of renin release.


Acute arteriolar lesions of rat intestine caused by kidney extract. Lysosomal fraction of renal cortical extract, which showed high renin activity, and equipressor dosis of synthetic angiotensin II amide were administered into one-hour nephrectomized rats. Sixty minutes after the sustained elevation of 20 mmHg in mean arterial pressure by each pressor substance, the rats were sacrificed and the intraperitoneal organs were fixed. Five minutes prior to the administration of each pressor substance ferritin solution, as a test substance for vascular permeability, was intravenously injected. Medial changes in the arterioles in the intestinal submucosa were observed by electron microscopy. In angiotensin II group early lytic lesions of the muscle cells were limited to the single muscle cells. Ferritin particles were rarely found in the media. In lysosomal fraction group the lytic lesions were more advanced. Some regions of the media exhibited focal loss of smooth muscle cells manifesting focal medial necrosis. Ferritin particles were distrubuted in some areas of the necrotic media. The results suggested that the kidney extract with high renin content contained substance(s) to produce both medial necrosis and plasma insudation into the media of the arterioles.


Effects of energy-containing nutrients on blood pressure of salt-loaded rats. The present study was performed to investigate whether blood pressure of salt-loaded rats was influenced by the diet. Salt-loaded rats of Wistar strain were fed a high protein high fat diet or a high carbohydrate diet from the age of one month. The experiment was designed so that the intake of sodium chloride was equal in two groups. The body weight on the 14th week of the experiment was 394 +/- 15 g (Mean +/- SE) in the high protein high fat group, and 348 +/- 13 g in the high carbohydrate group. Blood pressure measured weekly by a tail plethysmographic method rose gradually and reached 176 +/- 5 mmHg (Mean +/- SE) on the 14th week in the high carbohydrate group. It was significantly higher than that (127 +/- 7 mmHg) of the high protein high fat group. The pressor responses to angiotensin and noradrenalin were also examined to investigate the mechanism through which salt hypertension was produced more easily by feeding a high carbohydrate diet. These responses to both drugs tended to be greater in the high carbohydrate group, but the differences between the two groups was not significant.


Blood pressure response to [1-sarcosine, 8-isoleucine] angiotensin II in patients with liver cirrhosis and ascites. [1-Sarcosine, 8-Isoleucine] angiotensin II was given to 8 patients with cirrhosis and ascites and 7 cirrhotic patients without ascites on a regular diet. The 3 ascitic patients with high plasma renin activity (PRA) gave a depressor response, but the other ascite patients with normal or low PRA gave a pressor response or no response. All the non-ascitic patients gave a pressor response. There was an inverse correlation between the PRA before infusion and the change in blood pressure induced by this compound. In the patient with the highest PRA, who had ascites of a few days' duration, a marked reduction in blood pressure was observed on infusion of this compound. These results suggest that the renin-angiotensin system might be involved in maintenance of a normal blood pressure in some patients with cirrhosis and ascites, whose ascites is presumably in an early stage.


Acute aortic regurgitation with congestive heart failure due to bacterial endocarditis: diagnosed by echocardiogram and treated successfully by surgery (a case report). A 23-year-old Japanese male with no evidence of previous heart disease was presented with bicuspid aortic valve and a life threatening acute aortic regurgitation due to subacute bacterial endocarditis. By echocardiographic techniques, a precise diagnosis was made based on the following findings: 1) premature mitral valve closure, 2) snowfall-like echoes between the systolic aortic cusps, 3) eccentricity of a diastolic aortic valvular echo. The echocardiographic diagnosis was confirmed on surgery, in which aortic valve replacement was performed with satisfactory postoperative results.


Cardiovascular function in chronic glomerulonephritis: mechanocardiographic study. The relations between mechanocardiographic measurements, types of chronic glomerulonephritis (CGN) and clinical data were examined in 70 cases of CGN (20 cases of the latent type, 6 cases of the nephritic type, 14 cases of the nephrotic type, 10 cases of the hypertensive type and 20 cases of the endstage). (1) In the different types of CGN, mechanocardiographic abnormalities increased in the order: latent type less than nephritic type less than nephrotic type less than hypertensive type less than endstage. (2) In the endstage, prolongations of ICT, ICT2 and PEP (p less than 0.01), shortening of LVET (p less than 0.05) and decrease of LVET/PEP (p less than 0.01) were observed. These abnormalities may be related to decreased myocardial contractility. (3) Analysis of the relations between mechanocardiographic measurements and results of various tests in all the cases showed that ICT, ICT2 and PEP were most nearly related to GFR, DBP, gamma-globulin and serum sodium and Q-T, Q-II/Q-T and (Q-T) -- (Q-II) were nearly related to Ht and age. The changes in cardiac function may be entirely due to increased blood pressure, decreased renal function, electrolyte disturbance, dysproteinemia and anemia associated with CGN. Abnormality in cardiac function seems to depend on the relative abnormalities of these factors and the extents of their influences.


Comparison of hemodynamic effects of exercise and isoproterenol infusion in normal young and old men. Hemodynamic comparison of ergometer exercise with isoproterenol infusion was carried out in normal young and old men, and age associated difference in responses to exercise and isoproterenol was evaluated. Ergometer exercises of 50, 100 and 150 W in young men, averaging 23.0 years, increased heart rate in linear fashion from 73.8 to 149.2, while stroke index was raised at 50 W and remained at the same level thereafter. The isoproterenol infusion of 0.02 and 0.04 microgram/kg/min increased heart rate, stroke index and cardiac index by similar amount to 50 and 100 W or ergometer exercise respectively. Ergometer exercise elevated systolic, diastolic and mean blood pressure linearly, while isoproterenol infusion lowered diastolic and mean blood pressure. In old men, averaging 73.0 years, the tolerable limit of ergometer exercise was 40 W. The increases in heart rate, cardiac index and blood pressure at the comparable work level were by similar amount to the young subjects, indicating the identical hemodynamic responses in young and old men at the same work load. Cardiac index to isoproterenol infusion of 0.02 microgram/kg/min showed less increase than ergometer exercise of 40 W in the aged. Furthermore, the increase in cardiac index to isoproterenol was less in old than young men, showing a decreased response to beta adrenergic stimulation in the aged.


Factors influencing the normal heart weight--a study of 140 hearts. Weight of the heart and its various components (muscular and non muscular portions) was measured in 138 specimens. Average heart weight for Indians was comparatively less then that of western population. Difference between the average heart weights for males and females was found to be statistically significant. The heart weight was not influenced by age and body length but by the body built. A statistically significant difference was noticed in emaciated persons. Ventricular weight constituted 50 to 80 percent of the total heart weight. A close correlation between the heart weight and ventricular weight was seen. Ventricular wall thickness did not correlate well with the heart weight.


Work intensities of different modes of exercise testings in clinical use. Several different exercise testings with treadmill, bicycle ergometer and two-step were carried out by healthy Japanese men to study oxygen consumption per minute and circulatory responses. Stress imposed on the heart by dynamic leg exercise varied depending on the mode of exercise even if energy expenditure expressed in VO2 was identical. This should be fully taken into consideration in comparison of results of different modes of exercise testing. For estimation of VO2 during treadmill slope walk, an equation was derived by multiple regression analysis with use of belt speed and slope as independent variables.


Exercise stress testing and systolic time intervals. Changes in ET/PEP in normal subjects are characterized by initial increase associated with the increase in the heart rate, stroke volume and cardiac contractility and are subsequently followed by plateuing or slightly decrease after exceeding the 70% heart rate level of the age predicted maximal heart rate. The decrease in ET/PEP is thought to be mainly due to decrease in stroke volume. After exceeding the predicted maximal heart rate ET/PEP reveals remarkable decrease that may reflect decreased cardiac function (CF). Some patients with ischemic heart diseases revealed decrease of ET/PEP at the heart rate less than the 60% level of the age predicted maximal heart rate. This may indicate decreased cardiac contractility associated with decreased stroke volume (Fig. 10). Since transient left ventricular failure is thought to take place in anginal attack, decreased ET/PEP at the heart rate below the 60% of age predicted maximal heart rate may indicate decreased cardiac function, although invasive evaluation of the cardiac function was not performed in the present study.


Systolic time intervals in progressive muscular dystrophy. Indirect systolic time intervals corrected for heart rate were measured at rest, during, and immediately after the isometric handgrip exercise in 70 patients with progressive muscular dystrophy, and these were compared with the values of normal subjects. Those with dystrophy included 47 patients with Duchenne type, 19 with limb girdle type and 4 with facioscapulohumeral type, and each type was subdivided into 2 groups by the severity of the skeletal muscle involvement: 1) mild group, included patients who were still able to walk, 2) severe group, included those who were restricted to wheel chair or confined to bed. Over a half of the patients of the severe Duchenne type group had a longer pre-ejection period (PEP), shorter left ventricular ejection time (LVET), and larger PEP/LVET ratio at rest than the normal group. Increased PEP/LVET ratio during and after isometric handgrip exercise was observed in the severe group of Duchenne type. The patients with limb girdle type, and facioscapulohumeral type showed no significant difference in values of the systolic time intervals at rest and during handgrip exercise compared with the normal subjects. The measurements of resting and exercise systolic time intervals may be useful for clinical recognition of latent left ventricular functional impairement in subjects with progressive muscular dystrophy.